Low sodium diet protects from aldosterone-induced endothelial dysfucntion and left ventricular hypertrophy in subjects with resistant hypertension

Experimental models have demonstrated that aldosterone-induced cardiovascular damage requires concomitant high dietary sodium exposure. Studies from this and other laboratories have linked aldosteronism to endothelial dysfunction and left ventricular (LV) hypertrophy in human subjects. The current study was designed to determine if low sodium intake can blunt aldosterone-induced endothelial dysfunction and LV hypertrophy (LVH). Consecutive subjects (n=155) with resistant hypertension were prospectively evaluated with an early morning plasma aldosterone, renin and 24-hr urinary aldosterone and sodium. Changes in brachial artery diameter during hyperemia (flow-mediated dilation or FMD) were measured as an index for endothelial function. FMD was negatively correlated and LV end-diastolic diameter (LVDD) and LV mass (LVM) were positively correlated with aldosterone excretion (r=0.38, p<0.0001 and r=0.26, p=0.004). However the product of 24-hr sodium and aldosterone was an even stronger predictor of FMD and LVH than aldosterone alone (FMD: r=−0.59, p<0.0001, LVM: r=0.35, p<0.0001). Among subjects with high aldosterone excretion (> 12 μg/24-hr), low dietary sodium ingestion (<100 meq/24-hr) was associated with significantly less endothelial dysfunction and significantly less LVH. Three-month treatment with spironolactone significantly increased FMD and decreased LVH in subjects with and without aldosteronism, independent of blood pressure reduction level. However, these improvements were significantly greater in subjects with a high aldosterone and sodium excretion. These results are the first demonstration that low dietary sodium ingestion can protect from aldosterone-induced vascular and ventricular dysfunction in humans. Further, these results suggest that cardiovascular risk in subjects with resistant hypertension may be predicted by the product of urinary aldosterone and sodium excretion.