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Published on: January 28, 2020
Circulating Cystatin C Is an Independent Risk Marker for Cardiovascular Outcomes, Development of Renal Impairment,
Malcolm West1, Adrienne Kirby2, Ralph A Stewart3
1Department of Medicine University of Queensland Brisbane Australia.
Insights
Elevated cystatin C levels predict long-term cardiovascular events and mortality, independent of kidney function. This biomarker also indicates chronic kidney disease risk, even when renal function is estimated differently.
Area of Science:
- Cardiology
- Nephrology
- Biomarker Research
Background:
- Elevated plasma cystatin C is linked to reduced renal function and increased cardiovascular risk.
- Long-term implications and independence from renal function require further investigation.
Purpose of the Study:
- To assess if elevated cystatin C predicts long-term cardiovascular events and mortality.
- To determine if cystatin C's predictive power is independent of renal function and other biomarkers.
- To evaluate cystatin C's role in predicting chronic kidney disease development.
Main Methods:
- Analysis of baseline and 1-year measurements of cystatin C and other biomarkers in 7863 patients from the LIPID study.
- Outcomes ascertained over 6-year and 16-year follow-ups.
- Glomerular filtration rate (GFR) estimated using creatinine and cystatin C-based equations.
Main Results:
- Higher baseline cystatin C (Quartile 4 vs. 1) was associated with increased risk of coronary heart disease mortality (HR 1.37) and major cardiovascular events (HR 1.47) over 6 years.
- Long-term associations (16 years) of cystatin C with cardiovascular, coronary heart disease, and all-cause mortality persisted, independent of GFR.
- Cystatin C predicted chronic kidney disease development over 6 years, independently of creatinine-based GFR, but this was not significant when using cystatin C-based GFR.
Conclusions:
- Cystatin C independently predicts major cardiovascular events, chronic kidney disease development, and mortality.
- Long-term mortality prediction by cystatin C is independent of improved GFR estimation.
- Cystatin C serves as a valuable prognostic biomarker in patients with ischemic heart disease.
Abstract:
Background Elevated plasma cystatin C levels reflect reduced renal function and increased cardiovascular risk. Less is known about whether the increased risk persists long-term or is independent of renal function and other important biomarkers. Methods and Results Cystatin C and other biomarkers were measured at baseline (in 7863 patients) and 1 year later (in 6106 patients) in participants in the LIPID (Long-Term Intervention with Pravastatin in Ischemic Disease) study, who had a previous acute coronary syndrome. Outcomes were ascertained during the study (median follow-up, 6 years) and long-term (median follow-up, 16 years). Glomerular filtration rate (GFR) was estimated using Chronic Kidney Disease Epidemiology Collaboration equations (first GFR-creatinine, then GFR-creatinine-cystatin C). Over 6 years, in fully adjusted multivariable time-to-event models, with respect to the primary end point of coronary heart disease mortality or nonfatal myocardial infarction, for comparison of Quartile 4 versus 1 of baseline cystatin C, the hazard ratio was 1.37 (95% CI, 1.07-1.74; P=0.01), and for major cardiovascular events was 1.47 (95% CI, 1.19-1.82; P<0.001). Over 16 years, the association of baseline cystatin C with coronary heart disease, cardiovascular, and all-cause mortality persisted (each P<0.001) and remained significant after adjustment for estimated GFR-creatinine-cystatin C. Cystatin C also predicted the development of chronic kidney disease for 6 years (odds ratio, 6.61; 95% CI, 4.28-10.20) independently of estimated GFR-creatinine and other risk factors. However, this association was no longer significant after adjustment for estimated GFR-creatinine-cystatin C. Conclusions Cystatin C independently predicted major cardiovascular events, development of chronic kidney disease, and cardiovascular and all-cause mortality. Prediction of long-term mortality was independent of improved estimation of GFR. Registration URL: https://anzctr.org.au; Unique identifier: ACTRN12616000535471.
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