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.
Genetic and Clinical Characteristics of Patients With Homozygous and Compound Heterozygous Familial Hypercholesterolemia From Three Different Populations: Case Series
