Causal Role for Lp(a) in Atrial Fibrillation
Using data from 435,579 participants in the UK Biobank, the researchers identified 20,432 cases of incident AF over a median of 11 years of follow-up. They also constructed a genetic risk score for Lp(a) using genetic variants within 500 kb of the LPA gene. After common AF risk factors were controlled for, results showed a 3% increased risk for incident AF per 50 nmol/L increase in Lp(a) at enrollment (hazard ratio [HR], 1.03; 95% CI, 1.02 - 1.05).

A Mendelian randomization analysis showed a similar association between genetically predicted Lp(a) and AF (odds ratio [OR], 1.03; 95% CI, 1.02 - 1.05). To replicate the results, the investigators performed separate Mendelian randomization analyses using publicly available genome-wide association study (GWAS) statistics from the largest GWAS of AF involving more than 1 million participants and from the FinnGen cohort involving more than 114,000 Finnish residents.

The analyses showed a 3% increase in risk for AF in the genome-wide study (OR, 1.03; 95% CI, 1.02 - 1.05) and an 8% increase in risk in the Finnish study (OR, 1.08; 95% CI, 1.04 - 1.12) per 50 nmol/L increase in Lp(a). There was no evidence that the effect of observed or genetically predicted Lp(a) was modified by prevalent ischemic heart disease or aortic stenosis. Thus, a nominally significant effect of Lp(a) on AF.