Elevated Lp(a) levels increase risk of Atrial fibrillation

Atrial fibrillation (AF) is a cardiac arrhythmia associated with an elevated risk of stroke, heart failure, and mortality. However, preventative therapies are needed with ancillary benefits on its cardiovascular comorbidities. Lipoprotein(a) (Lp[a]) is a recognized risk factor for atherosclerotic cardiovascular disease (ASCVD), which itself increases atrial fibrillation risk, but it remains unknown whether Lp(a) is a causal mediator of AF independent of atherosclerotic cardiovascular disease.

Objectives

This study investigated the role of Lp(a) in atrial fibrillation and whether it is independent of atherosclerotic cardiovascular disease. Measured and genetically predicted Lp(a) levels were tested for association with 20,432 cases of incident atrial fibrillation in the UK Biobank Mendelian randomization analyses were performed by using summary-level data for AF from publicly available genome-wide association studies (N = 1,145,375).

Results:

• In the UK Biobank, each 50 nmol/L (23 mg/dL) increase in Lp(a) was associated with an increased risk of incident atrial fibrillation using measured Lp(a) and genetically predicted Lp(a)
• Mendelian randomization analyses using independent data replicated the effect
• There was no evidence of risk-conferring effect from low-density lipoprotein cholesterol or triglycerides, and only 39% of Lp(a) risk was mediated through atherosclerotic cardiovascular disease, suggesting that Lp(a) partly influences atrial fibrillation independent of its known effects on atherosclerotic cardiovascular disease.

Thus, the findings implicate Lp(a) as a potential causal mediator in the development of atrial fibrillation which show that the effects of Lp(a) extend across myocardial tissues. Ongoing clinical trials for Lp(a)-lowering therapies should evaluate effects on atrial fibrillation prevention.

Reference:

Elevated Lipoprotein(a) and Risk of Atrial Fibrillation: An Observational and Mendelian Randomization Study by Pedrum Mohammadi-Shemirani et al. published in the Journal of the American College of Cardiology.

https://www.jacc.org/doi/10.1016/j.jacc.2022.02.018

Keywords:

Elevated, Lp(a) levels, increase, risk, atrial fibrillation, independent, association, ischemic heart disease, aortic valve stenosis, Journal of the American College of Cardiology, Pedrum Mohammadi-Shemirani, Michael Chong, Sukrit Narula, Nicolas Perrot, David Conen, Jason D. Roberts, Sébastien Thériault, Yohan Bossé, Matthew B. Lanktree, Marie Pigeyre, and Guillaume Paré, atherosclerotic cardiovascular disease