High-Sensitivity CRP Modifies the CV Risk of Lp(a)

Sep 07, 2021
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Authors:
Zhang W, Speiser JL, Ye F, et al.
Citation:
High-Sensitivity C-Reactive Protein Modifies the Cardiovascular Risk of Lipoprotein(a). J Am Coll Cardiol 2021;78:1083-1094.
Summary By:
Melvyn Rubenfire, MD, FACC

Quick Takes

  • The observation that Lp(a) does not increase risk of CVD events without a concomitant hsCRP >2 mg/dl requires confirmation in the very large historic statin trials and other large observational studies.
  • In the MESA study of coronary artery calcification by computed tomography, primary care physicians were aware of the coronary calcium scores at baseline and free to monitor and treat CV risk factors with statins and aspirin as they felt indicated.
  • The impact of the >20% increase in Lp(a) and 60% decrease in hsCRP by statins, as well as the anti-inflammatory effect of aspirin without an effect on hsCRP, are confounders that could have seriously impacted the results.

Study Questions:

Is lipoprotein (a) [Lp(a)]-associated atherosclerotic cardiovascular disease (ASCVD) risk modified by high-sensitivity C-reactive protein (hsCRP) in the context of primary prevention?

Methods:

The study included 4,679 participants from the MESA (Multi-Ethnic Study of Atherosclerosis) apolipoprotein ancillary data set. Cox proportional hazards models and Kaplan-Meier curves were used to assess the association among Lp(a), hsCRP, and time to cardiovascular disease (CVD) events.

Results:

During a mean follow-up of 13.6 years, 684 CVD events occurred. A significant interaction was observed between Lp(a) and hsCRP (p = 0.04). With hsCRP <2 mg/L, no significant CVD risk was observed at any level of Lp(a) from <50 mg/dl to >100 mg/dl. However, with hsCRP ≥2 mg/L, a significant CVD risk was observed with Lp(a) of 50-99.9 mg/dl (hazard ratio [HR], 1.36; 95% confidence interval [CI], 1.02-1.81) and Lp(a) ≥100 mg/dl (HR, 2.09; 95% CI, 1.40-3.13). Isolated elevations of either Lp(a) or hsCRP were not associated with increased CVD risk. In contrast, the combination of elevated Lp(a) (≥50 mg/dl) and hsCRP ≥2 mg/L) was independently associated with significant CVD risk (HR, 1.62; 95% CI, 1.25-2.10) and all-cause mortality (HR, 1.39; 95% CI, 1.12-1.72).

Conclusions:

Lp(a)-associated ASCVD risk is observed only with concomitant elevation of hsCRP. Individuals with concomitant presence of elevated Lp(a) and systemic inflammation have greater ASCVD risk and all-cause mortality, and thus may merit closer surveillance and more aggressive ASCVD risk management.

Perspective:

The findings are derived from baseline lipids and limited to low-risk persons without CVD with an average age of 62 years who had an annual CVD event rate including strokes of about 1% over nearly 14 years. Since the findings were independent of other known CVD risk factors, when either Lp(a) or hsCRP is elevated, it is reasonable to assess the other, and when both are elevated, consider more aggressive ASCVD management. But much needs to be done prior to incorporating the strategy into guidelines.

Clinical Topics: Dyslipidemia, Prevention, Advanced Lipid Testing, Lipid Metabolism, Nonstatins, Novel Agents, Statins

Keywords: Apolipoproteins, Atherosclerosis, Cardiovascular Diseases, C-Reactive Protein, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Inflammation, Lipoprotein(a), Lipids, Primary Prevention, Risk Factors, Stroke, Vascular Diseases


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