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

Author:

West Malcolm1,Kirby Adrienne2,Stewart Ralph A.3,Blankenberg Stefan4,Sullivan David5ORCID,White Harvey D.3ORCID,Hunt David6,Marschner Ian2,Janus Edward7,Kritharides Leonard89ORCID,Watts Gerald F.10,Simes John2,Tonkin Andrew M.11ORCID,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

Affiliation:

1. Department of Medicine University of Queensland Brisbane Australia

2. National Health and Medical Research Council Clinical Trials CentreUniversity of Sydney Sydney Australia

3. Green Lane Cardiovascular Service Auckland City HospitalUniversity of Auckland Auckland New Zealand

4. University Heart and Vascular Centre Hamburg Hamburg Germany

5. Department of Chemical Pathology Royal Prince Alfred Hospital Sydney Australia

6. Cardiology Department Royal Melbourne Hospital Melbourne Australia

7. Department of Medicine Western Health Chronic Disease AllianceWestern HealthMelbourne Medical SchoolUniversity of Melbourne Melbourne Australia

8. Department of Cardiology Concord Repatriation General HospitalSydney Local Health District Sydney Australia

9. ANZAC Medical Research InstituteFaculty of MedicineUniversity of Sydney Sydney Australia

10. School of Medicine Faculty of Health and Medical Sciences University of Western Australia Perth Australia

11. School of Public Health and Preventive Medicine Monash University Perth Australia

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.

Publisher

Ovid Technologies (Wolters Kluwer Health)

Subject

Cardiology and Cardiovascular Medicine

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