High Lp (a), the key driver for CVD and aortic valve stenosis regardless of CRP levels

The findings, published in the European Heart Journal, are clinically significant given the several pharmaceutical trials investigating Lp (a) lowering drugs.

The study found high lipoprotein(a) to be the main driver for the risk of aortic valve stenosis, myocardial infarction, and atherosclerotic cardiovascular disease at both low and high levels of C-reactive protein (CRP). The highest absolute risk was found in women and men, with a concomitant increase of CRP and Lp (a).

Recent studies have suggested that lipoprotein(a)-associated risk of ASCVD may be observed only in people with low-grade systemic inflammation (C-reactive protein ≥2 mg/l). Børge G Nordestgaard, Copenhagen University Hospital—Herlev and Gentofte, Denmark, and colleagues hypothesized that high lipoprotein(a) is a primary driver for the risk of ASCVD, aortic valve stenosis and myocardial infarction irrespective of C-reactive protein levels.

The investigators included 68 090 individuals from a prospective cohort study, Copenhagen General Population Study. Five thousand hundred four individuals developed ASCVD, 1220 aortic valve stenosis, and 2432 myocardial infarctions during a medical follow-up of 8.1 years.

The authors reported the following findings:

• The risk of ASCVD, myocardial infarction, and aortic valve stenosis increased with higher lipoprotein(a) and C-reactive protein values.
• For individuals with lipoprotein(a) in the 91st–100th percentiles (≥70 mg/dl, ≥147 nmol/l) versus the 1st–33rd percentiles (≤6 mg/dl, ≤9 nmol/l), the multivariable-adjusted hazard ratio for ASCVD was 1.61 for those with C-reactive protein <2 mg/l and 1.57 for those with C-reactive protein ≥2 mg/l.
• The corresponding values were 2.08 and 1.65 for myocardial infarction and 2.01 and 1.73 for aortic valve stenosis, respectively.
• The highest absolute 10-year risks were found in men aged 70–79 with lipoprotein(a) levels in the 91st–100th percentiles and C-reactive protein ≥2 mg/l, with 34% for ASCVD, 19% for myocardial infarction, and 13% for aortic valve stenosis. The corresponding values in women were 20%, 10%, and 8%, respectively.

"Our findings showed lipoprotein(a) to be the main driver for the risk of cardiovascular disease, aortic valve stenosis, and heart attack independent of C-reactive protein levels," the researchers wrote. "These are novel findings, as analyses like these have not been performed previously for aortic valve stenosis."

"On the risk of ASCVD, our results contrast those reported in two previous studies with less statistical power and performed respectively in a primary prevention cohort and a post hoc analyses of a clinical trial.," they conclude.

Reference:

Peter E Thomas, Signe Vedel-Krogh, Pia R Kamstrup, Børge G Nordestgaard, Lipoprotein(a) is linked to atherothrombosis and aortic valve stenosis independent of C-reactive protein, European Heart Journal, 2023;, ehad055, https://doi.org/10.1093/eurheartj/ehad055