Differential associations seen between Lp(a) levels and stroke, depending on AF-status

Associations of Lipoprotein(a) Levels With Incident Atrial Fibrillation and Ischemic Stroke: The ARIC (Atherosclerosis Risk in Communities) Study

Literature - Aronis KN, Zhao D, Hoogeveer RC et al., - J Am Heart Assoc. 2017;6:e007372. Originally published December 15, 2017


Lipoprotein(a) [Lp(a)] has similar lipid composition to LDL-c, with the distinguishing apolipoprotein(a) covalently bound to apoB-100 [1]. Lp(a) has been associated with an increased risk of coronary heart disease (CHD) and stroke, and has increasingly been recognized as an important CV risk factor [2]. This is the result of both its proatherogenic effects as a lipoprotein and the prothrombotic effects, as a consequence of its resemblance to plasminogen. Mendelian randomization studies suggested a causal relationship of Lp(a) with CHD [3]. Other effects of Lp(a) on the CV system that have been described include calcific aortic sclerosis [4].

The link between Lp(a) and atrial fibrillation (AF) is unclear to date, and it has not been studied prospectively. Atherosclerotic CV disease and markers of atherosclerosis such as coronary calcium score and cIMT have been associated with AF [5,6], but the role of Lp(a) as an independent risk factor for AF remains to be elucidated. Although blacks and women have higher Lp(a) than whites and men, respectively, both former groups show lower incidences of AF. Limited data are also available on the relationship between Lp(a) and AF-related stroke.

This study aimed to prospectively evaluate associations between Lp(a) and incident AF and to assess potential interactions with race and sex. Moreover, associations between Lp(a) and stroke in persons with or without AF were assessed prospectively. Data of the biracial ARIC (Atherosclerosis

Risk in Communities) study [7] were benefitted from. For the primary aim, 9908 ARIC participants free of prevalent or incident AF were included (median follow-up: 13.9 years, IQR: 12.4-14.8), and for the second aim all ARIC participants free of prevalent or incident stroke were included (n=10127, median follow-up: 15.8 years, IQR: 13.6-16.7 years).

Main results

  • In participants free of AF at baseline, the overall AF incidence rate was 8.8 events per 1000 person-years (PY). Blacks showed a lower rate than whites (6.1 vs. 9.5 per 1000 PY) and women a lower rate than men (7.3 vs. 10.8 per 1000 PY).
  • No association was observed between Lp(a) levels and AF incidence. In a fully adjusted model, the HR for AF for Lp(a) ≥50 mg/dL compared with <10 mg/dL was 0.98 (95%CI: 0.82-1.17).
  • No effect modification of the relation between Lp(a) and AF risk was seen by race or sex.
  • The incidence of stroke was four times higher in participants with AF compared to those without (10.8 vs. 2.9 events per 1000 PY).
  • In those without a history of AF, those with Lp(a) ≥50 mg/dL had 42% higher risk of stroke compared with those with <10 mg/dL (HR: 1.42, 95%CI: 1.07-1.90), even after adjustment for various CVD risk factors, other lipid markers and the CHA2DS2-VASc score. Lower levels of Lp(a) did not show a significantly higher risk of stroke in these participants.
  • No statistically significant relative increase in ischemic stroke risk was observed with high Lp(a) in participants with a history of prevalent AF (HR: 1.06, 95%CI: 0.70-1.61).
  • Race or sex did not modify the effect of Lp(a) on stroke risk.


In this large community-based cohort, no association was observed between elevated Lp(a) levels and AF risk, in black nor whites, and in men nor women. Participants in the highest Lp(a) category (≥50 mg/dL) without AF did show a 40% higher risk of ischemic stroke, as compared with the lowest Lp(a) category (<10 mg/dL). This elevated risk is, however about 10-fold lower than the risk of stroke conveyed by AF itself.


1. Fless GM, Rolih CA, Scanu AM. Heterogeneity of human plasma lipoprotein (a). Isolation and characterization of the lipoprotein subspecies and their apoproteins. J Biol Chem. 1984;259:11470–11478.

2. Expert Panel on Detection E and Treatment of High Blood Cholesterol in A. Executive summary of the third report of the National Cholesterol Education Program (NCEP) expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (adult treatment panel III). JAMA. 2001;285:2486–2497.

3. Kamstrup PR, Tybjaerg-Hansen A, Steffensen R, Nordestgaard BG. Genetically elevated lipoprotein(a) and increased risk of myocardial infarction. JAMA. 2009;301:2331–2339.

4. Kamstrup PR, Tybjaerg-Hansen A, Nordestgaard BG. Elevated lipoprotein(a) and risk of aortic valve stenosis in the general population. J Am Coll Cardiol. 2014;63:470–477.

5. Chen LY, Leening MJ, Norby FL, et al. Carotid intima-media thickness and arterial stiffness and the risk of atrial fibrillation: the Atherosclerosis Risk in Communities (ARIC) Study, Multi-Ethnic Study of Atherosclerosis (MESA), and the Rotterdam Study. J Am Heart Assoc. 2016;5:e002907. DOI: 10.1161/JAHA.115.002907.

6. O’Neal WT, Efird JT, Dawood FZ, et al. Coronary artery calcium and risk of atrial fibrillation (from the Multi-Ethnic Study of Atherosclerosis). Am J Cardiol. 2014;114:1707–1712.

7. The Atherosclerosis Risk in Communities (ARIC) study: design and objectives. The ARIC Investigators. Am J Epidemiol. 1989;129:687–702.25

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