Association of proprotein convertase subtilisin/kexin type 9 (PCSK9) levels with abnormally high ankle-brachial index in atrial fibrillation.

Abstract

High ankle-brachial index (ABI) has been associated with increased risk of worse outcomes in the general population. Few data on atrial fibrillation (AF) do exist. Experimental data suggest that proprotein convertase subtilisin/kexin type 9 (PCSK9) contribute to vascular calcification but clinical data on this association are lacking. We want to investigate the relationship between circulating PCSK9 levels and abnormally high ABI in patients suffering from AF. We analysed data from 579 patients included in the prospective ATHERO-AF study. An ABI ≥1.4 was considered as high. PCSK9 levels were measured coincidentally with ABI measurement. We used an optimized cut-offs of PCSK9 for both ABI and mortality obtained from ROC curve analysis. All-cause mortality according to the ABI value was also analysed. 115 (19.9%) had an ABI ≥1.4. The mean (SD) age was 72.1 (7.6) years and 42.1% of patients were women. Patients with ABI ≥1.4 were older, more frequently male and diabetic. Multivariable logistic regression analysis showed an association between ABI ≥1.4 and serum levels of PCSK9 >1150 pg/ml (odds ratio [OR], 1.649; 95% confidence interval [CI], 1.047-2.598; P = 0.031). During a median follow up of 41 months, 113 deaths occurred. At multivariable Cox regression analysis, ABI ≥1.4 (hazard ratio [HR], 1.626; 95% CI, 1.024-2.582; P = 0.039), CHA₂DS₂-VASc score (HR, 1.249; 95% CI, 1.088-1.434; P = 0.002), antiplatelet drug use (HR, 1.775; 95% CI, 1.153-2.733; P = 0.009), and PCSK9 >2060 pg/ml (HR, 2.200; 95% CI, 1.437-3.369; P <0.001) were associated with all-cause death. In AF patients, PCSK9 levels relate to an abnormally high ABI ≥1.4. Our data suggest a role for PCSK9 in favouring vascular calcification in AF patients.