Plasma Renin and Risk of Cardiovascular Disease and Mortality
Plasma Renin and Risk of Cardiovascular Disease and Mortality
Aims: Previous studies relating plasma renin to cardiovascular disease (CVD) and mortality yielded conflicting results. We related plasma renin to incidence of CVD and mortality in 3408 individuals (mean age 59; 53% women) and in a hypertensive subset (n = 1413).
Methods and results: On follow-up (mean 7.1 years), 176 participants (122 hypertensives) developed CVD and 215 individuals (127 hypertensives) died. Overall, log-renin was associated with mortality [multivariable-adjusted hazards ratio (HR) per SD increment: in whole sample, 1.14, 95% confidence interval (CI) 1.00-1.30, P = 0.046; hypertensives, 1.16, 95% CI 1.00-1.35, P = 0.046], but relations varied over time (P < 0.02). Log-renin was associated with mortality at 2.5 years of follow-up (HR per SD increment: whole sample at 2.5 years, 1.23, 95% CI 1.04-1.45; hypertensives at 2 years, 1.28, 95% CI 1.06-1.54), but not during longer follow-up (HR per SD increment at 5 years: whole sample, 1.02, 95% CI 0.80-1.29; hypertensives, 0.98, 95% CI 0.74-1.30). The time-dependent relation of renin and mortality risk was maintained upon excluding participants with prevalent CVD. Renin was not associated with CVD incidence (HR per SD increment log-renin: whole sample, 0.99, 95% CI 0.85-1.14; hypertensives, 0.96, 95% CI 0.82-1.12).
Conclusion: Higher plasma renin was associated with greater short-term mortality but not with CVD incidence in the community.
The prognostic significance of plasma renin levels in hypertensive patients has been a subject of debate for many decades. Although individuals with hypertension should have lower plasma renin levels (relative to persons without hypertension) because of a physiological feedback response to higher blood pressure (BP),between 12 and 20% of hypertensive patients have plasma renin levels at the upper end of the distribution. Experimental research suggests that higher plasma renin levels may increase vascular risk via several mechanisms. Higher plasma renin is associated with increased activity of the renin-angiotensin-aldosterone system (RAAS), which may directly contribute to vascular injury.Additional mechanisms include myocardial remodelling initiated by downstream RAAS components, especially in post-myocardial infarction patients. Indeed, blockade of downstream RAAS components by angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, and aldosterone antagonists are among the critical pharmacological advances for preventing mortality and cardiovascular (CVD) morbidity in patients with coronary artery disease, hypertension, or congestive heart failure.
The experimental and clinical studies noted above have fuelled the expectation that knowledge of plasma renin may aid vascular risk stratification. However, clinical investigations examining this premise have yielded inconsistent results. In a large prospective community-based study, plasma renin activity (PRA) was not associated with the risk of myocardial infarction among non-hypertensive people or in hypertensive individuals. Two separate studies that focused on hypertensive patients reported a significantly increased risk of myocardial infarction, CVD, and all-cause mortality among those with higher PRA. Based on the results of the latter two reports, some experts have advocated renin profiling of hypertensive patients in order to identify high-risk individuals who may derive maximal benefit from pharmacological blockade of RAAS system. A post hoc, nested case-control study of a clinical trial of ACE-inhibitors in stroke patients also suggested that those with higher baseline renin values were at greater risk of incident myocardial infarction. Recently, Framingham investigators reported a positive association between plasma renin and all-cause mortality in a study evaluating a multimarker strategy of risk prediction; that report did not examine the association of plasma renin with CVD and mortality in the subset of persons with hypertension. Accordingly, we investigated the relations of plasma renin levels to all-cause mortality and CVD risk in hypertensive individuals, and among all participants in our large community-based sample.
Abstract and Introduction
Abstract
Aims: Previous studies relating plasma renin to cardiovascular disease (CVD) and mortality yielded conflicting results. We related plasma renin to incidence of CVD and mortality in 3408 individuals (mean age 59; 53% women) and in a hypertensive subset (n = 1413).
Methods and results: On follow-up (mean 7.1 years), 176 participants (122 hypertensives) developed CVD and 215 individuals (127 hypertensives) died. Overall, log-renin was associated with mortality [multivariable-adjusted hazards ratio (HR) per SD increment: in whole sample, 1.14, 95% confidence interval (CI) 1.00-1.30, P = 0.046; hypertensives, 1.16, 95% CI 1.00-1.35, P = 0.046], but relations varied over time (P < 0.02). Log-renin was associated with mortality at 2.5 years of follow-up (HR per SD increment: whole sample at 2.5 years, 1.23, 95% CI 1.04-1.45; hypertensives at 2 years, 1.28, 95% CI 1.06-1.54), but not during longer follow-up (HR per SD increment at 5 years: whole sample, 1.02, 95% CI 0.80-1.29; hypertensives, 0.98, 95% CI 0.74-1.30). The time-dependent relation of renin and mortality risk was maintained upon excluding participants with prevalent CVD. Renin was not associated with CVD incidence (HR per SD increment log-renin: whole sample, 0.99, 95% CI 0.85-1.14; hypertensives, 0.96, 95% CI 0.82-1.12).
Conclusion: Higher plasma renin was associated with greater short-term mortality but not with CVD incidence in the community.
Introduction
The prognostic significance of plasma renin levels in hypertensive patients has been a subject of debate for many decades. Although individuals with hypertension should have lower plasma renin levels (relative to persons without hypertension) because of a physiological feedback response to higher blood pressure (BP),between 12 and 20% of hypertensive patients have plasma renin levels at the upper end of the distribution. Experimental research suggests that higher plasma renin levels may increase vascular risk via several mechanisms. Higher plasma renin is associated with increased activity of the renin-angiotensin-aldosterone system (RAAS), which may directly contribute to vascular injury.Additional mechanisms include myocardial remodelling initiated by downstream RAAS components, especially in post-myocardial infarction patients. Indeed, blockade of downstream RAAS components by angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, and aldosterone antagonists are among the critical pharmacological advances for preventing mortality and cardiovascular (CVD) morbidity in patients with coronary artery disease, hypertension, or congestive heart failure.
The experimental and clinical studies noted above have fuelled the expectation that knowledge of plasma renin may aid vascular risk stratification. However, clinical investigations examining this premise have yielded inconsistent results. In a large prospective community-based study, plasma renin activity (PRA) was not associated with the risk of myocardial infarction among non-hypertensive people or in hypertensive individuals. Two separate studies that focused on hypertensive patients reported a significantly increased risk of myocardial infarction, CVD, and all-cause mortality among those with higher PRA. Based on the results of the latter two reports, some experts have advocated renin profiling of hypertensive patients in order to identify high-risk individuals who may derive maximal benefit from pharmacological blockade of RAAS system. A post hoc, nested case-control study of a clinical trial of ACE-inhibitors in stroke patients also suggested that those with higher baseline renin values were at greater risk of incident myocardial infarction. Recently, Framingham investigators reported a positive association between plasma renin and all-cause mortality in a study evaluating a multimarker strategy of risk prediction; that report did not examine the association of plasma renin with CVD and mortality in the subset of persons with hypertension. Accordingly, we investigated the relations of plasma renin levels to all-cause mortality and CVD risk in hypertensive individuals, and among all participants in our large community-based sample.
