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 24h 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. 24h 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.
Oterdoom
Leendert H
LH
Department of Internal Medicine, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Gansevoort
Ron T
RT
Schouten
Jan P
JP
de Jong
Paul E
PE
Gans
Reinold O B
RO
Bakker
Stephan J L
SJ
D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000652:urine; D002318:Cardiovascular Diseases / Q000209:etiology* / Q000401:mortality* / Q000473:pathology / Q000503:physiopathology / Q000652:urine; D003404:Creatinine / Q000652:urine*; D005260:Female; D006801:Humans; D015994:Incidence; D007333:Insulin Resistance; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D009135:Muscular Diseases / Q000150:complications* / Q000401:mortality* / Q000473:pathology / Q000503:physiopathology / Q000652:urine; D009426:Netherlands / Q000453:epidemiology; D009929:Organ Size; D016016:Proportional Hazards Models; D011446:Prospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors
D015415:Biomarkers; D003404:Creatinine