Renin turning full circle as cardiovascular risk factor

Abstract

Renin released from the kidneys, along the cascade of the renin–angiotensin–aldosterone axis, is a major regulator of blood pressure via the generation of angiotensin II and of body sodium and potassium via aldosterone release. Under normal conditions, renin decreases with age and higher blood pressure, whereas salt depletion stimulates renin release. In 1972, Brunner and Laragh first introduced the concept of classifying hypertensive patients according to plasma renin activity in relation to the daily sodium excretion.1 Among patients with essential hypertension, those with normal (57%) or high (16%) renin had an 11 and 14% frequency of heart attacks or strokes, respectively, whereas none of the low renin patients (27%) had such complications.1 Several subsequent studies noticed an increased risk of myocardial infarction,2–5 cardiovascular disease,3 or all-cause mortality2,3,6 with higher circulating renin levels, but other investigators failed to replicate these findings [7]. Parikh et al. 8 provided some insights based on the Framingham Heart Study, which might help in explaining the controversy in the literature. The key finding was that all-cause mortality increased with higher plasma renin at baseline in the whole sample [standardized hazard ratio (HR), 1.14; P = 0.046] as well as in hypertensive patients (HR, 1.16; P = 0.046), but that the strength of these associations decreased with the length of follow-up. The HR of total mortality fell … *Corresponding author. E-mail address : jan.staessen{at}med.kuleuven.be