Aims: Plasma renin activity (PRA) has been shown to predict future cardiovascular (CV) events in observational studies and in clinical trials and to be associated with the prevalence of chronic renal disease in hypertensive subjects. In a nested case-control study, we explored the relationship between CV and renal outcomes and all-cause mortality with baseline measurements of PRA among hypertensive adults randomized in the ASCOT trial.
Methods and results: In the UK and Ireland, ASCOT included 9098 hypertensive adults randomized to either calcium channel blocker (CCB)- or β-blocker (BB)-based treatment. Four thousand eight hundred and fifty-three patients with total cholesterol ≤6.5 mmol/L (250 mg/L) were further randomized to atorvastatin or placebo. Over 5.5 years, there were 399 CV events (fatal coronary heart disease (CHD), non-fatal myocardial infarction, coronary revascularization, and fatal and non-fatal stroke), 96 cases of new-onset renal impairment, and 220 deaths. Cases were age, sex, and ethnicity matched with 1525 controls. Conditional logistic regression models were used to evaluate the association between CV events, renal impairment, all-cause mortality, and PRA. For those on antihypertensive (AHT) treatment at the baseline (91.5%), PRA was influenced by prior drug treatment. The median (inter-quartile range; ng/mL/h) levels were 1.04 (0.52, 1.3) for BBs, 1.30 (0.78, 2.72) for CCBs, 1.56 (0.91, 3.50) for diuretics, and 2.33 (1.30, 5.57) for angiotensin-converting enzyme inhibitors or angiotensin receptor blockers. Odds ratios (OR) and 95% confidence intervals (CIs) for CV and other events were estimated for 1-SD increase in log-transformed PRA levels and by categorizing PRA into quartiles with the lowest as the referent category. Baseline PRA did not predict CV events in models adjusted for baseline characteristics [OR 0.92 (CI 0.81, 1.06, P = 0.25)] and for pre-randomized AHT treatment [OR 0.91 (CI 0.79, 1.04, P = 0.17)] and was not associated with all-cause mortality [OR 1.12 (CI 0.92, 1.37, P = 0.25) and OR 1.06 (CI 0.91, 1.24, P = 0.46)] in the fully adjusted model. Baseline levels of PRA were positively but non-significantly associated with the development of renal impairment in models adjusted for baseline characteristics [OR 1.39 (CI 0.97, 1.97, P = 0.07)] and also for pre-randomized antihypertensive (AHT) treatment [OR 1.35 (CI 0.95, 1.94, P = 0.10)]. Quartile analyses, however, demonstrated a significant positive association of higher levels of PRA with the development of impaired renal function (P = 0.03 and 0.05 in adjusted models, respectively) compared with the lowest quartile.
Conclusion: These analyses suggest an association between elevated baseline PRA and the subsequent development of renal impairment but do not support its use to predict future CV events or all-cause mortality in treated hypertensive patients without diagnosed CHD.