No abstract

Aims Physical activity has been shown to reduce mortality in a dose-response fashion. Current guidelines recommend 500–1000 metabolic equivalent task (MET)-min per week of regular physical activity. This study aimed to compare the impact of leisure-time physical activity on mortality in primary versus secondary cardiovascular prevention. Methods and results This study included a total of 131 558 and 310 240 subjects with and without cardiovascular disease (CVD), respectively, from a population-based cohort. Leisure-time physical activity was measured by self-report questionnaires. The study subjects were followed-up for a median of 5.9 years, and the main study outcome was all-cause mortality. There was an inverse relationship between the physical activity level and the mortality risk in both groups. The benefit in the secondary prevention group was shown to be greater than that in the primary prevention group: every 500 MET-min/week increase in physical activity resulted in a 14% and 7% risk reduction in mortality in the secondary and primary prevention groups, respectively (interaction P < 0.001). In addition, while individuals without CVD benefited the most between 1 and 500 MET-min/week of physical activity, the benefit in those with CVD continued above 500 − 1000 MET-min/week. The adjusted mortality risk of individuals with CVD who performed a high level of physical activity (≥1000 MET-min/week) was shown to be comparable to or lower than that of their counterparts without CVD. Conclusion Individuals with CVD may benefit from physical activity to a greater extent than do healthy subjects without CVD.

The coxsackievirus and adenovirus receptor (CAR) is a transmembrane protein that belongs to the family of adhesion molecules. In the postnatal heart, it is localized predominantly at the intercalated disc, where its function is not known. Here, we demonstrate that a first degree or complete block of atrioventricular (AV) conduction developed in the absence of CAR in the adult mouse heart and that prolongation of AV conduction occurred in the embryonic heart of the global CAR-KO mouse. In the cardiac-specific CAR-KO (CAR-cKO) mouse, we observed the loss of connexin 45 localization to the cell-cell junctions of the AV node but preservation of connexin 40 and 43 in contracting myocardial cells and connexin 30.2 in the AV node. There was also a marked decrease in β-catenin and zonula occludens-1 (ZO-1) localization to the intercalated discs of CAR-cKO mouse hearts at 8 weeks before the mice developed cardiomyopathy at 21 weeks of age. We also found that CAR formed a complex with connexin 45 via its PSD-95/DigA/ZO-1-binding (PDZ-binding) motifs. We conclude that CAR expression is required for normal AV-node conduction and cardiac function. Furthermore, localization of connexin 45 at the AV-node cell-cell junction and of β-catenin and ZO-1 at the ventricular intercalated disc are dependent on CAR.