Abstract
BACKGROUND: The difference in estimated glomerular filtration rate (eGFR) derived from creatinine and cystatin C (eGFR(diff)) has been noticed recently and the relationship with poor cardiovascular prognosis has been proven. However, primary prevention of the risk of coronary artery disease (CAD) is equally important but there is a lack of studies specifically investigating this implication. METHODS: This prospective cohort study utilized data from the UK Biobank, including 437,536 participants without CAD at baseline. The primary outcome was defined as CAD. The eGFR(diff) was calculated by subtracting creatinine-based eGFR from cystatin C-based eGFR. Participants were then categorized into a negative, intermediate range, and positive group based on thresholds of -15 mL/min/1.73 m(2) and 15 mL/min/1.73 m(2). Cox proportional risk models were used to evaluate the associations of eGFR(diff) with CAD and the relationship among different genetic risks of CAD. RESULTS: During a median follow-up of 13.8 years, CAD occurred in 36,797 participants. In the fully adjusted model, compared to midrange eGFR(diff,) participants with a positive eGFR(diff) had a lower risk of CAD (HR 0.717, 95%CI 0.675-0.762), while with a negative eGFR(diff) had a higher risk (HR 1.433, 95%CI 1.399-1.468). When eGFR(diff) was treated as a continuous variable, a statistically significant trend toward a lower risk of CAD as eGFR(diff) increased (HR 0.982, 95% CI 0.981-0.982). Moreover, this relationship is independent of genetic susceptibility. CONCLUSIONS: eGFR(diff) was associated with CAD risk, where a high eGFR(diff) corresponded to a decreased likelihood of CAD onset no matter genetic susceptibility.