Spironolactone improves blood pressure and left ventricular hypertrophy in patients with resistant hypertension

Background: Hyperaldosteronism is being recognized to be increasingly prevalent particularly in patients with resistant hypertension and is believed in addition to raising blood pressure (BP) to induce cardiac fibrosis and LVH. We hypothesize that spironolactone a mineralocorticoid receptor antagonist, could improve blood pressure control and LVH in this high risk population. Methods: Patients with resistant hypertension (defined as requiring 4 or more antihypertensive agents) were treated with spironolactone 25mg once daily and up titrated to 50mg daily. Clinic BP, 24-hr ambulatory BP, cardiac MRI, plasma renin activity (PRA), brain natriuretic peptide (BNP) were measured before and 6 months after treatment with spironolactone. Results: Eleven subjects with a mean age 54.5_7.2 years and BMI 36.1_6.2 kg/m2 were evaluated. Ten of 11 subjects were receiving optimal doses of a thiazide diuretic as part of their treatment regimen. Clinic BP (134_13/81_7 vs. 120_11/76_7 mm Hg; p _ 0.015, p_ns), ambulatory daytime BP (142_15/83_10 vs. 132_16/76_12 mm Hg; p_ns), nighttime BP (132_16/ 74_14 vs. 121_14/65_11 mm Hg; p_0.05), 24-hr ABPM (139_15/80_11 vs. 129_15/ 73_12 mm Hg; p_ns), BNP (44.1_52.0 vs. 16.1_18.1 pg/ml; p _ 0.02), left ventricular (LV) end diastolic volume (170.0_43.9 vs. 160.9_46.4 ml; p_ns), end diastolic LV mass (178.4_48.6 vs. 148.5_33.4 gm; p _ 0.006), end systolic LV mass (195.2_55.6 vs. 155.5_34.6 gm; p _ 0.003), mean LV mass (186.8_51.9 vs. 151.9_33.8 gm; p _ 0.004), LV posterior wall thickness (10_1.9 vs. 9_1.8 mm; p_ns), interventricular septal thickness (11.3_2.4 vs. 9.6_2.2 mm; p _ 0.008) were lower at the end of six months following spiranolactone treatment compared to baseline. Serum potassium (3.7_0.4 vs. 4.3_0.5 mEq/L; p _ 0.006), serum creatinine (0.99_0.2 vs. 1.2_0.3 mg/dl; p_0.02) and PRA (1.7_2.2 vs. 12.2_16.1 ng/ml/hr; p_0.002) were higher. Conclusion: Our findings demonstrate for the first time in humans that spironolactone improves BP control and reduces LVH in patients with resistant hypertension who are receiving optimal doses of thiazide diuretics. These results suggest that mineralocorticoid receptor blockade specifically benefits patients with resistant hypertension beyond conventional diuretic therapy