Ascertainment Bias in the Association Between Elevated Lipoprotein(a) and Familial Hypercholesterolemia.

Background: Lipoprotein(a) is an atherogenic low-density lipoprotein-like particle and circulating levels are largely determined by genetics. Patients with familial hypercholesterolemia (FH) have elevated lipoprotein(a); however, it remains unclear why.

Objectives: This study compared the levels of lipoprotein(a) and associated genetic factors between individuals that were ascertained for FH clinically versus genetically.

Lipoprotein(a) the Insurgent: A New Insight into the Structure, Function, Metabolism, Pathogenicity, and Medications Affecting Lipoprotein(a) Molecule.

Lipoprotein(a) [Lp(a)], aka "Lp little a", was discovered in the 1960s in the lab of the Norwegian physician Kåre Berg. Since then, we have greatly improved our knowledge of lipids and cardiovascular disease (CVD). Lp(a) is an enigmatic class of lipoprotein that is exclusively formed in the liver and comprises two main components, a single copy of apolipoprotein (apo) B-100 (apo-B100) tethered to a single copy of a protein denoted as apolipoprotein(a) apo(a).

Risk of Premature Atherosclerotic Disease in Patients With Monogenic Versus Polygenic Familial Hypercholesterolemia.

Background: A pathogenic variant in LDLR, APOB, or PCSK9 can be identified in 30% to 80% of patients with clinically-diagnosed familial hypercholesterolemia (FH). Alternatively, ∼20% of clinical FH is thought to have a polygenic cause. The cardiovascular disease (CVD) risk associated with polygenic versus monogenic FH is unclear.

Simplified Canadian Definition for Familial Hypercholesterolemia.

Familial hypercholesterolemia (FH) is an autosomal codominant lipoprotein disorder characterized by elevated low-density lipoprotein cholesterol (LDL-C) and high risk of premature atherosclerotic cardiovascular disease. Definitions for FH rely on complex algorithms that are on the basis of levels of total or LDL-C, clinical features, family history, and DNA analysis that are often difficult to obtain. We propose a novel simplified definition for FH.

Attainment of Recommended Lipid Targets in Patients With Familial Hypercholesterolemia: Real-World Experience With PCSK9 Inhibitors.

Background: Familial hypercholesterolemia (FH) is the most common inherited dyslipidemia and is characterized by elevated low-density lipoprotein cholesterol (LDL-C) and markedly increased risk for atherosclerotic cardiovascular disease. Lipid-lowering therapy is the mainstay of treatment, but few patients with FH are able to achieve commonly recommended lipid targets.

Methods: We examined changes in LDL-C levels in patients in the British Columbia FH Registry from 2015 to 2017, corresponding to the period immediately before, and the first 2 years after, availability of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors in Canada.

Increased prevalence of clinical and subclinical atherosclerosis in patients with damaging mutations in ABCA1 or APOA1.

Background: A low level of high-density lipoprotein cholesterol (HDL-C) is a common clinical scenario and poses challenges for management. Many patients with low HDL-C harbor a damaging mutation in ABCA1 or APOA1, but the clinical implications of genetic testing for these mutations are unclear.

Objective: The purpose of this study was to investigate the prevalence of clinical or subclinical atherosclerosis among patients with low HDL-C due to a mutation in ABCA1 or APOA1, compared with patients with low HDL-C without such a mutation.

Statin-Associated Muscle Adverse Events: Update for clinicians.

Statins are potent medications which reduce low-density lipoprotein cholesterol (LDL-C) levels. Their efficacy in cardiovascular risk reduction is well established and indications for their use are expanding. While statins are generally well tolerated and safe, adverse events are relatively common, particularly statin-associated muscle adverse events (SaMAEs), which are the most frequently encountered type of adverse event.

Contemporary Trends in the Management and Outcomes of Patients With Familial Hypercholesterolemia in Canada: A Prospective Observational Study.

Background: Heterozygous familial hypercholesterolemia (HeFH) is one of the most common genetic diseases in the world and an important cause of premature cardiovascular (CV) disease. The purpose of this study was to characterize the clinical features, current treatment patterns, and CV outcomes of patients with HeFH in British Columbia, Canada.

Methods: We conducted a longitudinal observational study of patients with HeFH attending a specialized lipid clinic.

Diagnosis, Prevention, and Management of Statin Adverse Effects and Intolerance: Canadian Consensus Working Group Update (2016).

The Canadian Consensus Working Group has updated its evaluation of the literature pertaining to statin intolerance and adverse effects. This overview introduces a pragmatic definition of statin intolerance (goal-inhibiting statin intolerance) that emphasizes the effects of symptoms on achieving nationally vetted goals in patients fulfilling indications for lipid-lowering therapy and cardiovascular risk reduction. The Canadian Consensus Working Group provides a structured framework for avoiding, evaluating and managing goal-inhibiting statin intolerance.

Lipoprotein (a), an independent cardiovascular risk marker.

Epidemiological and genetic studies have identified elevated levels of lipoprotein (a) ((Lp(a)) as a causal and independent risk factor for cardiovascular diseases (CVD). The Lp(a)-induced increased risk of CVD may be mediated by both its proatherogenic and prothrombotic mechanisms. Several guidelines recommend screening of Lp(a) level; however, there are few treatment options for the management of patients with elevated Lp(a).

Coronary artery calcification score as tool for risk assessment among families with premature coronary artery disease.

Introduction: There is discussion about incorporating a family history (FamHis) of premature coronary artery disease (CAD) in risk score algorithms. However, FamHis provides information on individual risk. Coronary artery calcification score (CACS) is a metric of atherosclerosis that may determine the individual risk within families at high risk of premature CAD.

Targeted next-generation sequencing to diagnose disorders of HDL cholesterol.

A low level of HDL cholesterol (HDL-C) is a common clinical scenario and an important marker for increased cardiovascular risk. Many patients with very low or very high HDL-C have a rare mutation in one of several genes, but identification of the molecular abnormality in patients with extreme HDL-C is rarely performed in clinical practice. We investigated the accuracy and diagnostic yield of a targeted next-generation sequencing (NGS) assay for extreme levels of HDL-C.

Lipid lowering efficacy and safety of Ezetimibe combined with rosuvastatin compared with titrating rosuvastatin monotherapy in HIV-positive patients.

Background: HIV-infected patients on antiretroviral therapy frequently develop dyslipidemias and, despite therapy with potent lipid-lowering agents, a high percentage does not achieve guideline recommended lipid targets. In this study, we examined the efficacy of combination treatment with a statin and the cholesterol transport blocker, ezetimibe, vs. monotherapy with a statin in HIV-infected patients not achieving lipid goals.

Canadian Cardiovascular Society position statement on familial hypercholesterolemia.

Familial hypercholesterolemia (FH) is the most common genetic disorder causing premature cardiovascular disease and death. Heterozygous FH conservatively affects approximately 1:500 Canadians, and the more serious homozygous form affects approximately 1:1,000,000 Canadians, although these numbers might be underestimated. Of approximately 83,500 Canadians estimated to have FH, most are undiagnosed, which represents a simultaneous public health deficit and opportunity, because early treatment of heterozygous FH can normalize life expectancy.

Consumption of a dietary portfolio of cholesterol lowering foods improves blood lipids without affecting concentrations of fat soluble compounds.

Background: Consumption of a cholesterol lowering dietary portfolio including plant sterols (PS), viscous fibre, soy proteins and nuts for 6 months improves blood lipid profile. Plant sterols reduce blood cholesterol by inhibiting intestinal cholesterol absorption and concerns have been raised whether PS consumption reduces fat soluble vitamin absorption.

Objective: The objective was to determine effects of consumption of a cholesterol lowering dietary portfolio on circulating concentrations of PS and fat soluble vitamins.

Clinical, Biochemical, and Molecular Characterization of Novel Mutations in ABCA1 in Families with Tangier Disease.

Tangier disease is a rare, autosomal recessive disorder caused by mutations in the ABCA1 gene and is characterized by near absence of plasma high-density lipoprotein cholesterol, accumulation of cholesterol in multiple tissues, peripheral neuropathy, and accelerated atherosclerosis. Here we report three new kindreds with Tangier disease harboring both known and novel mutations in ABCA1. One patient was identified to be homozygous for a nonsense mutation, p.

Clinical usefulness of lipid ratios to identify men and women with metabolic syndrome: a cross-sectional study.

Background: Waist circumference, a metabolic syndrome (MetSy) criterion, is not routinely measured in clinical practice making early identification of individuals with MetSy challenging. It has been argued that ratios of commonly measured parameters such as lipids and lipoproteins may be an acceptable alternative for identifying individuals with MetSy. The objective of our study was to explore clinical utility of lipid ratios to identify men and women with MetSy; and to explore the association between lipid ratios and the number of MetSy components.

Implementing phytosterols into medical practice as a cholesterol-lowering strategy: overview of efficacy, effectiveness, and safety.

More than 200 clinical trial reports and several meta-analyses have demonstrated that phytosterols (PSs), natural components of plants, induce clinically relevant reductions in blood low-density lipoprotein cholesterol levels. Here we review data regarding the biochemical effects and potential cardiovascular benefit of PSs as part of the dietary management of dyslipidemia. In addition to discussing the efficacy, effectiveness, and safety of PSs as hypocholesterolemic agents, this review provides an overview of PSs as an adjunctive therapy to cholesterol-lowering pharmaceuticals.

A review on lecithin:cholesterol acyltransferase deficiency.

Lecithin cholesterol acyl transferase (LCAT) is a plasma enzyme which esterifies cholesterol, and plays a key role in the metabolism of high-density lipoprotein cholesterol (HDL-C). Genetic disorders of LCAT are associated with lipoprotein abnormalities including low levels of HDL-C and presence of lipoprotein X, and clinical features mainly corneal opacities, changes in erythrocyte morphology and renal failure. Recombinant LCAT is being developed for the treatment of patients with LCAT deficiency.

Dramatic lowering of very high Lp(a) in response to niacin.

We describe a patient with markedly elevated lipoprotein(a) (Lp(a)) without any other lipid abnormalities. After a myocardial infarction, she was treated with combination of extended-release niacin and statin. An 88% reduction in Lp(a) was observed during 5 years of treatment, which is much better response than usually reported.

Marked effects of extreme levels of lipoprotein(a) on estimation of low-density lipoprotein cholesterol.

Background: Low-density lipoprotein cholesterol (LDL-C) is usually calculated using the Friedewald equation. However, this calculation method does not account for the cholesterol associated with lipoprotein(a) [Lp(a)]. Using the Dahlen equation, Li et al.

Risk stratification of patients with familial hypercholesterolemia in a multi-ethnic cohort.

Background: Heterozygous Familial hypercholesterolemia (FH) is a common autosomal dominant disorder resulting in in very high blood cholesterol levels and premature cardiovascular disease (CVD). However, there is a wide variation in the occurrence of CVD in these patients. The aim of this study is to determine risk factors that are responsible for the variability of CVD events in FH patients.

A kindred with fish eye disease, corneal opacities, marked high-density lipoprotein deficiency, and statin therapy.

A kindred affected with fish eye disease (FED) from Oklahoma is reported. Two probands with corneal opacification had mean levels of high-density lipoprotein (HDL) cholesterol (C), apolipoprotein (apo) A-I, and apoA-I in very large alpha-1 HDL particles that were 9%, 17%, and 5% of normal, whereas their parents and 1 sibling had values that were 61%, 77%, and 72% of normal. The probands had no detectable lipoprotein-X, and had mean low-density lipoprotein cholesterol (LDL-C) and triglyceride levels that were elevated.

Diagnosis, prevention, and management of statin adverse effects and intolerance: Canadian Working Group Consensus update.

The Proceedings of a Canadian Working Group Consensus Conference, first published in 2011, provided a summary of statin-associated adverse effects and intolerance and management suggestions. In this update, new clinical studies identified since then that provide further insight into effects on muscle, cognition, cataracts, diabetes, kidney disease, and cancer are discussed. Of these, the arenas of greatest controversy pertain to purported effects on cognition and the emergence of diabetes during long-term therapy.