Cystatin C and Mortality Risk in the Elderly

Abstract

Kidney dysfunction is known to decrease life expectancy in the elderly. Cystatin C is a novel biomarker of kidney function that may have prognostic utility in older adults. The association of cystatin C with mortality was evaluated in a biracial cohort of black and white ambulatory elderly and compared with that of serum creatinine concentrations. The Health, Aging and Body Composition study is a cohort of well-functioning elderly that was designed to evaluate longitudinal changes in weight, body composition, and function. A total of 3075 participants who were aged 70 to 79 yr and had no disability were recruited at sites in Memphis, TN, and Pittsburgh, PA, between April 1997 and June 1998 with a follow-up of 6 yr. At entry, the mean cystatin C was 1.05 mg/L and the mean creatinine was 1.06 mg/dl. After 6 yr of follow-up, 557 participants had died. The mortality rates in each ascending cystatin C quintile were 1.7, 2.7, 2.9, 3.1, and 5.4%/yr. After adjustment for demographic risk factors, comorbid health conditions, and inflammatory biomarkers (C-reactive protein, IL-6. and TNF-␣), each quintile of cystatin C was significantly associated with increased mortality risk compared with the lowest: Hazard ratios (HR; 95% confidence intervals) quintile 1, ؊1.0 (referent); quintile 2, ؊1.74 (1.21 to 2.50); quintile 3, ؊1.51 (1.05 to 2.18); quintile 4, ؊1.49 Cystatin C is a strong, independent risk factor for mortality in the elderly. Future studies should investigate whether cystatin C has a role in clinical medicine.

Cystatin C: current position and future prospects

“…This association between inflammatory markers (CRP, interleukin-6 and tumour necrosis factor) and serum cystatin concentrations has been reported in most of the studies which showed a relationship between CysC and cardiovascular disease (218,224,229,233) or in populations at high renal or cardiac risk, such as diabetics (234). Except for the PRIME study (224), however, the association of CysC/cardiovascular event remains when inflammatory markers are included in the multivariate analysis (218,229). Interestingly, the association between inflammatory markers and CysC appeared to be linear in the ''Cardiovascular Health Study'' cohort, whereas it produces a U-shaped curve with creatinine (177).…”

Cystatin C Associates with Arterial Stiffness in Older Adults

“…Several studies have suggested that the prevalence of arterial stiffness may be higher in black than in white individuals, possibly because the severity of hypertension and diabetes is worse in black individuals. 25,26 Similarly, studies in both CKD and non-CKD have reported higher PWV in those with diabetes in comparison with those without diabetes. 27,28 Finally, one could hypothesize that prevalent CHD may modify the relationship between kidney function and aPWV.…”

“…Because the splines did suggest a possible nonlinear association of cystatin and PWV, especially in those with cystatin C Ն2.0 mg/L, we also modeled cystatin C as a categorical variable represented as low (Ͻ0.84 mg/L), medium (0.84 to 1.18 mg/L), and high (Ն1.19 mg/L) on the basis of our previous work. 25 In the case of eGFR Ͻ60 ml/min per 1.73 m 2 , the percentage increase in aPWV corresponds to a percentage change from the reference eGFR category of Ͼ60 ml/min per 1.73 m 2 . Because race, diabetes, and CHD could modify the relationship between cystatin C and aPWV, we evaluated interactions with these covariates and conducted stratified analyses within subgroups.…”

Combined Association of Creatinine, Albuminuria, and Cystatin C with All-Cause Mortality and Cardiovascular and Kidney Outcomes

“…Data suggest that eGFR by cystatin C (eGFR cystatin ) has a stronger association with mortality and cardiovascular disease than does eGFR creatinine (4)(5)(6)(7)(8)(9)(10)(11).…”