Evidence-based hypertension treatment in patients with diabetes

Abstract

Both impaired glucose tolerance and diabetes are associated with substantially increased prevalence of hypertension, cardiovascular and renal disease. The goal for hypertension treatment in diabetic patients is in evolution, because of recent clinical trials. For example, the results of the recent Action to Control Cardiovascular Risk in Diabetes-BP Arm (ACCORD BP) trial failed to show an additional benefit on cardiovascular event reduction at a mean systolic BP of 119 mm Hg. A post hoc analysis of 6,400 patients with type 2 diabetes from the International Verapamil-Trandolapril Study (INVEST) also failed to show additional cardiovascular risk reduction among patients who achieved a BP <130/80 mm Hg. While the evidence fails to support a lower BP goal to reduce coronary events, there was a risk reduction in stroke events both in ACCORD and the Appropriate Blood Pressure Control in NIDDM (ABCD) trial. A number of other clinical trials also demonstrate that when systolic pressures fall to less than 130 mm Hg, a reduction in stroke but not coronary disease events occurs. Thus, the precise BP goal for diabetic patients remains unresolved. We would posit that a BP goal of 135/85 mm Hg may be a reasonable compromise when viewing the impact of BP reduction on composite stroke and coronary artery disease in extant trials.

Figure 1

Potential effects of insulin resistance on endothelial cell (EC) and skeletal muscle cell (SMC) insulin metabolic signaling. Improved EC and SMC insulin‐stimulated nitric oxide (NO) bioavailability and glucose utilization ultimately improves endothelial function and systemic insulin sensitivity. Akt indicates protein kinase B; eNOS, endothelial NO synthase; FFA, free fatty acids; GLUT4, glucose transporter‐4; IR, insulin receptor; IRS‐1, IR substrate‐1; PI3‐K, phosphoinositol 3‐kinase; ROS, reactive oxygen species; TCA, tricarboxylic acid. With permission from Whaley‐Connell A, Sowers JR. Hypertension and insulin resistance. Hypertension. 2009;54:462–464.

Figure 2

Relative risk of the primary outcome and of the main secondary outcome. The primary composite outcome was death from cardiovascular causes, myocardial infarction, stroke, or hospitalization for heart failure. The main secondary outcome was death from cardiovascular causes, myocardial infarction, or stroke, which was used as the primary outcome in the Heart Outcomes Prevention Evaluation (HOPE) trial 5. The P value is for the comparison with the noninferiority margins. With permission from Buchner N, Banas B, Kramer BK. Telmisartan, ramipril, or both in patients at high risk of vascular events. N Engl J Med. 2008;359:426–427.