Abstract

Introduction: Elevated Lipoprotein(a) (Lp[a]) levels are strongly and linearly associated with coronary artery disease (CAD) and calcific aortic valve stenosis (CAVS). Observational studies in primary and secondary prevention settings revealed that Lp(a) and other CAD risk factors such as C-reactive protein (CRP) levels, a biomarker of systemic inflammation, may jointly predict CAD risk. Whether Lp(a) and CRP levels also jointly predict CAVS risk is unknown. Methods: We investigated the long-term associations of Lp(a) with CAD and CAVS according to CRP levels in the European Prospective Investigation Into Cancer and Nutrition (EPIC)-Norfolk study. Lp(a) and CRP levels were measured in 18,459 participants who were followed for 20 years. During the follow-up, 3915 and 418 participants had incident CAD and CAVS, respectively. Results: As presented in Figure 1, in comparison to individuals with low Lp(a) levels (<30 mg/dL) and low CRP levels (<2.0 mg/dL), those with elevated Lp(a) (>30 mg/dL) and low CRP levels (<2.0 mg/dL) and those with elevated Lp(a) (>30 mg/dL) and elevated CRP levels (>2.0 mg/dL) had a higher CAD risk (hazard ratio [HR] = 1.38 [95% CI, 1.28-1.49] and 1.93 [95% CI, 1.74-2.13] , respectively), and a higher CAVS risk (HR = 1.46 [95% CI, 1.08-1.98] and 1.87 [95% CI, 1.40-2.49], respectively). Conclusions: Results of this study confirm the joint association of high Lp(a) and CRP levels on incident CAD and extend these joint associations to valvular diseases such as CAVS. Lowering Lp(a) levels may warrant further investigation in the prevention of CAD and CAVS, especially in the context of systemic inflammation.

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