PCSK9 Inhibitor Induces a Transient Decrease in Neutrophil-Lymphocyte Ratio and Monocyte-Lymphocyte Ratio in Homozygous/Compound Heterozygous Familial Hypercholesterolemia Patients

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Abstract Background: Homozygous/compound heterozygous familial hypercholesterolemia (HoFH/cHeFH) is characterized by extremely elevated low-density lipoprotein-cholesterol (LDL-C) levels that have been reported to contribute to a long-term chronic systemic inflammation. The aims of this study are to describe the inflammatory profile of HoFH/cHeFH patients and explore the effect of PCSK9 inhibitor (PCSK9i) on a series of inflammatory biomarkers, neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), monocyte-HDL ratio (MHR), monocyte-lymphocyte ratio (MLR) and mean platelet volume-lymphocyte ratio (MPVLR). Methods: In this prospective cohort study, 21 definitive HoFH/cHeFH on high-intensity statins plus ezetimibe were placed on subcutaneous injections of PCSK9i 450mg every 4 weeks (Q4W). The biochemical parameters and inflammatory profile were analyzed at the day before PCSK9i therapy, 3 months and 6 months after PCSK9i therapy.Results: We found that HoFH/cHeFH on maximum tolerated statin dose plus ezetimibe displayed an elevated lipid and disturbed blood biomarker profile. After 3 months of add-on PCSK9i therapy, a significant reduction of LDL-C was observed. Meanwhile, percentage and count of neutrophils, monocyte counts, MPV, as well as two inflammatory biomarkers, NLR and MLR were reduced. However, at 6-month PCSK9i treatment, NLR and MLR returned to pre-PCSK9i treatment levels.Conclusions: PCSK9i induces a transient decrease in NLR and MLR in HoFH/cHeFH patients. Our results add evidence in evaluating the effects of PCSK9i on systemic inflammation.

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