Lipoprotein(a): Silent killer or crystal ball?

Lipoproteins are made up of lipids and the proteins that transport lipids. Lipoproteins in the blood shuttle lipids such as cholesterol and triglycerides from the intestine to tissues throughout the body.

Lipoprotein (a), or Lp(a), consists of cholesterol and two proteins, Apo-B 100 and Apo(a). High levels of Lp(a) accelerate the buildup of cholesterol on artery walls, increasing a person’s risk for acute coronary syndrome, or ACS, a blanket term for several diseases associated with sudden reduced blood flow to the heart. In the U.S., ACS affects 15.5 million people and is a leading cause of death.

Elena Aikawa’s lab at Brigham and Women’s Hospital in Boston focuses on studying the drivers of ACS and finding diagnostic biomarkers to identify populations at risk for cardiovascular diseases. In a collaborative study with Pawel Szulc’s lab at the University of Lyon published in the Journal of Lipid Research, postdoc Francesca Bartoli–Leonard and a team of researchers assessed whether a relationship exists between high levels of Lp(a) and ACS in older men.

“With the American Heart Association estimating a person has a heart attack every 41 seconds, it’s imperative we as scientists investigate how to predict these events in patients before they happen,” Bartoli–Leonard said.

The Lp(a) levels in the blood are determined by variations in the LPAgene locus. Hence even individuals with healthy diet and exercise habits may be at high risk for ACS if they have genetic variants that produce high Lp(a) levels.

“Unfortunately, the guidelines from the American Heart Association only suggest clinicians measure lipoprotein(a) in individuals with hypercholesterolemia,” Bartoli–Leonard said, “meaning there are large parts of the American population who may be at risk for lipoprotein(a)-driven cardiovascular disease who are simply unaware.”

Doctors manage ACS with apheresis, a filtering process that removes Lp(a) particles from the blood. No drugs are approved for reducing Lp(a) levels; however, some therapies are currently in clinical trials.

“Clinical treatment for cardiovascular disease can be costly,” Bartoli–Leonard said. “We wanted to find a marker that could be assessed once, and for a relatively low cost, that may help stratify which patients will have a coronary event.”

To determine risk, the team tracked Lp(a) in 755 men over age 60 who live in the same community, following their coronary events and overall health for up to eight years. The researchers report that participants with blood Lp(a) levels higher than 50 milligrams per deciliter had an increased incidence of ACS.

For, this investigation, only Caucasian males living in France were recruited in the study population. “However, these results are consistent with reports that included more diverse ethnic backgrounds and those assigned female at birth," the authors wrote in the paper.

The study provides further evidence that Lp(a) levels predict the likelihood of a coronary event independent of common risk factors such as smoking, body mass index and cholesterol levels.

“We hope that our work, alongside with the other studies, which also look at Lp(a) in the general population, encourage the health care providers to assess Lp(a) routinely in the clinic,” Bartoli–Leonard said.