Cardiovascular disease (CVD) is the leading cause of morbidity and mortality for individuals with diabetes. At least 68% of adults 65 years or older with diabetes die of some form of CVD, whereas 16% die of stroke. Adults with diabetes are 2 to 4 times more likely to have heart disease or stroke than adults without diabetes.1 Hypertension and dyslipidemia are major risk factors for CVD, and they commonly coexist in people with diabetes.2 An added concern is that diabetes itself is independently associated with increased CVD risk.3 A number of large clinical trials have demonstrated the benefits of controlling hypertension or dyslipidemia in preventing and slowing CVD in adults with diabetes. The global management of multiple CVD risk factors yields even greater results.2
An estimated 70% to 80% of people with diabetes are also hypertensive. The presence of hypertension in this population increases the risk of myocardial infarction (MI), stroke, heart failure, nephropathy, and all-cause mortality.3 Epidemiological studies show that blood pressure (BP) readings greater than 115/75 mm Hg are associated with increased CVD events and mortality. Given the relationship between lower BP and better long-term clinical outcomes, 2 landmark trials, Action to Control Cardiovascular Risk in Diabetes (ACCORD)4 and Action in Diabetes and Vascular Disease: Preterax and Diamicron MR Controlled Evaluation—Blood Pressure,5 were conducted to evaluate the clinical benefit of achieving tight BP control in those with type 2 diabetes mellitus (DM2).
The ACCORD trial assessed whether a systolic BP of less than 120 mm Hg provided greater CVD risk reduction compared with the accepted systolic BP goal of 130 to 140 mm Hg. The findings showed no additional benefit in achieving the more aggressive target; yet, there were increased costs and more adverse events associated with the use of more medications at higher doses.4 In the Action in Diabetes and Vascular Disease: Preterax and Diamicron MR Controlled Evaluation—Blood Pressure trial, there was a significant CVD prevention benefit—fewer major CVD events and fewer deaths attributed to CVD as well as all cause mortality—in those who were randomized to the treatment arm and given a fixed-dose combination of angiotensin converting enzyme inhibitor (perindopril) and thiazide diuretic (indapamide). The baseline BP among study subjects was 145/81 mm Hg. The treatment arm achieved an average BP of 136/73 mm Hg, not nearly as low or aggressive as those achieved in the ACCORD trial, but with fewer side effects and less cost.5
These trials, taken together with previous epidemiologic observational studies, have resulted in slightly higher thresholds for treatment in patients with diabetes. The 2015 American Diabetes Association (ADA) Standards for Medical Care in Diabetes amended their recommended BP threshold to 140/90 mm Hg, up from previous recommendation of 130/80 mm Hg. They do state, however, that lower treatment targets may be appropriate for individuals who are at high risk for stroke or chronic kidney disease or younger patients who can easily achieve lower BP levels without undue treatment burden.2
Patients with DM2 have an increased prevalence of lipid abnormalities, contributing to their high risk of CVD. Subgroup analysis of diabetic patients within large clinical trials and trials in patients with diabetes showed significant reductions in incident and recurrent cardiovascular events and CVD-related mortality. Meta-analyses including data from over 18 000 patients with diabetes from 14 randomized trials of statin therapy demonstrate a 9% proportional reduction in all-cause mortality and 13% reduction in vascular mortality for each mmol/L reduction in low-density lipoprotein cholesterol (LDL-C). Statins are the drug of choice for LDL-C lowering and cardio-protection.2
Most trials of statins and CVD outcomes tested specific doses of statins against placebo or other statins rather than aiming for specific LDL-C targets. With consideration of the conduct and outcomes of these trials, the 2015 ADA Standards of Care were revised to recommend when to initiate and intensify statin therapy based on a patient’s risk level (Table 1).2 The standards recommend screening lipid panels at the time of diagnosis of diabetes and at least annually thereafter mainly to evaluate for adherence to medication therapy.
Hypertriglyceridemia and low cardio-protective high-density lipoprotein cholesterol (HDL-C) are the most prevalent pattern of dyslipidemia in persons with DM2. The evidence base for medications that target these lipid particles is much less robust than that for statin therapy. The ADA standards recommend dietary and lifestyle modifications as first line of management of hypertriglyceridemia, unless the triglyceride level is greater than 1000 mg/dL, in which case immediate pharmacologic therapy with omega-3 fatty acids or fibric acid derivatives may reduce the risk of acute pancreatitis.2 In a large clinical trial specific to diabetic patients, fenofibrate showed no benefit for CVD risk reduction. In the ACCORD study, combination therapy with simvastatin and fenofibrate showed no added CVD risk reduction benefit when compared with simvastatin alone.6
The Atherothrombosis Intervention in Metabolic Syndrome With Low HDL/High Triglycerides: Impact on Global Health Outcomes trial evaluated the benefit of statin plus extended-release niacin in patients with established CVD, low LDL-C and HDL-C levels, and high triglyceride levels; about a third of the study population were also diabetic. The trial was halted early because of lack of efficacy in relation to the primary CVD outcome (death from coronary heart disease, nonfatal MI, ischemic stroke, hospitalization for acute coronary syndrome, or revascularization) and a possible increase in ischemic stroke risk in those on combination therapy.7 Combination therapy with niacin is therefore not recommended. The ADA standards suggest that the use of niacin and fibric acid derivatives may be limited to patients with hypertriglyceridemia and low HDL-C levels who are intolerant of statins.2
Lifestyle intervention including dietary changes, increased physical activity, weight loss, and smoking cessation, together with medication management, is helpful in managing many CVD risk factors, including hypertension and dyslipidemia. Nutrition intervention should be individualized with a general focus on reducing saturated fat, cholesterol, and trans-fat intake while increasing omega-3 fatty acids and viscous fiber. Glycemic control can also help to improve plasma lipid levels, particularly in patients with very high triglyceride levels and poor glycemic control.2
Lifestyle interventions targeting weight loss through decreased caloric intake and increased physical activity as implemented in the Action for Health in Diabetes (Look AHEAD) trial may be considered for improving glucose control, fitness, and some CVD risk factors. However, the trial was stopped early on the basis of a futility analysis that demonstrated no reduction in the rate of CVD events in overweight or obese adults with DM2 as a result of intensive lifestyle intervention.8 One explanation of these findings is that those with improved CVD risk factor profiles stopped taking known cardioprotective therapies such as statins for dyslipidemia.3 Thus, it is reassuring to know that there was no increase in CVD events in those who were able to control risk factors with accepted lifestyle changes.
Antiplatelet therapy with aspirin has been shown to be effective in reducing CVD morbidity and mortality in high-risk patients with previous MI or stroke (secondary prevention). It is less clear whether aspirin is helpful in people without CVD, including those with diabetes (primary prevention). Two randomized controlled trials that specifically looked at aspirin use in adults with diabetes, failed to show a significant reduction in CVD end points. The Antithrombotic Trialists’ collaborators published a meta-analysis of 6 large trials of aspirin for primary prevention in the general population. Of the 95 000 participants included in this analysis, approximately 4000 were diabetic. The effects of aspirin on major vascular events (MI and stroke) were similar for patients with or without diabetes: relative risk of 0.88 (95% confidence interval, 0.67–1.15) and 0.87 (95% confidence interval, 0.79–0.96), respectively.9 Aspirin seems to have a modest effect on CVD event reduction, with the greatest benefit for those with the highest CVD risk. The benefit of aspirin use must be evaluated in context with the risk of gastrointestinal bleeding. The ADA therefore suggests that aspirin therapy (75–162 mg/d) may be considered as a primary prevention strategy in those with type 1 diabetes or DM2 at increased CVD risk (10-year risk of CVD events >10%). This includes most men older than 50 years and women older than 60 years who have at least 1 additional major CVD risk factor (hypertension, dyslipidemia, smoking).2
In 2011 to 2012, the estimated prevalence of diabetes was 12% to 14% among US adults. Between 1988–1994 and 2011–2012, the prevalence of diabetes increased in the overall population and in all subgroups evaluated.10 Given these growing numbers and the strong association between diabetes and CVD risk, it is imperative that we adopt an “all hands on deck” mentality when it comes to management of diabetes and its coexisting metabolic CVD risk factors. Nurse-led diabetes self-management programs have demonstrated benefit with regard to improved glycemic control and reduction in CVD risk factors.11 These programs should be used and expanded to meet the growing demand. Healthcare providers in all community, primary and cardiovascular care settings must be empowered to screen and treat CVD risk factors in people with diabetes with current, evidenced-based lifestyle and pharmacologic interventions to reduce risk and prevent disease.
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