In a randomized, double-blind, placebo-controlled study, 968 patients with symptomatic coronary artery disease were treated with statins alone or combined with the PCSK9 inhibitor, evolocumab, and assessed for change in percent, total volume, and regression of coronary atheroma.
Autosomal dominant hypercholesterolemia (ADH), a major risk for coronary heart disease, is associated with mutations in the genes encoding the low-density lipoproteins receptor (LDLR), its ligand apolipoprotein B (APOB) or PCSK9 (Proprotein Convertase Subtilin Kexin 9).
The R46L variant in the proprotein-convertase subtilisin-kexin type 9 (PCSK9) gene was associated with reduced levels of LDL and total cholesterol and with a lower risk of coronary artery disease.
In contrast, the regulatory effects of other GWAS risk SNPs were tissue-specific; abdominal fat emerged as an important gene-regulatory site for blood lipids, such as for the low-density lipoprotein cholesterol and coronary artery disease risk gene PCSK9 STARNET provides insights into gene-regulatory mechanisms for CMD risk loci, facilitating their translation into opportunities for diagnosis, therapy, and prevention.
Soon after, studies uncovered the role of PCSK9 in the regulation of LDL-receptor recycling and identified loss-of-function variants of PCSK9 that were associated with low circulating levels of LDL cholesterol (LDL-C) and a reduced risk of coronary artery disease.
Since the loss-of-function mutations in humans are associated with protection against coronary heart disease, and with no apparent deleterious effects, PCSK9 inhibition is becoming attractive as a new strategy for lowering LDL cholesterol (LDL-C) levels, particularly in combination with statins.
The aim of this review is to summarize the recent major advances in cardiovascular pharmacotherapy, with a focus on (1) the new approved drug for treatment of heart failure with reduced ejection fraction-sacubitril/valsartan; (2) proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors; (3) the novel reversal agents for non-vitamin K oral anticoagulants (NOACs); and finally, (4) new evidence on pharmacological treatment of coronary artery disease.
Polymorphisms in myocyte enhancer factor 2A, a transcription factor, tumor necrosis factor (ligand) superfamily, member 4, the OX40 ligand, and proprotein convertase subtilisin/kexin type 9, which affect low-density lipoprotein levels, have all been associated with an altered risk of coronary artery disease and myocardial infarction.
Gain-of-function PCSK9 mutations are associated with high low-density lipoprotein cholesterol (LDL-C) levels and increased risk of coronary artery disease, while loss-of-function variants result in low LDL-C and decreased risk of cardiovascular events.
Proprotein convertase subtilisin kexin 9 (PCSK9) is a new actor discovered in 2003 that is implicated in autosomal dominant hypercholesterolemia, cholesterol homeostasis and coronary heart disease.
Serum PCSK9 concentrations are higher in patients with coronary artery lesions, and are associated with SYNTAX and GRACE scores, suggesting that PCSK9 is a potential biomarker of the severity of coronary artery disease.
Familial Hypercholesterolaemia (FH) is an autosomal dominant disease, caused by mutations in LDLR, APOB or PCSK9, which results in high levels of LDL-cholesterol (LDL-C) leading to early coronary heart disease.
Few studies have investigated the relationship between PCSK9 levels and the severity of coronary artery disease in patients with acute coronary syndrome; thus, we herein aimed to investigate this relationship in patients with non-ST-elevation myocardial infarction (NSTEMI) who underwent coronary angiography.
Increased sortilin and its independent effect on circulating proprotein convertase subtilisin/kexin type 9 (PCSK9) in statin-naive patients with coronary artery disease.
The addition of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor, evolocumab, to statin therapy produced incremental regression of atherosclerotic plaques and a collaborative prevention of cardiovascular events in patients with coronary artery disease.