HEART STROKE CHOLESTEROL

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NAME="general_information"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="1" ALIGN="bottom" WIDTH="1" HSPACE="0" VSPACE="0" ></A><FONT SIZE="4" COLOR="#660099" FACE="Arial" ><A HREF="#general_information_1" TITLE=" HEART STROKE CHOLESTEROL"><U><B>GENERAL INFORMATION</B></U></A></FONT></div> </tD> </tR> <tR> <tD VALIGN=TOP BGCOLOR=#33FFFF HEIGHT= 23 WIDTH="766"><div> <A HREF="#risk" TITLE=" HEART STROKE CHOLESTEROL"><U><B><IMG BORDER="0" SRC="Symb075c00b7011899006600.png" HEIGHT="19" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">RISK</B></U></A></div> </tD> </tR> <tR> <tD VALIGN=TOP BGCOLOR=#FFFFCC HEIGHT= 23 WIDTH="766"><div> <A HREF="#predictors_of_heart_disease" TITLE=" HEART STROKE CHOLESTEROL"><U><B><IMG BORDER="0" SRC="Symb075c00b7011899006600.png" HEIGHT="19" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">PREDICTORS OF HEART DISEASE</B></U></A></div> </tD> </tR> <tR> <tD VALIGN=TOP BGCOLOR=#33FF66 HEIGHT= 23 WIDTH="766"><div> <A HREF="#nutrition" TITLE=" HEART STROKE CHOLESTEROL"><U><B><IMG BORDER="0" SRC="Symb075c00b7011899006600.png" HEIGHT="19" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">NUTRITION</B></U></A></div> </tD> </tR> <tR> <tD VALIGN=TOP BGCOLOR=#FFCC00 HEIGHT= 23 WIDTH="766"><div> <A HREF="#medications" TITLE=" HEART STROKE CHOLESTEROL"><U><B><IMG BORDER="0" SRC="Symb075c00b7011899006600.png" HEIGHT="19" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">MEDICINES</B></U></A></div> </tD> </tR> <tR> <tD VALIGN=TOP BGCOLOR=#C0DCC0 HEIGHT= 23 WIDTH="766"><div> <A HREF="#stroke" TITLE=" HEART STROKE CHOLESTEROL"><U><B><IMG BORDER="0" SRC="Symb075c00b7011899006600.png" HEIGHT="19" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">STROKE</B></U></A></div> </tD> </tR> <tR> <tD VALIGN=TOP BGCOLOR=#FFFF80 HEIGHT= 44 WIDTH="766"><div> <B><IMG BORDER="0" SRC="Symb075c00b7011899006600.png" HEIGHT="19" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">HIGH BLOOD PRESSURE(HYPERTENSION)</B></div> <div> <A HREF="id157.htm" TARGET="_top" TITLE="BLOOD PRESSURE"><U><B><IMG BORDER="0" SRC="Symb075c00b7011899006600.png" HEIGHT="19" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">HIGH BLOOD PRESSURE PAGE</B></U></A></div> </tD> </tR> <tR> <tD VALIGN=TOP HEIGHT= 432 ><NOBR><div>  <A NAME="general_information_1"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="1" ALIGN="bottom" WIDTH="1" HSPACE="0" VSPACE="0" ></A><FONT SIZE="1" COLOR="#FF0000" FACE="Verdana" ><B>GENERAL INFORMATION</B></FONT></div> <div> <A HREF="id53_heart.htm" TARGET="_top" TITLE=" ANATOMY"><U><IMG BORDER="0" SRC="Symb075c00b700b499006600.png" HEIGHT="12" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">PICTURES OF THE HEART AND CORONARY ARTERIES </U></A></div> <div> <A HREF="http://www.americanheart.org/Heart_and_Stroke_A_Z_Guide/" TARGET="_top" TITLE="http://www.americanheart.org/Heart_and_S"><U><IMG BORDER="0" SRC="Symb075c00b700b499006600.png" HEIGHT="12" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">HEART AND STROKE A–Z GUIDE</U></A> </div> <div> <A HREF="http://www.medem.com/medlb/sub_detaillb.cfm?parent_id=68&act=disp" TARGET="_top" TITLE="http://www.medem.com/medlb/sub_detaillb."><U><IMG BORDER="0" SRC="Symb075c00b700b499006600.png" HEIGHT="12" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">HEART PAGE</U></A> (AMA)</div> <div> <A HREF="#heart_attack_warning_signs_" TITLE=" HEART STROKE CHOLESTEROL"><U><IMG BORDER="0" SRC="Symb075c00b700b499006600.png" HEIGHT="12" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">HEART ATTACK WARNING SIGNS</U></A></div> <div> <A HREF="http://www.bioscience.org/atlases/heart/sound/sound.htm" TARGET="_top" TITLE="http://www.bioscience.org/atlases/heart/"><U><IMG BORDER="0" SRC="Symb075c00b700b499006600.png" HEIGHT="12" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">listen to heart sounds</U></A></div> <div> <A HREF="#how_exercise_protects_the_heart_" TITLE=" HEART STROKE CHOLESTEROL"><U><IMG BORDER="0" SRC="Symb075c00b700b499006600.png" HEIGHT="12" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">How Exercise Protects the Heart </U></A></div> <div> <A HREF="http://www.nlm.nih.gov/medlineplus/ency/article/002946.htm" TARGET="_top" TITLE="http://www.nlm.nih.gov/medlineplus/ency/"><U><IMG BORDER="0" SRC="Symb075c00b700b499006600.png" HEIGHT="12" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">BYPASS-EXPLAINED WITH PICTURES</U></A></div> <div> <A HREF="id50.htm" TARGET="_top" TITLE="CHOLESTEROL PAGE"><U><IMG BORDER="0" SRC="Symb075c00b700b499006600.png" HEIGHT="12" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">CHOLESTEROL</U></A></div> <div> <A HREF="http://www.americanheart.org/presenter.jhtml?identifier=4778" TARGET="_top" TITLE="http://www.americanheart.org/presenter.j"><U><IMG BORDER="0" SRC="Symb075c00b700b499006600.png" HEIGHT="12" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">TRIGLYCERIDES</U></A></div> <div> <A HREF="#new_heart_tube" TITLE=" HEART STROKE CHOLESTEROL"><U><IMG BORDER="0" SRC="Symb075c00b700b499006600.png" HEIGHT="12" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">New Heart Tube</U></A></div> <div> <A HREF="#periodontal_disease" TITLE=" HEART STROKE CHOLESTEROL"><U><IMG BORDER="0" SRC="Symb075c00b700b499006600.png" HEIGHT="12" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Periodontal disease-cardiovascular disease link?</U></A></div> <div> <IMG BORDER="0" SRC="Symb075c00b700b499006600.png" HEIGHT="12" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Half of all myocardial infarctions occur in persons in whom plasma lipid levels are normal</div> <div> <A HREF="#syndrome_x" TITLE=" HEART STROKE CHOLESTEROL"><U><IMG BORDER="0" SRC="Symb075c00b700b499006600.png" HEIGHT="12" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">SYNDROME X</U></A></div> <div> <A HREF="http://ndep.nih.gov/control/CVD.htm" TARGET="_top" TITLE="http://ndep.nih.gov/control/CVD.htm"><U><IMG BORDER="0" SRC="Symb075c00b700b499006600.png" HEIGHT="12" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Link with Diabetes and Cardiovascular Disease explained</U></A></div> <div> <A HREF="#antibiotics_for_heart_attacks" TITLE=" HEART STROKE CHOLESTEROL"><U><IMG BORDER="0" SRC="Symb075c00b700b499006600.png" HEIGHT="12" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Antibiotics May Prevent Second Heart Attack </U></A></div> <div> <A HREF="#antibiotics_may_prevent_second_heart" TITLE=" HEART STROKE CHOLESTEROL"><U><IMG BORDER="0" SRC="Symb075c00b700b499006600.png" HEIGHT="12" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">BIAXIN may prevent heart attack</U></A></div> <div> <A HREF="#exercise_capacity_" TITLE=" HEART STROKE CHOLESTEROL"><U><IMG BORDER="0" SRC="Symb075c00b700b499006600.png" HEIGHT="12" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">exercise capacity was the best predictor of death risk:The New England Journal of Medicine:</U></A></div> <div> <A HREF="#cross_talk_between_iron_metabolism_and" TITLE=" HEART STROKE CHOLESTEROL"><U><IMG BORDER="0" SRC="Symb075c00b700b499006600.png" HEIGHT="12" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Iron Metabolism and Diabetes</U></A></div> <div> <A HREF="id100_insulin_and_coronary_artery_disease.htm" TARGET="_top" TITLE="diabetes"><U><IMG BORDER="0" SRC="Symb075c00b700b499006600.png" HEIGHT="12" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">insulin and coronary artery disease</U></A></div> <div> <A HREF="#women" TITLE=" HEART STROKE CHOLESTEROL"><U><IMG BORDER="0" SRC="Symb075c00b700b499006600.png" HEIGHT="12" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Heart Disease: A Woman's Biggest Health Threat</U></A></div> <div> <A HREF="#framingham_heart_study" TITLE=" HEART STROKE CHOLESTEROL"><U><IMG BORDER="0" SRC="Symb075c00b700b499006600.png" HEIGHT="12" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Framingham Heart Study</U></A></div> <div> <A HREF="#raising_hdl_levels_may_be_as_important" TITLE=" HEART STROKE CHOLESTEROL"><U><IMG BORDER="0" SRC="Symb075c00b700b499006600.png" HEIGHT="12" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Raising HDL levels may be as important as lowering LDL</U></A></div> </NOBR></tD> </tR> <tR> <tD VALIGN=TOP HEIGHT= 412 ><NOBR><div>  <A NAME="nutrition"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="1" ALIGN="bottom" WIDTH="1" HSPACE="0" VSPACE="0" ></A><FONT SIZE="1" COLOR="#FF0000" FACE="Verdana" ><B>NUTRITION</B></FONT></div> <div> <A HREF="http://www.wholehealthmd.com/hk/remedies/disp/0,1459,475,00.html" TARGET="_top" TITLE="http://www.wholehealthmd.com/hk/remedies"><U><IMG BORDER="0" SRC="Symb075c00b700b499006600.png" HEIGHT="12" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Food remedies for high blood pressure</U></A></div> <div> <A HREF="http://www.docguide.com/news/content.nsf/PaperFrameSet?OpenForm&id=120A7441200E0509852568AF003444E7&newsid=8525697700573E1885256A880053AF3E&u=http://www.ajcn.org/cgi/content/abstract/74/1/57&ref=/news/content.nsf/news/8525697700573E1885256A880053AF3E?OpenDocument&id=120A7441200E0509852568AF003444E7&c=&count=10" TARGET="_top" TITLE="http://www.docguide.com/news/content.nsf"><U><IMG BORDER="0" SRC="Symb075c00b700b499006600.png" HEIGHT="12" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">HIGH PROTEIN DIET AND CHOLESTEROL</U></A></div> <div> <A HREF="#cost_effectiveness_of_vitamin_therapy" TITLE=" HEART STROKE CHOLESTEROL"><U>B-12 AND FOLIC ACID GOOD FOR HEART DISEASE(JAMA ARTICLE 8/2001)</U></A></div> <div> <A HREF="id18_walnuts_may_decrease_risk_of_cvd.htm" TARGET="_top" TITLE=" MEDICAL NEW"><U><IMG BORDER="0" SRC="Symb075c00b700b499006600.png" HEIGHT="12" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">WALNUTS GOOD FOR YOUR HEART</U></A></div> <div> <A HREF="http://www.healthcastle.com/salmon.shtml" TARGET="_top" TITLE="http://www.healthcastle.com/salmon.shtml"><U><IMG BORDER="0" SRC="Symb075c00b700b499006600.png" HEIGHT="12" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">EATING SALMONS LOWERS CHOLESTEROL?</U></A></div> <div> <A HREF="#even_in_small_doses_may_hurt_arteries_" TITLE=" HEART STROKE CHOLESTEROL"><U><IMG BORDER="0" SRC="Symb075c00b700b499006600.png" HEIGHT="12" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Caffeine, Even in Small Doses, May Hurt Arteries </U></A></div> <div> <A HREF="#fish_oil_for_arrythmias" TITLE=" HEART STROKE CHOLESTEROL"><U><IMG BORDER="0" SRC="Symb075c00b700b499006600.png" HEIGHT="12" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">FISH OIL FOR ARRYTHMIAS</U></A></div> <div> <A HREF="#new_research_antioxidants_battle" TITLE=" HEART STROKE CHOLESTEROL"><U><IMG BORDER="0" SRC="Symb075c00b700b499006600.png" HEIGHT="12" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">High-fat meal raises blood's proinflammatory factors; vitamins E and C counter that response </U></A></div> <div> <A HREF="id18_study_soy_helps_even_with_normal.htm" TARGET="_top" TITLE=" MEDICAL NEW"><U><IMG BORDER="0" SRC="Symb075c00b700b499006600.png" HEIGHT="12" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Soy Helps Even with Normal Cholestero</U></A>l</div> <div> <IMG BORDER="0" SRC="Symb075c00b700b499006600.png" HEIGHT="12" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Fish (salmon)Cuts Risk of Heart Attack and Sudden Death</div> <div> <A HREF="id50.htm" TARGET="_top" TITLE="CHOLESTEROL PAGE"><U><IMG BORDER="0" SRC="Symb075c00b700b499006600.png" HEIGHT="12" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">CHOLESTEROL</U></A></div> <div> <A HREF="id104.htm" TARGET="_top" TITLE="FISH OIL"><U><IMG BORDER="0" SRC="Symb075c00b700b499006600.png" HEIGHT="12" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">FISH OIL</U></A></div> <div> <A HREF="id88_antioxidants_battle_inflammation.htm" TARGET="_top" TITLE="NUTRITION"><U><IMG BORDER="0" SRC="Symb075c00b700b499006600.png" HEIGHT="12" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Antioxidants Battle Inflammation</U></A></div> <div> <IMG BORDER="0" SRC="Symb075c00b700b499006600.png" HEIGHT="12" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Tea May Protect Heart Attack Survivors: Study </div> <div> <IMG BORDER="0" SRC="Symb075c00b700b499006600.png" HEIGHT="12" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Folate a B vitamin. can decrease a person's risk of having a stroke</div> <div> <IMG BORDER="0" SRC="Symb075c00b700b499006600.png" HEIGHT="12" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">vitamin D may prevent heart disease</div> <div> <IMG BORDER="0" SRC="Symb075c00b700b499006600.png" HEIGHT="12" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Daily consumption of whole-grain oat cereal reduces blood pressure,</div> <div> <A HREF="id104_omega_3_fatty_acids_improve_systemic.htm" TARGET="_top" TITLE="FISH OIL"><U><IMG BORDER="0" SRC="Symb075c00b700b499006600.png" HEIGHT="12" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Omega-3 Fatty Acids Improve Systemic Arterial Compliance</U></A></div> <div> <A HREF="#linoleic_acid_intake_may_cut_stroke" TITLE=" HEART STROKE CHOLESTEROL"><U><IMG BORDER="0" SRC="Symb075c00b700b499006600.png" HEIGHT="12" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Linoleic Acid Intake May Cut Stroke Risk: Study </U></A></div> <div> <A HREF="id18_title_fruit_vegetables_do_matter.htm" TARGET="_top" TITLE=" MEDICAL NEW"><U><IMG BORDER="0" SRC="Symb075c00b700b499006600.png" HEIGHT="12" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Fruit, Vegetables Do Matter Against Heart Disease</U></A></div> <div> <A HREF="id100_toxic_compound_is_formed_when_sugar.htm" TARGET="_top" TITLE="diabetes"><U><IMG BORDER="0" SRC="Symb075c00b700b499006600.png" HEIGHT="12" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">long cooking increases blood vessel damage</U></A></div> </NOBR></tD> </tR> <tR> <tD VALIGN=TOP HEIGHT= 373 ><NOBR><div>  <A NAME="predictors_of_heart_disease"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="1" ALIGN="bottom" WIDTH="1" HSPACE="0" VSPACE="0" ></A><FONT SIZE="1" COLOR="#FF0000" FACE="Arial" ><B>PREDICTORS OF HEART DISEASE</B></FONT></div> <div> <A HREF="#c_reactive_protein_serumis_the_first" TITLE=" HEART STROKE CHOLESTEROL"><U><IMG BORDER="0" SRC="Symb075c00b700b499006600.png" HEIGHT="12" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Cardio CRP(CCRP)</U></A><A HREF="#c_reactive_protein_serumis_the_first" TITLE=" HEART STROKE CHOLESTEROL"><U>(C-reactive protein)</U></A></div> <div> <A HREF="#rosuvastatin_to_prevent_vascular_events" TITLE=" HEART STROKE CHOLESTEROL"><U><IMG BORDER="0" SRC="Symb075c00b700dc99006600.png" HEIGHT="15" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Rosuvastatin to prevent vascular events in men and women with high creactive protein</U></A></div> <div> <A HREF="#b_type_natriuretic_peptide___a" TITLE=" HEART STROKE CHOLESTEROL"><U><IMG BORDER="0" SRC="Symb075c00b700b499006600.png" HEIGHT="12" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">B-Type Natriuretic Peptide </U></A></div> <div> <A HREF="#uc_davis_study_identifies_c_reactive" TITLE=" HEART STROKE CHOLESTEROL"><U><IMG BORDER="0" SRC="Symb075c00b700b499006600.png" HEIGHT="12" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">C-Reactive Protein as Cause of Blood Clot Formation</U></A></div> <div> <A HREF="#exercise__lowers_levels_of_c_reactive" TITLE=" HEART STROKE CHOLESTEROL"><U><IMG BORDER="0" SRC="Symb075c00b700b499006600.png" HEIGHT="12" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Exercise  lowers levels of C-reactive protein </U></A></div> <div> <A HREF="#homocysteine_may_speed_post_angioplasty" TITLE=" HEART STROKE CHOLESTEROL"><U><IMG BORDER="0" SRC="Symb075c00b700b499006600.png" HEIGHT="12" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Homocysteine May Speed Post-Angioplasty Artery Narrowing </U></A></div> <div> <A HREF="#hyperhomocystinemia_and_coronary_artery" TITLE=" HEART STROKE CHOLESTEROL"><U><IMG BORDER="0" SRC="Symb075c00b700b499006600.png" HEIGHT="12" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">homocystine and Coronary Artery Disease</U></A></div> <div> <A HREF="#soluble_cd40_ligand_in_acute_coronary" TITLE=" HEART STROKE CHOLESTEROL"><U><IMG BORDER="0" SRC="Symb075c00b700b499006600.png" HEIGHT="12" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">CD40 </U></A></div> <div> <A HREF="#marker_may_predict_risk_of_heart_attack_" TITLE=" HEART STROKE CHOLESTEROL"><U><IMG BORDER="0" SRC="Symb075c00b700b499006600.png" HEIGHT="12" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">MARKER May Predict Risk of Heart Attack  </U></A><A HREF="#marker_may_predict_risk_of_heart_attack_" TITLE=" HEART STROKE CHOLESTEROL"><U>interleukin-18 (IL-18)</U></A></div> <div> <A HREF="id18_exp_heart_protein.htm" TARGET="_top" TITLE=" MEDICAL NEW"><U><IMG BORDER="0" SRC="Symb075c00b700b499006600.png" HEIGHT="12" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">NEW HEART ATTACK PREDICTOR</U></A>(troponin T and C-reactive protein )</div> <div> <A HREF="#ima____a_marker_of_ischemia" TITLE=" HEART STROKE CHOLESTEROL"><U><IMG BORDER="0" SRC="Symb075c00b700b499006600.png" HEIGHT="12" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">IMA™ – A Marker of Ischemia</U></A></div> <div> <A HREF="#endothelial_progenitor_cells_and" TITLE=" HEART STROKE CHOLESTEROL"><U><IMG BORDER="0" SRC="Symb075c00b700b499006600.png" HEIGHT="12" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Endothelial Progenitor Cells and Cardiovascular Risk</U></A></div> <div> <A HREF="#new_england_journal_article" TITLE=" HEART STROKE CHOLESTEROL"><U><IMG BORDER="0" SRC="Symb075c00b700b499006600.png" HEIGHT="12" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Coronary Magnetic Resonance Angiography for the Detection of Coronary Stenoses</U></A></div> <div> <A HREF="#exercise_capacity_" TITLE=" HEART STROKE CHOLESTEROL"><U><IMG BORDER="0" SRC="Symb075c00b700b499006600.png" HEIGHT="12" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">exercise is best indicater of death risk</U></A></div> <div> <A HREF="http://www.americanheart.org/presenter.jhtml?identifier=4778" TARGET="_top" TITLE="http://www.americanheart.org/presenter.j"><U><IMG BORDER="0" SRC="Symb075c00b700b499006600.png" HEIGHT="12" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">TRIGLYCERIDES</U></A></div> <div> <A HREF="id50.htm" TARGET="_top" TITLE="CHOLESTEROL PAGE"><U><IMG BORDER="0" SRC="Symb075c00b700b499006600.png" HEIGHT="12" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">CHOLESTEROL</U></A></div> <div> <A HREF="#waist_circumference_helps_predict" TITLE=" HEART STROKE CHOLESTEROL"><U><IMG BORDER="0" SRC="Symb075c00b700b499006600.png" HEIGHT="12" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Waist Circumference Helps Predict Cardiovascular Risk </U></A></div> <div> <A HREF="#u_s__approves_test_to_help_predict" TITLE=" HEART STROKE CHOLESTEROL"><U><IMG BORDER="0" SRC="Symb075c00b700dc99006600.png" HEIGHT="15" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">PLAC test</U></A></div> <div> <A HREF="id100_serum_ferritin_and_risk_of_metabolic.htm" TARGET="_top" TITLE="diabetes"><U><IMG BORDER="0" SRC="Symb075c00b700c899006600.png" HEIGHT="13" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">IRON AS A PREDICTOR OF HEART DISEASE AND DIABETES</U></A></div> </NOBR></tD> </tR> <tR> <tD VALIGN=TOP HEIGHT= 173 WIDTH="766"><div>  <A NAME="risk"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="1" ALIGN="bottom" WIDTH="1" HSPACE="0" VSPACE="0" ></A><FONT SIZE="1" COLOR="#FF0000" FACE="Verdana" >RISK</FONT></div> <div> <A HREF="http://www.americanheart.org/Heart_and_Stroke_A_Z_Guide/riskfact.html" TARGET="_top" TITLE="http://www.americanheart.org/Heart_and_S"><U><IMG BORDER="0" SRC="Symb075c00b700b499006600.png" HEIGHT="12" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">RISK FACTORS IN  HEART DISEASE</U></A></div> <div> <A HREF="#top_blood_pressure_number_key_for" TITLE=" HEART STROKE CHOLESTEROL"><U><IMG BORDER="0" SRC="Symb075c00b700b499006600.png" HEIGHT="12" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Top Blood Pressure Number Key for Gauging Risk </U></A></div> <div> <A HREF="http://www.americanheart.org/Heart_and_Stroke_A_Z_Guide/riskfact.html" TARGET="_top" TITLE="http://www.americanheart.org/Heart_and_S"><U><IMG BORDER="0" SRC="Symb075c00b700b499006600.png" HEIGHT="12" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">RISK FACTORS IN CORONARY HEART DISEASE</U></A></div> <div> <A HREF="http://hin.nhlbi.nih.gov/atpiii/calculator.asp?usertype=prof#moreinfo" TARGET="_top" TITLE="http://hin.nhlbi.nih.gov/atpiii/calculat"><U><IMG BORDER="0" SRC="Symb075c00b700b499006600.png" HEIGHT="12" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Risk Assessment  for Estimating 10-year Risk of Developing Heart Attack </U></A></div> <div> <A HREF="http://www.med.yale.edu/library/heartbk/10.pdf" TARGET="_top" TITLE="http://www.med.yale.edu/library/heartbk/"><U><IMG BORDER="0" SRC="Symb075c00b700b499006600.png" HEIGHT="12" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Diagnosing Heart Problems</U></A> Yale University School of Medicine Heart BooK</div> <div> <A HREF="id18_obese_kids_heart_disease_link_found.htm" TARGET="_top" TITLE=" MEDICAL NEW"><U><IMG BORDER="0" SRC="Symb075c00b700b499006600.png" HEIGHT="12" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Obese Kids, Heart Disease Link Found</U></A> </div> <div> <A HREF="#asian_americans_at_risk_" TITLE=" HEART STROKE CHOLESTEROL"><U><IMG BORDER="0" SRC="Symb075c00b700b499006600.png" HEIGHT="12" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Asian Americans at Risk of 'Silent' Heart Disease</U></A></div> <div> <A HREF="#fitness_cuts_men_s_heart_disease_risk" TITLE=" HEART STROKE CHOLESTEROL"><U><B><IMG BORDER="0" SRC="Symb075c00b700dc99006600.png" HEIGHT="15" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> Fitness Cuts Men's Heart Disease Risk in Half  NEW STUDY 9/2005</B></U></A></div> </tD> </tR> <tR> <tD VALIGN=TOP HEIGHT= 444 WIDTH="766"><div>  <A NAME="medications"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="1" ALIGN="bottom" WIDTH="1" HSPACE="0" VSPACE="0" ></A><FONT SIZE="1" COLOR="#FF0000" FACE="Verdana" >MEDICATIONS</FONT></div> <div> <A HREF="http://www.intelihealth.com/IH/ihtIH/WSIHW000/8124/23697/152228.html?d=dmtContent" TARGET="_top" TITLE="http://www.intelihealth.com/IH/ihtIH/WSI"><U><IMG BORDER="0" SRC="Symb075c00b700b499006600.png" HEIGHT="12" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">ASPIRIN THERAPY IS IT FOR YOU?</U></A></div> <div> <A HREF="#baby_coated_aspirin_may_not_prevent" TITLE=" HEART STROKE CHOLESTEROL"><U><IMG BORDER="0" SRC="Symb075c00b700b499006600.png" HEIGHT="12" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Baby, Coated Aspirin May Not Prevent Stroke-Study</U></A></div> <div> <A HREF="id106.htm" TARGET="_top" TITLE="STATINS"><U><IMG BORDER="0" SRC="Symb075c00b700b499006600.png" HEIGHT="12" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">STATINS</U></A></div> <div> <A HREF="#lipitor_cuts_artery_clogs_after_heart" TITLE=" HEART STROKE CHOLESTEROL"><U><IMG BORDER="0" SRC="Symb075c00b700f099006600.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Lipitor Cuts Artery Clogs After Heart Attack</U></A></div> <div> <A HREF="id106_crestor_drug_beats_lipitor_in_study.htm" TARGET="_top" TITLE="STATINS"><U><IMG BORDER="0" SRC="Symb075c00b700f099006600.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Crestor Drug Beats Lipitor in Study</U></A></div> <div> <A HREF="id50_zetia_new_cholesterol_drug.htm" TARGET="_top" TITLE="CHOLESTEROL PAGE"><U><IMG BORDER="0" SRC="Symb075c00b700b499006600.png" HEIGHT="12" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">ZETIA</U></A></div> <div> <A HREF="#ace_inhibito" TITLE=" HEART STROKE CHOLESTEROL"><U><IMG BORDER="0" SRC="Symb075c00b700b499006600.png" HEIGHT="12" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">ACE inhibitors</U></A></div> <div> <A HREF="id104.htm" TARGET="_top" TITLE="FISH OIL"><U><IMG BORDER="0" SRC="Symb075c00b700b499006600.png" HEIGHT="12" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">FISH OIL</U></A></div> <div> <A HREF="http://www.berkeleywellness.com/html/ds/dsFlaxseed.php" TARGET="_top" TITLE="http://www.berkeleywellness.com/html/ds/"><U><IMG BORDER="0" SRC="Symb075c00b700b499006600.png" HEIGHT="12" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">flaxseed oil </U></A></div> <div> <A HREF="#vitamin_b3____niacin_" TITLE=" HEART STROKE CHOLESTEROL"><U><IMG BORDER="0" SRC="Symb075c00b700b499006600.png" HEIGHT="12" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Vitamin B3 (Niacin)</U></A></div> <div> <A HREF="#drug_niacin_mix_may_reverse_disease_" TITLE=" HEART STROKE CHOLESTEROL"><U><IMG BORDER="0" SRC="Symb075c00b700b499006600.png" HEIGHT="12" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">NIACIN PLUS STATIINS HELP HEART DISEASE</U></A></div> <div> <A HREF="#homocysteine_blockers" TITLE=" HEART STROKE CHOLESTEROL"><U><IMG BORDER="0" SRC="Symb075c00b700b499006600.png" HEIGHT="12" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">HOMOCYSTEINE BLOCKERS</U></A></div> <div> <A HREF="#_vitamin_b_may_not_be_good_for_heart_" TITLE=" HEART STROKE CHOLESTEROL"><U><IMG BORDER="0" SRC="Symb075c00b700dc3300ff00.png" HEIGHT="15" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> </U></A><FONT SIZE="2" COLOR="#FF0033" FACE="Arial" ><A HREF="#_vitamin_b_may_not_be_good_for_heart_" TITLE=" HEART STROKE CHOLESTEROL"><U><B>Vitamin B May Not be good for heart </B></U></A></FONT></div> <div> <A HREF="#antibiotics_for_heart_attacks" TITLE=" HEART STROKE CHOLESTEROL"><U><IMG BORDER="0" SRC="Symb075c00b700b499006600.png" HEIGHT="12" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Antibiotics For Heart Attacks</U></A></div> <div> <A HREF="#antibiotics_may_prevent_second_heart" TITLE=" HEART STROKE CHOLESTEROL"><U><IMG BORDER="0" SRC="Symb075c00b700b499006600.png" HEIGHT="12" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">BIAXIN may prevent heart attack</U></A></div> <div> <A HREF="id18_blood_pressure_drugs_fend_off_stroke.htm" TARGET="_top" TITLE=" MEDICAL NEW"><U><IMG BORDER="0" SRC="Symb075c00b700b499006600.png" HEIGHT="12" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Blood Pressure Drugs Fend Off Stroke</U></A></div> <div> <A HREF="#effects_of_an" TITLE=" HEART STROKE CHOLESTEROL"><U><IMG BORDER="0" SRC="Symb075c00b700b499006600.png" HEIGHT="12" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">ACE inhibitors and How they affect cardiac risk</U></A></div> <div> <A HREF="#aspirin_for_ulcer_patients" TITLE=" HEART STROKE CHOLESTEROL"><U><IMG BORDER="0" SRC="Symb075c00b700b499006600.png" HEIGHT="12" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Cardiac Aspirin for ulcer patients</U></A></div> <div> <IMG BORDER="0" SRC="Symb075c00b700b499006600.png" HEIGHT="12" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Aspirin at Bedtime to Cut Blood Pressure </div> <div> <IMG BORDER="0" SRC="Symb075c00b700b499006600.png" HEIGHT="12" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">altace prevents strokes</div> <div> <A HREF="#ibuprofen_could_be_bad_for_heart" TITLE=" HEART STROKE CHOLESTEROL"><U><IMG BORDER="0" SRC="Symb075c00b700b499006600.png" HEIGHT="12" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Ibuprofen Could Be Bad for Heart Patients </U></A></div> <div> <A HREF="#new_drug_cuts_risk_of_second_stroke" TITLE=" HEART STROKE CHOLESTEROL"><U><IMG BORDER="0" SRC="Symb075c00b700dc99006600.png" HEIGHT="15" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">New Drug(plavix) Cuts Risk of Second Stroke, Heart Attack</U></A></div> </tD> </tR> <tR> <tD VALIGN=TOP HEIGHT= 173 WIDTH="766"><div>  <A NAME="stroke"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="1" ALIGN="bottom" WIDTH="1" HSPACE="0" VSPACE="0" ></A><FONT SIZE="1" COLOR="#FF0000" FACE="Verdana" >STROKE</FONT></div> <div> <A HREF="#stroke_warning_signs_" TITLE=" HEART STROKE CHOLESTEROL"><U><IMG BORDER="0" SRC="Symb075c00b700b499006600.png" HEIGHT="12" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">STROKE WARNING SIGNS</U></A></div> <div> <A HREF="#new_evidence_for_stroke_prevention_" TITLE=" HEART STROKE CHOLESTEROL"><U><IMG BORDER="0" SRC="Symb075c00b700b499006600.png" HEIGHT="12" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Stroke Prevention</U></A><A HREF="#new_evidence_for_stroke_prevention_" TITLE=" HEART STROKE CHOLESTEROL"><U> </U></A></div> <div> <A HREF="http://www.intelihealth.com/IH/ihtIH/EMIHC000/8772/21903.html" TARGET="_top" TITLE="http://www.intelihealth.com/IH/ihtIH/EMI"><U><IMG BORDER="0" SRC="Symb075c00b700b499006600.png" HEIGHT="12" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">STROKE-EXPLAINED</U></A></div> <div> <A HREF="http://www.intelihealth.com/IH/ihtIH/EMIHC000/9339/10861.html" TARGET="_top" TITLE="http://www.intelihealth.com/IH/ihtIH/EMI"><U><IMG BORDER="0" SRC="Symb075c00b700b499006600.png" HEIGHT="12" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">THROMBOTICE STROKE</U></A></div> <div> <A HREF="http://www.intelihealth.com/IH/ihtIH/EMIHC000/9339/10118.html" TARGET="_top" TITLE="http://www.intelihealth.com/IH/ihtIH/EMI"><U><IMG BORDER="0" SRC="Symb075c00b700b499006600.png" HEIGHT="12" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">HEMORAGIC STROKE</U></A></div> <div> <A HREF="http://www.americanheart.org/Heart_and_Stroke_A_Z_Guide/" TARGET="_top" TITLE="http://www.americanheart.org/Heart_and_S"><U><IMG BORDER="0" SRC="Symb075c00b700b499006600.png" HEIGHT="12" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">HEART AND STROKE A–Z GUIDE</U></A> </div> <div> <A HREF="#drug_cuts_women_s_stroke_risk_study__by" TITLE=" HEART STROKE CHOLESTEROL"><U><IMG BORDER="0" SRC="Symb075c00b700b499006600.png" HEIGHT="12" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">D</U></A><A HREF="#drug_cuts_women_s_stroke_risk_study__by" TITLE=" HEART STROKE CHOLESTEROL"><U>rug Cuts Women's Stroke Risk-Study</U></A></div> <div> <A HREF="#mri_artery_scans_predict_stroke" TITLE=" HEART STROKE CHOLESTEROL"><U><IMG BORDER="0" SRC="Symb075c00b700f099006600.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">MRI Artery Scans Predict Stroke Risk-Studies</U></A></div> </tD> </tR> <tR> <tD VALIGN=TOP HEIGHT= 19 WIDTH="766"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="19" ALIGN="bottom" WIDTH="766" HSPACE="0" VSPACE="0"></tD> </tR> </TABLE></B></div> <bR> <bR> <bR> <div>   <A NAME="the_plac_test"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="1" ALIGN="bottom" WIDTH="1" HSPACE="0" VSPACE="0" ></A></div> <bR> <div>  <A NAME="rosuvastatin_to_prevent_vascular_events"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="1" ALIGN="bottom" WIDTH="1" HSPACE="0" VSPACE="0" ></A>Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein.</div> <div> <B>N Engl J Med. 2008; 359(21):2195-207</B> (ISSN: 1533-4406) Ridker PM ; Danielson E ; Fonseca FA ; Genest J ; Gotto AM ; Kastelein JJ ; Koenig W ; Libby P ; Lorenzatti AJ ; MacFadyen JG ; Nordestgaard BG ; Shepherd J ; Willerson JT ; Glynn RJ ; </div> <div> Center for Cardiovascular Disease Prevention, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02215, USA. pridker@partners.org</div> <div> BACKGROUND: Increased levels of the inflammatory biomarker high-sensitivity C-reactive protein predict cardiovascular events. Since statins lower levels of high-sensitivity C-reactive protein as well as cholesterol, we hypothesized that people with elevated high-sensitivity C-reactive protein levels but without hyperlipidemia might benefit from statin treatment. METHODS: We randomly assigned 17,802 apparently healthy men and women with low-density lipoprotein (LDL) cholesterol levels of less than 130 mg per deciliter (3.4 mmol per liter) and high-sensitivity C-reactive protein levels of 2.0 mg per liter or higher to rosuvastatin, 20 mg daily, or placebo and followed them for the occurrence of the combined primary end point of myocardial infarction, stroke, arterial revascularization, hospitalization for unstable angina, or death from cardiovascular causes. RESULTS: The trial was stopped after a median follow-up of 1.9 years (maximum, 5.0). Rosuvastatin reduced LDL cholesterol levels by 50% and high-sensitivity C-reactive protein levels by 37%. The rates of the primary end point were 0.77 and 1.36 per 100 person-years of follow-up in the rosuvastatin and placebo groups, respectively (hazard ratio for rosuvastatin, 0.56; 95% confidence interval [CI], 0.46 to 0.69; P<0.00001), with corresponding rates of 0.17 and 0.37 for myocardial infarction (hazard ratio, 0.46; 95% CI, 0.30 to 0.70; P=0.0002), 0.18 and 0.34 for stroke (hazard ratio, 0.52; 95% CI, 0.34 to 0.79; P=0.002), 0.41 and 0.77 for revascularization or unstable angina (hazard ratio, 0.53; 95% CI, 0.40 to 0.70; P<0.00001), 0.45 and 0.85 for the combined end point of myocardial infarction, stroke, or death from cardiovascular causes (hazard ratio, 0.53; 95% CI, 0.40 to 0.69; P<0.00001), and 1.00 and 1.25 for death from any cause (hazard ratio, 0.80; 95% CI, 0.67 to 0.97; P=0.02). Consistent effects were observed in all subgroups evaluated. The rosuvastatin group did not have a significant increase in myopathy or cancer but did have a higher incidence of physician-reported diabetes. CONCLUSIONS: In this trial of apparently healthy persons without hyperlipidemia but with elevated high-sensitivity C-reactive protein levels, rosuvastatin significantly reduced the incidence of major cardiovascular events. (ClinicalTrials.gov number, NCT00239681.)</div> <bR> <bR> <bR> <div>  <A NAME="lipitor_cuts_artery_clogs_after_heart"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="1" ALIGN="bottom" WIDTH="1" HSPACE="0" VSPACE="0" ></A>Lipitor Cuts Artery Clogs After Heart Attack</div> <bR> <div> NEW YORK (Reuters Health) - Early treatment with Lipitor (news - web sites) (atorvastatin), a "statin" cholesterol-lowering drug, reduces the build-up of artery-clogging plaque in patients who've had a recent heart attack, new research suggests. </div> <bR> <div> "This is the first evidence that plaque can regress with early statin treatment in heart attack patients," lead author Dr. Shinya Okazaki, from Juntendo University School of Medicine in Tokyo, said in a statement. "This evidence provides further support for the use of statins after a heart attack." </div> <bR> <bR> <div> The study involved 70 patients who experienced a heart attack or related problem and were treated with atorvastatin or instructed to eat a cholesterol-lowering diet. The findings are reported in the American Heart Association (news - web sites)'s journal Circulation. </div> <bR> <bR> <div> During the 6-month study, levels of LDL ("bad") cholesterol decreased by 42 percent in the Lipitor group, but rose by 1 percent in the diet group. Similarly, in Lipitor-treated patients, plaque size fell by 13 percent, while in diet-treated patients, the size increased by 9 percent. </div> <bR> <bR> <div> Further analysis showed that the drop in plaque size was related to the LDL cholesterol level at follow-up, and with the overall reduction in LDL cholesterol. This was observed even in patients with low LDL cholesterol levels from the start. </div> <bR> <bR> <div> "The positive effect of (Lipitor) was evident whether people went into the study with an LDL cholesterol above 125 mg/dL or not, indicating that this...therapy would be beneficial whether people who have heart attacks have very high cholesterol or not," Okazaki noted. </div> <bR> <bR> <div> Further studies are needed to determine how Lipitor stabilize plaques and whether the benefits seen with Lipitor apply to other statins, the authors state. </div> <bR> <bR> <div> SOURCE: Circulation, August 31, 2004.<B> </B></div> <bR> <bR> <bR> <div>   <A NAME="fitness_cuts_men_s_heart_disease_risk"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="1" ALIGN="bottom" WIDTH="1" HSPACE="0" VSPACE="0" ></A>"Fitness Cuts Men's Heart Disease Risk in Half: New Queen's Study"</div> <bR> <bR> <div> KINGSTON, ON -- September 2, 2005 -- Being physically fit can dramatically reduce men's deaths from heart disease -- even when their cholesterol rates are high, says Queen's researcher Peter Katzmarzyk. His new study to be published Tues. Sept. 6 by Circulation: Journal of the American Heart Association shows that, regardless of their cholesterol level, men can cut by half their risk of dying from cardiovascular disease if they are physically fit. Other Queen's members of the team, from the School of Physical and Health Education, are Chris Ardern and Ian Janssen. Researchers Timothy Church and Steven Blair from the Cooper Institute Centres for Integrated Health Research in Dallas, Texas, are also on the team. The primary aim of the study was to analyze the effectiveness of last year's modifications to the guidelines from the U.S. National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) for lowering bad (LDL) cholesterol to predict death from cardiovascular diseases. "We wanted to find out if the new guidelines could identify men at risk for cardiovascular disease," says Dr. Katzmarzyk. "We confirmed that the guidelines do accurately identify men at risk not only of disease, but also at risk of cardiovascular death. We also discovered that fitness is important across the board – at every level of cholesterol." Results also suggest that within a given risk category, physical fitness is associated with a greater than 50-per-cent lower risk of mortality. In this study, physical fitness was four to five, 30-minute segments of activity per week: equivalent to walking 130 to 138 minutes per week. Researchers analyzed the cardiovascular risk factors and cardio-respiratory fitness of 19,125 men ages 20 to 79, who were treated at a preventive medicine clinic from 1979 -1995, prior to the revised treatment guidelines. Using the new ATP III classifications: • 58 per cent of the men would have met the criteria for being "at or below LDL (bad) cholesterol goal"; • 18 per cent would have met the criteria for "therapeutic lifestyle change" – meaning diet, physical activity and weight management could lower LDL; and • 24 per cent would have met the criteria for "drug consideration" for lowering LDL. There were 179 deaths from cardiovascular disease over more than 10 years of follow-up. Overall, compared to men who met the acceptable LDL level under the revised guidelines: • Men who met the criteria for therapeutic lifestyle intervention had twice the risk of cardiovascular disease death; and • Men eligible for aggressive cholesterol-lowering therapy had almost seven-times the risk. "Lowering the threshold for consideration of cholesterol-lowering drug therapy for those at high risk will ultimately save lives and also have important implications for the healthcare system," says Dr. Katzmarzyk. The research was partly funded by the U.S. National Institutes of Health. SOURCE: Queen's University </div> <bR> <bR> <bR> <bR> <div> <B> <A NAME="asian_americans_at_risk_"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="1" ALIGN="bottom" WIDTH="1" HSPACE="0" VSPACE="0" ></A></B><B>Asian Americans at Risk of 'Silent' Heart Disease </B><FONT SIZE="2" COLOR="#660099" FACE="Arial" >Reuters to My Yahoo! </FONT></div> <div> NEW YORK (Reuters Health) - Asian Americans are disproportionately affected by a painless heart condition that can lead to heart attack, researchers reported this week. </div> <bR> <div>    </div> <div> Because Asian Americans have an increased risk of the condition, known as silent myocardial ischemia, they would benefit from a more aggressive approach to early diagnosis and management of heart disease, Dr. Antonio Q. Chan of Stanford University Medical Center in California told Reuters Health </div> <bR> <div> Silent myocardial ischemia is a narrowing of the arteries that restricts blood flow to the heart, but, unlike ordinary myocardial ischemia, does not cause pain or other symptoms. The condition predisposes one to later heart problems, including heart attack. </div> <bR> <div> "Any Asian American who complains of shortness of breath after climbing a flight or two of stairs, gets tired easily, or is over age 45 should be examined for the presence of ischemic heart disease," Chan said in a statement. </div> <bR> <div> This is especially important for people with high blood pressure, diabetes or a family history of heart disease, he added. </div> <bR> <div> In an interview with Reuters Health, Chan said "physicians caring for Asian Americans at risk for silent myocardial ischemia should have an interpreter during clinic visits to improve awareness of their symptoms." </div> <bR> <div> He also believes the federal government should waive the mandated five-year waiting period before immigrants can qualify for federal or state health insurance. </div> <bR> <div> "A lot of the folks that I am seeing don't qualify for Medicare because they have not stayed in the U.S. for a minimum of five years," Chan told Reuters Health. "A lot of these patients are in their late 60s and 70s, so waiting for five years might be too late. By the time they are seen, usually they have full-blown heart disease." </div> <bR> <div> Chan and his colleagues presented the results of their study during the American Heart Association (news - web sites)'s Second Asia Pacific Scientific Forum in Honolulu. </div> <bR> <div> In the study, the researchers reviewed the medical records of 973 patients from a largely Asian-American practice in the San Francisco Bay area, and those of 662 patients from a predominantly Caucasian practice in the Chicago area. </div> <bR> <div> All patients were asked in their native language about symptoms of heart disease and underwent several types of cardiac testing. </div> <bR> <div> Among patients with myocardial ischemia, only 30 percent of Asian Americans experienced chest pain, compared with 83 percent of Caucasian Americans. </div> <bR> <div> However, Asian Americans were more likely than whites to have other symptoms, including shortness of breath after exercise (63 percent, versus 36 percent), fatigue (59 percent, versus 22 percent) and heart palpitations (65 percent, versus 24 percent). </div> <div>  </div> <div> Prevention of Preterm Delivery   </div> <div>   </div> <div> Women with a history of preterm delivery are at high risk for recurrence in subsequent pregnancies, and an effective strategy to reduce this risk has been lacking. In this randomized, placebo-controlled trial, weekly injections of 17 alpha-hydroxyprogesterone caproate reduced the risk of delivery before 37 weeks of gestation by one third among such high-risk women. </div> <bR> <div> Therapy with this agent may substantially reduce the likelihood of preterm delivery and its attendant complications in high-risk women and their infants. </div> <bR> <div>     </div> <div> <B><U> <A NAME="new_drug_cuts_risk_of_second_stroke"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="1" ALIGN="bottom" WIDTH="1" HSPACE="0" VSPACE="0" ></A></U></B><B><U>New Drug Cuts Risk of Second Stroke, Heart Attack</U></B></div> <bR> <div> WEDNESDAY, Nov. 12 (HealthDayNews) -- The anti-clotting medicine clopidogrel reduces the risk of recurrent heart attack and stroke and is cost-effective.</div> <bR> <div> That's the conclusion of an Emory University study presented Nov. 12 at the American Heart Association (news - web sites)'s annual conference in Orlando, Fla.</div> <bR> <bR> <div> "We have three separate investigations showing uniform results in both the short- and long-term use of clopidogrel. Specifically, the use of clopidogrel in addition to aspirin produces a significant risk reduction in recurrent heart attack, stroke or cardiovascular death," Dr. William Weintraub, a researcher at the Emory Center for Outcomes Research, says in a prepared statement.</div> <bR> <bR> <bR> <div>  </div> <div> <B><U>Ambulatory Blood-Pressure Measurements in Patients with Treated Hypertension </U></B> </div> <div> FROM THE  NEW ENGLAND JOURNAL 6/03</div> <div> In this prospective, multicenter study of treated hypertensive patients, ambulatory blood-pressure readings predicted the risk of cardiovascular events during five years of follow-up, even after adjustment for office-based blood-pressure measurements and other cardiovascular risk factors. </div> <bR> <div> Twenty-four–hour ambulatory blood-pressure monitoring may be used to improve the stratification of treated hypertensive patients according to cardiovascular risk, although the role of these measures in the care of such patients remains uncertain. </div> <bR> <div>  </div> <bR> <bR> <bR> <bR> <div> <B><U> <A NAME="mri_artery_scans_predict_stroke"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="1" ALIGN="bottom" WIDTH="1" HSPACE="0" VSPACE="0" ></A></U></B><B><U>MRI Artery Scans Predict Stroke Risk-Studies</U></B></div> <div> Mon Jun 9, 5:30 PM ET  Add Health - Reuters to My Yahoo! </div> <div>  </div> <div> By Ransdell Pierson </div> <bR> <div> NEW YORK (Reuters) - Magnetic resonance imaging can help predict which patients are at risk of strokes from clogged arteries, and thereby alert patients to have surgery or take protective drugs, according to two studies released on Monday. </div> <bR> <div>    </div> <div> The studies involving the carotid artery, appearing in Circulation: Journal of the American Heart Association (news - web sites), were the first to use MRI scans to detect bleeding within fatty plaque material that lines and clogs arteries. </div> <bR> <div> Such bleeding indicates the plaque has become "complicated," meaning the surface of the deposit has broken apart and pieces of it could travel to the brain, forming clots that cause stroke. </div> <bR> <div> Strokes often occur when branches of the carotid artery, the main blood vessel supplying blood from the neck to the brain, become clogged and brain cells become starved of blood and oxygen. </div> <bR> <div> MRI scans used in the two studies detected high-risk complicated plaque in the carotid arteries of 60 percent of patients who had shown signs and symptoms that precede stroke -- including "mini-strokes" which cause no major permanent damage but indicate danger of serious future strokes. </div> <bR> <div> By contrast, MRI scans found no complicated plaque in the carotid arteries of a smaller group of people who had no previous signs or symptoms of stroke. </div> <bR> <div> One of the studies involved 63 patients who had surgery to remove obstructions in the carotid artery. </div> <bR> <div> Fatty deposits removed during the surgeries were later analyzed by conventional pathology techniques and showed complicated plaque in 44 patients. </div> <bR> <div> MRI scans taken before surgery successfully predicted complicated plaque in 41 of the patients, an accuracy rate of 93 percent. </div> <bR> <bR> <div> "The MRI studies show that plaque is not some benign quiet process in which the arteries gradually harden," said Dr. Alan Moody, who helped write the two Circulation reports. </div> <bR> <bR> <div> "In up to 60 percent of cases, active bleeding is going on within the plaque -- making the plaque bigger and further clogging the artery," said Moody, who is chief radiologist at Sunnybrook and Women's College Health Sciences Center in Toronto. </div> <bR> <div> He said all patients with such bleeding are at elevated risk of stroke and that many could benefit from surgery or certain drugs that help keep plaque from breaking up into dangerous pieces. They include statins, a popular class of cholesterol-lowering medicines. </div> <bR> <div> Angiography is currently the "gold standard" for verifying plaque in arteries. But Moody said the procedure, which involves running a catheter between the patient's groin and neck and then filling it with dye, actually causes strokes in 1 percent of patients. </div> <bR> <div> He said other screening procedures -- including ultrasound, computed tomography and positron emission tomography -- can also indicate the presence of plaque but without the convenience and detailed information available from MRI scans. </div> <bR> <div> "In the future, the new gold standard of identification may be a combination of ultrasound and MRI scans," Moody said, adding that other studies suggest combined use of those non-invasive tests may provide the same detailed level of information as angiography. </div> <bR> <div> Moody said angiography procedures currently cost about $1,000, compared with $250 for ultrasound and $400 for MRI scans. </div> <bR> <div> The Circulation articles said MRI scans might also hold promise in detecting elevated risk of heart attack in patients with complicated plaque. </div> <bR> <bR> <bR> <bR> <div> <B><U> <A NAME="raising_hdl_levels_may_be_as_important"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="1" ALIGN="bottom" WIDTH="1" HSPACE="0" VSPACE="0" ></A></U></B><B><U>Raising HDL levels may be as important as lowering LDL</U></B></div> <div> Researchers find that changing the focus of lipid-lowering therapy may improve outcomes, but some experts say it is too soon to alter recommendations.</div> <div> By <FONT SIZE="3" COLOR="#0000FF" FACE="Arial" ><U>Victoria Stagg Elliott</U></FONT>, <I>AMNews</I> staff. April 28, 2003. </div> <bR> <div> Targeting drug therapy to raise levels of HDL cholesterol alone may be sufficient to reduce the risk of heart disease and improve cardiovascular health, according to several studies presented at the American College of Cardiology meeting held earlier this month in Chicago.</div> <div> One study, which was presented by researchers at the Heart Institute, Sheba Medical Center in Tel Hashomer, Israel, found that raising HDL cholesterol was associated with improved long-term survival among more than 1,500 patients with coronary disease.</div> <div> <TABLE BORDER="0" CELLPADDING="1" CELLSPACING="1" WIDTH="170" BORDERCOLORLIGHT="#C0C0C0" BORDERCOLORDARK="#808080" FRAME="VOID" RULES="NONE" HSPACE="0" VSPACE="0" > <tR> <tD VALIGN=CENTER HEIGHT= 19 WIDTH="166"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="19" ALIGN="bottom" WIDTH="166" HSPACE="0" VSPACE="0"></tD> </tR> </TABLE></div> <div> Another from the Uniformed Services University of Health Sciences in Bethesda, Md., randomized nearly 150 patients with stable coronary disease to receive either medications to raise HDL or a placebo. Those on meds increased their HDL as well as decreasing their total cholesterol significantly and had far fewer heart-related mortality or morbidity events.</div> <div> "There's ample epidemiologic evidence that HDL cholesterol is very predictive of cardiovascular events," said Maj. Richard A. Krasuski, MD, the study's lead author and director of cardiovascular research at Uniformed Services University. "This study suggests that it could be possible that aiming to raise the HDL may be as good or maybe even better than trying to lower the LDL."</div> <div> Although these studies focused on people who have already had cardiac events, the strategy does have the potential to impact prevention for those who do not yet have heart disease. "If you have a primary prevention group that has a number of cardiovascular risk factors and a low level of HDL cholesterol, I think looking at ways to raise HDL is certainly a viable option, but it's certainly one that needs further study," said Dr. Krasuski.</div> <div> Low HDLlevels have long been acknowledged as a heart disease risk factor. Last November's guidelines, the most recent, from the National Institutes of Health's National Cholesterol Education Project, "Detection, Evaluation and Treatment of High Blood Cholesterol in Adults," raised the bar by increasing the definition of low HDL to less than 40 mg/dl from less than 35 mg/dl. </div> <div> <TABLE BORDER="0" CELLPADDING="1" CELLSPACING="1" WIDTH="95" BORDERCOLORLIGHT="#C0C0C0" BORDERCOLORDARK="#808080" FRAME="VOID" RULES="NONE" HSPACE="0" VSPACE="0" > <tR> <tD VALIGN=CENTER HEIGHT= 19 WIDTH="91"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="19" ALIGN="bottom" WIDTH="91" HSPACE="0" VSPACE="0"></tD> </tR> </TABLE></div> <div> Traditional treatment goals have always been to lower the total cholesterol as well as levels of LDL, and the new guidelines did not suggest an HDL goal. "In all persons with low HDL cholesterol, the primary target of therapy is LDL cholesterol," spelled out the guidelines.</div> <div> But increasingly, experts are recognizing HDL as an independent risk factor that needs to be addressed. "The epidemiology is strong, and the population data are compelling," said Andrew Tonkin, MD, head of cardiovascular disease epidemiology and prevention at Monash University in Melbourne, Australia.</div> <div> Experts said, though, that more data were needed before clinical practice should be altered. Head-to-head trials pitting drugs that primarily lower LDL against ones that are most effective at raising HDL are needed.</div> <div> "I'm kind of a [National Cholesterol Education Program] guideline person, and they were the biggest on the LDL," said Paul Thompson, MD, director of preventive cardiology at Hartford Hospital in Hartford, Conn. "We have less outcome data on raising the HDL than we do on lowering the LDL, and we need outcome data."</div> <div> No escaping lifestyle changes</div> <div> The conference was not solely focused on the role of various drug therapies. Experts were quick to point out that lifestyle changes can be just as effective or even more so at improving a patient's cardiac risk profile, either by themselves or with medications. Several studies were presented highlighting that drastic lifestyle alterations can improve heart health.</div> <div> One study from Indiana University School of Medicine in Indianapolis suggested that exercise could increase the number of vessel wall repair cells circulating in the blood. Another from the University of Texas Medical School at Houston suggested that exercise as well as extreme dietary changes accompanied by traditional lipid-lowering medications may offer advantages over medication with only minor lifestyle changes.</div> <div> In the UT study, more than 400 patients with coronary artery disease were randomized to receive either no intervention; an intervention involving an extremely low-fat diet combined with exercise and medication; or an intervention combining minor lifestyle changes and traditional drug therapies. The group that exercised and ate an extremely low-fat diet had a cardiac event rate of just over 6%. Those who made only minor changes had a rate of around 20%. Those who did nothing had a rate of 30%.</div> <div> "Pills don't substitute for diet and exercise," said Stefano Sdringola, MD, lead author and assistant professor of cardiology at the University of Texas Medical School, Houston.</div> <bR> <div> ADDITIONAL INFORMATION: </div> <div>  <A NAME="s1_1"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="1" ALIGN="bottom" WIDTH="1" HSPACE="0" VSPACE="0" ></A></div> <div> Focus on HDL levels to reduce coronary disease</div> <div> <B>Objective:</B> Does therapy targeted at raising HDL cholesterol improve outcomes for heart disease patients? </div> <div> <B>Method: </B>143 coronary patients already receiving aggressive dietary and exercise interventions were randomized to receive placebo or gemfibrozil, niacin and cholestyramine to raise their HDL cholesterol. </div> <div> <B>Results: </B>Total cholesterol increased 3% in the placebo group, but went down 16% in the drug group. Nineteen patients in the placebo group experienced heart-related morbidity or mortality, including unstable angina, transient ischemic attack or stroke. Nine of the drug group experienced such events. </div> <div> <B>Conclusion:</B> A combination of drugs aimed at increasing HDL improves cholesterol profiles and results in significant reduction in cardiovascular events.</div> <div> Source: American College of Cardiology, 52nd Annual Scientific Sessions, April 2</div> <bR> <div> Weblink</div> <div> 52nd annual scientific sessions <FONT SIZE="3" COLOR="#0000FF" FACE="Arial" ><U>program</U></FONT>, American College of Cardiology, (http://www.acc03online.acc.org/)</div> <div> Third <FONT SIZE="3" COLOR="#0000FF" FACE="Arial" ><U>report</U></FONT> of the National Cholesterol Education Program expert panel, "Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III)," National Heart, Lung, and Blood Institute (http://www.nhlbi.nih.gov/guidelines/cholesterol/)</div> <bR> <bR> <bR> <div> <B><U> <A NAME="framingham_heart_study"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="1" ALIGN="bottom" WIDTH="1" HSPACE="0" VSPACE="0" ></A></U></B><B><U>Framingham Heart Study</U></B><FONT SIZE="3" COLOR="#660099" FACE="Arial" >: The beat goes on</FONT></div> <div> A long-running Massachusetts study on heart disease has dramatically changed the way medicine is practiced today, and it promises to continue to break new ground.</div> <div> By <FONT SIZE="3" COLOR="#0000FF" FACE="Arial" ><U>Susan J. Landers</U></FONT>, <I>AMNews</I> staff. Feb. 18, 2002. </div> <bR> <div> In 1948 President Harry S. Truman won an upset victory over Thomas Dewey, Mahatma Gandhi was assassinated, the average income was less than $3,000 a year, life expectancy was 63 years and great numbers of people were dying of cardiovascular disease. </div> <div> Also in that year, the Framingham Heart Study was begun in an attempt to identify factors that contributed to this growing epidemic of heart disease. </div> <div> <TABLE BORDER="0" CELLPADDING="1" CELLSPACING="1" WIDTH="170" BORDERCOLORLIGHT="#C0C0C0" BORDERCOLORDARK="#808080" FRAME="VOID" RULES="NONE" HSPACE="0" VSPACE="0" > <tR> <tD VALIGN=CENTER HEIGHT= 56 ><NOBR><div> With this article </div> <div> <U>Research milestones</U><FONT SIZE="3" COLOR="#660099" FACE="Arial" > </FONT></div> <div> <U>Links</U><FONT SIZE="3" COLOR="#660099" FACE="Arial" > </FONT></div> </NOBR></tD> </tR> </TABLE></div> <div> Intended as a 20-year study, it's still going strong. After 53 years it is the longest running prospective epidemiologic study of heart disease ever and researchers are now enrolling the grandchildren of the study's original participants. </div> <div> Its success is legendary among heart specialists, boosting the fame of the town of Framingham, Mass., and even making its participants somewhat celebrities. </div> <div> There's no doubt that the study's findings have been important. "The Framingham Heart Study provided the foundation for preventive cardiology as we know it today," said Roger Blumenthal, MD, director of preventive cardiology at Johns Hopkins Hospital in Baltimore. </div> <div> "It was one of the first to alert doctors and the public that there are major risk factors for heart disease that we now take for granted. But 50 years ago there was still a lot of controversy about what caused heart attacks and strokes," said Dr. Blumenthal, who is also a national spokesperson for the American Heart Assn. </div> <div> <TABLE BORDER="0" CELLPADDING="1" CELLSPACING="1" WIDTH="95" BORDERCOLORLIGHT="#C0C0C0" BORDERCOLORDARK="#808080" FRAME="VOID" RULES="NONE" HSPACE="0" VSPACE="0" > <tR> <tD VALIGN=CENTER HEIGHT= 19 WIDTH="91"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="19" ALIGN="bottom" WIDTH="91" HSPACE="0" VSPACE="0"></tD> </tR> </TABLE></div> <div> "We've had an enormous impact using data from the Framingham Heart Study to identify people who are at risk and then modifying those risk factors," said Teri Manolio, MD, PhD, director of epidemiology and biometry at the National Institutes of Health National Heart Lung and Blood Institute. </div> <div> "We've seen heart disease death rates come down dramatically and a lot of that is due to this study," she said. </div> <div> When the study began, people knew very little about heart disease, much less about its causes and virtually nothing about what could be done to prevent it, said its current director, cardiologist Daniel Levy, MD. </div> <div> But through the vision of its first director, Thomas Dawber, MD, the Framingham Heart Study was the first to apply the discipline of epidemiology to a chronic, noninfectious disease. </div> <div> Previously, epidemiology had mostly to do with tracking such diseases as tuberculosis, syphilis, malaria and polio, said Philip Wolf, MD, principal investigator in the Framingham study and a professor of neurology at Boston University. </div> <div> "The idea that you could use the methods of epidemiology to study chronic disease evolved after World War II, and that's when the Framingham study was conceived," Dr. Wolf said. </div> <div> Risk factors identified</div> <div> The assumption was that heart disease would develop in some of the subjects during the study's run. It did. </div> <div> Researchers were provided the opportunity to closely examine the lifestyles of the participants. And from that examination, the term "risk factor" emerged. "This is really the first time the term was used in the history of the world," Dr. Wolf said. </div> <div> <TABLE BORDER="0" CELLPADDING="1" CELLSPACING="1" WIDTH="95" BORDERCOLORLIGHT="#C0C0C0" BORDERCOLORDARK="#808080" FRAME="VOID" RULES="NONE" HSPACE="0" VSPACE="0" > <tR> <tD VALIGN=CENTER HEIGHT= 19 WIDTH="91"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="19" ALIGN="bottom" WIDTH="91" HSPACE="0" VSPACE="0"></tD> </tR> </TABLE></div> <div> Researchers found that it was possible from an initial examination to determine which people were at the highest risk of developing heart disease: namely, smokers with high blood pressure and high cholesterol levels. </div> <div> Previously, physicians saw patients who had already had a stroke or heart attack, said Dr. Wolf, and questions about a patient's lifestyle were answered after the fact. With this study, measurements were made before the illness occurred, he said, allowing researchers to make an unbiased assessment and have a whole group with which to compare. </div> <div> The discovery of risk factors is not the only finding the study revealed. It has produced more than 1,000 scientific papers and has branched out into other areas. </div> <div> There have been a number of projects related to the study of arthritis and osteoporosis, noted Dr. Levy. Additional projects underway are related to hearing loss and eye diseases as well as dementia, he added. </div> <div> The project was funded and run exclusively by the NHLBI until 1971 when Boston University became the principal subcontractor for the study, Dr. Levy said. </div> <div> The researchers worked with a pool of 5,209 men and women between the ages of 30 and 62 recruited from Framingham, a small town about 20 miles west of Boston. This town was chosen from among several others because it had a successful track record with community projects and its near-Boston location provided proximity to a number of prominent medical researchers, Dr. Levy said. </div> <div> <TABLE BORDER="0" CELLPADDING="1" CELLSPACING="1" WIDTH="95" BORDERCOLORLIGHT="#C0C0C0" BORDERCOLORDARK="#808080" FRAME="VOID" RULES="NONE" HSPACE="0" VSPACE="0" > <tR> <tD VALIGN=CENTER HEIGHT= 134 WIDTH="91"><div> The study has produced more than 1,000 scientific papers. </div> </tD> </tR> </TABLE></div> <div> Framingham was also fairly isolated in 1948, before construction of the nearby Massachusetts Turnpike. </div> <div> Since its inception, participants have undergone extensive physical examinations and lifestyle interviews every two to four years. </div> <div> Many of the original participants have returned for biennial exams for 26 years. For any particular exam at least 85% of the participants return, said Dr. Wolf. The youngest participant in the original cohort is now 84, several are older than 100 and some of the exams are carried out in nursing homes or assisted living facilities, Dr. Wolf said. </div> <div> "But many still come in," he said. "We had about 300 of the original group turn up for an MRI of their brain." </div> <div> Meanwhile, the study has also grown from this base. For instance, in 1971, the study recruited 5,124 children and their spouses of the original participants for a second study, called the "Offspring Study." </div> <div> In 1995, researchers began recruiting from Framingham's growing minority community, the result of an influx of immigrants from Brazil, India and Pakistan. With this effort, known as the Omni study, researchers are investigating whether the risk factors associated with heart disease in these minority populations are the same as risk factors found in the other cohorts. </div> <div> And last year, researchers mailed about 5,200 cards to the third generation of the original participants. The plan is to recruit about 3,500 grandchildren and their spouses. </div> <div> By late December, 3,000 or so cards had been returned and about 95% said, "Sure, sign me up," Dr. Wolf said. </div> <div> Loyal participants</div> <div> The trust that has built between researchers and subjects is what keeps participants returning for follow-up exams, said Dr. Levy. "It's a mutual relationship," he said. </div> <div> Study participants return for a variety of reasons, he noted. "Some are motivated by altruism, and some found it an opportunity for a free exam." </div> <div> No one had health insurance in 1948, he remarked, and for some of the participants the prospect of a free exam was probably enough of an enticement. </div> <div> As results came in, participants began to understand the importance of the study, a fact that reinforced their resolve to continue. </div> <div> While the original participants may have thought their volunteerism could, some day, help their own children, little did they know that their children and grandchildren would also become participants in the study. </div> <div> Thomas Berardi is one of the third-generation participants recently recruited for the study. His mother, described by Berardi as "a worrier," urged her son to take advantage of the opportunity. She was concerned that he wasn't attending to his health as he should be, Berardi said. </div> <div> With a family history of heart disease -- a grandmother died at about age 70 of a sudden heart attack, a grandfather died of heart disease and his father has had some heart problems -- Berardi, at 49, admits that self-interest is partially responsible for his participation. </div> <div> "By volunteering, I am going to get the checkups that I may have put off," he said. </div> <div> But he acknowledges a feeling of pride in the role he and his family have played in helping many people lead longer and healthier lives. </div> <div> Berardi has a cousin who lives in Florida and is also a study participant. His cousin, who receives his checkups during return visits for family reunions, noted that his Florida physician treated him like a celebrity when he revealed his involvement in the Framingham study. </div> <div> Poised for the future</div> <div> Crucial to the study's longevity has been its ability to move with the times and adopt the latest in technology. </div> <div> When research began, blood pressure, electrocardiogram, medical history and physical exams were the tools employed. Those measures are still used today, Dr. Wolf said. "We try to make the same measurements in 2001 that we used in 1951," he said, "so we can look at changes over time." </div> <div> But technology marches on. Now researchers have added echocardiography, carotid artery ultrasound and densitometry to their measures. </div> <div> One important sign that researchers are keeping abreast with modern science is their new focus on genetics. They have much material to work with given the study's multigenerational nature. </div> <div> "The expansion to a third generation opens up the chance to explore important new questions about disease risk, especially those related to genetics," said NHLBI Director Claude Lenfant, MD. </div> <div> The researchers have been collecting DNA for about 15 years and developing cell lines for about five years, Dr. Levy said. Thousands of genetic tests will be able to be performed on a single tube of blood, he noted. "We're hoping that with this unique family structure in Framingham and the long-term nature of the data collection here, we will be able to contribute in important ways to understanding the genetic basis for common conditions that are involved in heart disease and stroke." </div> <div> Participation of the third generation of subjects is also expected to further scientists' understanding of the role of genetics in the development and progression of such diseases as stroke, dementia, osteoarthritis, vision and hearing loss, Dr. Wolf said. </div> <div> "We'll be able to look at all sorts of things, such as the genetic and environmental characteristics of healthy aging," Dr. Levy pointed out. Framingham researchers are working to identify a region of the human genome that appears to contain a gene that protects individuals from developing heart disease. The gene in this region is related to the production of increased amounts of high density lipoprotein, the "good cholesterol." </div> <div> Researchers are also looking for locations of genes that increase the risk for heart disease and are focusing on a region containing a gene that appears to cause high levels of low density lipoprotein, the "bad cholesterol." </div> <div> It is doubtful that there will be an end to the diseases studied by the Framingham Heart Study anytime soon. So does that mean the study will go on forever? </div> <div> There are no guarantees. The study has to sing for its supper every five, six or seven years, and justify why it should continue, Dr. Manolio said. But it has been very successful in doing so, she added, explaining that the NHLBI soon will be announcing another six- or seven-year extension for the study. </div> <div> "All I can say is that we are here today because of a track record of productivity and not just that we were productive, but the lessons learned from Framingham in many ways changed the way medicine is practiced in the United States," Dr. Levy said. </div> <div> <U>Back to top.</U><FONT SIZE="3" COLOR="#660099" FACE="Arial" > </FONT></div> <bR> <div> ADDITIONAL INFORMATION: </div> <div>  <A NAME="s1"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="1" ALIGN="bottom" WIDTH="1" HSPACE="0" VSPACE="0" ></A></div> <div> Research milestones</div> <bR> <div> <B>1948:</B> Start of the Framingham Heart Study. </div> <div> <B>1960:</B> Cigarette smoking found to increase the risk of heart disease. </div> <div> <B>1961:</B> Cholesterol level, blood pressure and electrocardiogram abnormalities found to increase the risk of heart disease. </div> <div> <B>1971:</B> Framingham Offspring Study begins. </div> <div> <B>1976:</B> Menopause found to increase the risk of heart disease. </div> <div> <B>1981:</B> Filter cigarettes found to give no protection against coronary heart disease. </div> <div> <B>1988:</B> High levels of HDL cholesterol found to reduce risk of death. </div> <div> <B>1990:</B> Homocysteine found to be a possible risk factor for heart disease. </div> <div> <B>1995:</B> Omni study of minorities begins. </div> <div> <B>1998:</B> New risk prediction formula to calculate a patient's risk for developing coronary disease over the next 10 years is published. </div> <div> Source: The Framingham Heart Study </div> <bR> <div> Study directors brought a variety of expertise</div> <div> The Framingham Heart Study has had four directors in its more than 50-year life span. Daniel Levy, MD, the current director, is a clinical cardiologist. He is expanding the study to include the third generation of participants and, in doing so, is refocusing research on the family patterns of disease. </div> <div> But each of those who came before him left important footprints in the direction the study took and the findings that resulted. </div> <div> Thomas Dawber, MD, the director from 1949 to 1966, was the architect of the initial project. "He made it happen," Dr. Levy said. Dr. Dawber recruited participants and instituted scientific rigor in the field of epidemiology, which was a fledgling field in medicine. </div> <div> After him came William Kannel, MD, who directed the study from 1966 to 1979. He was an "amazingly productive researcher," according to Dr. Levy, and the first to take the notion of risk factors and develop it fully. Dr. Kannel was probably the key scientist in the history of the study. </div> <div> From 1979 to 1995, William Castelli, MD, took the helm. Dr. Levy considers him the ambassador. He got out on the lecture circuit and, with an "evangelical-like fervor," stressed the role of cholesterol as a critical risk factor for heart disease before others joined the fight. </div> <bR> <div> <U>Framingham Heart Study</U><FONT SIZE="3" COLOR="#660099" FACE="Arial" > (http://www.framingham.com/heart/) </FONT></div> <bR> <bR> <bR> <div> <B><U> <A NAME="exercise__lowers_levels_of_c_reactive"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="1" ALIGN="bottom" WIDTH="1" HSPACE="0" VSPACE="0" ></A></U></B><B><U>Exercise  lowers levels of C-reactive protein </U></B></div> <bR> <div> In a study of nearly 3,000 adults, Harvard researchers found that those who got the most exercise had the lowest levels of C-reactive protein (CRP), a marker of inflammation that has been tied to the risk of artery disease, heart attack and stroke. </div> <bR> <div> In fact, the same researchers recently found in a large study of women that CRP levels were better predictors of heart attack and other cardiovascular problems than levels of "bad" LDL cholesterol were -- although there's no agreement yet on whether people's CRP levels should be routinely checked. </div> <bR> <div> These latest findings "have enormous public health implications," study author Dr. Michelle A. Albert reported at the meeting. </div> <bR> <div> "Physical activity may attenuate inflammation and modify cardiovascular risk without drug therapy," she said. </div> <bR> <div> The study involved 2,833 men and women, 41 percent of whom had a history of coronary artery disease. Participants were divided into four groups based on exercise habits: those who exercised less than once a week; once a week; two or three times a week; or at least four times a week. </div> <bR> <div> According to Albert, the typical CRP level declined with increasing exercise. And the relationship was seen in all subgroups, including smokers, nonsmokers and those with and without heart disease. </div> <bR> <div> "There was a progressive drop in CRP levels with exercise, even after adjusting for smoking, lipid (cholesterol) levels and age," Albert said. </div> <bR> <div> But greater exercise-related drops in CRP were seen in men than in women, she noted. </div> <bR> <div> The reason is unclear, but Albert speculated that women may engage in less intense exercise or may have a lower overall activity level than men. </div> <bR> <bR> <bR> <bR> <bR> <bR> <bR> <bR> <div> <B><U> <A NAME="soluble_cd40_ligand_in_acute_coronary"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="1" ALIGN="bottom" WIDTH="1" HSPACE="0" VSPACE="0" ></A></U></B></div> <div> <U>Soluble CD40 Ligand in Acute Coronary Syndromes</U></div> <div>  FROM  NEW ENGLAND JOURNAL Volume 348:1104-1111 March 20, 2003 Number 12</div> <bR> <div> Christopher Heeschen, M.D., Stefanie Dimmeler, Ph.D., Christian W. Hamm, M.D., Marcel J. van den Brand, M.D., Eric Boersma, Ph.D., Andreas M. Zeiher, M.D., Maarten L. Simoons, M.D., for the CAPTURE Study Investigators </div> <div>       </div> <div> <U>ABSTRACT</U></div> <div> Background CD40 ligand is expressed on platelets and released from them on activation. We investigated the predictive value of soluble CD40 ligand as a marker for clinical outcome and the therapeutic effect of glycoprotein IIb/IIIa receptor inhibition in patients with acute coronary syndromes. </div> <div> <U>Methods</U> </div> <div> Serum levels of soluble CD40 ligand were measured in 1088 patients with acute coronary syndromes who had previously been enrolled in a randomized trial comparing abciximab with placebo before coronary angioplasty and in 626 patients with acute chest pain. </div> <div> <U>Results </U></div> <div> The levels of soluble CD40 ligand were elevated (above 5.0 µg per liter) in 221 patients with acute coronary syndromes (40.6 percent). Among patients receiving placebo, elevated soluble CD40 ligand levels indicated a significantly increased risk of death or nonfatal myocardial infarction during six months of follow-up (adjusted hazard ratio as compared with patients with low levels of the ligand [5.0 µg per liter], 2.71; 95 percent confidence interval, 1.51 to 5.35; P=0.001). The prognostic value of this marker was validated in the patients with chest pain, among whom elevated soluble CD40 ligand levels identified those with acute coronary syndromes who were at high risk for death or nonfatal myocardial infarction (adjusted hazard ratio as compared with those with low levels of the ligand, 6.65; 95 percent confidence interval, 3.18 to 13.89; P<0.001). The increased risk in patients with elevated soluble CD40 ligand levels was significantly reduced by treatment with abciximab (adjusted hazard ratio as compared with those receiving placebo, 0.37; 95 percent confidence interval, 0.20 to 0.68; P=0.001), whereas there was no significant treatment effect of abciximab in patients with low levels of soluble CD40 ligand. </div> <div> <U>Conclusions</U></div> <div>  In patients with unstable coronary artery disease, elevation of soluble CD40 ligand levels indicated an increased risk of cardiovascular events. Elevation of soluble CD40 ligand identifies a subgroup of patients at high risk who are likely to benefit from antiplatelet treatment with abciximab. </div> <div> <U>Source Information</U></div> <div> From the c7E3 Fab Antiplatelet Therapy in Unstable Refractory Angina (CAPTURE) Study (C.H., S.D., C.W.H., M.J.B., E.B., A.M.Z., M.L.S.); Molecular Cardiology, Department of Internal Medicine IV, University of Frankfurt, Frankfurt, Germany (C.H., S.D., A.M.Z.); the Kerckhoff Heart Center, Bad Nauheim, Germany (C.W.H.); and the Thoraxcentre, Erasmus University, Rotterdam, the Netherlands (M.J.B., E.B., M.L.S.). </div> <bR> <div> Address reprint requests to Dr. Heeschen at the Department of Molecular Cardiology, Internal Medicine IV, University of Frankfurt, Theodor-Stern-Kai 7, 60590 Frankfurt, Germany, or at c.heeschen@em.uni-frankfurt.de.</div> <bR> <bR> <bR> <div> <U> <A NAME="women"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="1" ALIGN="bottom" WIDTH="1" HSPACE="0" VSPACE="0" ></A></U></div> <div> <U>Heart Disease: A Woman's Biggest Health Threat</U></div> <div> Fri Feb 28,11:56 PM ET  Add Health - HealthScoutNews to My Yahoo! By Ross Grant HealthScoutNews Reporter </div> <bR> <div> FRIDAY, Feb. 28 (HealthScoutNews) -- When it comes to heart disease, what women don't know can kill them. </div> <bR> <div> For instance, most women don't realize that heart disease is a bigger threat than any other illness they might face. A recent American Heart Association (news - web sites) survey found that a majority of women thought breast cancer (news - web sites) was the leading cause of death.</div> <bR> <div> "One in 28 women will die of breast cancer, whereas almost one in two will die of heart disease," says Dr. Robert Bonow, president of the heart association and chief of cardiology at Northwestern University in Chicago.</div> <bR> <div> "Partly, it's that women are less aware of their risk factors. They are less likely to see heart disease as an illness that will kill them rather than men," Bonow adds.</div> <bR> <div> In 2000, cardiovascular diseases claimed the lives of 505,661 American women. In the same year, 440,175 men died from these diseases, which range from heart attack to atherosclerosis, a buildup of plaque in the arteries.</div> <bR> <div> With those disturbing statistics as a backdrop, February has been designated American Heart Month. And the American Heart Association (AHA) is working to spread the word that preventive measures and early screening of risk factors can help Americans thwart heart disease before it strikes.</div> <bR> <div> "If we're really going to change this epidemic, it's going to take prevention. People need to know their blood pressure and cholesterol, and they need to be treated effectively," Bonow says.</div> <bR> <div> "Also, people need to be more careful about their diet," he adds. "Our younger population is becoming more obese. And fewer schools are providing physical education."</div> <bR> <div> To underscore the heightened risk facing women, consider these statistics: In 1980, 4 percent more American men died of cardiovascular disease than women. But by 1984, that gap had disappeared.</div> <bR> <div> Today, 15 percent more women than men die of heart disease.</div> <bR> <div> "These diseases claim the lives of more than half a million females every year -- about a death a minute. That's more lives than the next seven causes of death combined," states the American Heart Association.</div> <bR> <div> Part of the problem can be traced to a historical lack of attention on women's health issues. While much research has been done on heart disease in men, it's only in the last decade that researchers have focused studies on women, says Dr. Nieca Goldberg, chief of the Women's Heart Program at Lenox Hill Hospital in New York City.</div> <bR> <div> "I remember in medical school, when instructors referred to heart disease, they would show slides of a middle-aged businessman clutching his chest," says Goldberg, who wrote the book, "Women are Not Small Men: Lifesaving strategies for preventing and healing heart disease in women."</div> <bR> <div> Another point for women to consider is that women and men get heart disease at different points in the lives. For men, it generally shows up in their 40s, but for women it usually doesn't appear until after menopause, around 60. And as the population ages, a growing number of women are being diagnosed with heart disease, Goldberg says.</div> <bR> <div> What's more, men survive heart attacks more often than women. This is partly due to medical improvements in fighting heart attacks, but also because men are generally younger when they are stricken, Bonow says.</div> <bR> <div> And the warning signs for heart attack differ between the sexes. Instead of the characteristic chest pain men get, women often have shortness of breath, exhaustion and discomfort in the lower chest, which can be mistaken for stomach illness. As a result, they frequently don't realize they are having a heart attack, Goldberg says.</div> <bR> <div> "They need to be aware that the earlier they get to the hospital, the more likely we can save them," she says.</div> <bR> <div>    To prevent heart disease, women and men must address the three largest risk behaviors -- being overweight, lack of physical activity, and smoking.</div> <bR> <div> Exercise and a diet rich in fruits, vegetables, grains and fish are essential. But so is early screening for high cholesterol and blood pressure. The sooner doctors can detect the warning signs of heart disease in a person, the more likely they can prevent it, experts say.</div> <bR> <div> As part of American Heart Month, the AHA is also stressing the value of CPR training, which can save a heart attack victim's life. The group is also pushing an initiative to increase the number of portable defibrillators in public places.</div> <bR> <div> "Heart disease is not just a U.S. issue. It's also an international issue," Bonow says. "You start with public awareness."</div> <bR> <bR> <bR> <bR> <bR> <div> <B> <A NAME="time_of_day_affects_drug_s_blood"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="1" ALIGN="bottom" WIDTH="1" HSPACE="0" VSPACE="0" ></A></B></div> <div> <B>Time of Day Affects Drug's Blood Pressure Control</B></div> <div> <B>Tue Jan 21, 5:51 PM ET  Add Health - Reuters to My Yahoo! </B></div> <div> <B> </B></div> <bR> <div> <B>By Keith Mulvihill </B></div> <bR> <div> <B>NEW YORK (Reuters Health) - Several different classes of drugs can be used to get blood pressure under control, and now a small study suggests that some may be more effective at certain times of the day than others. </B></div> <bR> <div> <B>  </B></div> <bR> <div> <B>"Different classes of drugs act more effectively at different times of the day," Dr. Trefor O. Morgan told Reuters Health. "This differential effect has not previously been clearly shown." </B></div> <bR> <bR> <div> <B>The new findings suggest that prescribing more than one blood pressure medication may provide more effective treatment, according to Morgan, of the University of Melbourne in Australia. </B></div> <bR> <bR> <div> <B>Normally, a person's blood pressure dips and climbs over a 24-hour period. Blood pressure climbs most rapidly in the morning after awakening and typically plateaus during the middle-to-late portion of the day. It then declines in the evening and is lowest during sleep. </B></div> <bR> <bR> <div> <B>In the current investigation, Morgan and co-author Adrianne Anderson looked at the effects of four different blood pressure medications on 24 people over age 65 with elevated systolic blood pressure--the first number in a blood pressure reading. </B></div> <bR> <bR> <div> <B>Each of the patients took one medication or a placebo for two months before switching to the next treatment. Blood pressure measurements were taken three times over a 24-hour period at the end of each of five treatment periods. </B></div> <bR> <bR> <div> <B>The medications evaluated include a diuretic (hydrochlorothiazide), a beta-blocker (atenolol), an angiotensin converting enzyme (ACE) inhibitor (perindopril), and a calcium channel blocker (felodipine). </B></div> <bR> <bR> <div> <B>Their results are published in the January issue of the American Journal of Hypertension. </B></div> <bR> <bR> <div> <B>The investigation found that diuretics and calcium channel blockers were relatively consistent at lowering blood pressure around the clock, said Morgan. Beta-blockers, on the other hand, lowered daytime blood pressure but had little effect on nighttime blood pressure. ACE inhibitors lowered blood pressure more at night than during the day, Morgan noted. </B></div> <bR> <bR> <div> <B>"Experiments in animals and human observations indicate that nighttime blood pressure elevation is associated with more cardiac enlargement and a higher morbidity and mortality," Morgan told Reuters Health. </B></div> <bR> <bR> <div> <B>As a result, combinations of drugs may need to be used to obtain optimal blood pressure control over a 24-hour interval, according to Morgan. </B></div> <bR> <bR> <div> <B>"The reason that beta blockers may not have as good results as diuretics on complications may result from (its) failure of blood pressure control at night," Morgan added. </B></div> <bR> <bR> <div> <B>Currently, the majority of patients with hypertension are on one drug, Morgan said. However, single drug therapy controls blood pressure in less than 30% of patients, according to the Australian researcher. </B></div> <bR> <bR> <div> <B>"This may explain why control of blood pressure achieved in the community is so poor," he concluded. </B></div> <bR> <bR> <div> <B>SOURCE: American Journal of Hypertension 2003;16:46-50. </B></div> <bR> <bR> <div> <B>In conclusion, blood pressure is controlled by a large number of variables. </B></div> <bR> <bR> <div> <B>We recognize this by the individual variation that occurs in response to specific drugs. </B></div> <bR> <bR> <div> <B>The evidence from this study those different times of the day may require us to rethink our therapeutic strategies. </B></div> <bR> <div> <B>It is probably an additional reason to use multiple drugs rather than relying on high dose monotherapy </B></div> <bR> <bR> <bR> <div> <B><U> <A NAME="uc_davis_study_identifies_c_reactive"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="1" ALIGN="bottom" WIDTH="1" HSPACE="0" VSPACE="0" ></A></U></B></div> <div> UC Davis Study Identifies C-Reactive Protein as Cause of Blood Clot Formation </div> <div> <TABLE BORDER="0" CELLPADDING="1" CELLSPACING="1" WIDTH="296" BORDERCOLORLIGHT="#C0C0C0" BORDERCOLORDARK="#808080" FRAME="VOID" RULES="NONE" HSPACE="0" VSPACE="0" > <tR> <tD VALIGN=CENTER HEIGHT= 38 WIDTH="115"><div> Fri Jan 10, 7:00 PM ET</div> </tD> <tD VALIGN=CENTER WIDTH="174"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="38" ALIGN="bottom" WIDTH="174" HSPACE="0" VSPACE="0"></tD> </tR> </TABLE></div> <div> <I>Source: University of California, Davis - Medical Center </I></div> <div> Further underscoring the limitations of cholesterol screening in assessing a patient's risk for heart disease, a new study by UC Davis physicians is the first to conclusively link C-reactive proteins (CRP) to formation of blood clots, a major cause of heart attacks, strokes and other vascular disease. Until now, CRP had been recognized mainly as a risk marker of heart disease. The study appears in the January 25, 2003, print edition of the journal Circulation, a publication of the American Heart Association (<FONT SIZE="3" COLOR="#0000FF" FACE="arial" ><U>news</U></FONT> - <FONT SIZE="3" COLOR="#0000FF" FACE="arial" ><U>web sites</U></FONT>), and is available on the Web at www.circulationaha.org. </div> <bR> <div> "The study provides further conclusive evidence that CRP, until now viewed as an 'innocent bystander' in the formation of heart disease, is in fact a key culprit that causes inflammation in the arteries, resulting in formation of clots and plaque that lead to heart attacks and strokes," said Ishwarlal Jialal, professor of pathology and director of the Laboratory for Atherosclerosis and Metabolic Research at UC Davis School of Medicine and Medical Center. </div> <bR> <div> The study demonstrates that CRP causes cells in the arteries, known as human aortic endothelial cells, to produce higher levels of an enzyme that inhibits the breakdown of clots. The enzyme, plasminogen activator inhibitor-1 (PAI-1) is also a strong risk marker for heart disease, especially in diabetics (<FONT SIZE="3" COLOR="#0000FF" FACE="arial" ><U>news</U></FONT> - <FONT SIZE="3" COLOR="#0000FF" FACE="arial" ><U>web sites</U></FONT>). The study used a variety of techniques to convincingly show how CRP activates PAI-1 in aortic cells, causing lesions in the arteries that ultimately lead to formation of plaque and blood clots. </div> <bR> <div> The study underscores the need to use CRP screening to more accurately assess at-risk populations, according to Jialal, who is the Robert E. Stowell Endowed Chair in Experimental Pathology. </div> <bR> <div> "Based on these findings, if a patient has normal cholesterol but high levels of CRP, an aggressive course of treatment is recommended to help the patient reduce the risk of heart attack, stroke and other heart diseases," said Jialal. "By relying on cholesterol alone, a physician could significantly underestimate a patient's risk level." </div> <bR> <div> High CRP levels can occur in otherwise healthy individuals, according to the study. Patients with high levels of CRP can reduce risk by losing weight, exercising on a regular basis, stopping cigarette smoking, or taking statin drugs, Jialal added. </div> <bR> <div> The study also closely links CRP and PAI-1 to diabetes and metabolic syndrome, a disorder characterized by a disproportionate amount of abdominal fat, elevated blood pressure, blood sugar and triglycerides and low levels of HDL, the "good" kind of cholesterol. </div> <bR> <div> "In another important discovery, this study shows that in the presence of high blood-glucose levels, CRP is especially active in the stimulation of PAI-1. As a result, the effect of CRP is especially acute for patients with diabetes and metabolic syndrome," said Sridevi Devaraj, a co-investigator and assistant professor of pathology at UC Davis. "Given the current pandemic of obesity which increases one's risk of diabetes, the study's insights about the active role of CRP and PAI-1 in heart disease are especially valuable." </div> <bR> <div> The new study adds to the findings of another landmark study on CRP by Jialal's team at UC Davis that showed CRP actually damages the blood vessel wall by blocking a critical "protector" protein and inhibiting nitric oxide. </div> <bR> <div> "Interestingly, the new study indicates that activation of PAI-1 was unrelated to the nitric oxide inhibition identified in the earlier study," said Jialal. "This indicates that CRP has multiple, independent effects that cause heart disease." </div> <bR> <div> Dan Yan Xu, a physician and postgraduate researcher in the pathology department at UC Davis, also contributed to the study. </div> <bR> <div> This study was supported by grants from the National Institutes of Health (<FONT SIZE="3" COLOR="#0000FF" FACE="arial" ><U>news</U></FONT> - <FONT SIZE="3" COLOR="#0000FF" FACE="arial" ><U>web sites</U></FONT>), the Juvenile Diabetes Foundation and American Diabetes Association. </div> <bR> <bR> <bR> <bR> <div> <B> <A NAME="periodontal_disease"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="1" ALIGN="bottom" WIDTH="1" HSPACE="0" VSPACE="0" ></A></B><B>NEW YORK (Reuters Health) - Individuals with severe periodontal disease may be prone to releasing endotoxins into their bloodstream, which may help explain the link between gum infections and cardiovascular disease, Belgian researchers report.</B></div> <bR> <bR> <bR> <div> <B><U> <A NAME="drug_cuts_women_s_stroke_risk_study__by"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="1" ALIGN="bottom" WIDTH="1" HSPACE="0" VSPACE="0" ></A></U></B><B><U>Drug Cuts Women's Stroke Risk-</U></B><B>Study  By Julie Steenhuysen </B></div> <bR> <div> <B>CHICAGO (Reuters) - The use of Evista, Eli Lilly and Co.'s drug to treat post-menopausal osteoporosis, cut the risk of stroke by nearly two-thirds in women at high risk for heart disease, researchers said on Sunday. </B></div> <bR> <div> <B>  The data, presented at the American Heart Association (news - web sites)'s annual Scientific Sessions conference in Chicago, showed that Evista was linked with a 62% reduction in the risk of all strokes--fatal and non-fatal--in post-menopausal women at high risk for heart disease. </B></div> <bR> <div> <B>The research comes in the wake of recent findings by a Women's Health Initiative study that showed Wyeth's hormone replacement therapy Prempro, which is often prescribed for post-menopausal osteoporosis, increased the risk of stroke by 41%. </B></div> <bR> <div> <B>The WHI study's results, released in July, triggered a huge debate over how doctors treat post-menopausal women. </B></div> <bR> <div> <B>Lilly's Evista findings were part of a four-year study of 7,705 post-menopausal women with osteoporosis. It found that of the 1,035 women in the group who were at high risk of heart disease, Evista cut the risk of non-fatal strokes by 68%. </B></div> <bR> <div> <B>"These data are particularly interesting in light of recent findings from the WHI trial examining hormone therapy," said Dr. Elizabeth Barrett-Connor, professor of family and preventative medicine at the University of California, San Diego, who presented the results. "While raloxifene and hormone therapy are both prescribed for osteoporosis, the WHI data showed that combined estrogen-progestin hormone therapy actually increased the risk of stroke." </B></div> <div> <B>A TIME FOR 'SMART' ESTROGEN </B></div> <bR> <div> <B>Dr. Cheryl Keech, clinical research physician at Lilly, said the Evista results suggest a place for "smart" estrogen therapy that can target specific receptors within a cell. </B></div> <bR> <div> <B>"The one thing WHI has shown us is you have to do randomized controlled trials," Keech told Reuters. </B></div> <bR> <div> <B>Known by the chemical name of raloxifene HCI, Evista is a selective estrogen receptor modulator used for both the prevention and treatment of osteoporosis. </B></div> <bR> <div> <B>Along with the decreased risk of stroke in the subgroup of women at high risk for heart disease, Evista showed no increased risk of stroke among the total 7,705-patient population. Evista also did not increase blood pressure, a risk factor for stroke. </B></div> <bR> <div> <B>Lilly said it is studying Evista to determine its ability to reduce the risks of serious heart-related events and breast cancer (news - web sites) in post-menopausal women in a number of clinical trials. </B></div> <bR> <div> <B>In an ongoing 10,000-patient study of Evista in preventing heart disease, Lilly aims to determine whether Evista can have positive benefits without the problems of hormone replacement therapy. </B></div> <bR> <div> <B>"We don't see any harm and we see both benefits in stroke and coronary," she said, adding that the observations need to be proven in a prospective trial. </B></div> <bR> <div> <B>The company plans to use the data from that trial as part of a submission to the US Food and Drug Administration (news - web sites) to use Evista as a treatment to prevent heart disease. Early results of that study will be available in 2005. </B></div> <bR> <bR> <bR> <div> <B><U> <A NAME="cross_talk_between_iron_metabolism_and"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="1" ALIGN="bottom" WIDTH="1" HSPACE="0" VSPACE="0" ></A></U></B><B><U>Cross-Talk Between Iron Metabolism and Diabetes</U></B></div> <div> <B>José Manuel Fernández-Real, Abel López-Bermejo, and Wifredo Ricart</B> </div> <div> Diabetes 51(8):2348-2354, 2002. © 2002 American Diabetes Association, Inc.</div> <div> Posted 08/29/2002 </div> <div> Abstract and Introduction</div> <div> Abstract</div> <div> Emerging scientific evidence has disclosed unsuspected influences between iron metabolism and type 2 diabetes. The relationship is bi-directional—iron affects glucose metabolism, and glucose metabolism impinges on several iron metabolic pathways. Oxidative stress and inflammatory cytokines influence these relationships, amplifying and potentiating the initiated events. The clinical impact of these interactions depends on both the genetic predisposition and the time frame in which this network of closely related signals acts. In recent years, increased iron stores have been found to predict the development of type 2 diabetes while iron depletion was protective. Iron-induced damage might also modulate the development of chronic diabetes complications. Iron depletion has been demonstrated to be beneficial in coronary artery responses, endothelial dysfunction, insulin secretion, insulin action, and metabolic control in type 2 diabetes. Here, we show that iron modulates insulin action in healthy individuals and in patients with type 2 diabetes. The extent of this influence should be tested in large-scale clinical trials, searching for the usefulness and cost-effectiveness of therapeutic measures that decrease iron toxicity. The study of individual susceptibility and of the mechanisms that influence tissue iron deposition and damage are proposed to be valuable in anticipating and treating diabetes complications.</div> <div> Introduction</div> <div> It is increasingly recognized that iron influences glucose metabolism, even in the absence of significant iron overload. In the generalpopulation, body iron stores are positively associated with the development of glucose intolerance, type 2 diabetes,<FONT SIZE="1" COLOR="#660099" FACE="Arial" >[1-7]</FONT> and gestational diabetes.<FONT SIZE="1" COLOR="#660099" FACE="Arial" >[8, 9]</FONT> Among U.S. adults, men with newly diagnosed diabetes had an odds ratio (OR) of 4.94 (95%confidence interval [CI] 3.05-8.01) and women had an OR of 3.61 (2.01-6.48) of having elevated ferritin concentrations.<FONT SIZE="1" COLOR="#660099" FACE="Arial" >[6]</FONT> These figures are especially remarkable when considering the increased prevalence of elevated iron stores in the healthy, free-living U.S. elderly population (28% of men and 12.2% of women showed high iron stores in a recent study).<FONT SIZE="1" COLOR="#660099" FACE="Arial" >[10]</FONT></div> <div> Frequent blood donations, leading to decreased iron stores, have been demonstrated to reduce postprandial hyperinsulinemia in healthy volunteers,<FONT SIZE="1" COLOR="#660099" FACE="Arial" >[11]</FONT> to improve insulin sensitivity,<FONT SIZE="1" COLOR="#660099" FACE="Arial" >[12]</FONT> and to constitute a protective factor for the development of type 2 diabetes.<FONT SIZE="1" COLOR="#660099" FACE="Arial" >[13]</FONT> Phlebotomy was followed by decreases in serum glucose, cholesterol, triglycerides and a poprotein B,<FONT SIZE="1" COLOR="#660099" FACE="Arial" >[14]</FONT> and by improvement in both -cell secretion and peripheral insulin action in patients with type 2 diabetes.<FONT SIZE="1" COLOR="#660099" FACE="Arial" >[15]</FONT> A significant impact of tissue iron excess on systemic effects of diabetes is suggested by recent reports in which iron appears to influence the development of diabetic nephropathy and vascular dysfunction. In this sense, intravenous administration of deferoxamine resulted in improved coronary artery responses to cold stress testing in type 2 diabetic subjects<FONT SIZE="1" COLOR="#660099" FACE="Arial" >[16]</FONT> and in amelioration of endothelial dysfunction in subjects with coronary heart disease.<FONT SIZE="1" COLOR="#660099" FACE="Arial" >[17]</FONT></div> <div> All these observations suggest that iron is more intimately linked to human pathophysiology than previously thought. In fact, iron metabolism is closely associated with the clinical presentation of numerous systemic diseases.<FONT SIZE="1" COLOR="#660099" FACE="Arial" >[18]</FONT> Tissue iron excess contributes to produce and amplify the injury caused by free radicals as well as to modulate various steps involved in the inflammatory lesion.</div> <div> In this article, we summarize the relationships between iron, insulin resistance, and type 2 diabetes and discuss the therapeutical and clinical implications of reducing body iron.</div> <div> Iron Stores are Associated With Insulin Sensitivity, Insulin Secretion, and Type 2 Diabetes</div> <div> Iron and Insulin Sensitivity</div> <div> Iron stores, expressed as serum ferritin concentration, have been proposed to be a component of the insulin-resistance syndrome. Indeed, the concentration of circulating ferritin was significantly associated with centrally distributed body fatness as well as with several other measurements of obesity.<FONT SIZE="1" COLOR="#660099" FACE="Arial" >[19]</FONT> In the apparently healthy general population, serum levels of ferritin were also positively correlated with baseline serum glucose and with the area under the curve for glucose during the glucose oral tolerance test.<FONT SIZE="1" COLOR="#660099" FACE="Arial" >[20, 21]</FONT> In gestational diabetes, both BMI and serum ferritin levels were found to be independent predictors of 2-h glucose during an oral glucose tolerance test.<FONT SIZE="1" COLOR="#660099" FACE="Arial" >[8, 9]</FONT> Ferritin levels also correlated with diastolic arterial blood pressure, even after adjustment for BMI. Of note is the beneficial effect of blood letting, a means of reducing iron stores, in the treatment of resistant hypertension<FONT SIZE="1" COLOR="#660099" FACE="Arial" >[22]</FONT> and in posttrans plant hypertension associated with erythrocytosis.<FONT SIZE="1" COLOR="#660099" FACE="Arial" >[23]</FONT> Serum ferritin concentration was also directly associated with uric acid (another component of the insulin resistance syndrome) and inversely related with HDL cholesterol and the HDL<FONT SIZE="1" COLOR="#660099" FACE="Arial" >2</FONT>-to-HDL<FONT SIZE="1" COLOR="#660099" FACE="Arial" >3</FONT> ratio.<FONT SIZE="1" COLOR="#660099" FACE="Arial" >[21]</FONT></div> <div> Insulin resistance itself, assessed by either the euglycemic clamp <FONT SIZE="1" COLOR="#660099" FACE="Arial" >[24]</FONT> or the minimal model,<FONT SIZE="1" COLOR="#660099" FACE="Arial" >[25, 26]</FONT> was found to be associated with total body iron stores, even in the presence of normal glucose tolerance. Dmochowski et al.<FONT SIZE="1" COLOR="#660099" FACE="Arial" >[25]</FONT> reported that serum concentrations of ferritin were negatively correlated with insulin sensitivity (<I>r</I> = -0.58) in subjects with hemosiderosis. Cavallo-Perinet al.<FONT SIZE="1" COLOR="#660099" FACE="Arial" >[26]</FONT> reported that insulin sensitivity, which correlated closely with iron overload (<I>r</I> = -0.70), was reduced by 40% in thalassemia patients. Insulin resistance also appeared to be closely linked to total body iron stores in the general population.<FONT SIZE="1" COLOR="#660099" FACE="Arial" >[21]</FONT> Serum ferritin levels could be a useful marker of insulin resistance beyond a given threshold.<FONT SIZE="1" COLOR="#660099" FACE="Arial" >[20, 21]</FONT> In the study by Toumainen et al.,<FONT SIZE="1" COLOR="#660099" FACE="Arial" >[20]</FONT> the increase in serum insulin concentrations was clearly apparent in the upper two quintiles of ferritin levels. In a different study, the correlation between circulating ferritin and insulin resistance was only observed in the upper two quartiles of ferritin levels.<FONT SIZE="1" COLOR="#660099" FACE="Arial" >[21]</FONT> Below this threshold, the potential tissue effects of siderosis would be negligible.</div> <div> Some comments on the specifity of serum ferritin as an indicatorof iron stores seem necessary. The relationship between serum ferritin and histochemical assessment of stainable tissue iron contributes to define threshold values for serum ferritin, indicating exhausted, small, normal, ample, and increased iron stores. However, the barrier between "normal" and " small" or "ample" iron stores is not well defined and remains controversial. Approximately 10% of type 2 diabetic patients with high ferritin levels had transferrin saturations greater than normal (40%). On the other hand, serum ferritin should be cautiously evaluated in patients with type 2 diabetes, because it may falsely indicate "normal iron stores." It should not be ignored that chronic inflammation could contribute, to some extent, to increased ferritin concentration (see below).</div> <div> Iron and Beta-cell Function</div> <div> Recent in vitro studies have shown that H-ferritin mRNA is four-to eightfold higher in rat islets treated with 20 mmol/l glucose than in islets treated with 1 mmol/l glucose.<FONT SIZE="1" COLOR="#660099" FACE="Arial" >[27]</FONT> The potential reason for the increased ferritin in the -cell is that ferritin exhibits antioxidant properties and the -cell is particularly sensitive to oxygen radicals. This high amount of ferritin can explain why iron is preferentially retained in the -cell. In fact, iron deposition in islets, albeit variable, is restricted to -cells.<FONT SIZE="1" COLOR="#660099" FACE="Arial" >[28]</FONT></div> <div> An increase in -cell mass was demonstrated in a small number of nondiabetic or mildly diabetic patients with iron overload.<FONT SIZE="1" COLOR="#660099" FACE="Arial" >[28]</FONT> In agreement with this increase in -cell mass, raised basal and stimulated C-peptide secretion were observed in type 2 diabetic patients with increased serum ferritin concentration. Furthermore, significantly lowered C-peptide secretion was found after phlebotomy-induced iron depletion, suggesting increased-cell insulin sensitivity.<FONT SIZE="1" COLOR="#660099" FACE="Arial" >[15]</FONT></div> <div> Iron Overload and Type 2 Diabetes</div> <div> Five additional pieces of scientific evidence favor the hypothesis that iron plays a role in type 2 diabetes. First, increased prevalence of hemochromatosis was found among unselected patients with type 2 diabetes. Phelps et al.<FONT SIZE="1" COLOR="#660099" FACE="Arial" >[29]</FONT> and Conte et al.<FONT SIZE="1" COLOR="#660099" FACE="Arial" >[30]</FONT> reported that diabetes confers increased risk for hereditary hemochromatosis, which was 2.4% and 1.34% higher in Australian and Italian populations, respectively.</div> <div> This evidence, however, is not always consistent. The recent characterization of <I>HFE</I> has allowed a more direct study of the prevalence of its mutations in type 2 diabetes. Homozygosity for the C282Y change is generally associated with clinically evident hereditary hemochromatosis (83% of hemochromatosis patients are YY homozygotes). Compound heterozygotes for H63D mutation(C282Y/H63D) succumb to the disease, although with reduced penetrance. An increased frequency of C282Y mutations in subjects with type 2 diabetes has been described in some studies.<FONT SIZE="1" COLOR="#660099" FACE="Arial" >[31-32]</FONT> Notwithstanding, at least four additional studies reported nosignificant differences in the prevalence of C282Y mutations between patients with type 2 diabetes and control subjects of Caucasian origin.<FONT SIZE="1" COLOR="#660099" FACE="Arial" >[33-36]</FONT> In the Spanish population, the frequency of the H63D mutation was significantly higher in type 2 diabetic subjects.<FONT SIZE="1" COLOR="#660099" FACE="Arial" >[36]</FONT> The H63D mutation is also associated with other nonclassical conditions of iron overload. On the other hand, it is interesting to mention that genetic hemochromatosis contributed to 1% of late-onset type 1 diabetes.<FONT SIZE="1" COLOR="#660099" FACE="Arial" >[37]</FONT></div> <div> Second, frequent blood donations, leading to decreasing iron stones, have been demonstrated to constitute a protective factor for the development of diabetes.<FONT SIZE="1" COLOR="#660099" FACE="Arial" >[13]</FONT> This finding is especially important given the high prevalence of increased iron stores in the general population of western countries<FONT SIZE="1" COLOR="#660099" FACE="Arial" >[10]</FONT> and the observation that increased iron stores appear to predict an increased incidence of type 2 diabetes.<FONT SIZE="1" COLOR="#660099" FACE="Arial" >[5]</FONT> In experimental models, the incidence of diabetes was reduced from 78 to 22%at 120 days of age after serial blood withdrawals in the BBrat.<FONT SIZE="1" COLOR="#660099" FACE="Arial" >[38]</FONT></div> <div> Third, a recent randomized study also suggests that iron stores may influence insulin action in type 2 diabetes.<FONT SIZE="1" COLOR="#660099" FACE="Arial" >[15]</FONT> In this report, 28 type 2 diabetic patients with increased serum ferritin concentration and negative for C282Y mutation of hereditary hemochromatosis were randomized to blood letting (three 500ml phlebotomies at 2-week intervals) or to observation. Insulin secretion and sensitivity were tested at baseline and at 4 and 12 months thereafter. The two groups were matched for age, BMI, pharmacological treatment, and chronic diabetes complications.<FONT SIZE="1" COLOR="#660099" FACE="Arial" >[15]</FONT> Baseline glycated hemoglobin and insulin sensitivity were not significantly different between the two groups. A statistically significant increase in insulin sensitivity was observed in the blood-letting group (from 2.30 ± 1.81 to 3.08 ±2.55 mg · dl<FONT SIZE="1" COLOR="#660099" FACE="Arial" >-1</FONT> · min<FONT SIZE="1" COLOR="#660099" FACE="Arial" >-1</FONT> at 4 months to 3.16 ±1.85 mg · dl<FONT SIZE="1" COLOR="#660099" FACE="Arial" >-1</FONT> · min<FONT SIZE="1" COLOR="#660099" FACE="Arial" >-1</FONT> at 12 months, <I>P</I> = 0.045) in contrast to patients subjected to observation in whom insulin sensitivity did not significantly change (from 3.24 ±1.9 to 3.26 ± 2.05 mg · dl<FONT SIZE="1" COLOR="#660099" FACE="Arial" >-1</FONT> · min<FONT SIZE="1" COLOR="#660099" FACE="Arial" >-1</FONT> at 4 months to 2.31 ± 1.35 mg · dl<FONT SIZE="1" COLOR="#660099" FACE="Arial" >-1</FONT> · min<FONT SIZE="1" COLOR="#660099" FACE="Arial" >-1</FONT>at 12 months). Accordingly, blood HbA<FONT SIZE="1" COLOR="#660099" FACE="Arial" >1c</FONT> decreased significantly only in the blood-letting group at 4 months (mean differences-0.61, 95% CI -0.17 to -1.048, <I>P</I> = 0.01).</div> <div> Fourth, a novel syndrome of hepatic iron overload has been described that associates hyperferritinemia with normal transferrin saturation and is not linked to the HLA-A3 antigen, a common marker for hereditary hemochromatosis.<FONT SIZE="1" COLOR="#660099" FACE="Arial" >[39]</FONT> This condition is known as insulin resistance-associated hepatic iron overload (IR-HIO) and combines abnormalities in iron metabolism (isolated hyperferritinemia with normal transferrin saturation), steatohepatitis, and the insulin resistance syndrome (obesity, hyperlipidemia, abnormal glucose metabolism, and hypertension).<FONT SIZE="1" COLOR="#660099" FACE="Arial" >[39-41]</FONT> In IR-HIO, iron overload occurs in both hepatocytes and sinusoid cells, being higher in the latter cells in 45% of cases, a finding seen in only 3% of subjects with hemochromatosis.<FONT SIZE="1" COLOR="#660099" FACE="Arial" >[42]</FONT> Approximately two-thirds of these patients develop steatosis, whereas the remaining third show isolated signs of inflammation.<FONT SIZE="1" COLOR="#660099" FACE="Arial" >[42]</FONT> Thus, these patients are at high risk for developing liver fibrosis, a complication observed in 60% of all cases, even in the presence of moderate iron overload. In contrast, liver fibrosis affects only 33% of patients with hemocromatosis. Because patients with IR-HIO are prone to experience significant tissue damage and because this can be prevented with simple and inexpensive therapies (i.e., phlebotomy), higher awareness in order to diagnose the disease has been suggested.</div> <div> It cannot be ruled out, however, that IR-HIO is the same process of iron overload-related insulin resistance that associate sliver steatosis and fibrosis in susceptible patients. It is important to recognize that in one study, liver iron stores were found within the normal range in patients with type 2 diabetes<FONT SIZE="1" COLOR="#660099" FACE="Arial" >[43]</FONT> in contrast to other studies.<FONT SIZE="1" COLOR="#660099" FACE="Arial" >[29, 30]</FONT> Under this assumption, IR-HIO would be at one end of the spectrum of iron overload-related insulin resistance.</div> <div> Fifth, insulin resistance features are frequently seen in patients chronically infected with the hepatitis C virus. In these subjects, BMI, elderliness, iron stores, and family history of diabetes and advanced liver fibrosis were found to predict the development of diabetes.<FONT SIZE="1" COLOR="#660099" FACE="Arial" >[44]</FONT></div> <div> Interacting Pathways Linking Glucose and Iron Metabolism</div> <div> A. Insulin Influences Iron Metabolism</div> <div> Insulin is an anabolic hormone that stimulates the cellular uptake of many nutrients, including hexoses, amino acids, cations and anions. Intestinal absorption of nonheme iron is tightly regulated in keeping with the body requirements, and absorption of iron is minimal when body iron stores are normal. Absorption of heme iron (largely provided by red meat in western countries) does not appear to be dependent on body iron content. In the steady state, circulating iron is bound to transferrin and is taken up from the blood by a high-affinity specific transferrin receptor. The transferrin-receptor complex is internalized by endocytosis and released into a nonacidic cellular compartment, where it can be used in the synthesis of essential cellular components. Insulin is known to cause a rapid and marked stimulation of iron uptake by fat cells, redistributing transferrin receptors from an intracellular membrane compartment to the cell surface.<FONT SIZE="1" COLOR="#660099" FACE="Arial" >[45]</FONT> Insulin is also responsible for the increased ferritin synthesis in cultured rat glioma cells.<FONT SIZE="1" COLOR="#660099" FACE="Arial" >[46]</FONT> Importantly, transferrin receptors have been shown to colocalize with insulin-responsive glucose transporters and insulin-like growth factor II receptors in the microsomal membranes of cultured adypocytes, suggesting that regulation of iron uptake by insulin occurs in parallel with its effects on glucose transport.<FONT SIZE="1" COLOR="#660099" FACE="Arial" >[47]</FONT></div> <div> B. Iron Influences Glucose Metabolism</div> <div> Reciprocally, iron influences insulin action. Iron interferes with insulin inhibition of glucose production by the liver. Hepatic extraction and metabolism of insulin is reduced with increasing iron stores, leading to peripheral hyperinsulinemia.<FONT SIZE="1" COLOR="#660099" FACE="Arial" >[48]</FONT> In fact, the initial and most common abnormality seen in iron overload conditions is liver insulin resistance.<FONT SIZE="1" COLOR="#660099" FACE="Arial" >[49]</FONT>There is some evidence that iron overload also affects skeletal muscle,<FONT SIZE="1" COLOR="#660099" FACE="Arial" >[50]</FONT> the main effector of insulin action.</div> <div> C. Oxidative Stress Influences Both Glucose and Iron Metabolism</div> <div> Oxidative stress induces both insulin resistance [by decreasing internalization of insulin<FONT SIZE="1" COLOR="#660099" FACE="Arial" >[51]</FONT>] and increased ferritin synthesis.</div> <div> Iron is intimately linked to oxidative stress. Iron participates, through the Fenton reaction, in the formation of highly toxic free radicals, such as hydroxide and the superoxide anion, which are capable of inducing lipid peroxidation. For iron to act as a prooxidant agent, it must be in its free form. Iron can be released from ferritin by the action of reducing agents that convert Fe<FONT SIZE="1" COLOR="#660099" FACE="Arial" >3+</FONT> into Fe<FONT SIZE="1" COLOR="#660099" FACE="Arial" >2+</FONT>.<FONT SIZE="1" COLOR="#660099" FACE="Arial" >[52]</FONT> Glycation of transferrin decreases its ability to bind ferrous iron<FONT SIZE="1" COLOR="#660099" FACE="Arial" >[53]</FONT> and, by increasing the pool of free iron, stimulates ferritin synthesis. Glycated holotransferrin is additionally known to facilitate the production of free oxygen radicals, such as hydroxide, that further amplify the oxidative effects of iron.<FONT SIZE="1" COLOR="#660099" FACE="Arial" >[53]</FONT></div> <div> The fraction of nonused and highly toxic iron is stored as ferritin molecules in order to be neutralized. Apoferritin, the protein fraction of ferritin, is spatially folded to create a central groove that holds oxidized iron molecules [Fe<FONT SIZE="1" COLOR="#660099" FACE="Arial" >3+</FONT>]. apoferritin is a high-molecular weight (450 kDa) multimeric protein (24subunits of heavy and light chains) that exhibits exquisite high capacity for iron storage (4, 500 mol iron per mole of ferritin). Synthesis of apoferritin is induced at both the transcriptional and posttranscriptional levels by the presence of free iron. The increase in Fe<FONT SIZE="1" COLOR="#660099" FACE="Arial" >2+</FONT> down regulates the affinity of iron-regulatory element (IRE) binding protein (BP) for its IRE binding site in the 5' region of ferritin mRNA, leading to increased ferritin translation.</div> <div> The heavy chain in the apoferritin molecule exerts ferroxidase activity, catalyzing the oxidation of Fe<FONT SIZE="1" COLOR="#660099" FACE="Arial" >2+</FONT> into Fe<FONT SIZE="1" COLOR="#660099" FACE="Arial" >3+</FONT>, which prevents iron-induced cyclic red-ox reactions that would spread and amplify the oxidative damage. This activity occurs underaerobic conditions, allowing the storage of intracellular iron. When concentrations of antioxidants are low, the reducing potential and anaerobiosis progressively increase, facilitating a rapid release of iron from ferritin. Additionally, the ferroxidase activity in the heavy chain is down regulated in this setting, decreasing the incorporation of iron into ferritin. The overall result of oxidative reactions is an increase in the availability of free iron from the ferritin molecule as well as from other molecules undergoing degradation, such as the heme group. These events, in turn, can enhance and amplify the process of generation of free radicals, causing cellular and tissue damage. The oxidative stress also down regulates the affinity of IRE for IRE-BP. Thus, ferritin can act both as a source or iron, which induces oxidative stress, and as a mechanism that protects against iron toxicity.<FONT SIZE="1" COLOR="#660099" FACE="Arial" >[54]</FONT></div> <div> Hyperferritininemia is present in 6.6% of unselected patients with type 2 diabetes.<FONT SIZE="1" COLOR="#660099" FACE="Arial" >[55]</FONT> Serum concentrations of ferritin are usually increased in poorly controlled type 1 and type 2diabetic subjects, and ferritin has been shown to predict HbA<FONT SIZE="1" COLOR="#660099" FACE="Arial" >1c</FONT> independently of glucose,<FONT SIZE="1" COLOR="#660099" FACE="Arial" >[21]</FONT> probably reflecting increase doxidative stress. Short-term improvement in glycemic control is followed by variable decreases in serum ferritin concentration.</div> <div> D. Cytokines Influence Iron and Glucose Metabolism</div> <div> Cytokines simultaneously cause an increase in transferrin receptors on the cell surface, favoring tissue deposition of iron<FONT SIZE="1" COLOR="#660099" FACE="Arial" >[56]</FONT> and insulin resistance.<FONT SIZE="1" COLOR="#660099" FACE="Arial" >[57]</FONT></div> <div> In summary, a scenario can be envisioned in which the physiological action of insulin leads to increased uptake of different nutrients and iron. Any factor causing hyperinsulinemia (weight gain, aging, repeated usual-life infections, or perio