The Fixed-Dose Combination of Losartan/Hydrochlorothiazide Elicits Potent Blood Pressure Lowering During Nighttime in Obese Hypertensive Patients

BACKGROUND: Hypertension is one of the most powerful predictor of the future cardiovascular events, and antihypertensive therapy adopting multiple drug regimen is often needed to obtain the appropriate blood pressure (BP) control. To clarify the blood pressure-lowering effect of the fixed-dose combination (FDC) of an angiotensin receptor blocker (ARB) and diuretic agent in poorly controlled hypertensive patients, we intended a multicenter prospective observational study (Investigation for Normalized Blood pressure control with the Appropriate medication: INBA) by means of the sequential ambulatory blood pressure monitoring (ABPM). METHODS: One hundred and thirteen hypertensive patients who had not achieved the target BP control proposed in the guidelines with medication containing any ARB but without diuretic agents (54 men; mean age, 66 years old; mean office systolic/diastolic BP (SBP/DBP), 158/82 mmHg) were enrolled. Daytime and nighttime blood pressures were assessed with ABPM before and at 12 weeks after switching the ARB to the FDC of 50 mg of losartan, and 12.5 mg of hydrochlorothiazide (HCTZ). RESULTS: Daytime SBP/DBP (mean ± SD) decreased from 151 ± 14/88 ± 8 mmHg to 140 ± 11/82 ± 8 mmHg (P < 0.001, P < 0.001, respectively), and nocturnal SBP/DBP from 138 ± 18/78 ± 9 mmHg to 125 ± 14/72 ± 9 mmHg (P < 0.001, P < 0.001, respectively) during the 12 weeks treatment. Pulse rate did not change irrespective of the time window. Among various parameters (age, history of hypertension, body mass index (BMI), serum potassium, uric acid, estimated glomerular filtration rate, plasma B-type natriuretic peptide), BMI alone showed significant negative correlation with 12-weeks reduction in nocturnal SBP (r = -0.43, P < 0.05). No parameters correlated with reduction in daytime SBP during this period. Patients with BMI ≥ median (25.8 kg/m(2)) showed significantly greater reduction in nocturnal SBP for 12 weeks than patients with BMI < median (20.1 ± 15.6 mmHg vs 6.1 ± 10.9 mmHg, P < 0.001) although reduction in daytime SBP was comparable between the two groups (8.9 ± 13.5 mmHg vs 11.9 ± 12.7 mmHg). CONCLUSIONS: The administration of the FDC of losartan/HCTZ lowers BP both in day- and nighttime, and the nocturnal antihypertensive potency is remarkable in obese patients.