medwireNews: Results from two studies published in JAMA Cardiology show that elevated lipoprotein(a) levels are associated with an increased risk for progression of coronary plaque burden and aortic stenosis.
Both groups of researchers stress the need for clinical trials investigating the effect of lipoprotein(a)-lowering therapies on these outcomes.
The first study, by Nick Nurmohamed (University of Amsterdam, the Netherlands) and colleagues used coronary computed tomography angiography to measure coronary plaque burden at two timepoints a median of 10.2 years apart.
At baseline, the 267 patients (mean age 57 years, 57% men) with suspected coronary artery disease had a median lipoprotein(a) level of 25 nmol/L, and a median percent atheroma volume (PAV) of 3.3%, reflecting a median total plaque volume of 96.2 mm3.
The researchers report that, at baseline, the 61 patients with lipoprotein(a) levels of 125 nmol/L or higher had significantly greater PAV than the 206 with lipoprotein(a) levels below this threshold, at 5.8% vs 2.9%.
Furthermore, patients with high lipoprotein(a) levels had greater plaque progression between baseline and follow-up than those with lower lipoprotein(a) levels. Specifically, PAV increased by 3.6 percentage points during the follow-up period in patients with lipoprotein(a) levels of 125 nmol/L or higher and by 1.6 percentage points in those with lower levels.
After adjustment for age, sex, and clinical risk factors, Nurmohamed et al showed that every doubling of lipoprotein(a) resulted in a significant additional 0.32% increment in percent atheroma volume for every 10 years of follow-up.
In addition, each doubling of lipoprotein(a) level was associated with a significant 23% higher risk for the presence of low-density plaque at baseline and a 21% higher risk at follow-up.
Patients with higher lipoprotein(a) levels also had a significant 16% to 24% increased risk for pericoronary adipose tissue attenuation around both the right circumflex artery and left anterior descending coronary artery at baseline and follow-up.
Nurmohamed et al conclude: “Collectively, these data confirm the profound impact of elevated [lipoprotein](a) levels on coronary atherogenesis of high-risk, inflammatory, rupture-prone plaques which may explain the increased risk for myocardial infarction observed in prior studies.”
They add: “Future studies investigating the effect of [lipoprotein](a)-lowering therapies on coronary plaque burden and pericoronary inflammation are eagerly awaited.”
The second study, a systematic review and meta-analysis of 710 patients with aortic stenosis (mean age 65 years, 70% men) from five longitudinal clinical studies, showed that higher plasma lipoprotein(a) concentrations are associated with faster hemodynamic progression of the disease.
Benoit Arsenault (Université Laval, Québec, Canada) and co-authors found that patients in the top lipoprotein(a) tertile had a significant 41% faster progression of peak aortic jet velocity on echocardiography than those in the bottom tertile, and a significant 57% faster progression of mean transvalvular gradient.
They observed similar results when plasma lipoprotein(a) concentrations were treated as a continuous variable but found no associated between plasma lipoprotein(a) concentrations – either as tertiles or a continuous variable – and annualized progression rates of the aortic valve area.
The researchers say their findings suggest that lipoprotein(a) “represents an important potential therapeutic target in aortic stenosis,” particularly as it “is one of the last remaining cardiovascular conditions without an effective medical therapy.”
The believe “that large-scale randomized clinical trials should be performed to investigate whether the association between lipoprotein(a) and aortic stenosis progression is causal and whether lipoprotein(a)-lowering therapies could influence aortic stenosis progression.”
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JAMA Cardiol 2024; doi:10.1001/jamacardio.2024.1874
JAMA Cardiol 2024; doi:10.1001/jamacardio.2024.1882
