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Chronic Kidney Disease (CKD) is associated with abnormal vascular structure and function, including a high prevalence of hypertension and elevated large artery stiffness (LASt). While LASt has been associated with increased risk of atrial fibrillation (AF) in the general population, the relationship between LASt and AF has not been adequately evaluated in individuals with CKD. We aimed to examine the bidirectional relationship between LASt (measured by carotid-femoral pulse wave velocity [cfPWV]) and AF among participants of the Chronic Renal Insufficiency Cohort (CRIC).
Data were obtained from the CRIC Study, a longitudinal cohort study of patients with mild to moderate CKD, in which cfPWV was performed every two years during at least three study visits. New AF was determined by two physician adjudicators. Linear mixed effects modeling was used to evaluate the relationship of baseline AF status with the trajectory of cfPWV over time, restricted to individuals with at least two cfPWV measurements. Cox proportional hazards regression was used to evaluate the association of initial cfPWV with incident AF among participants without AF at baseline. All analyses were adjusted for age, sex, race, active smoking, cardiovascular disease, peripheral vascular disease, and diabetes. Effect modification was assessed by baseline CKD stage, mean arterial pressure, sex, race, and diabetes and, if present, interaction terms were incorporated into the final multivariable models.
CfPWV was measured in 2,407 CRIC participants without AF and 526 with AF at baseline. After restricting to participants with at least two cfPWV measurements, those with AF at baseline had a higher cfPWV (median 9.2, IQR 7.4-11.2) compared to those without AF (median 8.7, IQR 7.2-10.9). However, in adjusted mixed effects analyses, baseline AF status was not associated with any difference in cfPWV trajectory over time (β= –0.05, 95% confidence interval [CI] -0.12-0.03; interaction p-value with time= 0.258). Among participants without AF at baseline, those in the highest tertile of baseline cfPWV (median cfPWV 12.1 m/s, IQR 11.0-13.8) were older (median age 64 vs. 55 years), more often male (61% vs. 53%), smokers (13% vs. 9%), with higher mean arterial pressure (90 vs. 86 mmHg) and lower eGFR (38 vs. 49 mL/min/1.73m2) compared to participants in the lowest tertile (median cfPWV 6.8 m/s, IQR 6.1-7.3). After a median follow-up of 10 years, baseline cfPWV was associated with an increased risk of AF (unadjusted standardized hazard ratio [sHR] 1.68, 95% CI 1.56-1.80 per standard deviation increase in cfPWV), which decreased but remained significant after multivariable adjustment (adjusted sHR 1.60, 95% CI 1.35-1.90). There was significant effect modification by race and diabetes.
In adults with CKD, higher LASt was associated with an increased risk of new-onset AF among those without AF at baseline. Our findings suggest that cfPWV may be a useful indicator of heightened risk of incident AF among individuals with CKD.