SEQUENTIAL NEPHRON BLOCKADE WITH DIURETICS IMPROVES DIASTOLIC DYSFUNCTION IN PATIENTS WITH RESISTANT HYPERTENSION

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Abstract

Objective: Hypertension is one of the major contributors to cardiac diastolic dysfunction as observed in patients with heart failure and preserved ejection fraction. Different therapeutics strategies were proposed to control blood pressure (BP) but their independent impact on cardiac function remain undetermined. In patients referred to our center for uncontrolled hypertension, we compared changes in cardiac parameters between two strategies consisting of sequential nephron blockade with intensive diuretics (NBD) or sequential renin angiotensin blockade (RAB). We aimed to determine evolution of BNP levels and echocardiographic (TTE) parameters of diastolic dysfunction according to strategies to control BP. Design and method: After 4-weeks treatment with 300 mg irbesartan + 12.5 mg hydrochlorothiazide + 5 mg amlodipine, 140 patients with uncontrolled hypertension were randomized to either complete nephron blockade with sequential introduction of 25 mg spironolactone, 20 to 40 mg furosemide and 5 mg amiloride (NBD group, n = 74) or complete RAAS blockade with 5 to 10 mg ramipril and 5 to 10 mg bisoprolol (RAB group, n = 67). BNP levels and TTE parameters were assessed at baseline and week 12. Results: BNP levels were not significantly different in the two groups at baseline (mean ± SD 30.1 ± 37.0pg/mL in NBD versus 22.6 ± 22.3pg/mL in RAB, p = 0.147) but significantly decreased in NBD at week 12 (20.1 ± 22.7pg/mL in NBD versus 55.2 ± 60.4pg/mL in RAB, p 35 pg/mL versus 37 (55%) in RAB (p 1 criteria of diastolic dysfunction in NBD and RAB group respectively were 31.2% and 19.3% at baseline vs. 3.1% and 32.2% after 12 weeks (p = 0.001). In a multivariate analysis, NBD treatment was significantly associated with a decline in BNP levels (p < 0.01) even after adjustment on daytime systolic BP lowering, heart rate, renal function, age and gender. Conclusions: In patients with uncontrolled hypertension, intensive nephron blockade with sequential addition of diuretics improves markers of diastolic dysfunction independently of BP lowering.

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