May 25, 2017
3 min read

Personalized medicine may help patients with familial hypercholesterolemia

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PHILADELPHIA — Genomics, proteomics and imaging may enable a personalized medicine strategy for patients with familial hypercholesterolemia, an expert said at the National Lipid Association Scientific Sessions.

Eric Sijbrands, MD, PhD, professor of internal medicine, head of the division of pharmacology, vascular and metabolic diseases and head of the Erasmus cardiovascular genetics department at Erasmus Medical Center in Rotterdam, the Netherlands, said a personalized medicine approach could work in the familial hypercholesterolemia (FH) population, but “prospective testing is needed to identify the FH mutation and calculate a genomic risk score to guide an individual treatment plan. We should monitor the treatment effect with peptides and check this with coronary CTA.”

A challenge is that FH is a major locus disease, but “there are other factors involved as well, other genes ... and also environmental factors,” Sijbrands said, noting mortality rates for patients with FH have varied over time, indicating there is more at work than simply a genetic mutation.

Eric Sijbrands, MD, PhD
Eric Sijbrands

It is essential to obtain as much information as possible because FH is a lifelong disease with high burden, he said.

Of note, one study found that people with FH and CVD have much higher levels of lipoprotein(a) compared with people who have one or neither, Sijbrands said.

“Perhaps we are looking at a gene-gene interaction,” he said. “There has been a lot of work on additional genetic factors explaining CAD in this population.”

Out of that research, a genomic risk score was developed based on genes known to elevate CAD risk.

“This score correlates with what we’d like to identify in our patients,” he said. “The patients fear, and we do as well, that they might be carriers of a mutation and might be at higher risk for CVD. The gene score seems to help with that identification.”

Sijbrands said he is encouraged that “an increased genomic risk score is not a fact of life that you can do nothing against. We noticed that low BP, not smoking and low cholesterol all offset a higher [genomic] risk score. It might be that we have a starting point for tailored therapy and personalized medicine, starting with lifestyle interventions and perhaps more stringent efforts to achieve LDL targets and preferably [apolipoprotein B] targets.”

The question then becomes how best to monitor the program, he said. “Could it be that there is something from the atherosclerotic coronary arteries that tells us something about what we achieve with the therapy?”


In one study of patients with FH comparing those who were asymptomatic, those who had coronary artery calcium but no CAD and those who had CAD, the major differences between the groups were age, smoking status, HDL, use of antihypertensive medications and use of blood thinners, Sijbrands said.

From this cohort, six biomarker candidates “that we could connect to biological processes” were identified, he said. “If I had to bet, I would say histidine-rich lipoprotein is the winner. All the others might be related to medication use.” An area-under-the-curve analysis showed the C statistic for histidine-rich lipoprotein as a predictor of CVD was 0.922.

He said it was interesting that few people in the CAD group had any concentrations of the biomarkers left.

Risk prediction was further improved by CAC score, according to Sijbrands.

“What we need to do is combine the identification of the FH mutation with the genomic risk score,” he said. “Then we should come up with good treatment plans. During treatment, we can test the presence of these peptides, which in this respect are signals of healthy vasculature and successful treatment. If they drop, then we should perform imaging. I hope that with these methods that we can prove that we are able to treat patients instead of a disorder, that we are able to personalize medicine.” by Erik Swain


Sijbrands E. Role of noninvasive imaging in risk stratification and treatment of ASCVD. Presented at: National Lipid Association Scientific Sessions; May 18-21, 2017; Philadelphia.

Disclosure: Sijbrands reports receiving funding from Amgen, Astellas, Merck, Novartis and Pfizer.