Elevated levels of cystatin C linked to 28% increased risk of CVD after ACS

Cystatin C (Cys-C), an alternative to renal markers like creatinine and glomerular filtration rate, can effectively predict a patient’s risk for adverse CVD events after an acute coronary syndrome (ACS), researchers reported Oct. 12 in the Journal of the American Heart Association

Simon Correa, MD, spearheaded the SOLID-TIMI 52 trial, which randomized nearly 5,000 ACS patients to treatment with darapladib or a placebo. For two and a half years, the research team followed its subjects, noting the association between Cys-C levels and long-term CVD risk in the population.

Cys-C, a cysteine protease inhibitor produced by almost all human cells, is a serum measure of renal function since it’s filtered in the renal glomerulus, Correa and co-authors wrote in JAHA. Creatinine is another common renal marker, but unlike Cys-C, creatinine can be affected by age, sex and lean muscle mass.

“Prior studies have demonstrated an association between Cys-C and the risk of death, including cardiovascular death and incident heart failure among ambulatory people with coronary heart disease,” Correa, of the TIMI Study Group at Brigham and Women’s Hospital in Boston, and colleagues said. “In addition, studies have shown an association between Cys-C and the risk of adverse outcomes after ACS.

“However, the incremental value of assessing Cys-C beyond established and novel markers that reflect renal function, including estimated glomerular filtration rate (eGFR) and fibroblast growth factor-23 (FGF-23), remains disputed.”

Correa et al. accounted for a handful of those variables, including eGFR, FGF-23, high-sensitivity troponin I and brain-type natriuretic peptide, in their study. They found Cys-C was strongly correlated with creatinine and eGFR, moderately tied to FGF-23 and weakly correlated to troponin and natriuretic peptides.

After multivariable adjustment, the team said increasing concentrations of Cys-C were linked to a 28 percent higher risk of CVD or heart failure hospitalization. Patients with elevated levels of the inhibitor were also 17 percent more likely to have a heart attack and 15 percent more likely to experience a stroke.

A pair of physicians from the University of Brescia in Italy and the Vascular Institute in Falls Church, Virginia, however, suggest Correa and colleagues’ results be taken with a grain of salt.

“Measurement of Cys-C provides an accurate blood-based measurement to estimate GFR,” Federica Latta, MD, and Christopher de Filippi, MD, wrote in a related editorial. “The findings from SOLID-TIMI 52 ... represent an important update and suggest that, although Cys-C could provide incremental prognostic information compared with eGFR, this appears to have only a marginal usefulness in stratifying risk for patients with ACS.”

Further work is needed to determine if the method is truly superior to creatinine assessment, they said. And even if it is, it will take time to integrate into clinical workflow.

“Although Cys-C demonstrates a potentially important role in renal function evaluation, its adaptation as a prognostic factor after an ACS event—a domain with well-established prognostic biomarkers—will ultimately be driven by finding a novel role when used in isolation or at least when combined with other biomarkers to guide therapy to improve outcomes,” Latta and de Filippi wrote.