Background--Lipoprotein(a) (Lp[a]) is proatherosclerotic and prothrombotic, causally related to coronary disease, and associated with other cardiovascular diseases. The association of Lp(a) with incident atrial fibrillation (AF) and with ischemic stroke among individuals with AF remains to be elucidated. Methods and Results--In the community-based ARIC (Atherosclerosis Risk in Communities) study cohort, Lp(a) levels were measured by a Denka Seiken assay at visit 4 (1996-1998). We used multivariable-adjusted Cox models to compare AF and ischemic stroke risk across Lp(a) levels. First, we evaluated incident AF in 9908 participants free of AF at baseline. AF was ascertained by electrocardiography at study visits, hospital International Statistical Classification of Diseases, 9th Revision (ICD-9) codes, and death certificates. We then evaluated incident ischemic stroke in 10 127 participants free of stroke at baseline. Stroke was identified by annual phone calls, hospital ICD-9 Revision codes, and death certificates. The baseline age was 62.7±5.6 years. Median Lp(a) levels were 13.3 mg/dL (interquartile range, 5.2-39.7 mg/dL). Median follow-up was 13.9 and 15.8 years for AF and stroke, respectively. Lp(a) was not associated with incident AF (hazard ratio, 0.98; 95% confidence interval, 0.82-1.17), comparing those with Lp(a) ≥50 with those with Lp(a) < 10 mg/dL. High Lp(a) was associated with a 42% relative increase in stroke risk among participants without AF (hazard ratio, 1.42; 95% confidence interval, 1.07-1.90) but not in those with AF (hazard ratio, 1.06; 95% confidence interval, 0.70-1.61 [P interaction for AF=0.25]). There were no interactions by race or sex. No association was found for cardioembolic stroke subtype. Conclusions--High Lp(a) levels were not associated with incident AF. Lp(a) levels were associated with increased ischemic stroke risk, primarily among individuals without AF but not in those with AF.
Bibliographical noteFunding Information:
The ARIC study is performed as a collaborative trial supported by National Heart, Lung, and Blood Institute contracts (HHSN268201100005C, HHSN268201100006C, HHSN-268201100007C, HHSN268201100008C, HHSN26820-1100009C, HHSN268201100010C, HHSN268201100011C, and HHSN268201100012C). Drs Michos and Zhao are also supported by the Blumenthal Scholars Fund for Preventive Cardiology Research. Additional support was provided by American Heart Association grant 16EIA26410001 (Alonso).
Dr Ballantyne has received consultant fees/honoraria from Abbott Diagnostic, Amarin, Amgen, Astra Zeneca, Boehringer Ingelheim, Eli Lilly, Esperion, Ionis, Matinas Bio Pharma Inc, Merck, Novartis, Pfizer, Regeneron, Roche Diagnostic, and Sanofi-Synthelabo, and has received research grants from Abbott Diagnostic, Amarin, Amgen, Eli Lilly, Esperion, Ionis, Novartis, Pfizer, Regeneron, Roche Diagnostic, Sanofi-Synthelabo. Dr Michos has received consultant fees/honoraria from Siemens Healthcare Diagnostics and a speaking fee from Bioquest Global. Dr Hoogeveen has received research grants from Denka Seiken, Ltd. Nazarian has received consultant fees/honoraria Biosense Webster Inc, CardioSolv, St Jude Medical; and research grants from Biosense Webster Inc. Dr Martin has received consultant fees/honoraria from Amgen Inc., Quest Diagnostics, Sanofi-Regeneron and research grants from Aetna Foundation, Apple, Google. Dr. Aronis is supported by an NIH T32 training grant (5T32HL007227–42). The remaining authors have no disclosures to report.
© 2017 The Authors.
- Atrial fibrillation
- Cardioembolic stroke
- Lipoprotein (a)
- Risk factor