Integrated Impact of hs-CRP, LDL-C and Lp(a) on Platelet Reactivity in Coronary Heart Disease Patients Receiving Dual Antiplatelet Therapy

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Abstract Background A recent research showed that among initially healthy women, a composite measure incorporating high-sensitivity C-reactive protein (hs-CRP), low-density lipoprotein cholesterol (LDL-C), and lipoprotein (a) (Lp(a)) levels demonstrated predictive value for cardiovascular event occurrence over three decades of follow-up. However, the underlying mechanism of their potential combined enhancement has not been elucidated yet. Purpose This research aimed to investigate the effects of hs-CRP, LDL-C and Lp(a) on platelet reactivity and assessed the differential impact of individual versus combined effects in coronary heart disease patients receiving dual antiplatelet therapy (DAPT). Method A total of 6786 coronary heart disease patients receiving dual antiplatelet therapy with measurements of hs-CRP, LDL-C and Lp(a) were included in this study. HTPR was defined by thrombelastography (TEG) measurement as an adenosine diphosphate-induced platelet-fibrin clot maximum amplitude (MA-ADP) exceeding 47 mm. Hs-CRP, LDL-C, and Lp(a) levels were classified as high (≥2 mg/L, ≥3.38 mmol/L, ≥300 mg/L) or low (<2 mg/L, <3.38 mmol/L, <300 mg/L) using established cutoffs. Result The mean age was 58.22 ± 10.30 years and 5260 (77.5%) were male. Multivariable logistic regression analysis revealed that isolated elevations in three biomarkers - hs-CRP (≥2 mg/L)(OR:1.522, 95% CI 1.355-1.710), LDL-C (≥3.38 mmol/L)(OR:1.332, 95% CI 1.142-1.554), and Lp(a) (≥300 mg/L)(OR:1.130, 95% CI 1.006-1.270) - were each independently associated with HTPR (P<0.001 for all associations). In the combined analysis of hs-CRP, LDL-CL and Lp(a) levels, using non-elevated values as reference, we observed a dose-response relationship between the number of elevated biomarkers and HTPR risk. The adjusted odds ratios progressively increased from 1.460 (95% CI 1.278-1.667) for one factor elevation to 1.613 (95% CI 1.372-1.897) for two factors elevation, reaching maximum association strength with all three factors elevation (OR=2.123, 95% CI 1.589-2.836). Conclusion In this large-sample study on patients with coronary heart disease who received DAPT, the results showed that hs-CRP, LDL-C and Lp(a) not only have independent associations with HTPR, but more importantly, the simultaneous elevation of these three biomarkers shows a significant synergistic effect with enhanced platelet reactivity. Our research further reinforces the significance of detecting the levels of hs-CRP, LDL-C and Lp(a) in clinical practice, indicating that the simultaneous elevation of these indicators may have potential importance in predicting thrombotic risk.

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