CVD Risk Stratification in the PCSK9 Era: Is There a Role for LDL Subfractions?

Abstract

Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors reduce the risk of cardiovascular events and all-cause mortality in patients at high risk of cardiovascular disease (CVD). Due to high costs and unknown long-term adverse effects, critical evaluation of patients considered for PCSK9 inhibitors is important. It has been proposed that measuring low-density lipoprotein (LDL) subfractions, or LDL particle numbers (LDL-P), could be of value in CVD risk assessment and may identify patients at high risk of CVD. This review evaluates the evidence for the use of LDL subfractions, or LDL-P, when assessing CVD risk in patients for whom PCSK9 inhibitors are considered as a lipid-lowering therapy. Numerous methods for measuring LDL subfractions and LDL-P are available, but several factors limit their availability. A lack of standardization makes comparison between the different methods challenging. Longitudinal population-based studies have found an independent association between different LDL subfractions, LDL-P, and an increased risk of cardiovascular events, but definitive evidence that these measurements add predictive value to the standard risk markers is lacking. No studies have proven that these measurements improve clinical outcomes. PCSK9 inhibitors seem to be effective at lowering all LDL subfractions and LDL-P, but any evidence that measuring LDL subfractions and LDL-P yield clinically useful information is lacking. Such analyses are currently not recommended when considering whether to initiate PCKS9 inhibitors in patients at risk of CVD.

The heterogeneity of lipoproteins and their role in the development of cardiovascular diseases

“…Тем не менее, инсулинрезистентным пациентам, а также пациентам, страдающим метаболическим синдромом и гипертриглицеридемией, для которых только ХС ЛНП недостаточен и не способен адекватно отражать риск ССЗ, рекомендовано измерение подфракций ЛНП [4]. Определение концентрации мпЛНП в общей популяции может способствовать более точной стратификации рисков на фоне нормальных значений ХС ЛНП и обнаружению пациентов с высоким резидуальным риском на фоне проводимой гиполипидемической терапии [38]. Можно предположить, что повышенное содержание мпЛНП на фоне одного из существующих независимых факторов риска, способствует более раннему и тяжелому развитию атеросклероза и его осложнений.…”

Study the Relationship of PCSK9 Gene Polymorphism and PCSK9 Protein on Serum Bad Cholesterol and Risk of CVDs in Iraqi Patients

“…Identifying those at highest risk of CVDs and ensuring they receive appropriate therapy can prevent premature deaths. Access to essential non-communicable disease medicines and basic health technologies in all primary health care facilities is essential to ensure that those in need receive treatment and counseling (2) . Dyslipidemia has become an highly important risk factor to target in both the primary and secondary prevention of CVDs.…”

Chemical Constituents with Inhibitory Activities on Proprotein Convertase Subtilisin/kexin Type 9 Expression from the Aerial Parts of Penthorum chinense

“…In particular, extracts or individual constituents from P. chinense displayed therapeutic potentials for hepatic disorders such as hepatitis [5,6], fatty liver [3,4], and hepatocarcinoma [2]. As our ongoing project to pursue naturally occurring inhibitors on proprotein convertase subtilisin/kexin type 9 (PCSK9) [9][10][11], 39 compounds including two new neolignans and two naturally occurring chalcone glycosides were isolated and all isolates were evaluated for their inhibitory activities on the expression of PCSK9 which is involved in degrading low-density lipoprotein receptor (LDLR) and thereby results in inhibiting LDL uptake into cells [12][13][14]. In addition, PCSK9-LDLR interaction was tested for all isolated compounds.…”