1. Section VII: Diabetes and the impact of risk factor clustering on CV risk
Diabetes and coronary heart disease: A clustering of risk factors
Content points:
• The vast majority of morbidity, mortality, and expense in treating type 2 diabetes is related to macrovascular disease. Clearly, even perfect glycemic control would be unlikely to substantially reduce the cardiovascular event rate in people with diabetes because of the multitude of cardiovascular risk factors that coexist as part of the dysmetabolic syndrome.1
• In addition to being glucose intolerant, many patients with diabetes have hypertension, and some estimates suggest that almost all have some definable lipid abnormality. Additionally, central obesity is a common occurrence in the diabetic individual. These metabolically linked risk factors contribute to atherogenesis.
• Conservative estimates are that >40% of persons with diabetes have coronary heart disease and that at least 65% of mortality among diabetic patients is due to coronary heart disease.
• Post-MI patients with diabetes have a worse prognosis than nondiabetic individuals with a 5-year survival rate about half the survival rate of nondiabetic patients (38% vs 75%, respectively).2

2. CV events in patients with diabetes
Content points:
• A large body of epidemiological and pathological data documents that diabetes is an independent risk factor for cardiovascular disease in both men and women.
• Follow-up data from the Framingham Heart Study over 30 years show that men and women with diabetes are at significantly greater risk for cardiovascular events that nondiabetic individuals, including total cardiovascular disease, coronary heart disease, cardiac failure, intermittent claudication (P < for all values) and stroke (P < 0.05).3 Women are at a greater risk than men in each case, with the exception of stroke.
• Women with diabetes have a 4-fold increase in the risk for developing cardiovascular disease compared with nondiabetic women, while men with diabetes have an approximately 2.5-fold increase in risk compared compared with nondiabetic men.
• These findings reflect the fact that women with diabetes lose most of their inherent protection against developing cardiovascular disease.4 Because diabetes removes the differences between the genders in the prevalence of cardiovascular disease, they are at similar risk for cardiovascular morbidity and mortality. Therefore, women as well as men should be treated aggressively for all risk factors.

3. CV risk similar in patients with type 2 diabetes and no prior MI
as in nondiabetics with prior MI
Content points:
• Haffner and colleagues compared the incidence of MI (fatal and nonfatal) in diabetic and nondiabetic subjects over a 7-year follow up.2 The study included 1373 nondiabetic subjects and 1059 subjects with diabetes from a Finnish population study. The findings document the marked increase in the risk of coronary heart disease associated with type 2 diabetes.
• The 7-year incidence of MI in nondiabetic subjects with and without prior MI at baseline was 19% and 4%, respectively. By comparison, the 7-year incidence of MI in diabetic subjects with and without prior MI was 45% and 20%, respectively. Thus, diabetic individuals with no history of MI have a similar incidence of MI as nondiabetic subjects with a history of MI.
• The likelihood of dying from coronary heart disease was about the same in diabetic subjects without prior MI as in nondiabetic subjects with a history of MI.
• These data provide a rationale for treating cardiovascular risk factors in diabetic patients as aggressively as they are treated in nondiabetic patients with prior MI. That is, treatment should be at the level of secondary, rather than primary, prevention.

4. The Cardiovascular Dysmetabolic Syndrome
Content points:
• The cardiovascular dysmetabolic syndrome consists of hyperlipidemia, insulin resistance, obesity, and hypertension.5 Over the years, a variety of names have been given to this syndrome, among them syndrome X and insulin resistance syndrome.
• Patients with this syndrome are dyslipidemic, with elevated triglyceride levels, low HDL-C levels, and increased numbers of small, dense LDL-C particles.
• Such patients may also be insulin resistant or have frank type 2 diabetes. They are often overweight (body mass index > 25 kg/m2); central obesity is common. They are also usually hypertensive.
• Individuals with the cardiovascular dysmetabolic syndrome are at substantially greater risk of cardiovascular death than the general population because of this clustering of important risk factors. Early detection and aggressive treatment of each component of the syndrome is essential for reducing morbidity and mortality.
• The impact of risk factor clustering is discussed in the next few slides.

5. Clustering of major CV risk factors accelerates atherosclerosis
Content points:
• Mannami et al found strong and significant relationships between aggregation of major coronary risk factors and the acceleration of carotid atherosclerosis in the general population of the Japanese city of Suita.6
• The number of risk factors, including hypertension, hypercholesterolemia, and smoking strongly influenced carotid atherogenesis in both sexes.
• The mean carotid atherosclerotic index value, especially the mean intima media thickness (IMT) value of the subjects with 1 major coronary risk factor was on average (3.2%) higher for men and mm (2.9%) higher for women than that of the subjects without major coronary risk factors.
• For people with 2 risk factors, the mean IMT increased by mm (6.3%) for men and by mm (6.2%) for women.
• For high-risk subjects with 3 major risk factors, the carotid IMT increased by mm (15.8%) in men and by mm (15.4%) in women.
• The proportion of subjects with stenosis of at least 50% increased stepwise with increases in the number of coronary risk factors. There was a significant difference between men and women in the acceleration and progression of carotid atherosclerosis.

6. Clustering of risk factors affects fibrinolytic balance
Content points:
• Byberg et al conducted a cohort study in year-old men to investigate the relation between PAI-1 activity and cardiovascular risk factors.7
• As shown on the slide, they observed an association between the number of risk factors and PAI-1 activity. Risk factors were defined as hypertension (currently receiving antihypertensive therapy and/or diastolic blood pressure 95 mm Hg), body mass index >28.4 kg/m2, triglycerides >152 mg/dL, and fasting glucose >103 mg/dL.

7. Impact of increasing risk factors on CV death rate in diabetic vs
nondiabetic subjects
Content points:
• This slide is based on data from the long-term Multiple Risk Factor Intervention Trial (MRFIT), which assessed the efficacy of multifactorial intervention in reducing cardiovascular mortality in hypertensive men with no history of cardiovascular disease at baseline.8
• When the data from MRFIT were stratified by the number of additional risk factors present, including increased systolic blood pressure, elevated total serum cholesterol, and smoking, cardiovascular mortality was seen to increase linearly over a 12-year period according to increasing risk factors.
• However, as seen in this slide, which shows age-adjusted cardiovascular mortality rate per 10,000 person years in men with and without diabetes at baseline, men with diabetes were at a much higher risk for cardiovascular mortality than men without diabetes at any given number of additional risk factors.9

8. Expected vs observed prevalence of “deadly quartet” risk factors
in post-CABG patients
Content points:
• Sprecher and Pearce investigated whether a cluster of metabolic risk factors could predict mortality after CABG.10 The study cohort included patients undergoing primary CABG (n = 6428) between 1987 and They were followed for a median of 8 years.
• Specifically, they studied the “deadly quartet” of metabolic risk factors (obesity, diabetes, hypertension, and hypertriglyceridemia), which has been associated with coronary heart disease in healthy population studies. This clustering of risk factors is typically viewed as being associated with insulin resistance and the cardiovascular dysmetabolic syndrome.
• This slide summarizes the expected and observed prevalence of patients with zero, one, two, three, and four deadly quartet risk factors. The expected clustering of risk factors was 8% compared with the observed clustering of 10% in men and 21% in women.
• The post-CABG patient clearly showed risk factor clustering beyond that expected due to chance, particularly in women.
• The next slide discusses the increased mortality associated with risk factor clustering in post-CABG patients.

9. Clustering of risk factors increases mortality in post-CABG patients:
8-year follow-up
Content points:
• Sprecher and Pearson found that the sum of deadly quartet risk factors (obesity, diabetes, hypertension, and hypertriglyceridemia) present in post-CABG patients (ranging from none to four) showed a significant relationship to mortality.10
• The mortality increased as the number of identified metabolic risk factors increased in all cases (P < for all). The overall mortality for the study population was 13% (n = 860).
• Women had a higher raw mortality rate than men (17% vs 12%, but the difference was not significant after adjusting for age, surgical variables, and the identified metabolic risk factors.

10. New criteria for diagnosis of diabetes mellitus
Content points:
• The diagnostic criteria for diabetes mellitus have been modified from those previously recommended. Currently, three ways to diagnose diabetes are possible.11
• The diagnosis may be made on the basis of symptoms of diabetes plus a “casual” plasma glucose concentration of 200 mg/dL. Casual is defined as any time of day without regard to time since the last meal. The classic symptoms of diabetes include polyuria, polydipsia, and unexplained weight loss.
• A fasting plasma glucose level of 126 mg/dL is also diagnostic for diabetes. Fasting plasma glucose is defined as no caloric intake for at least 8 hours.
• A third means of diagnosing diabetes relies on a 2-hour plasma glucose level of 200 mg/dL during an oral glucose tolerance test (OGTT). However, the test is not recommended for routine clinical use. The test should be performed using a glucose load containing the equivalent of 75 g anhydrous glucose dissolved in water and according to strict WHO criteria.
• The diagnosis of diabetes must be confirmed by repeat testing on a different day using any one of the methods. The exception to repeat testing is if the patient has unequivocal hyperglycemia with acute metabolic decompensation.

11. Strategies for reducing macrovascular complications
Content points:
• Strategies to reduce the risk of macrovascular complications in the diabetic patient necessitate a multifactorial approach.
• Important strategies to reduce the risk of macrovascular complications in patients with diabetes that have been documented in intervention trials include treatment for dyslipidemia, the use of antihypertensive agents, and the use of antiplatelet therapies.
• Epidemiologic analyses suggest that macrovascular complications may be prevented by treatment of thrombolytic disorders and endothelial disorders.

12. MICRO-HOPE: Effects of ACE inhibition on cardiovascular and
microvascular outcomes in diabetes
Content points:
• MICRO-HOPE investigated whether ramipril could lower risks in people with diabetes.12
• The substudy included 3577 subjects with diabetes plus one other risk factor who were enrolled in HOPE.
• People with proteinuria, nephropathy, other severe renal disease, low ejection fraction, or CHF were excluded from the study.
• As in the HOPE study, participants in MICRO-HOPE were followed for 4.5 years.

13. MICRO-HOPE: Primary outcomes
Content points:
• This slide summarizes the effect of ramipril 10 mg on the primary endpoints in the diabetic cohort.12
• Significant reductions were seen in CV death (37%), nonfatal MI (22%), stroke (33%), and total mortality (24%).
• Not shown on the slide is the fact that after adjustment for the changes in systolic and diastolic blood pressures, ramipril still lowered the risk of the combined primary outcome significantly, by 25%.

14. MICRO-HOPE: Secondary outcomes
Content points:
• This slide summarizes the effect of ramipril 10 mg on the secondary endpoints in the diabetic cohort.12
• Signficant reductions were observed in nephropathy (24%, P = 0.024), heart failure (20%, P = 0.019), transient ischemic attacks (26%, P = 0.04), and the need for revascularization (P = 0.03).

15. HOPE & MICRO-HOPE: Primary outcomes
Content points:
• This slide summarizes the primary results in overall population of the HOPE study and in the diabetic participants in MICRO-HOPE.12,13
• The risk reductions observed in the diabetic population were even greater than the reductions seen on the overall study population.

16. CAPPP: Relative risk for CV events with ACEI or conventional therapy
in diabetic patients
Content points:
• CAPPP (CAPtopril Prevention Project) compared the effects of ACE inhibition with captopril and conventional antihypertensive therapy (diuretics, b-blockers) on cardiovascular mortality and morbidity in hypertensive patients over a 6-year follow-up. The primary outcome of CAPPP was a composite of fatal and nonfatal MI, stroke, and other cardiovascular events.14
• The overall study, which is not shown here, included patients and the results showed that captopril and conventional treatment did not differ in efficacy in preventing cardiovascular morbidity and mortality. Cardiovascular mortality was slightly lower with captopril, MI rates were similar, and stroke was more common.
• However, the results were strikingly different in a subgroup analysis of 572 patients who had diabetes at baseline. The results in patients with diabetes appear on this slide. The diabetic patients had a significantly better outcome with captopril than with conventional therapy.
• The one exception is stroke. In the diabetic cohort, blood pressure measurements at baseline were identical in the two treatment groups and the incidence of stroke was the same.
• Patients with diabetes treated with captopril had a significantly lower rate of the primary outcome (a composite of fatal and nonfatal MI, stroke, and other cardiovascular events), as well as fewer individual outcomes (fatal cardiovascular events, fatal and nonfatal MI, and all cardiac events). The frequency of cardiac events and total mortality was significantly lower in the captopril group.
• Overall, these findings strengthen the impression that an antihypertensive regimen based on ACE inhibitors is particularly appropriate for diabetic patients.

17. Survival of diabetic patients after acute MI is increased with ACE inhibition
Content points:
• Zuanetti et al evaluated whether treatment with an ACE inhibitor begun within 24 hours from the onset of symptoms of acute MI decreases mortality and morbidity of diabetic patients.15 They performed a retrospective analysis of data from the GISSI-3 study in patients with and without a history of diabetes.
• In the GISSI-3 study, patients with suspected acute MI were randomized to treatment with lisinopril with or without nitroglycerin within 24 hours and continued for 6 weeks. The main end point was mortality at 6 weeks.
• Information on diabetic status was available for patients (approximately 94% of the total population enrolled), of whom 2790 had a history of diabetes.
• Treatment with lisinopril reduced 6-week mortality in diabetic patients contrasted with conventional therapy (8.7% versus 12.4%). The effect was greater than in nondiabetic patients (5.6% versus 5.9%). The difference between the diabetic and nondiabetic patients is significant (P < 0.025).
• This effect corresponds to a 29.8% reduction in mortality, or 37 ± 12 lives saved per 1000 patients treated in the diabetic population and a 5.0% reduction or 3 ± 4 lives saved per 1000 patients treated in the nondiabetic population.
• The survival benefit in diabetics was mostly maintained at 6 months despite withdrawal from treatment at 6 weeks.
• This beneficial effect supports a widespread and early use of ACE inhibitors in diabetic patients with acute MI. The data from the present analysis indicate that the benefit from early ACE inhibition is particularly striking in diabetic patients. The findings support those of the HOPE and MICRO-HOPE and CAPPP studies.

18. Common pattern of dyslipidemia in type 2 diabetes
Content points:
• Diabetes increases the risk for atherosclerotic vascular disease. The risk is greatest in people who have other known risk factors such as dyslipidemia, hypertension, smoking, and obesity.
• In type 2 diabetes, there is an additional increased risk for obesity and lipid abnormalities independent of the level of glycemic control.16
• A common abnormal lipid pattern in diabetic patients is an elevation of very low density lipoprotein (VLDL), a reduction in HDL-C, and an LDL fraction that contains a greater proportion of small, dense LDL particles. Small dense LDL particles are particularly atherogenic because they are more susceptible to oxidation than intermediate dense LDL or large, buoyant LDL.

19. Treatment decisions based on LDL-C levels in adults with diabetes
Content points:
• The recommendations for treatment of elevated LDL-C, as shown on the slide, generally follow guidelines of both the National Cholesterol Education Program and the American Diabetes Association.17
• Diabetic subjects with clinical coronary heart disease and an LDL-C >100 mg/dL should be treated with pharmacologic agents. This should be initiated after nutrition therapy and glucose intervention are used.
• For diabetic patients without preexisting coronary heart disease, current ADA recommendations for starting drug treatment are 1) an LDL-C level of 130 mg/dL and 2) a goal of 100 mg/dL for LDL-C.
• Current recommendations are based not only on the high incidence of coronary heart disease in patients with diabetes, but also on their high fatality rate once they have the disease. Since many die before they reach the hospital, a preventive strategy based solely on secondary prevention would not be able to save large numbers of these diabetic patients.2,17
• The current ADA guidelines include the following caveats: In general, pharmacological therapy should be initiated after behavioral interventions are used. However, in patients with clinical coronary heart disease or very high LDL-C levels (200 mg/dL) pharmacological agents should be started at the same time as behavioral therapy.
• Because of frequent changes in glycemic control in diabetic patients and their effects of lipoprotein levels, levels of LDL, HDL, total cholesterol, and triglyceride should be repeated every 2 years.

20. Order of priorities for treatment of diabetic dyslipidemia in adults
Content points:
• This slide summarizes the order of priorities for treatment of dyslipidemia.17
• Lowering of LDL-C is the first priority for pharmacologic therapy of dyslipidemia: 1) Clinical trials (4S and CARE) showed the effectiveness of statins in reducing coronary heart disease in diabetic subjects; 2) In these studies, statins achieved greater risk reductions with narrower confidence levels than those achieved by reducing triglyceride levels with gemfibrozil in the Helsinki Study.18-20
• Initial therapy for hypertriglyceridemia is behavior modification (weight loss, increased physical activity, and moderation in alcohol consumption). Improved glycemic control is very effective for reducing triglyceride levels and should be used aggressively before fibrates are introduced.
• The critical issue is that gemfibrozil should not be started in diabetic patients with undesirable levels of LDL-C and triglyceride. Fenofibrate may be useful in these patients. In some studies, statins are moderately effective in reducing triglyceride levels in hypertriglyceridemic individuals (300 mg/dL).
• Although HDL-C is a powerful predictor of coronary heart disease in diabetic patients, raising HDL-C levels is difficult without pharmacologic intervention. Nicotinic acid, which should be used with caution in diabetic patients, and fibrates can increase HDL-C levels.

21. Order of priorities for treatment of diabetic dyslipidemia in adults
(cont’d)
Content points:
• This slide outlines the treatment for combined hyperlipidemia in diabetic adults.17
• Here again, the first choice for treatment is improved glycemic control plus a high-dose statin.
• In some cases, combined lipid therapy may be initiated. The combination of statins with nicotinic acid is extremely effective in modifying diabetic dyslipidemia, with the largest increases being in HDL-C levels. However, this combination may significantly worsen hyperglycemia. Therefore, it should be used with extreme caution, employing low doses of nicotinic acid ( 2g/day), and frequent monitoring of glucose levels.
• Importantly, the combination of statins with nicotinic acid and especially with gemfibrozil or fenofibrate may carry an increased risk of myositis, although the risk of myositis, as opposed to elevated creatinine phosphokinase levels, appears to be low.

22. Efficacy of statin therapy in hyperlipidemic patients with type 2 diabetes
Content points:
• Aguilar-Salinas et al evaluated the safety and efficacy of once-daily atorvastatin for the treatment of hyperlipidemia in patients with type 2 diabetes with plasma LDL-C >130 mg/dL.18
• Patients who entered the study receving 10 mg/day atorvastatin and those who reached the target LDL-C of 100 mg/dL maintained the same dosage until they completed the study at 16 weeks. Patients who did not reach the target underwent dose titration to atorvastatin 20, 40, and 80 mg at weeks 4, 8, and 12 respectively.
• Treatment with atorvastatin resulted in a mean reduction in plasma LDL-C of 50% across all of the doses from 177  34 mg/dL to 87  16 mg/dL (P < ). Triglycerides were reduced a mean of 18% across all of the doses. There was a trend toward increased plasma HDL-C (3.8%), but this did not reach significance.
• In the majority of the cases (59%), patients reached the target dose of LDL-C 100 mg/dL with the starting dose of 10 mg atorvastatin. Treatment with atorvastastin 10 mg reduced LDL-C by 47%, triglycerides by 13.6%, and VLDL-C by 29%.

23. 4S: Benefits of lipid lowering in diabetic subgroup with CHD
Content points:
• This slide summarizes findings of a post-hoc subgroup analysis from the Scandinavian Simvastatin Survival Study (4S) of 202 diabetic patients (4.6%) and 4242 nondiabetic patients with previous MI or angina pectoris.19
• 4S included hypercholesterolemic patients with coronary heart disease randomly assigned to double-blind treatment with simvastatin (20 mg/day up to 40 mg/day) or placebo. Patients were followed up for a mean of 5.4 years.
• Over the follow-up period, simvastatin produced mean changes in total-C, LDL-C, and HDL-C of -25%, -35%, and +8%, respectively, with few adverse effects.
• For nondiabetic patients, simvastatin significantly improved all outcomes examined except cerebrovascular disease (P = for all events except total mortality where P = 0.001).
• In patients with diabetes, the reduction in risk of total mortality and coronary heart disease mortality did not reach significance due to the small sample size. But there were significant reductions in the risk for major coronary heart disease events (P = 0.02), any coronary heart disease events (P = 0.015), and atherosclerosis events (P = 0.018).
• The results from this subgroup analysis indicate that diabetic patients, as well as nondiabetic patients benefit from lipid-lowering with a statin with reductions in adverse coronary heart disease events. Since the potential for coronary heart disease events is much greater in people with diabetes, they may benefit from statin therapy even more than nondiabetics.

24. CARE: Benefit of lipid lowering in diabetic subgroup with CHD and average
cholesterol levels
Content points:
• The Cholesterol And Recurrent Events (CARE) trial was a 5-year secondary prevention study that compared the effect of pravastatin and placebo in patients with coronary heart disease and average cholesterol levels.21
• Of the 4159 patients in the study, 586 patients (14%) had a clinical diagnosis of diabetes.22 By including patients with diabetes, the CARE trial afforded the opportunity to determine whether lowering LDL-C levels is beneficial in patients with diabetes, coronary heart disease, and average cholesterol levels.
• The diabetic group was older and had a higher prevalence of obesity, hypertension, and congestive heart failure than nondiabetics. Although the diabetic patients had average LDL-C levels (mean 136 mg/dL), they had higher triglycerides and lower HDL-C levels, the typical dyslipidemia associated with diabetes. LDL-C reduction with pravastatin was similar (27% and 28%) in the diabetic and nondiabetic cohorts.
• The diabetic patients in the placebo group suffered more recurrent coronary events (coronary heart disease death, nonfatal MI, CABG, and PTCA) than did the nondiabetic patients (37% vs 25%)
• The subgroup analysis shows that diabetic patients and nondiabetic patients with impaired fasting glucose have a high risk of recurrent coronary events that can be substantially reduced by lipid lowering with statin therapy.
• The risks for individual cardiovascular outcomes were consistently, but not always significantly, lower in the pravastatin than in the placebo group. Pravstatin reduced the relative risk for revascularization by 32% (P = 0.04) in the diabetic patients.
• The results of CARE demonstrate that the typical diabetic patient with average LDL-C levels benefits from further improvement in lipids with statin treatment.

25. CARE: Reduction in CV events (CHD death/nonfatal MI/CABG/PTCA)
in diabetic patients
Content points:
• In CARE, pravastatin treatment in the diabetes group was associated with a 25% reduction of risk of coronary events (coronary heart disease death, nonfatal MI, CABG and PTCA, P = 0.05), which was similar to the group without diabetes, which had a risk reduction of 23% (P < 0.01).22
• Because of their higher event rate, the diabetes group experienced a greater absolute risk reduction of 8.1% compared with 5.2% in the group without diabetes.
• As in 4S, the percentage risk reductions were similar in diabetic and nondiabetic groups, but the absolute risk reduction was greater in the diabetic than nondiabetic patients.
• Thus 4S and CARE present strong evidence that lowering lipid levels will reduce the risk of recurrent events in diabetic individuals with preexisting coronary artery disease whether they have hypercholesterolemia or normal lipid levels.

26. Key ongoing lipid intervention trials in diabetes: Primary and secondary
CHD prevention
Content points:
• Currently, studies are under way in diabetic populations with and without clinical coronary artery disease to test the “lipid hypothesis” that plasma lipid abnormalities are atherogenic and that correcting them will reduce the risk of atherosclerotic disease in patients with diabetes.23
• The Collaborative Atorvastatin Diabetes Study (CARDS), Fenofibrate Intervention and Event Lowering in Diabetes (FIELD), and Lipids in Diabetes Study (LDS) are primary prevention trials with clinical events as the primary outcome.
• CARDS uses atorvastatin, FIELD uses fenofibrate, and LDS uses cerivastatin and fenofibrate alone or in combination.
• CARDS is enrolling 2750 patients with type 2 diabetes and no history of coronary heart disease with <160 mg/dL LDL-C level.
• The Atorvastatin Study on Prevention of Endpoints in NIDDM (ASPEN) study is enrolling 2400 patients with type 2 diabetes with or without prior MI.
• The Diabetes Atherosclerosis Intervention Study (DIAS) using fenofibrate is an angiographic study that includes diabetic patients with and without pre-existing clinical coronary disease.

27. Current recommendations for diabetes management
based on clinical trials
Content points:
• Current recommendations for target guidelines for risk reduction in diabetes management are summarized on this slide. The recommendations rely on clinical trial evidence from prospective randomized outcomes studies.24
• These guideline targets for HbA1c, blood pressure, and lipid levels reflect recommendations of the American Diabetes Association, the National Cholesterol Education Program, and the Joint National Committee on Prevention, Detection, Evaluation and Treatment of Blood Pressure.25-28
• Current recommendations support the view that low-dose aspirin should be used as primary and secondary prevention therapy, if no contraindications exist.
• The HOPE study and MICRO-HOPE substudy recently demonstrated that ramipril 10 mg was associated with a significant reduction in cardiovascular events in patients > 55 years with known diabetes and an additional cardiovascular risk factor (hypertension, total-C >200 mg/dL, HDL-C <35 mg/dL, microalbuminuria, or current smoking).12,13 Therefore ACE inhibitors are now recommended for risk reduction in such patients.24

28. Cost-effectiveness of treating dyslipidemia in diabetic patients
without CVD
Content points:
• Epidemiological studies have shown that the risk of MI in diabetic patients without cardiovascular disease is comparable to the risk of MI in nondiabetic patients with cardiovascular disease.2
• Grover et al compared the long-term costs and benefits of treating dyslipidemia in diabetic patients without cardiovascular disease versus treating patients without diabetes who have cardiovascular disease in the US.29
• Cost-effective simulations of simvastatin treatment were performed for men and women aged 40 to 70 years with dyslipidemia. On the basis of the 4S study, they assumed a 35% reduction in LDL-C and an 8% increase in HDL-C with treatment.
• Treatment for nondiabetic patients with cardiovascular disease was cost-effective, with estimates ranging from $8800 to nearly $22,000 per year of life saved. Among diabetic individuals without cardiovascular disease, lipid therapy also was cost effective, with estimates ranging from approximately $5000 to $24,000 per year of life saved.
• Therefore, among diabetic men and women who do not have cardiovascular disease, lipid therapy is likely to be as cost-effective as treating nondiabetic individuals with cardiovascular disease.