C-reactive protein modifies lipoprotein(a)-related risk for coronary heart disease: the BiomarCaRE project

Natalie Arnold, Christopher Blaum, Alina Goßling, Fabian J Brunner, Benjamin Bay, Marco M Ferrario, Paolo Brambilla, Giancarlo Cesana, Valerio Leoni, Luigi Palmieri, Chiara Donfrancesco, Teresa Padró, Jonas Andersson, Pekka Jousilahti, Francisco Ojeda, Tanja Zeller, Allan Linneberg, Stefan Söderberg, Licia Iacoviello, Francesco GianfagnaSusana Sans, Giovanni Veronesi, Barbara Thorand, Annette Peters, Hugh Tunstall-Pedoe, Frank Kee, Veikko Salomaa, Renate B Schnabel, Kari Kuulasmaa, Stefan Blankenberg, Wolfgang Koenig, Christoph Waldeyer


BACKGROUND AND AIMS: Recent investigations have suggested an interdependence of lipoprotein(a) [Lp(a)]-related risk for cardiovascular disease with background inflammatory burden. The aim the present analysis was to investigate whether high-sensitive C-reactive protein (hsCRP) modulates the association between Lp(a) and coronary heart disease (CHD) in the general population.

METHODS: Data from 71 678 participants from 8 European prospective population-based cohort studies were used (65 661 without/6017 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).

RESULTS: Among CHD-free individuals, increased Lp(a) levels were associated with incident CHD irrespective of hsCRP concentration: fully adjusted sub-distribution 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 a hsCRP group of <2 and ≥2 mg/L, respectively, with no interaction found between these two biomarkers on CHD risk (Pinteraction = 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 a 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; Pinteraction = 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.

TidsskriftEuropean Heart Journal
StatusE-pub ahead of print - 18 jan. 2024


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