Log in to MyACC
CRP Modifies Lp(a)-Related Risk for CHD
Quick Takes
- While among CHD-free individuals Lp(a) was significantly associated with incident CHD regardless of hsCRP, in participants with CHD at baseline, Lp(a) was related to recurrent CHD events only in those with residual inflammatory risk as defined by hsCRP ≥2 mg/L.
- The only group where increased Lp(a) was not associated with outcome was the group of CHD patients with very low hsCRP levels of <1 mg/L.
- The study is not generalizable considering only 15% of those with CHD were on statins at baseline and statins reduce hsCRP by 35-50%, which would reduce the majority to <2 mg/dL and a significant percent to <1 mg/dL.
Study Questions:
Does high-sensitivity C-reactive protein (hsCRP) modulate the association between lipoprotein(a) [Lp(a)] and coronary heart disease (CHD) in the general population when defined as prevalent and incident events?
Methods:
Data from 71,678 participants from eight European prospective population-based cohort studies were used (65,661 without/6,017 with established CHD at baseline; median follow-up 9.8/13.8 years, respectively). Fine and Gray competing risk-adjusted models were calculated according to accompanying hsCRP concentration (<2 and ≥2 mg/L). The limit of detection of Lp(a) mass was 0.38 mg/dL with a measurement range of 1.3–90.0 mg/dL. Lp(a) values >90 mg/dL were set at 90 mg/dL. Lp(a) was categorized into fifths using baseline cohort-specific quintiles (Q) for the whole population, and those without and those with CHD at baseline.
Results:
Among CHD-free individuals, increased Lp(a) levels were associated with incident CHD irrespective of hsCRP concentration: fully adjusted subdistribution hazard ratios [sHRs (95% confidence interval)] for the highest vs. lowest fifth of Lp(a) distribution were 1.45 (1.23–1.72) and 1.48 (1.23–1.78) for an hsCRP group of <2 and ≥2 mg/L, respectively, with no interaction found between these two biomarkers on CHD risk (p for interaction = 0.82). In those with established CHD, similar associations were seen only among individuals with hsCRP ≥2 mg/L [1.34 (1.03–1.76)], whereas among participants with an hsCRP concentration <2 mg/L, there was no clear association between Lp(a) and future CHD events [1.29 (0.98–1.71)] (highest vs. lowest fifth, fully adjusted models; p for interaction = 0.024).
Conclusions:
While among CHD-free individuals Lp(a) was significantly associated with incident CHD regardless of hsCRP, in participants with CHD at baseline, Lp(a) was related to recurrent CHD events only in those with residual inflammatory risk. These findings might guide adequate selection of high-risk patients for forthcoming Lp(a)-targeting compounds.
Perspective:
Mendelian randomization analysis suggests a potential causal effect of absolute Lp(a) levels on human longevity defined as parental life span, health span, and all-cause mortality (JAMA Netw Open 2020;Feb 28). This large population study demonstrates a high incremental risk attributable to Lp(a) for recurrent CHD events when the hsCRP is ≥2 mg/L but I do not think it is generalizable. Other studies have not found similar relationships, possibly because in this study, only 15% of those with CHD at baseline were on statins and LDL-C was only 4 mg/dL higher at baseline in those with CHD. Most importantly, statins lower hsCRP by 35-50%, which would result in the majority <2 mg/dL and many <1 mg/dL. And while statins do not lower Lp(a), the lower the LDL-C, the less attributable risk to Lp(a), particularly when the highest quintile of Lp(a) in those with CHD is only mildly more elevated than those without baseline CHD.
Clinical Topics: Dyslipidemia, Advanced Lipid Testing, Lipid Metabolism, Prevention
Keywords: C-Reactive Protein, Lipoprotein(a), Coronary Disease
< Back to Listings
