Differential Associations of Cystatin C Versus Creatinine-Based Kidney Function With Risks of Cardiovascular Event and Mortality Among South Asian Individuals in the UK Biobank

BACKGROUND: South Asian individuals have increased cardiovascular disease and mortality risks. Reliance on creatinine-rather than cystatin C–based estimated glomerular filtration rate (eGFRcys) may underestimate the cardiovascular disease risk associated with chronic kidney disease. METHODS AND RESULTS: Among 7738 South Asian UK BioBank participants without prevalent heart failure (HF) or atheroscle-rotic cardiovascular disease, we investigated associations of 4 eGFRcys and creatinine-based estimated glomerular filtration rate categories (<45, 45–59, 60–89, and ≥90 mL/min per 1.73 m) with risks of all-cause mortality, incident HF, and incident atherosclerotic cardiovascular disease. The mean age was 53±8 years; 4085 (53%) were women. Compared with creatinine, cystatin C identified triple the number of participants with estimated glomerular filtration <45 (n=35 versus n=113) and 6 times the number with estimated glomerular filtration 45 to 59 (n=80 versus n=481). After multivariable adjustment, the eGFRcys 45 to 59 category was associated with higher risks of mortality (hazard ratio [HR], 2.38 [95% CI, 1.55–3.65]) and incident HF (sub-HR [sHR], 1.87 [95% CI, 1.09–3.22]) versus the eGFRcys ≥90 category; the creatinine-based estimated glomerular filtration rate 45 to 59 category had no significant associations with outcomes. Of the 7623 participants with creatinine-based estimated glomerular filtration rate ≥60, 498 (6.5%) were reclassified into eGFRcys <60 categories. Participants who were reclassified as having eGFRcys <45 had higher risks of mortality (HR, 4.88 [95% CI, 2.56–9.31]), incident HF (sHR, 4.96 [95% CI, 2.21–11.16]), and incident atherosclerotic cardiovascular disease (sHR, 2.29 [95% CI, 1.14–4.61]) versus those with eGFRcys ≥90; those reclassified as having eGFRcys 45 to 59 had double the mortality risk (HR, 2.25 [95% CI, 1.45–3.51]). CONCLUSIONS: Among South Asian individuals, cystatin C identified a high-risk chronic kidney disease population that was not detected by creatinine and enhanced estimated glomerular filtration rate–based risk stratification for mortality, incident HF, and incident atherosclerotic cardiovascular disease.