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
Authors: West Malcolm , Kirby Adrienne , Stewart Ralph A. , Blankenberg Stefan , Sullivan David , White Harvey D. , Hunt David , Marschner Ian , Janus Edward , Kritharides Leonard , Watts Gerald F. , Simes John , Tonkin Andrew M. , Anderson Neil , Stewart Ralph , White Harvey , Nestel Paul , Glasziou Paul , Gandy Marian , Joughin Jeannie , Seabrook Jennifer , Stephenson Jenny , Clague Alison , MacMahon Stephen , Aylward Philip , Whiting Malcolm , McNeil John , Tonkin Andrew , Anderson Craig , Baker Jenny , Barnes Elizabeth , Hague Wendy , Keech Anthony , Kirby Adrienne , Li Li‐Ping , Mulray Sarah , Pater Helen , Robledo Kristy , Simes R. John , Magnus Paul , Shaw John , Collins Rory , Hunt David , Thomson Andrew , Harris Phillip , Sullivan David , Sharpe Norman , Meier Paul , Janus Edward , West Malcolm , Barter Philip , Kritharides Leonard , Watson John , Beilin Lawrence , Hankey Graeme , Hobbs Michael , Thompson Peter , Watts Gerald , Colquhoun David 
Published: February 2022

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.