Author + information
- Received July 12, 2017
- Accepted July 17, 2017
- Published online September 11, 2017.
- Daniele Pastori, MDa,
- Cristina Nocella, MSca,b,
- Alessio Farcomeni, PhDc,
- Simona Bartimoccia, MSca,
- Maria Santulli, MDd,
- Fortunata Vasaturo, MDe,
- Roberto Carnevale, PhDa,b,
- Danilo Menichelli, MDa,
- Francesco Violi, MDa,
- Pasquale Pignatelli, PhDa,∗ (, )
- ATHERO-AF Study Group
- aI Clinica Medica, Department of Internal Medicine and Medical Specialties, Sapienza University of Rome, Rome, Italy
- bDepartment of Medical-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Latina, Italy
- cDepartment of Public Health and Infectious Diseases, Sapienza University of Rome, Rome, Italy
- dDepartment of Experimental Medicine, Sapienza University of Rome, Rome, Italy
- eAzienda Ospedaliera Universitaria Policlinico Umberto I, Rome, Italy
- ↵∗Address for correspondence:
Dr. Pasquale Pignatelli, I Clinica Medica, Department of Internal Medicine and Medical Specialties, Sapienza University of Rome, Viale del Policlinico 155, Rome, 00161, Italy.
Background Soluble proprotein convertase subtilisin/kexin type 9 (PCSK9) has been shown to be predictive of cardiovascular events (CVEs) in patients who are at high cardiovascular risk. No data on the effect of PCSK9 levels in patients with atrial fibrillation (AF) are available.
Objectives This study investigated the association between PCSK9 and CVEs in AF as well as the relationship between PCSK9 and urinary 11-dehydro-thromboxane B2 (11-dh-TxB2), a marker of platelet activation.
Methods We conducted a prospective, single-center cohort study, including 907 patients with AF treated with vitamin K antagonists (3,865 patient-years), to assess CVEs, including fatal and nonfatal myocardial infarction, ischemic stroke, and cardiovascular death. At admission, plasma PCSK9 and urinary 11-dh-TxB2 (n = 852) were measured. The population was divided into tertiles of PCSK9 for the analysis.
Results The mean age of patients was 73.5 ± 8.2 years, and 43.0% were women. At follow-up, 179 CVEs (4.6%/year) occurred: 43 (15.3%), 49 (15.5%), and 87 (28.0%) in the first, second, and third tertiles of PCSK9, respectively (log-rank test p = 0.009). Patients with CVEs had higher median PCSK9 compared with those without (1,500 pg/ml [IQR: 1,000 to 2,300 pg/ml] vs. 1,200 pg/ml [IQR: 827 to 1,807 pg/ml], respectively; p < 0.001). Multivariable Cox regression analysis showed that the third versus the first tertile of PCSK9 (hazard ratio: 1.640; 95% confidence interval: 1.117 to 2.407; p = 0.012), female sex, age, diabetes, smoking, heart failure, previous cerebrovascular and cardiac events, digoxin use, and total cholesterol to high-density lipoprotein cholesterol ratio were associated with CVEs. In 682 patients not treated with antiplatelet therapy, circulating PCSK9 and 11-dh-TxB2 were significantly correlated (Spearman's rho: 0.665; p < 0.001).
Conclusions Plasma PCSK9 levels are associated with an increased risk of CVEs in patients with AF. The direct correlation between PCSK9 and 11-dh-TxB2 suggests PCSK9 as a mechanism potentially implicated in platelet activation.
This work was supported by a university grant from Ateneo Sapienza. The authors have reported that they have no relationships relevant to the contents of this paper to disclose. Dr. Pastori and Ms. Nocella contributed equally to this work. Drs. Violi and Pignatelli are joint senior authors on this work.
- Received July 12, 2017.
- Accepted July 17, 2017.
- 2017 American College of Cardiology Foundation
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