Genetic study shows high Lp(a) levels increase ischemic stroke risk
High plasma levels of lipoprotein(a) were associated observationally and causally with elevated risk for ischemic stroke, according to a genetic study published in the Journal of the American College of Cardiology.
The researchers analyzed 49,699 participants from the Copenhagen General Population Study (mean age, 58 years; 54% women) and 10,813 people from the Copenhagen City Heart Study. All participants had measurements of plasma Lp(a), LPA kringle-IV type 2 number of repeats and LPA rs10455872.
The primary endpoint was ischemic stroke as recorded in Danish national health registries and validated by doctors.
Elevated stroke risk
In an observational analysis of the Copenhagen General Population Study, compared with the first to 50th percentile of plasma Lp(a) (< 10 mg/dL or < 18 mmol/L), the 96th to 100th percentile (> 93 mg/dL or > 199 mmol/L) had a 60% greater risk for ischemic stroke (adjusted HR = 1.6; 95% CI, 1.24-2.05) at 10 years, Anne Langsted, MD, PhD, from the department of clinical biochemistry and the Copenhagen General Population Study, Herlev and Gentofte Hospital, Copenhagen University Hospital, and colleagues wrote.
In the Copenhagen General Population Study, the age- and sex-adjusted HR for ischemic stroke of a 50 mg/dL or 105 mmol/L higher plasma Lp(a) level was 1.2 (95% CI, 1.13-1.28), and the age- and sex-adjusted genetic causal RR for ischemic stroke was 1.2 (95% CI, 1.02-1.43) for LPA kringle-IV type 2 number of repeats and 1.27 (95% CI, 1.06-1.51) for LPA rs10455872, according to the researchers.
At 10 years, the highest risk for ischemic stroke, 17%, was observed in smokers older than 70 years who were in the 96th to 100th percentile of plasma Lp(a) (> 93 mg/dL or > 199 mmol/L), the researchers wrote.
In the Copenhagen City Heart Study, the researchers observed similar trends that did not reach statistical significance.
“The clear association of the two LPA genotype variants determining high lipoprotein(a) levels with risk of ischemic stroke indicates that the association may be causal,” Langsted and colleagues wrote.
Routine screening suggested
In a related editorial, Christie M. Ballantyne, MD, FACC, FACP, FAHA, FNLA, professor of medicine, chief of the section of cardiovascular research and director of the Center for Cardiovascular Disease Prevention at Baylor College of Medicine, wrote that the study underscores that Lp(a) screening could be a valuable tool.
“As someone in the dual role of preventive cardiologist and patient with a strong family history of cardiovascular disease, I think that we have sufficient evidence that high Lp(a) is strongly associated with an increased risk of MI, stroke and aortic valve stenosis,” he wrote. “It is time we routinely perform onetime screening for Lp(a) and provide this valuable information so that individuals who have inherited high Lp(a) can try to avoid stroke and MI. Why prevent prevention?” – by Erik Swain
Disclosures: Ballantyne reports he has received grants from Akcea, Amgen and Novartis and has consulted for Amgen and Novartis. Langsted reports no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.