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

Background: 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.

Aim: 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.

Methods: In this substudy of the RESPONSE randomized trial, we used reactive hyperemia peripheral artery tonometry (RH-PAT) 4 to 6 weeks 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 (≥3.84 mg/L and >239 μg/L, respectively).

Results: Patients were 57.4 ± 9.7 years 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).

Conclusion: 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.