Association of Cystatin C with Poor Exercise Capacity and Heart Rate Recovery: Data from the Heart and Soul Study

Background: Cystatin C, an alternative serum measure of kidney function, is a stronger predictor of cardiovascular events than creatinine or estimated glomerular filtration rate (eGFR). We hypothesized that serum cystatin C concentration would have a stronger more linear association with cardiovascular functional status than creatinine-based measures in outpatients with established coronary heart disease (CHD).

Methods: We measured serum cystatin C, serum creatinine, and eGFR in 906 outpatients with established CHD. We examined the association of these 3 measures of kidney function with treadmill exercise capacity (metabolic equivalent tasks achieved) and heart rate recovery (HRR) between peak and 1 minute after exercise by using linear and logistic regression.

Results: Higher cystatin C concentrations were associated linearly with worse treadmill exercise capacity and HRR. The proportion of participants with poor exercise capacity (metabolic equivalent tasks achieved < 5) was 45% (99 of 222 participants) among those with cystatin C levels in the highest quartile (>1.30 mg/L) compared with 12% (29 of 241 participants) among those with cystatin C levels in the lowest quartile (<0.92 mg/L; adjusted odds ratio, 3.2; 95% confidence interval, 1.6 to 6.5; P = 0.001). The proportion of participants with poor HRR (<16 beats/min) was 42% (92 of 214 participants) among those with cystatin C levels in the highest quartile compared with 16% (37 of 238 participants) among those with cystatin C levels in the lowest quartile (adjusted odds ratio, 2.2; 95% confidence interval, 1.2 to 4.0; P = 0.01). The lowest quartile of eGFR (<61.8 mL/min [<1.03 mL/s]) was associated with decreased exercise capacity and prolonged HRR, but no difference was observed across the upper 3 quartiles of eGFR.

Conclusion: In patients with established CHD, cystatin C concentrations are associated linearly with worse exercise capacity and HRR. Cystatin C detects an association of impaired kidney function with decreased HRR and exercise capacity that is not fully captured using creatinine-based measurements.