1、PREVENTING CARDIOVASCUAR DISEASE IN TYPE 2 DIABETES: an evidence-based summary,W. Kenneth Ward MD and members of the American Diabetes Association (Oregon Affiliate Professional Education Committee),Objectives and Disclosure,At the conclusion of the program participants will be able to: Identify whi

2、ch interventions have been shown to reduce or prevent cardiovascular events in patients with Type 2 diabetes. Recognize the magnitude of the benefit of such interventions. Disclosure: W. Kenneth Ward, MD has disclosed that he has no relationship to the manufacturer of any product(s) mentioned in thi

3、s internet presentation. Slides used with permission of author. All Rights Reserved.,Introduction:,The greatest cause of mortality in persons with Type 2 diabetes is cardiovascular disease - and the problem is getting worse. Recent data from the US Centers for Disease Control and Prevention reveals

4、that between 1990 and 2000, there was a 49 percent increase in the incidence of diabetes among Americans. How can an epidemic of heart disease in persons with type 2 diabetes be prevented?,This study included 1501 hypertensive patients with diabetes aged 70-84. Subjects were randomized to achieve di

5、astolic BP (DBP) of 90, 85, or 80. A stepped care program was used for treatment. The drugs used were Felodipine (Plendil) initially, followed if necessary by an ACE inhibitor or B-blocker, followed by dose increases if necessary. Finally, a diuretic was added if needed.,STUDY CONCLUSION: This study

6、 showed a very large beneficial effect of tightly controlling blood pressure (down to a diastolic BP of 80) in persons with type 2 diabetes.,SECTION 1: Does tight BP control reduce CV disease in people with Type 2 diabetes?,Hypertension Optimal Treatment Study 1:,United Kingdom Prospective Diabetes

7、Study (UKPDS) 2: One goal of the UKPDS was to compare tight BP control (initially using atenolol or captopril, n=758) with conventional control (n=390). The tight control group reached a mean BP of 144/82 as compared to a level of 154/87 for the conventional control group. In the tight control group

8、, there was a 21% reduction of myocardial infarction (not significant) and a 44% reduction in stroke (significant).,STUDY CONCLUSION: In terms of preventing stroke and myocardial infarction, this study showed a benefit in lowering BP in type 2 diabetes.,SECTION 1: Does tight BP control reduce CV dis

9、ease in people with Type 2 diabetes?,SECTION 1 CONCLUSIONS (BP and Type 2 diabetes):,These studies suggest a benefit of tight control of blood pressure in persons with type 2 diabetes. Most diabetes organizations now recommend a goal blood pressure of 130-135/80.,SECTION 2: Can ACE inhibitors Preven

10、t CV Disease or atherosclerosis in Patients with Type 2 Diabetes?,The subjects included 3577 people with diabetes, aged 55 years or older, who had a previous cardiovascular event or at least one other cardiovascular risk factor and no heart failure. Subjects were randomly assigned to ramipril (10 mg

11、/day) or placebo. Other drugs could be added, such as beta blockers, diuretics and calcium channel blockers. Ramipril (Altace) lowered the risk of the combined primary outcome by 25% (p=0.0004), myocardial infarction by 22%, stroke by 33%, cardiovascular death by 37%, total mortality by 24%, and rev

12、ascularization by 17% (see figure). In the ramipril group, there was a 7.3% dropout rate because of ramipril-induced cough.,STUDY CONCLUSION: A marked benefit of the ACE inhibitor ramipril was found irrespective of its blood-pressure lowering effect.,Heart Outcomes Prevention Evaluation (HOPE) 7:,Ra

13、te of Progression of Carotid Atherosclerosis,Intimal thickness (mm/Yr),STUDY CONCLUSION: A marked benefit of the ACE inhibitor ramipril was found irrespective of its blood-pressure lowering effect.,The Study to Evaluate Carotid Ultrasound changes was a 4.5 year double-blind trial that evaluated the

14、effects of long-term treatment with the angiotensin-converting enzyme inhibitor ramipril and vitamin E on atherosclerosis progression in high-risk patients. METHODS AND RESULTS: A total of 732 patients who had vascular disease or diabetes and at least one other risk factor were randomly assigned to

15、receive ramipril 2.5 mg/d, 10 mg/d or placebo. Subjects also received vitamin E or placebo.,The Study to Evaluate Carotid Ultrasound changes in patients treated with Ramipril and vitamin E (SECURE) 8:,Atherosclerosis progression was evaluated by carotid ultrasound. The progression slope of the intim

16、al medial thickness was 0.0217 mm/year in the placebo group, 0.0180 mm/year in the ramipril 2.5 mg/d group, and 0.0137 mm/year in the ramipril 10 mg/d group (P=0.033). In the high dose ramipril group, there was a 37% reduction as compared to placebo. There were no differences in atherosclerosis prog

17、ression rates between patients on vitamin E and those on placebo.,SECTION 2 CONCLUSIONS: ACE inhibitors and vascular disease.,ACE inhibitors, especially ramipril, reduce the risk of coronary events and progression of atherosclerosis, at least in persons with known vascular disease (and even in those

18、 without heart failure).,SECTION 3: How do ACE inhibitors, beta blockers, and calcium channel blockers compare in terms of preventing heart disease?,United Kingdom Prospective Diabetes Study 4: Randomized controlled trial comparing an angiotensin converting enzyme inhibitor (captopril, n=400) with a

19、 beta blocker (atenolol, n=358) in patients with type 2 diabetes, aiming for a blood pressure of 150/85 mm Hg. Other drugs could be added for improved control. Captopril and atenolol were equally effective in reducing the risk of macrovascular end points.,STUDY CONCLUSION: This study provided no evi

20、dence that either drug has any specific advantage over the others.,SECTION 3: How do ACE inhibitors, beta blockers, and calcium channel blockers compare in terms of preventing heart disease?,Captopril Prevention Project (CAPPP) 3: This study compared the effects of captopril vs. atenolol/HCTZ . This

21、 study found no difference between the two agents in primary endpoints including fatal P = .001) and substantially reduced numbers of revascularizations (48% reduction; P = .005).,Cholesterol and Recurrent Event Study 11: This study addressed whether lipid-lowering treatment with pravastatin prevent

22、s recurrent cardiovascular events in diabetic patients with CHD and average cholesterol levels. METHODS: This 5-year trial compared the effect of pravastatin vs placebo in 586 patients with diabetes. The mean baseline lipid concentrations in the group with diabetes were: LDL: 136 mg/dL, HDL: 38 mg/d

23、L, and triglycerides: 164 mg/dL. LDL cholesterol was reduced by 27% in the pravastatin group. Pravastatin treatment reduced the relative risk of coronary events by 25% (P=0.05) and the relative risk for revascularization procedures by 32% (P=0.04).,STUDY CONCLUSION: Cholesterol lowering with simvast

24、atin substantially reduces the incidence of coronary events in type 2 patients with known coronary disease.,STUDY CONCLUSIONS: Recurrent coronary events in diabetic patients can be substantially reduced by pravastatin treatment.,SECTION 5: Can Lipid-lowering treatment Prevent recurrent Coronary Even

25、ts in People with Type 2 Diabetes and known heart disease?,Diabetes Atherosclerosis Intervention Study (DAIS) 12: The Diabetes Atherosclerosis Intervention Study (DAIS) was designed to assess the effects of correcting lipoprotein abnormalities on coronary atherosclerosis in type 2 diabetes. METHODS:

26、 731 men and women with type 2 diabetes were randomly assigned to fenofibrate (Tricor, 200 mg/day) or placebo for at least 3 years. They had mild lipoprotein abnormalities, and at least one visible coronary lesion. Initial and final angiograms were analyzed by a computer-assisted approach. FINDINGS:

27、 Total plasma cholesterol, HDL-cholesterol, LDL-cholesterol, and triglyceride concentrations all changed significantly more from baseline in the fenofibrate group (n=207) than in the placebo group (n=211). The fenofibrate group showed a significantly lower increase in percentage diameter stenosis th

28、an the placebo group (mean 2.11 vs 3.65 %, p=0.02) and a significantly lower decrease in minimum lumen diameter.,STUDY CONCLUSION: DAIS suggests that treatment with fenofibrate reduces the angiographic progression of coronary-artery disease in type 2 diabetes.,SECTION 5 CONCLUSIONS: Lipid Interventi

29、on.,Statin drugs given to patients with type 2 diabetes with known coronary disease have been shown to reduce coronary events, even in those with mild lipid abnormalities. Fenofibrate appears to reduce the rate of angiographic progression of atherosclerosis but has not been shown to reduce coronary

30、events.,SECTION 6: Can Improved Glycemic Control Alone Prevent CV Disease in People with Type 2 Diabetes?,United Kingdom Prospective Diabetes Study 13: Type 2 diabetic subjects were randomized to tight control or conventional control for a median duration of 10 years. The tight control group maintai

31、ned a Hgb A1C of almost 1 percentage point lower than the conventional group. There was a 16% reduction in incidence of myocardial infarctions in the tight control group, which was of borderline significance (p=0.052). The authors also found that each 1% reduction of HgbA1C reduced the rate of MI by

32、 14%.,STUDY CONCLUSION: Good glycemic control may have a favorable effect to prevent MI, a finding of borderline significance. Large studies that are designed to specifically address this issue are now underway. As to the question of which oral agents are the best, no answer is available.,SECTION 7:

33、 Can specific dietary therapy prevent CV Disease in Patients with Type 2 Diabetes?,A prospective study of egg consumption and risk of cardiovascular disease in men and women 14: There is a paucity of prospective studies addressing dietary variables in persons with diabetes. One such study examined t

34、he association between egg consumption and risk of coronary heart disease (CHD) and stroke in two very large prospective studies, the Health Professionals Follow-up Study (1986-1994) and the Nurses Health Study (1980-1994). In subgroup analyses, higher egg consumption appeared to be associated with

35、significantly increased risk of CHD only among diabetic subjects (relative risk of CHD comparing 1 egg per day with 1 egg per week among diabetic men = 2.02, and among diabetic women, 1.49).,STUDY CONCLUSION: An increased risk of CHD was associated with higher egg consumption among diabetic patients

36、. Therefore it appears reasonable to ask patients with diabetes to limit egg consumption.,Summary,Studies suggest a benefit of tight control of blood pressure in persons with type 2 diabetes. ACE inhibitors, especially ramipril, reduce the risk of coronary events and progression of atherosclerosis,

37、at least in persons with known vascular disease (and even in those without heart failure). When given as monotherapy, ACE inhibitors (and possibly beta blockers) are superior to calcium channel blockers (CCB) in terms of preventing cardiovascular events in persons with type 2 diabetes.,Summary cont.

38、,Treatment with aspirin was associated with a substantial reduction in cardiac- and total mortality in type 2 diabetic patients with coronary artery disease. Statin drugs given to patients with type 2 diabetes with known coronary disease have been shown to reduce coronary events, even in those with

39、mild lipid abnormalities. Good glycemic control may have a favorable effect to prevent MI, a finding of borderline significance. An increased risk of CHD was associated with higher egg consumption among diabetic patients.,References:,Hansson L, Zanchetti A, Carruthers SG, Dahlof B, Elmfeldt D, Juliu

40、s S, Menard J, Rahn KH, Wedel H, Westerling S. Effects of intensive blood-pressure lowering and low-dose aspirin in patients with hypertension: principal results of the Hypertension Optimal Treatment (HOT) randomised trial. HOT Study Group. Lancet 1998; 351(9118): 1755-62. Tight blood pressure contr

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43、vascular and microvascular complications in type 2 diabetes: UKPDS 39. UK Prospective Diabetes Study Group. BMJ 1998; 317(7160): 713-20. Tatti P, Pahor M, Byington RP, Di Mauro P, Guarisco R, Strollo G, Strollo F. Outcome results of the Fosinopril Versus Amlodipine Cardiovascular Events Randomized T

44、rial (FACET) in patients with hypertension and NIDDM. Diabetes Care 1998; 21(4): 597-603. Estacio RO, Jeffers BW, Hiatt WR, Biggerstaff SL, Gifford N, Schrier RW. The effect of nisoldipine as compared with enalapril on cardiovascular outcomes in patients with non-insulin-dependent diabetes and hyper

45、tension. N Engl J Med 1998; 338(10): 645-52. Dagenais GR, Yusuf S, Bourassa MG, Yi Q, Bosch J, Lonn EM, Kouz S, Grover J. Effects of ramipril on coronary events in high-risk persons: results of the Heart Outcomes Prevention Evaluation study. Circulation 2001; 104(5): 522-6.,References cont:,Lonn E,

46、Yusuf S, Dzavik V, Doris C, Yi Q, Smith S, Moore-Cox A, Bosch J, Riley W, Teo K. Effects of ramipril and vitamin E on atherosclerosis: the study to evaluate carotid ultrasound changes in patients treated with ramipril and vitamin E (SECURE). Circulation 2001; 103(7): 919-25. Harpaz D, Gottlieb S, Graff E, Boyko V, Kishon Y, Behar S. Effects of aspirin treatment on survival in non-insulin-dependent d