04065nas a2200433 4500008004100000022001400041245011900055210006900174260001600243300001100259490000800270520281000278653000903088653001503097653002803112653001503140653001503155653001403170653003103184653001103215653001103226653002503237653001403262653003203276653003303308653001703341100002403358700001603382700002003398700002003418700002003438700002903458700002403487700002203511700001703533700002203550700002403572856003503596 2006 eng d a1539-370400aCystatin C and prognosis for cardiovascular and kidney outcomes in elderly persons without chronic kidney disease.0 aCystatin C and prognosis for cardiovascular and kidney outcomes  c2006 Aug 15 a237-460 v1453 a

BACKGROUND: Cystatin C is an alternative measure of kidney function that may have prognostic importance among elderly persons who do not meet standard criteria for chronic kidney disease (estimated glomerular filtration rate [GFR] > or =60 mL/min per 1.73 m2).

OBJECTIVE: To evaluate cystatin C as a prognostic biomarker for death, cardiovascular disease, and incident chronic kidney disease among elderly persons without chronic kidney disease.

DESIGN: Cohort study.

SETTING: The Cardiovascular Health Study, a population-based cohort recruited from 4 communities in the United States.

PARTICIPANTS: 4663 elderly persons.

MEASUREMENTS: Measures of kidney function were creatinine-based estimated GFR by using the Modification of Diet in Renal Disease equation and cystatin C concentration. Outcomes were death, cardiovascular death, noncardiovascular death, heart failure, stroke, myocardial infarction, and incident chronic kidney disease during follow-up (median, 9.3 years).

RESULTS: At baseline, 78% of participants did not have chronic kidney disease (estimated GFR > or =60 mL/min per 1.73 m2) and mean cystatin C concentration, creatinine concentration, and estimated GFR were 1.0 mg/L, 79.6 micromol/L (0.9 mg/dL), and 83 mL/min per 1.73 m2, respectively. Cystatin C concentrations (per SD, 0.18 mg/L) had strong associations with death (hazard ratio, 1.33 [95% CI, 1.25 to 1.40]), cardiovascular death (hazard ratio, 1.42 [CI, 1.30 to 1.54]), noncardiovascular death (hazard ratio, 1.26 [CI, 1.17 to 1.36]), incident heart failure (hazard ratio, 1.28 [CI, 1.17 to 1.40]), stroke (hazard ratio, 1.22 [CI, 1.08 to 1.38]), and myocardial infarction (hazard ratio, 1.20 [CI, 1.06 to 1.36]) among these participants. Serum creatinine concentrations had much weaker associations with each outcome and only predicted cardiovascular death. Participants without chronic kidney disease who had elevated cystatin C concentrations (> or =1.0 mg/L) had a 4-fold risk for progressing to chronic kidney disease after 4 years of follow-up compared with those with cystatin C concentrations less than 1.0 mg/L.

LIMITATIONS: Because this study did not directly measure GFR or albuminuria, the extent to which cystatin C may be influenced by nonrenal factors was not determined and participants with albuminuria might have been misclassified as having no kidney disease.

CONCLUSIONS: Among elderly persons without chronic kidney disease, cystatin C is a prognostic biomarker of risk for death, cardiovascular disease, and chronic kidney disease. In this setting, cystatin C seems to identify a "preclinical" state of kidney dysfunction that is not detected with serum creatinine or estimated GFR.

10aAged10aBiomarkers10aCardiovascular Diseases10aCreatinine10aCystatin C10aCystatins10aGlomerular Filtration Rate10aHumans10aKidney10aLongitudinal Studies10aPrognosis10aProportional Hazards Models10aRenal Insufficiency, Chronic10aRisk Factors1 aShlipak, Michael, G1 aKatz, Ronit1 aSarnak, Mark, J1 aFried, Linda, F1 aNewman, Anne, B1 aStehman-Breen, Catherine1 aSeliger, Stephen, L1 aKestenbaum, Brian1 aPsaty, Bruce1 aTracy, Russell, P1 aSiscovick, David, S uhttps://chs-nhlbi.org/node/91202997nas a2200409 4500008004100000022001400041245003400055210003300089260001600122300001100138490000800149520198900157653000902146653001002155653001502165653001502180653001502195653001402210653001102224653002202235653003102257653001102288653001102299653000902310100002002319700001602339700002002355700002102375700002202396700002102418700001702439700001902456700002002475700002402495710003202519856003602551 2008 eng d a0003-992600aCystatin C and aging success.0 aCystatin C and aging success c2008 Jan 28 a147-530 v1683 a

BACKGROUND: To our knowledge, the effect of kidney function on successful aging has not been examined.

METHODS: We evaluated the relationship between cystatin C and aging success during a 6-year follow-up in the Cardiovascular Health Study, a community-based cohort of older adults (aged >or= 65 years). Successful aging was defined as remaining free of cardiovascular disease, cancer, and chronic obstructive pulmonary disease and having intact physical and cognitive functioning. In adjusted analysis, an accelerated failure time model was used to evaluate the percentage reduction in successful years by level of cystatin C. A separate Cox proportional hazards model evaluated whether cystatin C was related to incident physical and cognitive disability.

RESULTS: A total of 2140 participants had cystatin C measured and were free of the previously mentioned conditions at baseline. Their mean age was 74 years. The mean cystatin C level, creatinine level, and estimated glomerular filtration rate were 1.06 mg/L, 0.93 mg/dL, and 78 mL/min/1.73 m(2), respectively (to convert cystatin C to nanomoles per liter, multiply by 75; and to convert creatinine to micromoles per liter, multiply by 88.4). A total of 873 participants reached a first event in follow-up, 138 because of cognitive disability, 238 because of physical disability, 34 because of chronic obstructive pulmonary disease, 146 because of cancer, and 317 because of cardiovascular disease. The adjusted percentage reduction in successful life years in the highest vs the lowest quartile of cystatin C was 27% (95% confidence interval, 11%-39%). The highest vs lowest quartile of cystatin C also was independently associated with incident cognitive or physical disability (hazard ratio, 1.39; 95% confidence interval, 1.00-1.98).

CONCLUSION: A higher cystatin C level, even within a range of relatively normal kidney function, was associated with unsuccessful aging.

10aAged10aAging10aBiomarkers10aCreatinine10aCystatin C10aCystatins10aFemale10aFollow-Up Studies10aGlomerular Filtration Rate10aHumans10aKidney10aMale1 aSarnak, Mark, J1 aKatz, Ronit1 aFried, Linda, F1 aSiscovick, David1 aKestenbaum, Brian1 aSeliger, Stephen1 aRifkin, Dena1 aTracy, Russell1 aNewman, Anne, B1 aShlipak, Michael, G1 aCardiovascular Health Study uhttps://chs-nhlbi.org/node/1013