Benefit of losartan/hydrochlorothiazide-fixed dose combination treatment for isolated morning hypertension: The MAPPY study.

Morning hypertension is an established risk factor for cardiovascular events. In the Morning Hypertension and Angiotensin Receptor Blocker/Hydrochlorothiazide Combination Therapy (MAPPY) study, a 50-mg losartan/12.5-mg hydrochlorothiazide combination (Los/HCTZ) lowered morning blood pressure (BP) more effectively than 100-mg losartan (High-Los) in treated hypertensive patients with morning hypertension. The aim of this MAPPY study sub-analysis was to determine whether Los/HCTZ was effective for controlling isolated morning hypertension (morning BP ≥ 135/85 mmHg and evening BP < 135/85 mmHg), sustained hypertension (morning and evening BP ≥ 135/85 mmHg), or both. Of the 110 patients studied, 25 (22.7%) had isolated morning hypertension, and 85 (77.3%) had sustained hypertension at baseline. After 3-month treatment, isolated morning hypertension developed into controlled hypertension (morning and evening BP < 135/85 mmHg) in 9 of 11 Los/HCTZ patients (81.8%) and 3 of 14 High-Los patients (21.4%) (p = 0.003, chi-square test). Sustained hypertension developed into controlled hypertension in 21 of 44 Los/HCTZ patients (47.7%) and 13 of 41 High-Los patients (31.7%)(NS). The rates of achievement of SBP < 135 mmHg both in the morning and evening were: 81.8% and 21.4% in Los/HCTZ- and High-Los-treated isolated morning hypertension (p = 0.003), respectively; and 61.4% and 36.6% in Los/HCTX- and High-Los-treated sustained hypertension (p = 0.022), respectively. In conclusion, Los/HCTZ was effective for controlling both types of morning hypertension, especially isolated morning hypertension. Los/HCTZ was superior to High-Los in treating both types of morning hypertension.

Reduction in morning blood pressure is a key factor for ameliorating urinary albumin excretion in patients with morning hypertension irrespective of treatment regimen.

BACKGROUND: The Morning Hypertension and Angiotensin Receptor Blocker/Hydrochlorothiazide Combination Therapy (MAPPY) study has shown that losartan/hydrochlorothiazide (HCTZ) combination is superior to high-dose losartan in not only reducing morning systolic blood pressure (SBP) but also ameliorating urinary albumin excretion (UAE) after 3-month treatment. The purpose of the present study was to investigate factors associated with UAE reduction in on-treatment patients with morning hypertension. METHODS AND RESULTS: A total of 95 patients registered in the MAPPY study were analyzed. Patients were treated with either a losartan/HCTZ combination regimen (n=47) or a high-dose losartan regimen (n=48). Three-month treatment significantly reduced morning SBP, evening SBP, and clinic SBP (P<0.001, P<0.05, and P<0.01, respectively). UAE and serum uric acid were significantly decreased (P<0.01 for both) without the change in estimated glomerular filtration rate. Multiple linear regression analysis indicated that %morning SBP reduction and baseline UAE were independent determinants of the UAE reduction (P=0.001 for both). After adjustments for the reduction in morning-evening SBP difference, baseline UAE, and %uric acid reduction, estimated %UAE reduction level was positively correlated with the tertiles of the increasing %morning SBP reduction level (P=0.031 for trend). Moreover, subgroup analysis showed that morning SBP reduction was an independent determinant of UAE reduction in both treatment regimens. CONCLUSIONS: Reduction in morning SBP was a key factor in UAE reduction in patients with morning hypertension, irrespective of treatment regimen.

Losartan/hydrochlorothiazide combination vs. high-dose losartan in patients with morning hypertension--a prospective, randomized, open-labeled, parallel-group, multicenter trial.

The treatment of morning hypertension has not been established. We compared the efficacy and safety of a losartan/hydrochlorothiazide (HCTZ) combination and high-dose losartan in patients with morning hypertension. A prospective, randomized, open-labeled, parallel-group, multicenter trial enrolled 216 treated outpatients with morning hypertension evaluated by home blood pressure (BP) self-measurement. Patients were randomly assigned to receive a combination therapy of 50 mg losartan and 12.5 mg HCTZ (n=109) or a high-dose therapy with 100 mg losartan (n=107), each of which were administered once every morning. Primary efficacy end points were morning systolic BP (SBP) level and target BP achievement rate after 3 months of treatment. At baseline, BP levels were similar between the two therapy groups. Morning SBP was reduced from 150.3±10.1 to 131.5±11.5 mm Hg by combination therapy (P<0.001) and from 151.0±9.3 to 142.5±13.6 mm Hg by high-dose therapy (P<0.001). The morning SBP reduction was greater in the combination therapy group than in the high-dose therapy group (P<0.001). Combination therapy decreased evening SBP from 141.6±13.3 to 125.3±13.1 mm Hg (P<0.001), and high-dose therapy decreased evening SBP from 138.9±9.9 to 131.4±13.2 mm Hg (P<0.01). Although both therapies improved target BP achievement rates in the morning and evening (P<0.001 for both), combination therapy increased the achievement rates more than high-dose therapy (P<0.001 and P<0.05, respectively). In clinic measurements, combination therapy was superior to high-dose therapy in reducing SBP and improving the achievement rate (P<0.001 and P<0.01, respectively). Combination therapy decreased urine albumin excretion (P<0.05) whereas high-dose therapy reduced serum uric acid. Both therapies indicated strong adherence and few adverse effects (P<0.001). In conclusion, losartan/HCTZ combination therapy was more effective for controlling morning hypertension and reducing urine albumin than high-dose losartan.

Comparison of gene expression profiling in pressure and volume overload-induced myocardial hypertrophies in rats.

Gene expression profiling has been conducted in rat hearts subjected to pressure overload (PO). However, pressure and volume overload produce morphologically and functionally distinct forms of cardiac hypertrophy. Surprisingly, gene expression profiling has not been reported for in an animal model of volume overload (VO). We therefore compared the gene expression profiles in the hypertrophied myocardium of rats subjected to PO and VO using DNA chip technology (Affymetrix U34A). Constriction of the abdominal aorta and abdominal aortocaval shunting were used to induce PO and VO, respectively. The gene expression profiles of the left ventricle (LV) 4 weeks after the procedure were analyzed by DNA chips. There were comparable increases in the left ventricular weight/body weight ratio in rats subjected to PO and VO. Echocardiography revealed concentric hypertrophy in the PO animals, but eccentric hypertrophy in the rats subjected to VO. The expressions of many genes were altered in VO, PO, or both. Among the genes that were upregulated in both forms of hypertrophy, greatly increased expressions of B-type natriuretic peptide, lysyl oxidase-like protein 1 and metallothionein-1 (MT) were confirmed by real-time reverse transcription-polymerase chain reaction (RT-PCR). Because free radicals are increased in the hypertrophied heart and may contribute to apoptosis, we examined the role of MT, a free radical scavenger, in apoptosis. The over-expression of MT in H9c2 cells inhibited norepinephrine-induced apoptosis, suggesting that MT may act as an anti-apoptotic molecule in cardiac hypertrophy. In conclusion, we found that many genes were regulated in VO, PO, or both. In addition, a novel role of MT in the hypertrophied myocardium was suggested.

Pheochromocytoma presenting as recurrent hypotension and syncope.

We report a case with pheochromocytoma presenting as recurrent syncope due to hypotension. A 71-year-old man was admitted because of recurrent syncope and paroxysmal hypotension. He was diagnosed as having pheochromocytoma. In spite of a large volume of infusion and insulin therapy, syncope and paroxysmal hypotension continued. We speculated that hypotension was mainly due to vasodilatation caused by excess plasma epinephrine and prescribed a non-selective beta-adrenergic blocker. It stabilized blood pressure and syncope disappeared. The right adrenal tumor was excised and he was discharged in good condition. This case report provides some implications for the management of pheochromocytoma complicated with hypotension.