Antihypertensive treatment in patients with class 3 obesity.

BACKGROUND: Even though patients with class 3 obesity (body mass index ≥ 40 kg/m(2)) are prone to arterial hypertension and respond less to antihypertensive drugs, they are not considered in hypertension treatment guidelines and data from prospective clinical trials are lacking. METHODS: In a post hoc analysis of a clinical trial, we compared patients with class 3 obesity with patients with class 1/2 obesity. RESULTS AND CONCLUSIONS: Blood pressure control in class 3 obesity was less likely to be achieved with hydrochlorothiazide monotherapy. While addition of amlodipine, irbesartan, or aliskiren to hydrochlorothiazide improved the blood pressure response, amlodipine was less effective and induced peripheral edema in 19% of patients with class 3 obesity.

Effects of valsartan alone versus valsartan/simvastatin combination on ambulatory blood pressure, C-reactive protein, lipoproteins, and monocyte chemoattractant protein-1 in patients with hyperlipidemia and hypertension.

Angiotensin receptor blockers have been hypothesized to have synergistic effects with statins. We evaluated the effects of valsartan alone or combined with simvastatin on blood pressure (BP) and indexes of inflammation and oxidant stress in hypertensive patients with hyperlipidemia. In this double-blind trial, 404 patients were randomized to 12 weeks valsartan 160 mg (V) or valsartan 160 mg plus simvastatin 20 mg (V/S20) or 80 mg (V/S80). Twenty-four-hour mean ambulatory BP and biochemical marker measurements were recorded at baseline and study end. There were no statistically significant between-treatment differences for least-square mean reductions from baseline in systolic BP (V, -9.22; V/S20, -9.25; V/S80, -9.58 mm Hg; p <0.0001 for all within-treatment changes vs baseline). Plasma high-sensitivity C-reactive protein decreased with the combinations but not with V alone (least-square mean median change from baseline, -0.16, -0.20, -0.70 mg/L; p = 0.0001 for V/S80 vs baseline; p = 0.045 for V/S20 vs baseline; p = 0.0023 for V/S80 vs V/S20; p = 0.0045 for V/S80 vs V). Monocyte chemoattractant protein-1 was reduced by V, with no evidence for additional lowering with V/S combinations. In conclusion, addition of simvastatin to valsartan did not incrementally lower BP. However, V/S80 was superior to V and V/S20 in reducing high-sensitivity C-reactive protein.

Comparison of treatment benefit and outcome in women versus men with chronic heart failure (from the Valsartan Heart Failure Trial).

The comparison of treatment effect and co-morbidity between the genders in the Valsartan Heart Failure Trial showed equal benefit of treatment in men and women. Co-morbidities, such as diabetes and coronary artery disease, increased nonfatal cardiac morbidity more in women than in men.

Oral everolimus inhibits in-stent neointimal growth.

BACKGROUND: Rapamycin (sirolimus)-eluting stents are associated with reduced restenosis rates in animal studies and initial human trials. The present study evaluated whether orally administered everolimus (a macrolide of the same family as sirolimus) inhibits in-stent neointimal growth in rabbit iliac arteries. METHODS AND RESULTS: New Zealand white rabbits were randomized to everolimus 1.5 mg/kg per day starting 3 days before stenting and reduced to 1 mg/kg per day from days 14 to 28 (group 1), everolimus 1.5 mg/kg given 1 day before stenting followed by 0.75 mg/kg per day for 28 days (group 2), or matching placebo for each group. Drugs were administered by oral gavage. Stents were deployed in both iliac arteries, and arteries were harvested 28 days after stenting. Group 1 everolimus-treated rabbits experienced weight loss and anorexia, which resolved after the everolimus dose was lowered on day 14. Group 2 animals were healthy for the duration of everolimus dosing. Both everolimus treatment groups significantly reduced in-stent neointimal growth (46% reduction and 42% reduction in intimal thickness in groups 1 and 2, respectively). In group 2 everolimus-treated animals, the neointima was healed or healing, characterized by stent struts covered by a thin neointima, overlying endothelial cells, and only small foci of fibrin. Scanning electron microscopy showed >80% stent surface endothelialization in group 2 everolimus-treated rabbits. CONCLUSIONS: Oral everolimus suppresses in-stent neointimal growth in the rabbit iliac artery. At a dose of 1.5 mg/kg given 1 day before stenting followed by 0.75 mg/kg per day for 28 days, everolimus was well tolerated and was associated with significant neointimal healing.