Abstract 12842: Both Hyponatremia and Elevated Plasma Renin Activity Are Independent and Additive Cardiovascular Risk Factors in Patients With Angiographically Proven Coronary Artery Disease (CAD): The Intermountain Heart Collaborative Study

Abstract

Background: Several studies have documented an increased risk of future major adverse cardiovascular events (MACE) among CAD patients with elevated baseline plasma renin activity (PRA). One of the proposed mechanisms of elevated PRA is sodium depletion - hyponatremia. However, the relationship between PRA and hyponatremia is not well defined. Methods: A total of 1,781 pts with angiographic CAD (>50% stenosis) enrolled in the Intermountain Heart Collaborative Study were evaluated. Pts were excluded if they had a history of myocardial infarction (MI), heart failure (HF), left ventricular ejection fraction (EF) <45% or were discharged on beta blocker therapy. Baseline sodium levels were stratified between low (<135 mm/L) and normal (≥135 mm/L), and PRA between elevated (>2.3 ng/ml/h) and low (≤2.3 ng/ml/h) risk categories. The independent associations between these categories and MACE (death, MI, HF hospitalization, stroke and new onset renal failure) at five years were determined by multivariable Cox hazard regression analysis. Results: The mean pt age was 65.5 years; most pts were men (73.2%) and hypertensive (70.4%). Overall, PRA was elevated in 940 (52.8%) of the pts and sodium was low in 42 (2.4%) of the pts. The prevalence of elevated PRA was greater among pts with low sodium (66.7% versus 52.4% [p=0.07]). Five-year incidence of MACE was higher among pts with low sodium (61.9% versus 40.7%, p=0.006) and also among those with elevated PRA (43.7% versus 38.3%, p=0.02). After adjustment for baseline characteristics, among pts with low sodium, elevated PRA did not predict an increase in MACE (adjusted hazard ratio (HR)=0.72, p=0.53). However, among those with normal sodium, elevated PRA trended toward an association with MACE (HR=1.14, p=0.08). Conclusion: Among stable pts with angiographically documented CAD, both hyponatremia and elevated PRA are independently associated with future adverse cardiovascular events, although much of the adverse effect of elevated PRA may be explained by the concomitant presence of hyponatremia. The underlying physiology of these findings and its potential implications to future medical management of these pts deserves further study.