控制糖尿病患者心血管危险的干预治疗策略

控制糖尿病患者心血管危险 的干预治疗策略 糖尿病与心血管危险 影响心血管危险的因素 综合控制的理论与实践 Countries With Highest Numbers of Estimated Cases of Diabetes for 2000 and 2030 RankingCountry People with diabetes (millions) Country People with diabetes (millions) 20002030 1India31.7India79.4 2China20.8China42.3 3U.S.17.7U.S.30.3 4Indonesia8.4Indonesia21.3 5Japan6.8Pakistan13.9 6Pakistan5.2Brazil11.3 7Russian Federation4.6Bangladesh11.1 8Brazil4.6Japan8.9 9Italy4.3Pinecones7.8 10Bangladesh3.2Egypt16.7 Total: 177 million 366 MILLION BY 2030 Type 2 diabetes and CHD 7-Year Incidence of Fatal/Nonfatal MI (East West Study) Incidence During Follow-up (%) (n=69) Nondiabetics with prior MI Nondiabetics with no prior MI Diabetics with prior MI Diabetics with no prior MI 18.8 Haffner SM et al. N Engl J Med 1998;339:229-234. (n=1304)(n=169)(n=890) 3.00.57.83.2 3.5 45.0 20.2 Events per 100 person-yr: P0.001 p0.001 Type 2 diabetes and Stroke 7-Year Incidence of Fatal/Nonfatal Stroke (East West Study) Incidence During Follow-up (%) (n=69) Nondiabetics with prior MI Nondiabetics with no prior MI Diabetics with prior MI Diabetics with no prior MI 7.2 Haffner SM et al. N Engl J Med 1998;339:229-234. (n=1304) (n=169)(n=890) 1.20.33.41.6 1.9 19.5 10.3 Events per 100 person-yr: P=0.01 p0.001 Prevalence of CHD by the Metabolic Syndrome and Diabetes in the NHANES Population Age 50+ Alexander C et al. Diabetes 2003;52:1210-1214 25% 20% 15% 10% 5% 0% No MS/No DM 8.7% 13.9% 7.5% 19.2% MS/No DMDM/No MSDM/MS % of population = 54.2%28.7%2.3%14.8% CHD Prevalence 1.0 0.9 0.8 0.7 0.6 0.0 0246810 Follow-up, years # at risk 174214099062828935 No metabolic syndrome Metabolic syndrome log-rank = 45.4 p0.001 Event-free survival Schillaci G. JACC. 2004; 43:1817-1822 代谢综合征与心血管危险 Ml and Microvascular End Points: Incidence by Mean Systolic BP and HbA1c Concentration Ml Microvascular and points Ml Microvascular and points 50 40 30 20 10 0 80 60 40 20 0 Adjusted incidence per 1000 person-yr (%) 110 120130 140 150160170567891011 Updated mean systolic BP (mmHg)Updated mean HbA1c concentration (%) Adjusted incidence per 1000 person-yr (%) Adler Al et al. BMJ 2000;321:412-419 Stration IM et al. BMJ 2000;321:405-412 MetS和DM患者血脂异常特征 游离脂肪酸 TG HDL-C VLDL-C 小而密LDL颗粒 氧化LDL-C 餐后高脂血症 Male Gender-adjusted Female Reduced risk with small, dense LDL 0.1 Relative risk for myocardial infarction 110 Increased risk with small, dense LDL Small, dense LDL increases cardiovascular risk UKPDS Stepwise Selection of Risk Factors* in Patients with Type 2 Diabetes VariableVariable LDL-C HDL-C Hemoglobin A1c Systolic Blood Pressure Smoking P ValueP Value 0.0001 0.0001 0.0022 0.0065 0.056 Coronary Artery Disease (n=280) Position in ModelPosition in Model First Second Third Fourth Fifth *Adjusted for age and sex. Turner RC et al. BMJ 1998;316:823-828. Mangaging overweight in type 2 diabetics Effective weight management is the first step in treating type 2 diabetes Weight loss (kg) in first 12 monthsWeight loss (kg) in first 12 months Lean MEJ et al., Diabet Med, 1990;7:228-233 Life expectancy (years)Life expectancy (years)95% confidence interval95% confidence interval 1818 1616 1414 1212 1010 8 8 0 0 0 0 4 4 8 8 12121616 Good glycemic control is not enough UKPDS GOOD GLYCEMIC CONTROL MICROVASCULAR COMPLICATIONS Significant reductions MACROVASCULAR COMPLICATIONS No significant effect PROACTIVE Study Sept. 2005, 欧洲糖尿病会议 Pioglitazone vs Placebo ACCORD Study Action to Control Cardiovascular risk in Diabetes Prisant LM. J Clin Pharmacol 2004; 44(4):423-430 HbA1c: 6.0% vs 7.0-7.9% 糖尿病患者降压治疗临床试验 SHEP ALLHAT SYST-EUR HOPE CAPPP HOT NORDIL RENAAL STOP-2 PRIME INSIGHT LIFE UKPDS Major cardiovascular events (per 100 patients-years) in all treated hypertensive and in hypertensive patients with diabetes in relation to target blood pressures of 90. 85, and 80 mm Hg. 30 25 20 15 10 5 0 80 85 90 90 85 80 P=0.50 for trend P=0.005 for trend All hypertensive patients (n=18790) Hypertensive with diabetes (n=1501) Target blood pressure groups Major cardiovascular events/ 1000 patients-years HOT Study: Results in Patients with DM Effect of Intensive vs Moderate Antihypertensive Treatment on Stroke Incidence in Diabetic Normotensives IntensiveModerate Achieved BP (mmHg)128/75137/81 Stroke (%)1.75.4P = 0.03 Schrier et al., Kidney Int 2002; 61:1086 CHD Prevention Trials with Statins in Diabetic Subjects Subgroup Analyses Primary Prevention AFCAPS/TexCAPS Secondary Prevention CARE 4S LIPID 4S-Extended CHD RiskCHD Risk ReductionReduction (overall)(overall) DrugDrugNo.No. Lovastatin Pravastatin Simvastatin Pravastatin Simvastatin 43% 25% (p=0.05) 55% (p=0.002) 19% 42% (p=0.001) 37% 23% 32% 25% 32% 239 586 202 782 483 CHD RiskCHD Risk ReductionReduction (diabetes)(diabetes) StudyStudy Adapted from Downs JR et al. JAMA 1998;279:1615-1622; Goldberg RB et al. Circulation 1998;98:2513-2519; Pyrl K et al. Diabetes Care 1997;20:614-620; The Long-Term Intervention with Pravastatin in Ischaemic Disease (LIPID) Study Group. N Engl J Med 1998;339:1349-1357; Haffner SM et al. Arch Intern Med 1999;159:2661-2667. Trials with Fibrates in Patients with Diabetes StudyEffectp-valueComment Helsinki Heart Helsinki Heart StudyStudy ( (gemfibrozilgemfibrozil) ) 75% 75% eventsevents nsnsPrimary prevention; Primary prevention; post-hoc subgroup analysispost-hoc subgroup analysis SENDCAPSENDCAP ( (bezafibratebezafibrate) ) 65% 65% eventsevents 0.010.01Specifically conducted in Type 2 Specifically conducted in Type 2 diabetes; post-hoc analysis for IHDdiabetes; post-hoc analysis for IHD VA-HITVA-HIT ( (gemfibrozilgemfibrozil) ) 24%24% eventsevents 0.050.05Secondary intervention; pre-planned Secondary intervention; pre-planned subgroup analysissubgroup analysis DAISDAIS ( (fenofibratefenofibrate) ) 40-42%40-42% focal focal angioangio changeschanges 0.020.02Specifically conducted in Type 2 Specifically conducted in Type 2 diabetes; mixed primary and diabetes; mixed primary and secondary intervention; secondary intervention; angioangio study study FIELD Study Fenofibrate Intervention and Event Lowering in Diabetes Mazzone T. Am J Cardiol 2004;93:27C-31C 糖尿病患者心血管危险因素的控制目标 减轻体重 降糖: HbA1c 7.0% 降压: 130/80 调脂: LDL-C 1.81 mmol/L Steno-2 Study Multifactorial Intervention and Cardiovascular Disease in Patients with Type 2 Diabetes Grade P, et al. N ENGL J MED 2003;348:383-393 Steno-2: Intensive Therapy NEJM 2000; 342:905-912 Basic Intervention 脂肪摄入30% 饱和脂肪酸摄入10% 运动 3035次/w ACEI or ARB 多种维生素 Aspirin Pharmacology Intervention 降糖 metformin gliclazide metformin + gliclazide 降压 thiazide ACEI or ARB + CCB -blocker 降脂 statins Steno-2: Treatment Goals Variable Conventional Intensive Therapy Therapy SBP (mmHg) 140 130 DBP (mmHg) 85 80 Hba1c (%) 6.5 6.5 TC (mg/dl) 190