Etiology, pathophysiology, and treatment of left ventricular hypertrophy: Focus on severe hypertension

Left ventricular hypertrophy (LVH), a common finding in hypertensive patients, has emerged as one of the most potent risk factors for future cardiovascular mortality in patients with hypertension. LVH is associated with multiple physiologic abnormalities, which may account for the increased risk. These include coronary perfusion abnormalities such as reduced coronary flow reserve, altered coronary flow autoregulation, subendocardial hypoperfusion, and abnormal left ventricular (LV) diastolic function. Although abnormalities of LV diastolic function are more common in LVH, they may occur early in the course of the disease. There may be a threshold of average awake ambulatory blood pressure (BP), 130/85 mm Hg, below which neither diastolic abnormalities nor LVH is detected. The reasons for reduced reserve coronary flow reserve are complex and include structural and functional abnormalities of myocardial blood vessels such as reduced capillary density, reduced luminal diameter of intramyocardial small arteries, and increased vascular tone, possibly as a result of factors such as abnormal endothelium-dependent relaxation. Preliminary data suggest that regression of LVH is associated with improved survival. Severe hypertensive patients would be expected to achieve the greatest benefit, because, if left untreated, this group has nearly 20% mortality within 2 years. To evaluate the effect of nifedipine gastrointestinal therapeutic system (GITS) on LV mass, 16 patients with initial diastolic BP > 120 mm Hg were treated for 1 year with either monotherapy or in combination with a thiazide diuretic. Because it has not been unequivocally shown that changes in LV mass have physiologic benefit, associated alterations in LV systolic function, LV filling, plasma renin activity, atrial natriuretic peptide, and catecholamines were also evaluated. LV mass regressed over the course of 6 months, and this was sustained at 1 year. Treatment with nifedipine GITS did not adversely affect intrinsic LV contractility. LV filling appeared to improve over the course of the year. There was a trend toward a relationship between LV mass regression and an improvement in diastolic function. Atrial natriuretic peptide was markedly reduced at 2 months, and this effect was sustained at 1 year. Over the period of 1 year, there was no detectable activation of either the catecholamine or renin systems.