An alpha2C-adrenergic receptor polymorphism alters the norepinephrine-lowering effects and therapeutic response of the beta-blocker bucindolol in chronic heart failure.

Background: Adrenergic activation is an important determinant of outcomes in chronic heart failure. Adrenergic activity is regulated in part by prejunctional alpha(2C)-adrenergic receptors (ARs), which exhibit genetic variation in humans. Bucindolol is a novel beta-AR blocking agent that also lowers systemic norepinephrine and thus is also a sympatholytic agent.

Integrating smoking cessation into mental health care for post-traumatic stress disorder.

Background: Post-traumatic stress disorder (PTSD) is associated with a high prevalence of smoking, heavy cigarette consumption and low cessation rates.

Purpose: This manuscript describes the design of a randomized, multisite effectiveness trial to test whether integrating smoking cessation treatment into mental health care (integrated care) improves prolonged abstinence rates among veterans with PTSD, compared with referral to specialized smoking cessation clinics (usual standard of care). Secondary objectives are to assess the cost-effectiveness of integrated care relative to usual standard of care, identify treatment variables that mediate differences between conditions in outcome and determine whether smoking cessation is associated with worsening PTSD and/or depression.

A polymorphism within a conserved beta(1)-adrenergic receptor motif alters cardiac function and beta-blocker response in human heart failure.

Heterogeneity of heart failure (HF) phenotypes indicates contributions from underlying common polymorphisms. We considered polymorphisms in the beta(1)-adrenergic receptor (beta(1)AR), a beta-blocker target, as candidate pharmacogenomic loci. Transfected cells, genotyped human nonfailing and failing ventricles, and a clinical trial were used to ascertain phenotype and mechanism.

The role of a common adenosine monophosphate deaminase (AMPD)-1 polymorphism in outcomes of ischemic and nonischemic heart failure.

Background: A common variant of the adenosine monophosphate deaminase (AMPD)-1 gene (C34T) results in enzymatic inactivity and may increase adenosine in cardiac muscle and confer cardioprotection through ischemic preconditioning.

Methods And Results: We hypothesized that AMPD1 carriers with ischemic heart failure (HF) in the Beta-Blocker Evaluation of Survival Trial (BEST) might have a relative survival advantage. Patients (n = 1038, 20% black) with ischemic (58%) and nonischemic (42%) HF were followed for an average of 2.

Hormone replacement therapy is associated with improved survival in women with advanced heart failure.

Objectives: We sought to determine whether hormone replacement therapy (HRT) is associated with an improved prognosis in women with advanced heart failure (HF) and systolic dysfunction.

Background: There are about two million postmenopausal women in the U.S.