Plasma Cystatin C Levels and Cardiovascular and Renal Outcomes in Patients With Stable CHD

Blood sample tube for Cystatin-C-test diagnosis for renal disease
Investigators studied the relationship between long-term cardiovascular risk, renal function, and elevated plasma cystatin C levels.

For patients with stable coronary heart disease (CHD), elevated plasma cystatin C levels were found to be a marker for major cardiovascular events, chronic kidney disease, and mortality. These findings were published in the Journal of the American Heart Association.

Data for this study were sourced from the Long-Term Intervention with Pravastatin in Ischemic Disease (LIPID) study. Patients (N=7863) who had history of myocardial infarction or were hospitalized for unstable angina were randomly assigned to receive pravastatin or placebo. Laboratory biomarkers were evaluated at baseline and at 1 and 6 years. Most patients consented to be evaluated for outcomes up to 16 years.

Patients were stratified by cystatin C levels. After stratification, 2020 patients had low levels (≤0.72 mg/L), 1996 had low-intermediate levels (>0.72 to ≤0.81 mg/L), 1981 had high-intermediate levels (>0.81 to ≤0.93) mg/L, and 1866 had high levels (>0.93 mg/L). Patients with elevated cystatin C levels were older (P <.001), and more were women (P <.001), were obese (P <.001), had diabetes (P =.010), had history of stroke (P <.001), and were smokers (P =.003).

After adjusting for demographic features, clinical risk factors, and treatment allocation, elevated cystatin C was associated with 6-year CHD events (adjusted hazard ratio [aHR], 1.37; 95% CI, 1.07-1.74; P =.01), major cardiovascular disease (CVD) events (aHR, 1.47; 95% CI, 1.19-1.82; P <.001), CVD mortality (aHR, 1.44; 95% CI, 1.04-1.99; P =.03), stroke (aHR, 1.63; 95% CI, 1.02-2.59; P =.04), and all-cause mortality (aHR, 1.35; 95% CI, 1.04-1.75; P =.02).

At year 10, an increase in cystatin C levels from baseline was associated with elevated risk for CHD mortality (aHR, 1.26; 95% CI, 1.08-1.46; P =.004), CVD mortality (aHR, 1.31; 95% CI, 1.15-1.50; P <.001), non-CVD noncancer mortality (aHR, 1.43; 95% CI, 1.13-1.83; P =.002), and all-cause mortality (aHR, 1.27; 95% CI, 1.15-1.41; P <.001).

A positive relationship was observed between cystatin C levels and 16-year CHD mortality, CVD mortality, non-CVD noncancer mortality, and all-cause mortality rates.

There were 385 patients with a normal estimated glomerular filtration rate at baseline who developed chronic kidney disease (CKD) during follow-up. Baseline elevated cystatin C levels were associated with CKD risk (adjusted odds ratio [aOR], 6.6; 95% CI, 4.3-10.2).

This study may have been limited by the fact that the original LIPID study was conducted over 20 years ago and standard care for CHD has developed since that time.

“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 aging societies,” the study authors wrote. “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.”

Disclosure: Multiple authors declared affiliations with industry. Please refer to the original article for a full list of disclosures.


West M, Kirby A, Stewart RA, et al. 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. J Am Heart Assoc. Published online February 18, 2022. doi:10.1161/JAHA.121.020745