Urinary creatinine excretion, an indirect measure of muscle mass, is an independent predictor of cardiovascular disease and mortality in the general population

Objective: Low muscle mass often indicates poor health, but the relation with cardiovascular disease (CVD) is unknown. Skeletal muscles are responsible for approximately 75% of insulin stimulated whole body glucose disposal and therefore insulin resistance could underlie the relation between muscle mass and CVD. We aimed to determine whether muscle mass, as reflected by 24 h urinary creatinine excretion, is associated with CVD and whether this depends on insulin resistance. Methods: The study was performed in the prospective, community-based, observational cohort of the PREVEND study in Groningen, the Netherlands. 24 h creatinine excretion was assessed in 4044 women and 4048 men. Outcome events were incidence of major adverse cardiovascular events (MACE) and all-cause mortality, with a follow-up of 7.5 [7.3-7.9] years. Insulin resistance was estimated using fasting insulin and HOMA. Results: In women every doubling of creatinine excretion was associated with an approximate 60% decrease in risk for MACE (hazard ratio (HR) 0.41 [95% CI 0.26-0.64], P < 0.001) and 50% decrease in risk for all-cause mortality (HR: 0.52 [0.31-0.90], P=0.02) independent of age, smoking, CVD history, race, fasting insulin concentrations and components of the metabolic syndrome. In men every doubling of creatinine excretion was borderline associated with an approximately 25% decrease in risk for MACE (HR: 0.74 [0.53-1.03], P=0.07) and independently associated with a 55% decreased risk for all-cause mortality (HR: 0.45 [0.32-0.62], P < 0.001). Conclusions: Low creatinine excretion, as indirect measure of low muscle mass, is associated with MACE and all-cause mortality in the general population, independent of insulin resistance. Perhaps protein-calorie malnutrition or physical activity could underlie the association between muscle mass and CVD. (C) 2009 Elsevier Ireland Ltd. All rights reserved.