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Cardiovascular Health And Mitochondrial Function: Testing An Association

Marta Zampino, Richard G Spencer, Kenneth W Fishbein, Eleanor M Simonsick, Luigi Ferrucci

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Abstract Background Although mitochondrial dysfunction appears to be a contributing factor in the pathogenesis of cardiovascular and metabolic diseases, empirical data on this association are still lacking. This study evaluated whether mitochondrial oxidative capacity, as assessed by phosphorus magnetic resonance spectroscopy, was associated with cardiovascular risk, as estimated by the Framingham Risk Score (FRS), and with a clinical history of cardiovascular disease (CVD), in community-dwelling adults. Method A total of 616 subjects from the Baltimore Longitudinal Study of Aging (mean age 66 years) underwent a comprehensive clinical evaluation. Mitochondrial oxidative capacity in skeletal muscle was assessed as post-exercise phosphocreatine recovery time constant by phosphorus magnetic resonance spectroscopy. Multivariate regression models were employed to determine the cross-sectional association of mitochondrial oxidative capacity with FRS and history of CVD. Results Decreased mitochondrial oxidative capacity was strongly associated with higher FRS independent of age, body composition, and physical activity. Lower oxidative capacity was also associated with a history of positive of CVD and higher number of CVD events. Conclusions We speculate that the observed association could reflect the effect of an excessive production of oxidative species by dysfunctional mitochondria. Furthermore, decreased energy production could hamper the functionality of heart and vessels. In turn, a malfunctioning cardiovascular apparatus could fail to deliver the oxygen necessary for optimal mitochondrial energy production, therefore creating a vicious cycle. Longitudinal studies are necessary to ascertain the directionality of the association and the eventual presence of common pathogenetic roots. In conclusion, mitochondria could represent an important target for intervention in cardiovascular health.