Endothelial function after ST-elevation myocardial infarction in patients with high levels of high-sensitivity CRP and Lp-PLA2: A substudy of the RESPONSE randomized trial.

Jasveen J Kandhai-Ragunath,Jan Van Es,Harald T Jørstad,Carine J.M Doggen,Ron J.G Peters,Cees Doelman,Bjorn De Wagenaar,Clemens Von Birgelen

doi:10.1016/j.carrev.2016.12.019

Abstract

The combination of high levels of high-sensitive C-reactive protein (hs-CRP) and lipoprotein-associated phospholipase-A2 (Lp-PLA2) was recently shown to correlate with increased cardiovascular risk. Endothelial dysfunction is also known to be a risk factor for cardiovascular events. To test among patients with previous ST-elevation myocardial infarction (STEMI) the hypothesis that high levels of both hs-CRP and Lp-PLA2 may be associated with impaired endothelium-dependent vasodilatation. In this substudy of the RESPONSE randomized trial, we used reactive hyperemia peripheral artery tonometry (RH-PAT) 4 to 6weeks after STEMI and primary percutaneous coronary intervention (PPCI) to non-invasively assess endothelial function (RH-PAT index <1.67 identified endothelial dysfunction). Reliable measurements of RH-PAT, hs-CRP, and Lp-PLA2 were obtained in 68 patients, who were classified as high-risk if levels of both hs-CRP and Lp-PLA2 were in the upper tertile (≥3.84mg/L and >239μg/L, respectively). Patients were 57.4±9.7years and 53 (77.9%) were men. 11 (16%) patients were classified as high-risk and 57 (84%) as low-to-intermediate-risk. The RH-PAT index was 1.68±0.22 in high-risk and 1.95±0.63 in low-to-intermediate-risk patients (p=0.17). Endothelial dysfunction was present in 8 (72.7%) high-risk and 26 (45.6%) low-to-intermediate-risk patients (p=0.09). Framingham risk score, NT-proBNP and fibrinogen levels were higher in high-risk patients (p≤0.03). In this population of patients with recent STEMI and PPCI, we observed between patients with high hs-CRP and Lp-PLA levels and all other patients no more than numerical differences in endothelial function that did not reach a statistical significance. Nevertheless, further research in larger study populations may be warranted.

Highlights

While common cardiovascular risk factors at best provide a reasonable prediction of cardiovascular events [1], the addition of biomarkers of systemic inflammation, such as high-sensitive C-reactive protein, can improve risk prediction [2]
Lipoprotein-associated phospholipase A2 (Lp-PLA2), a specific marker for vascular inflammation, was found to predict future cardiovascular events independently of high-sensitive C-reactive protein (hs-CRP) [5,6,7], suggesting an additive role for risk prediction. This is supported by the fact that in a populationbased study, the combination of elevated levels of hs-CRP and lipoproteinassociated phospholipase-A2 (Lp-PLA2) correlated with increased cardiovascular risk [8]
A total of 11 patients with Lp-PLA2 and high-sensitive C-reactive protein (hsCRP) levels in the highest tertile were classified as high-risk, while the remaining 57 patients were classified as low-to-intermediate-risk

Summary

Introduction

Lipoprotein-associated phospholipase A2 (Lp-PLA2), a specific marker for vascular inflammation, was found to predict future cardiovascular events independently of hs-CRP [5,6,7], suggesting an additive role for risk prediction. This is supported by the fact that in a populationbased study, the combination of elevated levels of hs-CRP and Lp-PLA2 correlated with increased cardiovascular risk [8]. Conclusion: In this population of patients with recent STEMI and PPCI, we observed between patients with high hsCRP and Lp-PLA levels and all other patients no more than numerical differences in endothelial function that did not reach a statistical significance. Further research in larger study populations may be warranted

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