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1、DRUG INDUCED DIABETES DURING ANTIHYPERTENSIVE THERAPY IS IMPORTANT - BUT,CHINESE SOCIETY OF HYPERTENSION MICHAEL ALDERMAN MAY 22, 2008,Prevalence of diabetes among Chinese adults aged 3564 years in the 1994 Chinese National Survey (10) and 20002001 InterASIA Study,Gu et al Diabetologia. 2003;46:1190
2、.,Percent of deaths,Geiss LS, et al. In: Diabetes in America. National Institutes of Health;1995.,65% of Mortality in people with Diabetes is CVD,Ischemic heart disease,Other heart disease,Diabetes,Malignant neoplasms,Cerebrovascular disease,Pneumonia/ influenza,All other,CV mortality rate per 10,00
3、0 person-years,Systolic BP and CV Death in MRFIT,Nondiabetic (n=342,815),Diabetic (n=5,163),120,120-139,Systolic BP (mmHg),140-159,160-179,180-199,200,Stamler J, et al. Diabetes Care. 1993;16:434-444.,BP= blood pressure CV=cardiovascular MRFIT=Multiple Risk Factor Intervention Trial,Annual Incidence
4、 of Diabetes in Hypertensive Patients,SHEP 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-up NOD in US Women by Baseline BP,Conen, D. et al. Eur Heart J 2007 28:2937-2943,120,
5、120-129,130-139,140,mmHg,.,Conen, D. et al. Eur Heart J 2007 28:2937-2943,Age-adjusted incidence rates (A) and HRs (B) of NOD according to blood pressure category, stratified by baseline body mass index,THE ISSUES,CONSEQUENCES OF NOD CVD AND non-CVD HOW DO ANTIHYPERTENSIVE DRUGS EFFECT INCIDENCE OF
6、NOD AND CVD ONSEQUENCES? HOW SHOULD NOD EFFECT MANAGEMENT FOR CVD PROTECTION?,Non-CVD Consequences of NOD,Impaired BP control Behavioral and Psychological Microvascular consequences (?) Medical care demands Treatment changes,CVD Consequences,Short and Long term Antihypertensive Drug Related,.,Whelto
7、n, P. K. et al. Arch Intern Med 2005;165:1401-1409.,ALLHAT Incidence of Coronary heart disease by treatment group according to baseline diabetes mellitus, impaired fasting glucose level, or normoglycemia,Barzilay, J. I. et al ALLHAT. Arch Intern Med 2006;166:2191-2201.,HRs of a 10-mg/dL (0.56-mm) FB
8、G at 2 years for subsequent CVD and Renal Disease,Effect of ACEIs and ARBs on CVD Mortality,Gillespie, et al. Diabetes Care 28:2261-2266, 2005,Age-genderadjusted in treatment CVD and non-CVD by baseline FBG among hypertensive patients.,Alderman, Hypertension. 1999;33:1130-1134,Myocardial infarction
9、(fatal and nonfatal) in hypertensive patients according to DM status,Aksnes, T. A. et al. Hypertension 2007;50,Diabetes Incidence - 4 Years (follow-up FBS 126 mg/dL for those 126 mg/dL at baseline),*,*,* p.05 compared to chlorthalidone,JAMA 2002;288:2981-2997,Ramipril v. Placebo in high risk patient
10、s with IGT at baseline,Dream. NEJM;355:1551-1562,2006,Ramipril v. Placebo CVD & non-CVD Outcomes,Dream. 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
11、fasing glucose level (B), and normoglycemia (C) at baseline, for CHD, all-cause mortality, combined CHD, stroke, HF, all CVD, and ESRD,CV death (%),PLACEBO,ACTIVE,* = p 0.05 vs no diabetes,SHEP - 14 YEAR FOLLOW-UP,CONCLUSIONS FROM SHEP +,Chlorthalidone Rx of hypertension improves long-term outcomes.
12、 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 38/8
13、9 LDL/CHOL by Statin,Mazzone, T.The American Journal of Medicine 120;2007, S26-S32,Incidence of MI and Microvascular Endpoints by Mean SBP and HbA1c in UKPDS,Adjusted incidence per 1000 person-years (%),Updated mean HbA1c concentration (%),Mean SBP (mmHg),Adjusted incidence per 1000 person-years (%)
14、,5,6,7,8,9,10,11,110,120,130,140,150,160,170,Myocardial infarction,Microvascular endpoints,Microvascular endpoints,Myocardial infarction,Adler AI, et al. BMJ. 2000;321:412-419. Stratton IM, et al. BMJ. 2000;321:405-412. .,MI=myocardial infarction SBP=systolic blood pressure,UNCERTAINTY CONTINUES ACC
15、ORD AND ADVANCE,ACCORD - 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 HOT,HOT,Lancet 1998;351:1755,p = 0.005 51% risk reduction,Goal Diastolic mmHg,Diabetic population,Non-Diabetic subjects,CONCLUSIONS,DM serious whenev
16、er it occurs More common in hypertensive Rx Particularly with diuretics NOD has consequences Non-CVD in short term CVD long term Neither fear of, nor NOD, requires D/C Diuretic,CLINICAL IMPLICATIONS,SCREEN FOR NOD ATTEMPT TO REVERSE HYPERGLCEMIA CORRECT HYPOKAELMIA K SPARING DIURETIC ADD ACE OR ARB OPTIMIZE BP AND LIPID CONTROL TREAT HYPERGLYCEMIA (?) NO EVIDENCE OF CVD BENEFIT PREVENTION OF MICROVASCULAR EFFECTS,