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DRUG INDUCED DIABETES DURING ANTIHYPERTENSIVE THERAPY IS IMPORTANT-BUTCHINESE SOCIETY OF HYPERTENSIONMICHAEL ALDERMANMAY 22,2008Prevalence of diabetes among Chinese adults aged 3564 years in the 1994 Chinese National Survey(10)and 20002001 InterASIA StudyGu et al Diabetologia.2003;46:1190.Percent of deathsGeiss LS,et al.In:Diabetes in America.National Institutes of Health;1995.65%of Mortality in people with Diabetes is CVD Ischemic heart diseaseOther heart diseaseDiabetesMalignant neoplasmsCerebrovascular diseasePneumonia/influenzaAll otherCV mortality rate per10,000 person-yearsSystolic BP and CV Death in MRFITNondiabetic(n=342,815)Diabetic(n=5,163)120 120-139Systolic BP(mmHg)140-159160-179180-199 200Stamler J,et al.Diabetes Care.1993;16:434-444.BP=blood pressure CV=cardiovascular MRFIT=Multiple Risk Factor Intervention TrialAnnual Incidence of Diabetes in Hypertensive PatientsSHEP untreated controls=2.7%SHEP treated=3.9%Lancet.2006,368;1673-1679,Am J Cardiol.2005;95:29,Hypertension.2007;50:467,JAMA 2002;288:2981-2997 NHANES 18 year Follow-upNOD in US Women by Baseline BPConen,D.et al.Eur Heart J 2007 28:2937-2943140mmHg.Conen,D.et al.Eur Heart J 2007 28:2937-2943Age-adjusted incidence rates(A)and HRs(B)of NOD according to blood pressure category,stratified by baseline body mass indexTHE ISSUESCONSEQUENCES OF NODCVD AND non-CVDHOW DO ANTIHYPERTENSIVE DRUGS EFFECT INCIDENCE OF NOD AND CVD ONSEQUENCES?HOW SHOULD NOD EFFECT MANAGEMENT FOR CVD PROTECTION?Non-CVD Consequences of NODImpaired BP controlBehavioral and PsychologicalMicrovascular consequences(?)Medical care demandsTreatment changesCVD ConsequencesShort and Long termAntihypertensive Drug Related.Whelton,P.K.et al.Arch Intern Med 2005;165:1401-1409.ALLHATIncidence of Coronary heart disease by treatment group according to baseline diabetes mellitus,impaired fasting glucose level,or normoglycemiaBarzilay,J.I.et al ALLHAT.Arch Intern Med 2006;166:2191-2201.HRs of a 10-mg/dL(0.56-mm)FBG at 2 years for subsequent CVD and Renal Disease Effect of ACEIs and ARBs on CVD MortalitySource#studies#subjectsOR(95%CI)All11109,0520.96(0.91-1.01)ACEI674,6260.93(0.81-1.06)ARB534,4260.93(0.81-1.06)HTN786,4140.99(0.93-1.06)Gillespie,et al.Diabetes Care 28:2261-2266,2005Age-genderadjusted in treatment CVD and non-CVD by baseline FBG among hypertensive patients.Alderman,Hypertension.1999;33:1130-1134Myocardial infarction(fatal and nonfatal)in hypertensive patients according to DM statusAksnes,T.A.et al.Hypertension 2007;50Diabetes Incidence-4 Years(follow-up FBS 126 mg/dL for those 126 mg/dL at baseline)*p.05 compared to chlorthalidonep.05 compared to chlorthalidoneALLHATJAMA 2002;288:2981-2997Ramipril v.Placebo in high risk patients with IGT at baselineDream.NEJM;355:1551-1562,2006Ramipril v.Placebo CVD&non-CVD OutcomesDream.NEJM;355:1551-1562,2006.Whelton,P.K.et al.Arch Intern Med 2005;165:1401-1409.ALLHAT:RR(and 6-year rates per 100 for nondiuretic compared with diuretic for diabetes mellitus(A),impaired fasing glucose level(B),and normoglycemia(C)at baseline,for CHD,all-cause mortality,combined CHD,stroke,HF,all CVD,and ESRDCV death(%)PLACEBOACTIVE*=p 0.05 vs no diabetesSHEP-14 YEAR FOLLOW-UPCONCLUSIONS FROM SHEP+Chlorthalidone Rx of hypertension improves long-term outcomes.The diabetes related to chlorthalidone therapy has better prognosis than diabetes at baseline.The benefit of chlorthalidone-based therapy on long-term total and CV mortality is most pronounced in hypertensive patients with diabetes.Reduction in major CVD among 6,000 DM in HPS associated with 38/89 LDL/CHOL by StatinMazzone,T.The American Journal of Medicine 120;2007,S26-S32 Incidence of MI and Microvascular Endpoints by Mean SBP and HbA1c in UKPDSAdjusted incidence per 1000 person-years(%)Updated mean HbA1c concentration(%)Mean SBP(mmHg)Adjusted incidence per 1000 person-years(%)5678910 11110120130140150160170Myocardial infarctionMicrovascular endpointsMicrovascular endpointsMyocardial infarctionAdler AI,et al.BMJ.2000;321:412-419.Stratton IM,et al.BMJ.2000;321:405-412.MI=myocardial infarction SBP=systolic blood pressureUNCERTAINTY CONTINUESACCORD AND ADVANCEACCORD-Mortality greater with HbAlc 6.4 v.7.0-7.9%ADVANCE-No evidence of mortality with HbAlc 6.4 v.7,5%Major CV Event Rate In HOTHOTLancet 1998;351:1755 90 85 80 90 85 80 85.283.281.1 DBP achievedp=0.00551%riskreductionGoal Diastolic mmHgDiabetic populationNon-Diabetic subjectsCONCLUSIONSDM serious whenever it occursMore common in hypertensive Rx Particularly with diureticsNOD has consequences Non-CVD in short termCVD long termNeither fear of,nor NOD,requires D/C Diuretic CLINICAL IMPLICATIONSSCREEN FOR NODATTEMPT TO REVERSE HYPERGLCEMIACORRECT HYPOKAELMIAK SPARING DIURETICADD ACE OR ARBOPTIMIZE BP AND LIPID CONTROLTREAT HYPERGLYCEMIA(?)NO EVIDENCE OF CVD BENEFITPREVENTION OF MICROVASCULAR EFFECTS
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