Abstract P434: Insights Into Blood Pressure Control In Primary Aldosteronism Using Physiological Modeling

Abstract

For the last 20 years, we have observed that patients with drug resistant hypertension due to primary aldosteronism (PA) have significant lowering of blood pressure (BP) and improved hypokalemia when moving to a DASH dietary intervention (≤65 mEq/day Na + / ≥120 mEq/day K + ). However, current guidelines for PA treatment briefly recommend lowering Na + intake and make no specific mention of supplementing potassium intake or using DASH in PA. Because continuous monitoring of cardiovascular, neural, and hormonal changes during developing PA cannot be achieved experimentally, we used the mathematical model of human physiology, HumMod, to test the responses to a DASH diet during PA. Starting from baseline conditions with normal Na + /K + intake (150 and 50 mmol/day, respectively), we simulated an aldosterone secreting tumor to gradually increase plasma aldosterone to 20 ng/dL over 3 years. Baseline PA was associated with hypertension (150 mmHg systolic BP), very low endogenous renin and aldosterone secretion, hypokalemia (2.9 mmol/L K + ), and tumor aldosterone secretion of 43 μg/day. We simulated a chronic change in dietary intake: 1) Low Na + diet - Na + intake fixed at 65 mmol/day, 2) High K + diet - 120 mmol/day K + intake, or 3) DASH diet - Low Na + intake and high K + intake. Lowering Na + intake without or with high K + intake (DASH) were associated with lower systolic BP (-12 mmHg and -25 mmHg, respectively) over the first 4 weeks and persisted for up to 2 years despite continued activation of the renin-angiotensin system and increasing tumor aldosterone. Simulating mineralocorticoid blockade (MCB) was associated with reductions in systolic BP (-17 mmHg) and correction of hypokalemia (4.0 mmol/L) but BP still remained uncontrolled (134/81 mmHg), partly due to the compensatory increase in renin secretion. However, adding low Na + or DASH to the MCB simulation were associated with greater antihypertensive effects (-26 and -30, mmHg respectively). These current simulations may help better understand the sequence of physiological events in PA and yield new insights into its diagnosis and management. The physiological effects of the DASH diet desperately need to be tested in patients with PA as the simulation suggests beneficial effects beyond current treatment guidelines.