Atrial fibrillation is associated with lean body mass in postmenopausal women.

This study investigated the association between body composition and risk of atrial fibrillation (AF) in postmenopausal women. In a retrospective analysis we assessed data from 5704 postmenopausal women (age 70.7 ± 6.5 yrs.) who in 1999-2001 participated in The Prospective Epidemiological Risk Factor study with body composition assessed by dual-energy X-ray absorptiometry. Outcomes were obtained from Danish Health Registries and body composition association to risk of AF was evaluated by univariable and multivariable Cox Hazard regression. 850 women developed AF after baseline. High lean body mass was associated with increased risk of AF in multivariable analyses, adjusting for body mass index (BMI), height or weight (adjusted for: BMI, hazard ratio (HR) 1.49, 95% Confidence Interval (1.22-1.80); height, HR 1.27 (1.03-1.56); weight, 1.33 (1.06-1.65)). Height and weight were associated with increased risk of AF in multivariable analyses adjusting for body composition measures. When adjusting for total lean mass, only height remained statistically significant (HR 1.34 (1.09-1.64)). In a cohort of elderly Caucasian women, high lean body mass, height and weight were associated with increased risk of AF and the variables remained significant after adjusting for age and other known risk factors of AF.

The factor XIIa blocking antibody 3F7: a safe anticoagulant with anti-inflammatory activities.

The plasma protein factor XII (FXII) is the initiating protease of the procoagulant and proinflammatory contact system. FXII activates both the bradykinin (BK) producing kallikrein-kinin system and the intrinsic pathway of coagulation. Contact with negatively charged surfaces induces auto-activation of zymogen FXII that results in activated FXII (FXIIa). Various in vivo activators of FXII have been identified including heparin, misfolded protein aggregates, nucleic acids and polyphosphate. Murine models have established a central role of FXII in arterial and venous thromboembolic diseases. Despite the central function of FXII in pathologic thrombosis, its deficiency does not impair hemostasis in animals or humans. The selective role of FXIIa in thrombosis, but not hemostasis, offers an exciting novel strategy for safe anticoagulation based on interference with FXIIa. We have generated the recombinant fully human FXIIa-blocking antibody 3F7, which abolished FXIIa enzymatic activity and prevented thrombosis in a cardiopulmonary bypass system in large animals, in the absence of increased therapy-associated bleeding. Furthermore, 3F7 also interfered with BK-driven edema in the severe swelling disorder hereditary angioedema (HAE) type III. Taken together, targeting FXIIa with 3F7 appears to be a promising approach to treat edema disorders and thrombosis.