Sex differences in inflammatory biomarkers during long-term evolocumab therapy

Atherosclerotic cardiovascular disease remains a predominant cause of morbidity and mortality worldwide, driven by complex interactions between lipid metabolism and chronic inflammation. While evolocumab, a proprotein convertase subtilisin/kexin type 9 inhibitor, is established in lowering low-density lipoprotein cholesterol (LDL-C) and cardiovascular risk, its long-term effects on inflammatory biomarkers-and potential sex-specific responses-are not fully understood.

This study aimed to elucidate the impact of prolonged evolocumab therapy on inflammation markers in a routine clinical setting, focusing on sex-related differences.

We analyzed data from 202 hypercholesterolemic patients (111 men, 91 women) treated with evolocumab for at least 36 months. Key inflammatory indices, including the monocyte-to-high-density lipoprotein cholesterol ratio (MHR) and platelet-to-monocyte ratio (PMR), were assessed longitudinally alongside traditional lipid parameters.

Significant sex-related differences emerged in inflammatory profiles: men exhibited consistently higher MHR levels at baseline (P = .010) and throughout follow-up (P < .001), whereas women showed persistently elevated PMR values (P < .001). Intriguingly, a strong inverse correlation was observed between lymphocyte count and lipoprotein(a) levels in women (r_s = -0.885, P < .001), a pattern absent in men, suggesting distinct immunometabolic mechanisms.

Our findings reveal pronounced biological sex differences in inflammatory responses to long-term evolocumab therapy, highlighting the need to incorporate sex-specific considerations in cardiovascular risk management and treatment monitoring. These novel insights pave the way for personalized therapeutic strategies and call for further investigation into the clinical significance of inflammation in lipid-lowering treatment outcomes.