Individuals with high lipoprotein (a) [Lp(a)] and concomitant elevated high-sensitivity C-reactive protein (hsCRP) were associated with increased risk for atherosclerosis cardiovascular disease (ASCVD) and all-cause mortality. These findings were published in the Journal of the American College of Cardiology.

Researchers from Wake Forest University School of Medicine sourced data for this analysis from the Multi-Ethnic Study of Atherosclerosis (MESA), which recruited asymptomatic individuals from 6 communities in the United States. Individuals (N=6814) have been assessed on 6 occasions since 2000 by standard laboratory tests. Cardiovascular disease (CVD) and mortality risk were associated with elevations in Lp(a) and hsCRP.

At baseline, participants were aged mean 62±10.4 years, 52.5% were women, BMI was 28.2±5.5 kg/m2, 36.6% were White, 28.7% Black, 22.7% Hispanic, and 12.0% Asian. Stratified by low (<2 mg/L; n=2388) and high (³2 mg/L; n=2273) hsCRP, cohorts differed significantly by gender (P <.001), BMI (P <.001), and ethnicity (P <.001).

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Individuals who had high hsCRP tended to have higher rates of diabetes (14.0% vs 9.8%; P <.001), hypertension (48.8% vs 34.9%; P <.001), and to be on therapy for hypertension (39.1% vs 27.4%; P <.001).

Over a mean follow-up time of 13.6 years, a total of 684 cardiovascular events occurred.

Among individuals with high hsCRP (³50 mg/dL), risk for CVD associated with high Lp(a) (HR, 1.52; 95% CI, 1.18-1.95; P =.001), increasing with every log(Lp[a]) unit (HR, 1.32; 95% CI, 1.05-1.65; P =.016).

Individuals with both elevated Lp(a) and hsCRP were at highest risk for CVD (HR, 1.62; 95% CI, 1.25-2.10; P <.001) and had significantly shorter time to first event (P =.006) compared with other individuals.

Stratified by ethnicity, individuals with high Lp(a) and hsCRP who were not Black had similarly high risk for CVD (HR, 1.66; 95% CI, 1.17-2.35; P =.005) as Black individuals (HR, 1.63; 95% CI, 1.09-2.44; P=.016) compared with other patient groups. However, Black individuals were associated with shorter time to first event (P =.018).

Stratified by gender, both men (HR, 1.61; 95% CI, 1.12-2.31; P =.01) and women (HR, 1.52; 95% CI, 1.06-2.18; P =.02) with high Lp(a) and hsCRP had similar increased risk for CVD and shorter time to first event (both P £.01) compared with patients without concomitant elevations.

Risk for all-cause mortality was independently associated with elevations of both Lp(a) and hsCRP (HR, 1.39; 95% CI, 1.12-1.72; P <.01).

These findings may have been biased as some patients were on lipid-lowering therapies.

The study authors concluded that Lp(a)-associated ASCVD risk was only elevated among individuals who had concomitant high hsCRP, indicating that these patients likely require closer CVD surveillance.


Zhang W, Speiser JL, Ye F, et al. High-Sensitivity C-Reactive Protein Modifies the Cardiovascular Risk of Lipoprotein(a): Multi-Ethnic Study of Atherosclerosis. J Am Coll Cardiol. 2021;78(11):1083-1094. doi:10.1016/j.jacc.2021.07.016