Risk factors

Two decades on, LIPID study reveals a novel cardiorenal prognostic indicator for older CHD patients


The importance of chronic kidney disease as a cardiovascular risk factor in older people has been underscored by novel biomarker findings derived from the Australian-led LIPID trial.

Using blood biobank samples from patients enrolled in the trial two decades ago, researchers have shown that plasma cystatin C levels – a marker of renal function –  independently predicted major cardiovascular events and long term mortality in patients with cardiovascular disease.

The additional predictive value on mortality was independent of improved estimation of glomerular filtration rate (GFR), according to results published in the Journal of the American Heart Association by the LIPID Study Group including Professor Andrew Tonkin of Monash University.

In the study, cystatin C and other biomarkers were measured in 7863 patients who had a previous acute coronary syndrome enrolled in the LIPID (Long‐Term Intervention with Pravastatin in Ischaemic Disease) study.

The evaluation found that baseline cystatin C levels, and also change in cystatin C from baseline to one year following randomisation, had a significant association with most pre‐specified cardiovascular outcomes at the end of the trial period of six years.

In fully adjusted multivariable time‐to‐event models, for the primary end point of coronary heart disease mortality or nonfatal myocardial infarction, the hazard ratio for the highest quartile of cystatin C levels versus the lowest was 1.37 (95% CI, 1.07–1.74; P=0.01). For major cardiovascular events the hazard ratio was 1.47 (95% CI, 1.19–1.82; P<0.001).

Furthermore, over 16 years of follow up, the association of baseline cystatin C levels persisted  for 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 six 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.

The study authors said the predictive ability of cystatin C was likely inferior to BNP but similar to sensitive troponin I (TnI).

They said that it had previously been unclear how much of the prognostic value of cystatin C on cardiovascular events and deaths related to it being a better measure of eGFR or is attributable to other mechanisms. It now appeared that a cystatin C‐based definition of CKD was superior to a creatinine‐based definition in assessing cardiovascular risk since it remained a significant predictor after adjustment for eGFR using either the CKD‐EPI creatinine or creatinine‐cystatin C equations.

“Consequently, at least some of its prognostic value appears to be unrelated to it simply being a better measure of renal function,” they wrote.

However the possibility of incorporating cystatin C levels to refine cardiovascular risk estimation in routine practice would depend on the availability and reliability of assays and their cost‐effectiveness, they cautioned.

“The association of elevated circulating levels of cystatin C with adverse medium‐ and long‐term outcomes underscores the importance of CKD as a cardiovascular risk factor in our ageing societies. However, our data also support the additional prognostic value for major CVD events and long‐term mortality of measurement of circulating cystatin C beyond allowing improved assessment of eGFR,” they concluded.

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