Issues, goals, and guidelines in selecting first-line drug therapy for hypertension

Modern antihypertensive therapy is enriched by an explosion in drug development that makes available increasingly specific agents whose effects have advanced our understanding of pressor mechanisms. This and other research into hypertensive mechanisms has defined the clinical, pharmacological, and endocrinologic heterogeneity of human hypertension. The sum of these developments is a greatly enhanced ability to identify curable and definable causes of hypertension and to pathophysiologically stratify the remaining cases of essential hypertension. Modern treatment can be much more specific than before. When long-term drug therapy is indicated, the regimen is more likely to achieve a primary goal for each patient, that is, the fewest possible drugs in the smallest amount and in lowest frequency. Two clinically quantifiable mechanisms for long-term arteriolar vasoconstriction can be identified within the spectrum of human hypertension. The first, renin-mediated vasoconstriction, is directly related to the plasma renin level. The second, sodium-volume-related vasoconstriction, is marked by a reciprocally subnormal renin level and involves abnormal sodium retention and calcium transport. A baseline renin-sodium profile can identify the pressure of one of these two forms of vasoconstriction and therefore is the key for the diagnosis of the two curable disorders that fully express one of the two pressor mechanisms--renovascular hypertension and primary aldosteronism. Renovascular hypertension, more common than once thought, is often cured by angioplasty. It is important to diagnose these curable forms before beginning long-term drug therapy. The renin-sodium profile, used in conjunction with serum potassium and creatinine measurements, is valuable not only in screening patients for curable forms, but also for stratifying the remainder according to the pathophysiological vasoconstrictor mechanism that underlies the hypertension. Converting enzyme inhibitors or beta-blockers are, by themselves, often effective in correcting the hypertension of high- or medium-renin patients, whereas calcium antagonists, diuretic agents, or alpha-blockers alone are most effective against the low-renin form of vasoconstriction. In the large midzone of renin values, if monotherapy fails, a rational basis for combined antirenin-antisodium volume therapies can be developed.