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Cystatin C concentration as a risk factor for heart failure in older adults
Mark J Sarnak1, Ronit Katz, Catherine O Stehman-Breen
1Tufts-New England Medical Center, Boston, Massachusetts, USA.
Insights
Serum cystatin C levels predict heart failure risk in older adults more accurately than creatinine. This novel marker offers improved risk assessment for incident heart failure, highlighting kidney function
Area of Science:
- Cardiology
- Nephrology
- Biomarkers
Background:
- Previous studies on kidney function and heart failure risk were limited by the insensitivity of serum creatinine.
- Serum creatinine may not adequately detect kidney dysfunction relevant to cardiovascular outcomes.
Purpose of the Study:
- To compare serum cystatin C and creatinine as predictors of incident heart failure.
- To evaluate cystatin C as a novel marker for kidney function in heart failure risk assessment.
Main Methods:
- Observational study using frozen sera from the Cardiovascular Health Study (1992-1993).
- Included 4384 older adults (≥65 years) without prior heart failure, measuring serum cystatin C and creatinine.
- Follow-up every 6 months for incident heart failure over a median of 8.3 years.
Main Results:
- Sequential quintiles of cystatin C concentration showed a stepwise increased risk for heart failure after adjustment (HRs up to 2.16).
- Serum creatinine concentration quintiles were not associated with incident heart failure risk in adjusted analyses (HRs up to 1.14).
- Cystatin C demonstrated a significant association with heart failure risk, unlike creatinine.
Conclusions:
- Serum cystatin C concentration is an independent risk factor for heart failure in older adults.
- Cystatin C appears to provide a better measure of heart failure risk assessment than serum creatinine.
- The precise mechanism linking cystatin C to heart failure risk requires further investigation.
Background:
Previous studies that evaluated the association of kidney function with incident heart failure may be limited by the insensitivity of serum creatinine concentration for detecting abnormal kidney function.
Objective:
To compare serum concentrations of cystatin C (a novel marker of kidney function) and creatinine as predictors of incident heart failure.
Design:
Observational study based on measurement of serum cystatin C from frozen sera obtained at the 1992-1993 visit of the Cardiovascular Health Study. Follow-up occurred every 6 months.
Setting:
Adults 65 years of age or older from 4 communities in the United States.
Participants:
4384 persons without previous heart failure who had measurements of serum cystatin C and serum creatinine.
Measurements:
Incident heart failure.
Results:
The mean (+/-SD) serum concentrations of cystatin C and creatinine were 82 +/- 25 nmol/L (1.10 +/- 0.33 mg/L) and 89 +/- 34 micromol/L (1.01 +/- 0.39 mg/dL), respectively. During a median follow-up of 8.3 years (maximum, 9.1 years), 763 (17%) participants developed heart failure. After adjustment for demographic factors, traditional and novel cardiovascular risk factors, cardiovascular disease status, and medication use, sequential quintiles of cystatin C concentration were associated with a stepwise increased risk for heart failure in Cox proportional hazards models (hazard ratios, 1.0 [reference], 1.30 [95% CI, 0.96 to 1.75], 1.44 [CI, 1.07 to 1.94], 1.58 [CI, 1.18 to 2.12], and 2.16 [CI, 1.61 to 2.91]). In contrast, quintiles of serum creatinine concentration were not associated with risk for heart failure in adjusted analysis (hazard ratios, 1.0 [reference], 0.77 [CI, 0.59 to 1.01], 0.85 [CI, 0.64 to 1.13], 0.97 [CI, 0.72 to 1.29], and 1.14 [CI, 0.87 to 1.49]).
Limitations:
The mechanism by which cystatin C concentration predicts risk for heart failure remains unclear.
Conclusions:
The cystatin C concentration is an independent risk factor for heart failure in older adults and appears to provide a better measure of risk assessment than the serum creatinine concentration. *For a full list of participating Cardiovascular Health Study investigators and institutions, see http://www.chs-nhlbi.org.
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