Kidney function and the risk of sudden cardiac death in the general population

Abstract

Background: Chronic kidney disease increases sudden cardiac death (SCD) risk, but the association between kidney function and SCD in a general population is largely unknown. Therefore, we investigated the association between kidney function and SCD in a general middle-aged and elderly population.

Methods: We included individuals aged ≥45 years from a prospective population-based cohort study. The association between kidney function assessments [estimated glomerular filtration rate based on serum creatinine (eGFRcreat), cystatin C (eGFRcys) or both (eGFRcreat-cys)] and SCD was investigated using Cox proportional-hazards and joint models. Absolute 10-year risks were computed using competing risk analyses. Mediation analyses were performed using a four-way decomposition method.

Results: We included 9687 participants (median follow-up 8.9 years; mean age 65.3 years; 56.7% women; 243 SCD cases). Lower eGFRcys and eGFRcreat-cys were associated with increased SCD risk [hazard ratio (HR) 1.23, 95% confidence interval (CI) 1.12-1.34 and HR 1.17, 95% CI 1.06-1.29, per 10 mL/min/1.73 m² eGFR decrease]. A significant trend (P = 0.001) across eGFRcys categories was found, with an HR of 2.11 (95% CI 1.19-3.74) for eGFRcys <60 compared with eGFRcys >90 mL/min/1.73 m². Comparing eGFRcys of 90 to 60 mL/min/1.73 m², absolute 10-year risk increased from 1.0% to 2.5%. Identified subgroups at increased risk included older participants and participants with atrial fibrillation. The associations were not mediated by coronary heart disease, hypertension or diabetes.

Conclusions: Reduced kidney function is associated with increased SCD risk in the general population, especially with eGFRcys. eGFRcys could be added to prediction models and screening programmes for SCD prevention.

Keywords: creatinine; cystatin C; estimated glomerular filtration rate; kidney function; sudden cardiac death.

Graphical Abstract

FIGURE 1:

Absolute 10-year risks of sudden cardiac death by eGFRcys and eGFRcreat-cys at baseline. Absolute 10-year risks of sudden cardiac death were calculated taking the competing risk of death of other causes into account. Adjusted for age, sex, Rotterdam Study cohort, heart rate, body mass index, smoking, alcohol, serum cholesterol, history of CHD, diabetes and hypertension. CHD, coronary heart disease; eGFRcreat-cys, estimated glomerular filtration rate (eGFR) determined by serum creatinine and serum cystatin C; eGFRcys, eGFR determined by serum cystatin C.

FIGURE 2:

Absolute 10-year risks of sudden cardiac death by eGFRcys and eGFRcreat-cys at baseline, separately for age and sex strata. Absolute 10-year risks of sudden cardiac death were calculated taking the competing risk of death of other causes into account. Adjusted for Rotterdam Study cohort, heart rate, body mass index, smoking, alcohol, serum cholesterol, history of CHD, diabetes and hypertension. CHD, coronary heart disease, eGFRcreat-cys, estimated glomerular filtration rate (eGFR) determined by serum creatinine and serum cystatin C; eGFRcys, eGFR determined by serum cystatin C.