Cystatin C and the Risk of Frailty and Mortality in Older Men.
BACKGROUND
This study examines the association between cystatin C (cysC) levels and risks of progression of frailty status or death in older men.


METHODS
Prospective study of 2,613 men without overt frailty aged 67 years and older enrolled in the MrOS ancillary sleep study. Baseline measurements included serum cysC, serum creatinine, and frailty status. Repeat frailty status, performed an average of 3.4 years later, was assessed as an ordinal outcome of robust, intermediate stage (prefrail), frail or dead.


RESULTS
Mean age was 75.7 years. Men with higher cysC were older and had a higher comorbidity burden. After adjusting for age, clinical site, and race, higher cysC was associated with nearly twofold greater odds of being classified as intermediate stage versus robust (OR quartile 4 vs 1; 1.82, 95% confidence interval [CI] 1.35-2.45), a threefold greater odds of frailty versus robust (OR quartile 4 vs 1; 3.13, 95% CI 2.03-4.82), and a more than fivefold greater odds of death versus robust (OR quartile 4 vs 1; 5.48, 95% CI 2.98-10.08). Results were similar for cysC-based estimated glomerular filtration rate (eGFR). This relationship was attenuated but persisted after adjusting for additional potential confounders including baseline frailty status, body mass index, smoking status, comorbidity burden, self-reported disability, and serum albumin. In contrast, neither serum creatinine nor creatinine-based eGFR was associated in a graded manner with higher risks of development of frailty or death.


CONCLUSIONS
In this cohort of older men without overt frailty, higher cysC and cysC-based eGFR, but not creatinine or creatinine-based estimates of GFR, were associated with increased risks of frailty or death. These findings suggest that higher cysC level may be a promising biomarker for unsuccessful aging as manifested by increased risks of frailty and death.
Division of Nephrology, Hennepin County Medical Center, Minneapolis, Minnesota.|Department of Medicine, University of Minnesota, Minneapolis.
Allyson
A
Hart
Research Institute, California Pacific Medical Center, San Francisco.
Terri L
TL
Blackwell
NORC at the University of Chicago, Health Care Department, Bethesda, Maryland.|Division of Epidemiology and Community Health, University of Minnesota, Minneapolis.
Misti L
ML
Paudel
Division of Epidemiology and Community Health, University of Minnesota, Minneapolis.|Center for Chronic Disease Outcomes Research, VA Health Care System, Minneapolis, Minnesota.
Brent C
BC
Taylor
Bone and Mineral Unit, Oregon Health and Science University, Portland.
Eric S
ES
Orwoll
Research Institute, California Pacific Medical Center, San Francisco.
Peggy M
PM
Cawthon
Department of Medicine, University of Minnesota, Minneapolis.|Division of Epidemiology and Community Health, University of Minnesota, Minneapolis.|Center for Chronic Disease Outcomes Research, VA Health Care System, Minneapolis, Minnesota.
Kristine E
KE
Ensrud
D000368:Aged; D000375:Aging / Q000502:physiology*; D015415:Biomarkers / Q000097:blood; D015992:Body Mass Index; D055316:Cystatin C / Q000097:blood*; D016330:Frail Elderly / Q000706:statistics & numerical data*; D015577:Geriatric Assessment / Q000379:methods; D054624:Health Status Disparities; D006801:Humans; D008297:Male; D009026:Mortality; D000071069:Multiple Chronic Conditions / Q000453:epidemiology*; D012307:Risk Factors; D012907:Smoking / Q000453:epidemiology; D014481:United States / Q000453:epidemiology
D015415:Biomarkers; D055316:Cystatin C
Creatinine; Cystatin C; Frailty; Men; Mortality