Lp(a) Is Linked to Atherothrombosis Independent of CRP

Feb 24, 2023
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Authors:
Thomas PE, Vedel-Krogh S, Kamstrup PR, Nordestgaard BG.
Citation:
Lipoprotein(a) Is Linked to Atherothrombosis and Aortic Valve Stenosis Independent of C-Reactive Protein. Eur Heart J 2023;Feb 21:[Epub ahead of print].
Summary By:
Debabrata Mukherjee, MD, FACC

Quick Takes

  • High Lp(a) was a main driver for the risk of ASCVD, MI, and aortic valve stenosis at both high and low CRP.
  • There may be potential benefits of lowering Lp(a) regardless of the level of CRP.
  • Lp(a)-lowering drugs under development need investigation in randomized clinical trials to assess impact on lowering cardiovascular risk.

Study Questions:

Is high lipoprotein(a) [Lp(a)] a main driver for the risk of atherosclerotic cardiovascular disease (ASCVD), myocardial infarction (MI), and aortic valve stenosis irrespective of C-reactive protein (CRP) levels?

Methods:

The investigators analyzed a total of 68,090 individuals from the Copenhagen General Population Study, a prospective cohort study. For the present study, participants with information on both plasma Lp(a) and CRP were included. Associations of elevated plasma Lp(a) and elevated CRP with ASCVD, MI, and aortic valve stenosis were evaluated with Cox proportional hazard regression with age as underlying timescale (= age adjusted) and delayed entry at study examination (left truncation).

Results:

During a median follow-up of 8.1 years, 5,104 individuals developed ASCVD, 2,432 MI, and 1,220 aortic valve stenosis. The risk of ASCVD, MI, and aortic valve stenosis increased with higher values of both Lp(a) and CRP. For individuals with Lp(a) in the 91st-100th percentiles (≥70 mg/dL, ≥147 nmol/L) vs. the 1st-33rd percentiles (≤6 mg/dL, ≤9 nmol/L), the multivariable-adjusted hazard ratio for ASCVD was 1.61 (95% confidence interval, 1.43-1.81) for those with CRP <2 mg/L and 1.57 (1.36-1.82) for those with CRP ≥2 mg/L (p for interaction = 0.87). The corresponding values were 2.08 (1.76-2.45) and 1.65 (1.34-2.04) for MI, and 2.01 (1.59-2.55) and 1.73 (1.31-2.27) for aortic valve stenosis, respectively (p for interaction = 0.15 and = 0.18). The highest absolute 10-year risks were found in men aged 70-79 years with Lp(a) levels in the 91st-100th percentiles and CRP ≥2 mg/L, with 34% for ASCVD, 19% for MI, and 13% for aortic valve stenosis. The corresponding values in women were 20%, 10%, and 8%, respectively. Hospitalization >1 day occurred in 11.8% of patients, and in-hospital death was rare (n = 41 [0.05%]).

Conclusions:

The authors report that high Lp(a) was a main driver for the risk of ASCVD, MI, and aortic valve stenosis independent of CRP.

Perspective:

This analysis from the Danish general population reports that high Lp(a) was a main driver for the risk of ASCVD, MI, and aortic valve stenosis at both high and low CRP levels. These data suggest potential benefits of lowering Lp(a) regardless of the level of CRP. Furthermore, these findings become more clinically significant given that several pharmacological trials are currently investigating Lp(a)-lowering drugs, which needs hard cardiovascular outcomes assessment.

Clinical Topics: Diabetes and Cardiometabolic Disease, Dyslipidemia, Prevention, Valvular Heart Disease, Advanced Lipid Testing, Lipid Metabolism

Keywords: Aortic Valve Stenosis, Atherosclerosis, C-Reactive Protein, Dyslipidemias, Lipoprotein(a), Myocardial Infarction, Myocardial Ischemia, Risk Factors, Secondary Prevention, Thrombosis, Vascular Diseases


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