Genetic variant leaves patients at risk of heart disease despite statin treatment
People with high concentrations of lipoprotein(a) in their blood may not get the same preventive benefit from statins, even if their LDL cholesterol is effectively lowered with the medication.
According to a study published April 27 in Circulation, individuals on statin therapy with a genetic variant at the LPA locus—which can cause higher Lp(a) levels—were at a 58 percent increased risk of myocardial infarction or coronary revascularization than other statin-taking patients. About 7.8 percent of the 10,780 statin users in the study had the genetic variant rs10455872, which is similar to the prevalence previously reported from a European population.
“The finding in this genome-wide study adds to the evidence for an important role of Lp(a) in contributing to cardiovascular risk in patients on statin therapy,” wrote corresponding author Joshua C. Denney, MD, MS, with the department of biomedical informatics at Vanderbilt University Medical Center, and colleagues. “The potential for lowering Lp(a) with existing and emerging therapeutic agents thus holds promise for further reducing CHD (coronary heart disease) events in statin-treated patients.”
Denney et al. linked another six variants located in the LPA/PLG (plasminogen) region to an increased risk of myocardial infarction or revascularization, although rs10455872 had the strongest association.
The study included 3,099 people who experienced CHD events during statin therapy and 7,681 controls without CHD events who underwent statin therapy of similar duration and intensity as those in the other group. The researchers also replicated their findings in a smaller cohort, which showed a 71 percent increased risk of CHD events with the LPA genetic variant.
In the original cohort, individuals with LDL cholesterol levels at 70 mg/dL or below were 2.43 times as likely to experience a CHD event if they had the minor allele.
Denney and colleagues said one limitation of the study is it combined data from multiple statins at different dosages across four medical centers. In addition, most of the individuals in the analysis were of European ancestry.
“Further study is needed to determine whether rs10455872 is associated with similar residual CHD risk in other ethnic populations since Lp(a) levels vary widely across ethnic groups,” they wrote.
Daniel joined TriMed’s Chicago editorial team in 2017 as a Cardiovascular Business writer. He previously worked as a writer for daily newspapers in North Dakota and Indiana.