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BackgroundAtrial fibrillation is associated with higher mortality. Identification of causes of death and contemporary risk factors for all‐cause mortality may guide interventions.Methods and ResultsIn the Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF) study, patients with nonvalvular atrial fibrillation were randomized to rivaroxaban or dose‐adjusted warfarin. Cox proportional hazards regression with backward elimination identified factors at randomization that were independently associated with all‐cause mortality in the 14 171 participants in the intention‐to‐treat population. The median age was 73 years, and the mean CHADS 2 score was 3.5. Over 1.9 years of median follow‐up, 1214 (8.6%) patients died. Kaplan–Meier mortality rates were 4.2% at 1 year and 8.9% at 2 years. The majority of classified deaths (1081) were cardiovascular (72%), whereas only 6% were nonhemorrhagic stroke or systemic embolism. No significant difference in all‐cause mortality was observed between the rivaroxaban and warfarin arms (P=0.15). Heart failure (hazard ratio 1.51, 95% CI 1.33–1.70, P<0.0001) and age ≥75 years (hazard ratio 1.69, 95% CI 1.51–1.90, P<0.0001) were associated with higher all‐cause mortality. Multiple additional characteristics were independently associated with higher mortality, with decreasing creatinine clearance, chronic obstructive pulmonary disease, male sex, peripheral vascular disease, and diabetes being among the most strongly associated (model C‐index 0.677).ConclusionsIn a large population of patients anticoagulated for nonvalvular atrial fibrillation, ≈7 in 10 deaths were cardiovascular, whereas <1 in 10 deaths were caused by nonhemorrhagic stroke or systemic embolism. Optimal prevention and treatment of heart failure, renal impairment, chronic obstructive pulmonary disease, and diabetes may improve survival.Clinical Trial Registration URL: https://www.clinicaltrials.gov/. Unique identifier: NCT00403767.

Forty postmenopausal women with a former Colles' fracture were enrolled in a 1-year study to determine the dose-effect relationship of nasal salmon calcitonin (SCT) on bone mass. They were randomized to receive either placebo, 50, 100, or 200 IU per day of SCT given as a nasal spray. The rate of change in the bone mineral content of the lumbar spine was 0.7, 0.2, 1.1, and 2.0 gHA per year, respectively, and the rate of change in the bone mineral content in the forearm was -0.4, -0.1, 0.0, and -0.1 AU per year, respectively. The rate of change in the bone mineral content of the lumbar spine in patients receiving 200 IU of SCT per day differed significantly from zero (P less than 0.01). Except for one patient, who experienced intolerable nausea, no systemic side effects were observed. Seven patients withdrew, two patients from nasal intolerance to the spray. These preliminary data suggest that SCT given by the nasal route has a positive and dose-dependent effect on spinal bone mass, but affects forearm bone mass only minimally.

In order to evaluate the potential relationship between atrial pressure development and release of atrial natriuretic factor (ANF), 33 patients with congestive heart failure were investigated with rightsided heart catheterization during supine graded bicycle exercise. Resting plasma ANF levels were higher in patients with heart failure as compared with normal controls, 75.1 \ m=+-\45.6 pmol/l vs 12.3 \m=+-\6.2 pmol/l (mean \ m=+-\ SD, N = 33 and N = 42, respectively) and correlated with right atrial, pulmonary arterial and pulmonary capillary wedge pressures. During exercise, central pressures rose steeply with a simultaneous increase in plasma ANF in all patients. Plasma ANF levels correlated with heart rate at a workload of 25 w, to pulmonary arterial and pulmonary capillary wedge pressure at 50 w, and to pulmonary capillary wedge pressure at 75 w. The increments in ANF levels between the different workloads during exercise did not correlate with the corresponding increments in pressure values. In congestive heart failure, the capability of ANF secretion in consequence to pressure stimuli is preserved, and left atrial pressure seems to be the major stimulus for ANF release during exercise.

Increased plasma levels of atrial natriuretic peptide (ANP) during exercise have been reported. To investigate the role of tachycardia as a stimulus for release of ANP during exercise the following study was undertaken. Graded exercise was performed in six healthy volunteers before and after beta 1-adrenoceptor blockade. Plasma levels of ANP were determined at different workloads in both cases. At rest and at all workloads during exercise plasma levels of ANP were higher after beta 1-adrenoceptor blockade than without. Therefore, it is unlikely that tachycardia is a major stimulus for secretion of ANP during exercise. It is suggested that increased right atrial pressure and/or pulmonary arterial blood pressure and increased plasma levels of catecholamines are important secretory stimuli for ANP during exercise.