Combination Therapy and Target Organ Protection in Hypertension and Diabetes Mellitus

Both essential hypertension and diabetes mellitus affect the same major target organs-the brain, the fundi, the heart, and the kidneys. The common denominator of hypertensive/diabetic target organ disease is the vascular tree. Both hypertension and diabetes are well identified risk factors for atherogenesis. Coronary artery disease is much more common in diabetic hypertensive patients than in patients suffering from hypertension or diabetes alone. Typical for the diabetic hypertensive heart are extensive degenerative changes and a greater degree of hypertrophy compared with the nondiabetic hypertensive heart. The combined presence of hypertension and diabetes concomitantly affects glomerular filtration rate and renal blood flow, thereby greatly accelerating a decrease in renal function. Hypertension accelerates the development of diabetic retinopathy; hypertensive/diabetic cerebral disease leads to vascular dementia, transient ischemic attacks, and strokes. A decrease in the hemodynamic and glycemic burden is the primary goal in the management of the hypertensive diabetic patients. Both diuretics and beta-blockers have been reported to adversely affect the overall risk factor profile in the diabetic patient. In contrast, the postsynaptic alpha-blockers, the calcium antagonists, and the angiotensin-converting enzyme inhibitors have been reported to be either neutral or beneficial with regard to the overall metabolic risk factor profile. The combination of a heart rate lowering calcium antagonist, particularly verapamil, with an ACE inhibitor offers some potential to either prevent or reverse target organ disease associated with hypertension and diabetes.