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

Background: High ankle-brachial index (ABI) has been associated with increased risk of worse out-comes in the general population. Few data on atrial fibrillation (AF) exist. Experimental data suggest that proprotein convertase subtilisin/kexin type 9 (PCSK9) contributes to vascular calcification but clinical data on this association are lacking. Aims: We wanted to investigate the relationship between circulating PCSK9 levels and an abnormally high ABI in patients suffering from AF. Methods: We analyzed data from 579 patients included in the prospective ATHERO-AF study. An ABI >= 1.4 was considered high. PCSK9 levels were measured coincidentally with ABI measurement. We used optimized cut-offs of PCSK9 for both ABI and mortality obtained from Receiver Operator Characteristic (ROC) curve analysis. All-cause mortality according to the ABI value was also analyzed. Results: One hundred and fifteen patients (19.9%) had an ABI >= 1.4. The mean (standard deviation [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. In multivariable Cox regression analysis, an 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. Conclusions: In AF patients, PCSK9 levels relate to an abnormally high ABI >= 1.4. Our data suggest PCSK9 role in contributing to vascular calcification in AF patients.