Effect of Blood Pressure Management on Coronary Heart Disease Risk in Patients with Type 2 Diabetes

Epidemiologic Associations Between Blood Pressure and Coronary Heart Disease in People with Type 2 Diabetes Mellitus

On average, systolic BP (SBP) and diastolic BP (DBP) are consistently higher among individuals with T2DM compared with those without T2DM. ^, Nonoptimal BP is a well-established risk factor for people with and without diabetes. In general populations, there is clear log-linear association between both SBP and DBP and CHD, evident within any adult age group. This association appears continuous across the range of BP, down to at least SBP of 115 mm Hg and DBP of 75 mm Hg, such that for adults aged 40 to 89 years, a 20-mm Hg difference in SBP is associated with an approximate 45% difference in risk of CHD. In 386,307 people with diabetes included in the Asia Pacific Cohort Studies Collaboration, a similar continuous association was observed for both Asian and non-Asian populations. Among those with diabetes, a 10-mm Hg lower level of SBP was associated with an 18% lower level of CHD, which was not statistically different from the 23% lower level of CHD observed in people without diabetes ( Fig. 14-1 ).

Further data relating to epidemiologic associations have been derived from observational analyses of clinical trial populations. ^, The United Kingdom Prospective Diabetes Study (UKPDS) demonstrated that a higher level of average SBP within a range from below 120 mm Hg to above 160 mm Hg was associated with a greater risk of myocardial infarction (MI) of approximately 12%/10-mm Hg increment. More recently, observational subgroup analyses of the International Verapamil SR Trandolapril Study (INVEST) suggested a possible J-curve relationship with a threshold on-treatment SBP level of 125 to 130 mm Hg in diabetic patients with established stable coronary artery disease with respect to all-cause mortality. By and large, however, the epidemiologic data have formed a credible basis for the hypothesis that benefits of BP-lowering therapy might accrue to individuals with T2DM down to levels of SBP well below currently accepted thresholds for the diagnosis of hypertension.

Although these epidemiologic data provide a basis for expecting a reduction in CHD events from interventions that reduce BP in people with T2DM, the results from well-designed and appropriately powered randomized trials should inform recommendations for clinical and public health practice. Such trials have been conducted, evaluating both lifestyle interventions and drugs, and are summarized in the following sections.

Efficacy of Lifestyle Interventions on Blood Pressure Levels and Coronary Heart Disease Risk in Patients with Type 2 Diabetes Mellitus

Initial attempts at BP reduction through lifestyle modification are emphasized in guidelines for the management of hypertension worldwide in individuals with or without diabetes. These have principally focused on increasing physical activity, reducing body weight and/or adiposity, and performing dietary modification, including salt restriction. Although a number of studies have evaluated the effects of lifestyle interventions on diabetes incidence, the Look AHEAD (Action for Health in Diabetes) trial examined the sustained effects of an intensive lifestyle intervention in 5145 overweight or obese adults with T2DM. Over an average of 4 years and compared with a diabetes support and education control group, intensive lifestyle intervention was associated with significant improvements for a number of vascular risk factors, including significant net reductions in SBP (− 2.33 mm Hg) and DBP (− 0.44 mm Hg). The intervention evaluated and targeted both physical activity and diet, and separate effects of individual components of the lifestyle intervention on BP cannot be estimated. Inferences about how this might translate to reductions in CHD risk currently can be based only on projections from observational studies comparing BP level or changes in BP level with clinical outcomes. Published data from Look AHEAD to date are the result of a prespecified interim comparison of effects on risk factors only, in a trial designed to evaluate the effects of the intensive lifestyle intervention on clinical outcomes after an average of 13.5 years of follow-up. (See also Chapters 5 and 12 .)

Although not restricted to people with diabetes, the Dietary Approaches to Stop Hypertension (DASH) trials provide some indication of the likely effects of certain diets on BP. ^, Allocation to the DASH diet (rich in fruits, vegetables, and low-fat dairy foods and with reduced saturated and total fat) in 459 adults over an 8-week intervention period was associated with significant reductions in SBP and DBP of 5.5 mm Hg and 3.0 mm Hg, respectively, compared with a “typical” control diet. In the subsequent DASH-sodium trial, participants were randomly assigned different levels of sodium intake, within DASH or control diets. The effects of different levels of sodium intake in addition to the DASH diet were evaluated. Greatest benefits were observed with a low-sodium DASH diet, which compared with a control high-sodium diet, reduced SBP by 11.5 mm Hg in participants with hypertension and 7.1 mm Hg in those without a diagnosis of hypertension. With small numbers of participants, analysis in the subgroup with diabetes was not possible. A recent updated Cochrane Review of 167 studies concluded that dietary sodium reduction over at least 4 weeks resulted in significant reductions in BP, with greater effects among people with hypertension versus those considered normotensive and possibly in non-Caucasians versus Caucasians. Although there are some dissenting views, many believe the existing evidence adequately favors common recommendations for individual salt intake to be limited to less than 5 g/day, particularly in individuals with hypertension, although a Cochrane review of individual patient strategies to reduce salt intake suggest that more effective approaches to achieve such reductions are urgently required.

Efficacy and Safety of Blood Pressure–Lowering Drugs on Coronary Heart Disease in Patients with Type 2 Diabetes Mellitus

Multiple guidelines for pharmacologic lowering of BP in patients with T2DM exist worldwide, with some major examples summarized in Table 14-1 . Some of the evidence on which these recommendations are based is outlined here.