Cardiovascular Risk Reduction in Patients with Type 2 Diabetes

• What interventions should be used for primary prevention at this stage?

A number of interventions can decrease lifetime risk for cardiovascular disease in persons with diabetes. First, smoking increases risk for all forms of vascular disease, including progression to end-stage renal disease, and is an independent predictor of mortality. Smoking cessation is one of the most effective interventions at decreasing these risks [6]. Second, lifestyle interventions such as diet and exercise are often recommended. The Look AHEAD trial studied the benefits of weight loss and exercise in the treatment of T2DM through a randomized control trial involving more than 5000 overweight patients with T2DM. Patients were randomly assigned to intensive lifestyle interventions targeting weight loss or a support and education group. Although the Action for Health in Diabetes (Look AHEAD) trial did not demonstrate clinical outcome benefit with this intensive intervention, there was improvement in weight, cholesterol level, blood pressure, and glycemic control, and clinical differences may have been related to study power or differences in cardioprotective medication use [7]. Furthermore, at least 1 large randomized trial of dietary intervention in high-risk cardiovascular patients, half of whom had diabetes (Prevención con Dieta Mediterránea [PREDIMED]), showed significant benefits in cardiovascular disease, reducing the incidence of major cardiovascular events [8]. According to most diabetes guidelines, diet and exercise continue to be stressed as initial management for all patients with diabetes [9–12].

In addition, although intensive glucose control decreases microvascular complication rates, it has been more difficult to demonstrate a reduction in cardiovascular disease with more intense glycemic control. However, long-term follow-up of the United Kingdom Prospective Diabetes Study (UKPDS) cohort, a population that was earlier in their diabetes course, clearly demonstrated a reduction in cardiovascular events and mortality with better glycemic control over the long term [13,14]. For those who are later in their diabetes course, meta-analyses of glycemic control trials, along with follow-up studies, have also shown that better glycemic control can reduce cardiovascular events, but not mortality [15–17]. Therefore, glucose lowering should be pursued for cardiovascular risk reduction, in addition to its effects on microvascular complications.

It is well established that a multifactorial approach to cardiovascular risk reduction in patients with type 2 diabetes is effective. In the Steno-2 study, 160 patients with type 2 diabetes were randomly assigned to receive multidisciplinary, multifactorial intensive target-based lifestyle and pharmacologic intervention or standard of care. The intensive therapy group all received smoking cessation counseling, exercise and dietary advice, vitamin supplementation, and an angiotensin-converting enzyme (ACE) inhibitor or an angiotensin receptor blocker (ARB). Acetylsalicylic acid (ASA) was added for all patients with clinical macrovascular disease. Dyslipidemia, hypertension, and hyperglycemia were all treated in a protocolized way if lifestyle interventions did not achieve strict targets. During the mean 7.8 years of follow-up, the adjusted hazard ratio for a composite of cardiovascular death and macrovascular disease was 0.47 (95% confidence interval [CI] 0.22 to 0.74; P = 0.01) [18]. These patients were followed for an additional 5.5 years in an observational study with no further active intervention in both groups. Over the entire period, there was an absolute risk reduction of 20% for death from any cause, resulting in a number needed to treat of 5 for 13 years [19]. As a result of these compelling data, guidelines from around the world support a multifactorial approach, with the Canadian Diabetes Association (CDA) guidelines [20] promoting the use of the “ABCDES” of vascular protection: