Circulating Cystatin C Is an Independent Risk Marker for Cardiovascular Outcomes, Development of Renal Impairment, and Long-Term Mortality in Patients With Stable Coronary Heart Disease: The LIPID Study.

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.

• Authors: Malcolm West, Adrienne Kirby, Ralph A Stewart, Stefan Blankenberg, David Sullivan, Harvey D White, David Hunt, Ian Marschner, Edward Janus, Leonard Kritharides, Gerald F Watts, John Simes, Andrew M Tonkin, LIPID Study Group *
• Journal: Journal of the American Heart Association (J Am Heart Assoc) Vol. 11 Issue 5 Pg. e020745 (03 2022) ISSN: 2047-9980 [Electronic] England
• PMID: 35179040 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Biomarkers
• Cystatin C
• Lipids
• Creatinine

Topics

• Biomarkers (blood)
• Coronary Disease (blood, diagnosis)
• Creatinine (blood)
• Cystatin C (blood)
• Glomerular Filtration Rate
• Humans
• Lipids
• Myocardial Infarction (blood, diagnosis)
• Renal Insufficiency (blood, diagnosis)
• Renal Insufficiency, Chronic (blood, diagnosis)