Adherence to statin treatment in patients with familial hypercholesterolemia: A dynamic prediction model.

Background: Statins are the primary therapy in patient with heterozygous familial hypercholesterolemia (HeFH). Non-adherence to statin therapy is associated with increased cardiovascular risk.

Objective: We constructed a dynamic prediction model to predict statin adherence for an individual HeFH patient for each upcoming statin prescription.

Statin therapy reduces plasma angiopoietin-like 3 (ANGPTL3) concentrations in hypercholesterolemic patients via reduced liver X receptor (LXR) activation.

Background And Aims: Statins suppress hepatic mRNA expression of ANGPTL3 encoding angiopoietin-like 3 in healthy subjects, but it is unknown if plasma ANGPTL3 concentrations are affected by statins prescribed to hypercholesterolemic patients in clinical practice. We therefore investigated the effect of statin treatment on plasma ANGPTL3 concentrations in hypercholesterolemic patients. In addition, we explored the underlying mechanism by which statins regulate ANGPTL3 in vitro.

Interpretation of laboratory results after gastric bypass surgery: the effects of weight loss and time on 30 blood tests in a 5-year follow-up program.

Background: Long-term follow-up with blood tests is essential for bariatric surgery to be a successful treatment for obesity and related co-morbidities. Adverse effects, deficiencies, and metabolic improvements need to be controlled.

Objective: We investigated the effects of time and weight loss on laboratory results in each postoperative phase after laparoscopic Roux-en-Y gastric bypass (LRYGB).

Novel PCSK9 (Proprotein Convertase Subtilisin Kexin Type 9) Variants in Patients With Familial Hypercholesterolemia From Cape Town.

Objective: Familial hypercholesterolemia (FH) is characterized by elevated low-density lipoprotein-cholesterol and markedly increased cardiovascular risk. In patients with a genetic diagnosis, low-density lipoprotein receptor () mutations account for >90% of cases, apolipoprotein B () mutations for ≈5% of cases, while proprotein convertase subtilisin kexin type 9 () gain of function mutations are rare (<1% of cases). We aimed to evaluate the functional impact of several novel variants in a cohort of patients with FH by genetic cascade screening and in vitro functionality assays.

Risk Factors for Cholecystectomy After Laparoscopic Roux-En-Y Gastric Bypass.

Background: Patients who have undergone bariatric surgery are at risk for subsequent cholecystectomy. We aimed to identify risk factors for cholecystectomy after laparoscopic Roux-en-Y gastric bypass (LRYGB).

Methods: We conducted a retrospective case-control study of patients who underwent LRYGB between 2013 and 2015.

LDL-cholesterol target achievement in patients with heterozygous familial hypercholesterolemia at Groote Schuur Hospital: Minority at target despite large reductions in LDL-C.

Background And Aims: Familial hypercholesterolemia (FH) is characterized by markedly increased LDL-cholesterol (LDL-C) and premature cardiovascular disease (CVD). LDL-C lowering is the cornerstone of therapy. The aim of our study was to evaluate LDL-C target achievement and explore reasons for not reaching target in FH patients attending a public-sector lipid clinic at Groote Schuur Hospital in Cape Town, South Africa.

Achieved LDL cholesterol levels in patients with heterozygous familial hypercholesterolemia: A model that explores the efficacy of conventional and novel lipid-lowering therapy.

Background: A large proportion of patients with heterozygous familial hypercholesterolemia (heFH) do not reach low-density lipoprotein cholesterol (LDL-c) levels advocated by international guidelines (<70 mg/dL or <100 mg/dL).

Objective: We set out to model which proportion of patients reach targets using conventional and novel therapies.

Methods: We performed a cross-sectional analysis in a large cohort of genetically identified heFH patients and calculated the proportion reaching treatment targets in four scenarios: (1) after 50% LDL-c reduction (representing maximal dose statin); (2) after 70% LDL-c reduction (maximal dose statin + ezetimibe); (3) additional 40% LDL-c reduction representing cholesteryl ester transfer protein inhibitor (CETPi); and (4) 60% LDL-c reduction (proprotein convertase subtilisin/kexin type 9 inhibitors [PCSK9i]), on top of scenario 2.

Determining When to Add Nonstatin Therapy: A Quantitative Approach.

Background: Costs and uncertainty about the benefits of nonstatin therapies limit their use.

Objectives: The authors sought to identify patients who might benefit from the addition of a nonstatin to background statin therapy.

Methods: We performed systematic reviews of subgroup analyses from randomized trials and observational studies with statin-treated participants to determine estimated 10-year absolute risk of atherosclerotic cardiovascular disease (ASCVD) and to define high-risk and very high-risk patients.

Statins in Familial Hypercholesterolemia: Consequences for Coronary Artery Disease and All-Cause Mortality.

Background: A statin-induced reduction of coronary artery disease (CAD) events and mortality has not been adequately quantified in patients with heterozygous familial hypercholesterolemia (FH).

Objectives: This study estimated the relative risk reduction for CAD and mortality by statins in heterozygous FH patients.

Methods: The authors included all adult heterozygous FH patients, identified by the Dutch screening program for FH between 1994 and 2013, who were free of CAD at baseline.

Clinical phenotype in relation to the distance-to-index-patient in familial hypercholesterolemia.

Background And Aim: We evaluated whether the severity of the familial hypercholesterolemia (FH) phenotype, i.e. increased levels of low-density lipoprotein cholesterol (LDL-C) and cardiovascular disease (CVD) risk, decreases in more distantly related patients within one family.

PCSK9 inhibition: the way forward in the treatment of dyslipidemia.

Barely a decade after the discovery of the gene encoding proprotein convertase subtilisin/kexin type 9 (PCSK9) and its recognition as a key player in cholesterol metabolism, PCSK9 inhibition is now considered an exciting approach in the reduction of residual risk of cardiovascular disease. The progress from PCSK9 discovery to the development of targeted treatment has been unprecedented in terms of scale and speed. The first suggestion of a link between PCSK9 and hypercholesterolemia was published in 2003; a decade later, two meta-analyses of clinical trials comparing anti-PCSK9 treatment to placebo or ezetimibe, including >10,000 hypercholesterolemic individuals, were published.

The impact of LDLR function on fibroblast growth factor 21 levels.

Context: Fibroblast growth factor 21 (FGF21) has been described to have beneficial effects on glucose and lipid metabolism, and FGF21 analogs are currently evaluated in phase 1 trials. However, the complete spectrum of effects and regulators of FGF21 is yet partly elucidated. Recent studies have shown that FGF21 plays a role in transmembrane cholesterol transport.

Increased carotid intima-media thickness predicts cardiovascular events in aortic coarctation.

Background: Adult post-coarctectomy patients (CoA) demonstrate increased cardiovascular morbidity and mortality. The carotid intima-media thickness (CIMT), a marker for atherosclerosis, is increased in CoA. The aim was to evaluate the predictive value of CIMT for cardiovascular events.

Identifying genetic risk variants for coronary heart disease in familial hypercholesterolemia: an extreme genetics approach.

Mutations in the low-density lipoprotein receptor (LDLR) gene cause familial hypercholesterolemia (FH), a disorder characterized by coronary heart disease (CHD) at young age. We aimed to apply an extreme sampling method to enhance the statistical power to identify novel genetic risk variants for CHD in individuals with FH. We selected cases and controls with an extreme contrast in CHD risk from 17,000 FH patients from the Netherlands, whose functional LDLR mutation was unequivocally established.

Quality assessment of the genetic test for familial hypercholesterolemia in the Netherlands.

Introduction. Familial hypercholesterolemia (FH) is an inherited disorder associated with a severely increased risk of cardiovascular disease. Although DNA test results in FH are associated with important medical and ethical consequences, data on accuracy of genetic tests is scarce.

Inheritance pattern of familial hypercholesterolemia and markers of cardiovascular risk.

Studies in children and adults have resulted in conflicting evidence in the quest for the answer to the hypothesis that offspring from hypercholesterolemic mothers might have an increased cardiovascular risk. Previous studies might have suffered from limitations such as cohort size and clinical sampling bias. We therefore explored this hypothesis in large cohorts of both subjects with familial hypercholesterolemia (FH) and unaffected siblings in a wide age range.

Real-time MSE measurements for current profile control on KSTAR.

To step up from current day fusion experiments to power producing fusion reactors, it is necessary to control long pulse, burning plasmas. Stability and confinement properties of tokamak fusion reactors are determined by the current or q profile. In order to control the q profile, it is necessary to measure it in real-time.

Plasma PCSK9 levels and clinical outcomes in the TNT (Treating to New Targets) trial: a nested case-control study.

Objectives: The purpose of this study was to investigate whether high levels of circulating proprotein convertase subtilisin kexin type 9 (PCSK9) would increase cardiovascular risk in statin-treated patients.

Background: Statins activate low-density lipoprotein (LDL) receptor gene expression, thus lowering plasma LDL levels. But statins also activate the expression of PCSK9, a secreted inhibitor of the LDL receptor, thereby limiting their beneficial effects.

Advances in genetics show the need for extending screening strategies for autosomal dominant hypercholesterolaemia.

Aims Autosomal dominant hypercholesterolaemia (ADH) is a major risk factor for coronary artery disease. This disorder is caused by mutations in the genes coding for the low-density lipoprotein receptor (LDLR), apolipoprotein B (APOB), and proprotein convertase subtilisin/kexin 9 (PCSK9). However, in 41% of the cases, we cannot find mutations in these genes.

Cardiovascular risk in relation to functionality of sequence variants in the gene coding for the low-density lipoprotein receptor: a study among 29,365 individuals tested for 64 specific low-density lipoprotein-receptor sequence variants.

Aims: A plethora of mutations in the LDL-receptor gene (LDLR) underlie the clinical phenotype of familial hypercholesterolaemia (FH). For the diagnosis of FH, it is important, however, to discriminate between pathogenic and non-pathogenic mutations. The aim of the current study was to assess whether true pathogenic mutations were indeed associated with the occurrence of coronary artery disease (CAD) when compared with non-functional variants.

Plasma levels of PCSK9 and phenotypic variability in familial hypercholesterolemia.

The extent of hypercholesterolemia varies considerably in patients with familial hypercholesterolemia (FH). We hypothesized that the variability of the FH phenotype might be partly explained by variation in proprotein convertase subtilisin kexin type 9 (PCSK9) activity. Individuals between 18 and 53 years of age who had been tested for a pathogenic LDLR or APOB mutation were eligible.