21st European Meeting on Hypertension and Cardiovascular Prevention

Pre-treatment plasma renin activity (PRA) strongly predicts cardiovascular (CV) mortality in patients with hypertension, according to new findings from a long-term cohort study. Michael Alderman, MD, Albert Einstein College of Medicine, Bronx, New York, USA, presented results from the study.

The New York City Worksite Hypertension Control Program was a prospective cohort study that enrolled 9800 individuals with mild to moderate hypertension between 1980 and 1998. All participants began antihypertensive therapy with vasodilators, such as diuretics or calcium channel blockers (CCBs), and/or agents targeting the renin system, including angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), or beta blockers. The current analysis included 3791 patients with baseline PRA readings and cause-specific mortality data through 2007. The mean follow-up was 16.7 years.

Patients were classified into 3 groups according to baseline PRA level (Table 1). PRA groups inversely correlated with systolic blood pressure (SBP) across all study time points. Patients with the lowest PRA levels (<0.78 ng/mL/hr) had the highest mean SBP at baseline, after 1 year of antihypertensive therapy, and at the last study measurement compared with patients with the highest PRA levels (≥2.0 ng/mL/hr; p<0.001 for all comparisons).

Table 1. Blood Pressure and Antihypertensive Therapy by Baseline PRA

Measure Baseline PRA (ng/mL/hr) P value
T1: <0.78
(n = 1267)
T2: 0.78 to 2.0
(n = 1267)
T3: ≥2.0
(n = 1257)
Baseline SBP, mmHg 152 149 146 <0.001
1-year SBP, mmHg 139 137 135 <0.001
Last SBP, mmHg 137 136 134 <0.001
Last antihypertensive therapy, % <0.001
  • – Vasodilators only
46 26 20
  • – Renin-targeted agents only
19 41 55
  • – Both classes
32 30 21

PRA = plasma renin activity; SBP = systolic blood pressure.

Choice of antihypertensive therapy also correlated with baseline PRA level (p<0.001; Table 1). Patients with low baseline PRA levels were more likely than those with higher PRA levels to be treated with diuretics or CCBs only. In addition, patients with higher baseline PRA levels were more likely to be treated with renin-targeted agents. Many patients were treated with agents from both classes.

Baseline PRA significantly predicted several mortality outcomes adjusted for age, sex, and other standard prognostic factors. Compared with the lowest PRA group, the highest PRA group had a 37% higher risk for all-cause mortality (HR, 1.37; 95% CI, 1.15 to 1.63; p<0.0001) and a 70% higher risk for CV mortality (HR, 1.70; 95% CI, 1.29 to 2.23; p<0.0001).

Among CV deaths, the risk of fatal myocardial infarction was nearly 3-fold higher for patients in the highest PRA group compared with the lowest PRA group (HR, 2.89; 95% CI, 1.46 to 5.71; p = 0.002). There were no differences between the highest and lowest PRA groups with respect to non-CV mortality (p = 0.36), including cancer-related deaths (p = 0.38).

Baseline PRA can improve the prognostic power of current CV risk models. After adjusting for Framingham Risk Score, baseline PRA level remained a significant predictor of CV mortality when evaluated as a continuous variable (HR, 1.28; 95% CI, 1.14 to 1.44; p <0.0001) and when the highest and lowest tertiles were compared (HR, 1.76; 95% CI, 1.33 to 2.32; p <0.0001). In the future, including PRA measurements in the standard assessment of hypertensive patients may improve risk stratification and enhance the selection of antihypertensive therapy.