We posit that individuals who carry the LSD1 risk allele have increased mineralocorticoid receptor activity, which results in hypertension. Thus, our mechanistic clinical study will assess whether hypertensive LSD1 risk allele carriers will show significantly greater reductions in blood pressure with a specific aldosterone mediated treatment approach (mineralocorticoid receptor blockade) than with a non-specific approach (amlodipine). To test this hypothesis, we will perform a randomized, double-blind, active controlled study in hypertensive carriers of the LSD1 risk allele using a novel two-limb, proof-of-principle study. Our primary outcome will be a liberal salt diet systolic blood pressure. Therefore, this mechanistic trial will provide support for using a genetic marker that identifies individuals who are uniquely responsive to mineralocorticoid receptor blockade--personalized, precision medicine.

We posit that individuals who carry the LSD1 risk allele have increased mineralocorticoid receptor activity, which results in hypertension. Thus, our mechanistic clinical study will assess whether hypertensive LSD1 risk allele carriers will show significantly greater reductions in blood pressure with a specific aldosterone mediated treatment approach (mineralocorticoid receptor blockade) than with a non-specific approach (amlodipine). To test this hypothesis, we will perform a randomized, double-blind, active controlled study in hypertensive carriers of the LSD1 risk allele using a novel two-limb, proof-of-principle study. Our primary outcome will be a liberal salt diet systolic blood pressure. Therefore, this mechanistic trial will provide support for using a genetic marker that identifies individuals who are uniquely responsive to mineralocorticoid receptor blockade--personalized, precision medicine.

Dose escalations of eplerenone 50, 100, or 200mg

Subjects will be counseled regarding liberal salt dietary intake to ensure similar intakes in all subjects [Na+ (200 mEq), potassium (K+, 100 mEq) and calcium (800 mg)]. After completion of this diet for 6 days, the subject will collect a 24-hour ambulatory blood pressure. Procedure will be performed before randomization and after 4 weeks of therapy.