Predictors of blood pressure response to intensified and fixed combination treatment of hypertension: the ACCOMPLISH study.

BACKGROUND: Avoiding Cardiovascular events through COMbination therapy in Patients LIving with Systolic Hypertension (ACCOMPLISH) is an outcome study investigating aggressive antihypertensive combination treatment. It has achieved a larger fraction of overall patients with blood pressure (BP) <140/90 mmHg (73.3%) and diabetic patients <130/80 mmHg (43.3%) at 12 months of follow-up than any other large outcomes trial. We have analyzed baseline predictors of BPs and BP control at 12 months. METHODS: Blinded baseline and 12-month BP was available in 10,173 patients of whom 6132 had diabetes. Univariate and multivariate logistic regression models were used for BP control at 12 months; simple and multiple regression models were used for absolute BP value at 12 months. A stepwise procedure was used to select significant predictors in multivariate analyses. RESULTS: Mean (SD) BP fell from 145.5/80.2 mmHg (18.2/10.7 mmHg) at randomization to 132.7/74.7 mmHg (16/9.6 mmHg) at 12 months. The main baseline predictors of achieving BP control were region (USA), Caucasian race and taking lipid-lowering drugs. The predictors of uncontrolled BP were higher baseline systolic BP values, more previous antihypertensive medications, proteinuria and previous thiazide use. CONCLUSION: Patients in the USA, Caucasians and patients taking lipid-lowering therapy were most likely to reach BP targets with combination therapy. Strong predictors of uncontrolled hypertension were more severe hypertension, an established need for more antihypertensive drugs and target organ damage.

Lipopolysaccharide-induced pro-inflammatory cytokines in the brain of rats in the morphine-tolerant state.

Lipopolysaccharide (LPS) induces the production of inflammatory cytokines in the serum and brain; morphine has been shown to be immunosuppressive. However, we previously reported that serum levels of LPS-induced tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), and interleukin-6 (IL-6) are potentiated during morphine tolerance due to the HPA axis desensitization. In this study, we examined LPS-induced cytokine production in the brain of morphine-tolerant rats. The animals were implanted with two and four morphine (75 mg) pellets on days 1 and 2, respectively. On either day 4 or 5, 250 microg/kg LPS was administered (i.p.). Animals implanted with placebo and injected with saline were used as the control. The animals were sacrificed either 16 or 2 h post-injection, respectively, and TNF-alpha, IL-1beta, and IL-6 mRNA levels in the brain were determined by reverse transcriptase polymerase chain reaction. IL-1beta mRNA increased 2 h post-LPS treatment, whereas IL-6 decreased. At 16 h, TNF-alpha expression mRNA increased. These data suggest that the inflammatory response in the brain is heightened during morphine tolerance.