Management Of Familial Hypercholesterolemia Research Articles

NLA Recommendations for the Diagnosis and Management of Familial Hypercholesterolemia in Children and Adults

In May 2011 the National Lipid Association (NLA) issued new recommendations for the treatment of familial hypercholesterolemia (FH). This Journal of Clinical Lipidology open-source eCME activity (accessed at http:// multimedia.lipidjournal.com/2011/HDL) reviews public awareness, medical diagnosis, and current evidence-based treatment for FH. FH is caused by genetic mutations that affect the function of low-density lipoprotein (LDL)

Management of familial hypercholesterolaemia in children and adolescents

Familial hypercholesterolaemia is a disorder of low-density lipoprotein (LDL) cholesterol metabolism, which is associated with the onset of vascular changes associated with coronary heart disease in childhood. This disorder has co-dominant transmission with a prevalence of one in 500 in the general population. Cascade screening is the most effective method of identifying children. Children in the at-risk group should have their cholesterol levels checked between the age of 2 and 10 years. Children with LDL cholesterol levels ≥ 3.4 mmol/L are likely to suffer from this disorder, although at this level there is a significant false positive rate. Molecular genetic testing is available for the LDL receptor gene, APOB gene and the PCSK9 gene. This is the most specific test for familial hypercholesterolaemia but has a false negative rate of 20-50%. Once diagnosed, treatment should be considered in children with an LDL cholesterol level ≥ 4.9 mmol/L. If the child has two other risk factors or a positive family history, this threshold should be lowered to ≥4.1 mmol/L. Guidelines recommend that treatment should be commenced by the age of 10 years, although some advise waiting until menarche in females. Statin therapy is currently recommended as first line treatment. Randomised placebo trials have shown that statin therapy reduces LDL cholesterol levels by 25% and is not associated with increased risk of adverse events. These are short-term studies, and longer follow-up will be required to definitively prove efficacy and safety.

Role of apheresis in the management of familial hypercholesterolemia and elevated Lp(a) levels

Apheresis has an important role in the management of two common complex lipid disorders associated with a high risk of premature atherosclerotic disease, familial hypercholesterolemia (FH) and Lp(a) hyperlipidemia. More often than not, these high risk patients will first present to their primary care provider prior to consulting with a lipidologist. Because of this, FH and Lp(a)-hyperlipidemia require more emphasis globally in the public domain as well as in the medical community. Appropriate and aggressive treatment regimens include a combination of dietary and pharmacologic interventions with regularly scheduled apheresis sessions. LDL apheresis is a critical intervention for the successful treatment of homozygous FH patients, heterozygous FH patients intolerant to conventional therapy, patients with an elevated Lp(a) level or those patients with progressive cardiovascular disease despite maximum medical therapy. Newly released European guidelines emphasize the importance of screening and treatment of e...

The first ninety families diagnosed with mutation positive familial hypercholesterolaemia in two lipid clinics in a Scottish Health Board area

The publication of the NICE Guideline on Identification and Management of Familial Hypercholesterolaemia (FH) in 2008, served as a catalyst for the Scottish Lipid Forum to implement a system of genetic and cascade screening for familial heterozygous hypercholesterolaemia (FH) in Scotland. We describe the first ninety mutation positive families identified in one Health Board area where the prevalence is estimated at 1000 cases. There are two designated Lipid Clinics and also a two further clinics that deal with Lipid problems.

Management of familial hypercholesterolemia during pregnancy: Case series and discussion

With an occurrence of approximately 1 in 500 individuals worldwide, the heterozygous form of familial hypercholesterolemia is not uncommon. With statins being contraindicated in pregnancy (Category X), the management of pregnant women who carry this diagnosis has not been clearly defined. This case series describes five pregnant women seen at the Emory Center for Heart Disease Prevention between 2004 and 2010 who carried this diagnosis, their treatment, and subsequent outcomes. The article concludes with treatment options for clinicians in dealing with such individuals.

Identification and management of familial hypercholesterolaemia: what does it mean to primary care?

Familial hypercholesterolaemia is one of the most common dominantly inherited disorders to be identified in primary care, leading to raised serum cholesterol evident from the first year of life. Around 1 in 500 people are affected by this condition, but less than 15% of these are currently attending lipid clinics, suggesting that the vast majority are unrecognised in general practice. The recently released National Institute for Health and Clinical Excellence evidence-based guideline on the identification and management of familial hypercholesterolaemia provides an opportunity to bridge this gap. Primary care has a role in systematic and opportunistic case finding, such as recognising the relevance of a family history of premature coronary heart disease and/or grossly elevated cholesterol. Although affected individuals need specialist care, GPs can reinforce the information provided by specialists and support cascade screening to other affected members of the extended family.

Commentary: What's so special about familial hypercholesterolaemia?

Last year the National Institute for Health and Clinical Excellence (NICE) issued clinical guidance on the diagnosis and management of familial hypercholesterolaemia.1 The implications of this guidance for general practice are discussed by Qureshi et al in this issue of the BJGP .2 But why do we need such guidance? We know already that we should treat high-cholesterol patients with a statin to reduce the risk of vascular disease, so what's so special about familial hypercholesterolaemia? Isn't familial hypercholesterolaemia simply the tail-end of the cholesterol distribution in a population? Epidemiologists have been telling us for years that focusing on the treatment of tail-ends is a poor preventive strategy because most events (in this case strokes and myocardial infarctions) occur to people in the middle of the population distribution simply because there are so many of them.3 Wouldn't it be better for the NICE guidance to focus on shifting the whole population distribution of cholesterol rather than chopping off the tail? The rationale for treating familial hypercholesterolaemia differently is the disproportionately high mortality risk, particularly in young adults, which is higher than …

Auditing the management of familial hypercholesterolaemia

Steve Humphries and Katharine Young argue that the greatest opportunity for preventing the damage caused by coronary heart disease lies in diagnosing and treating people with familial hypercholesterolaemia and ‘cascade’ screening their families

NICE guidance for identification and treatment of familial hypercholesterolaemia: Commentary 1

The National Institute for Healthcare and Clinical Excellence (NICE) guidance on the identification and management of familial hypercholesterolaemia (FH) is welcome and much needed.1 FH is among the most common...

Controversies in familial hypercholesterolaemia: recommendations of the NICE Guideline Development Group for the identification and management of familial hypercholesterolaemia

Familial hypercholesterolaemia (FH) is one of the most common monogenic inherited conditions in clinical practice and has a prevalence of about 1 in 500, similar to type 1 diabetes. In...

NICE guidance for identification and treatment of familial hypercholesterolaemia: Commentary 2

Although the recently published NICE Guideline on the Identification and Management of Familial Hypercholesterolaemia contains no surprises for those involved in running specialist lipid clinics, it is a landmark in...

A commentary on the NICE guideline on identification and management of familial hypercholesterolaemia

Background: Familial hypercholesterolaemia (FH) is a genetic disorder with high serum cholesterol levels, early atherosclerosis and a high risk of premature coronary heart disease. It is both under-diagnosed and inadequately treated in some people, although the statin class of drugs is effective in reducing both morbidity and mortality. Recommendations: The basis for a diagnosis of FH is an LDL cholesterol (LDL-C) level of greater than 4.9 mmol/L in an adult or 4.0 mmol/L in a child under 16, combined with either, or both, a family history or clinical signs (xanthomata). Diagnosis can also be made by a genetic test. Because of the high risk of coronary heart disease, adults over 18 years should be treated with a high-potency statin. Patients should be reviewed at least annually, including a review of cardiovascular symptoms or risk factors. Primary care physicians should have a low threshold of suspicion for referral to a specialist in cardiology. Women of childbearing age need particular advice regarding contraception and specialist care in pregnancy. Children should be referred to a specialist centre for treatment.

Familial hypercholesterolaemia: A new focus on finding and managing increased CVD risk

Laura Robertson discusses the implications of the recently-released draft guidelines from NICE on screening for and management of familial hypercholesterolaemia

Guidelines for the Diagnosis and Management of Familial Hypercholesterolaemia

E on LDL-C levels and comparison to age and genderadjusted reference intervals. Females are protected from atherosclerotic disease prior to menopause, so the natural history of premature vascular disease is delayed by about one decade in women. Additional metabolic and clinical features of FH are listed below. Clearly there aremany other potential causes of premature cardiovascular disease and aortic stenosis. Likewise, corneal arcus and xanthelasma are non-specific signs,

The management of familial hypercholesterolaemia in Morocco

Familial hypercholesterolaemia (FH) is an autosomal dominant disorder characterized by high levels of low-density lipoprotein cholesterol (LDL-C) as a result of mutations that impair their removal from plasma.The clinical consequence is a high risk of premature cardiovascular disease. Because of the extreme risk of mortality and morbidity, diagnosis, recruitment and management of FH patients must be one of the priorities of public health. In Morocco, specialized consultation for dyslipidaemia and strategy for management of this cardiovascular major risk factor does not exist, making FH identification and management difficult. In this review, we present the first FH state of the art in our country through a sample of 66 subjects. By this analysis, we have tried to elucidate some points that impede the identification and recruitment of heterozygous FH and the management of both heterozygous and homozygous FH in Morocco. Also, we have attempted to propose some strategies for an adequate management of FH in our country, taking into account the local specifications.

New Cholesterol Guidelines for Children?

For children and adolescents, comprehensive guidelines for the diagnosis and management of elevated cholesterol have been published once, by the National Cholesterol Education Program in 1992.1 Since then, substantial research on early atherosclerosis and in related clinical areas has been conducted; simultaneously, the obesity epidemic has added the metabolic syndrome and its related high-triglyceride/low–high-density lipoprotein (HDL) phenotype to the agenda of those interested in establishing a consensus approach to early cardiovascular disease prevention.2 Article p 1056 Before assuming that new knowledge and secular trends in risk factors demand substantial revision of cardiovascular health guidelines for children, we must first consider several valuable, often prescient aspects of the 1992 report. First is an emphasis on the importance of nutritional management over pharmacological management of elevated low-density lipoprotein (LDL) cholesterol, unless levels clearly associated with premature cardiovascular disease exist and children are sufficiently old that advanced atherosclerotic lesions may be presumed to be present. Two randomized trials of dietary intervention, the DISC (Dietary Intervention Study in Children) and STRIP (Special Turku coronary Risk factor Intervention Project for babies) studies, have shown that the diet recommended by the 1992 report is safe and mildly effective in lowering LDL cholesterol and thus can be implemented in population-based strategies of cardiovascular disease risk lowering.3,4 Furthermore, the PDAY (Pathobiological Determinants of Atherosclerosis in Youth) study has shown that advanced, irreversible atherosclerotic lesions (American Heart Association grades IV and V) are rarely present before 19 years of age and that the relationship of risk to atherosclerosis in late adolescence is with regard to reversible early lesion grades (American Heart Association grades I through III).5 A second and woefully underrecognized virtue of the 1992 report is the definition of risk strata for LDL cholesterol, with borderline values being 110 to 129 mg/dL and high …

Mo-P5:355 Which management of familial hypercholesterolemia in Morocco?

Mo-P5:355 Which management of familial hypercholesterolemia in Morocco?

Familial hypercholesterolemia in South Africa.

South Africa, especially the Caucasian part of the population, has one of the highest incidences of familial hypercholesterolemia in the world. The founder effect in this region has led to this high incidence and to a limited number of mutations in the low-density lipoprotein-receptor gene. This chapter describes current situation concerning the management of familial hypercholesterolemia in South Africa.

The management of familial hypercholesterolaemia in childhood

Familial hypercholesterolaemia (FH) is the most common inherited metabolic disorder with an estimated incidence of 1 in 500 live births. It is an autosomal dominant trait mostly due to mutations in the low-density lipoprotein receptor gene, although other genetic defects occur. It is just one important risk factor for ischaemic heart disease. There is substantial evidence in the adult literature of the safety and efficacy of lipid-lowering therapy in both primary and secondary prevention of coronary events. Unfortunately, such evidence does not exist for children with FH. In this situation, education about a healthy life-style for the whole family is emphasized. The timing of the introduction of pharmacological therapy depends upon the severity of the family history, the biochemistry and the families' wishes. Those with homozygous FH with accelerated atherosclerosis must be treated early and aggressively with high-dose medications, lipid apheresis and/or liver transplantation.

Atorvastatin: a hydroxymethylglutaryl-coenzyme A reductase inhibitor.

The pharmacology, pharmacokinetics, clinical efficacy, adverse effects, interactions, and formulary considerations of atorvastatin relative to other hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors (statins) are discussed. Atorvastatin calcium, a synthetic stereoisomer of a pentasubstituted pyrrole, prevents the conversion of HMG-CoA by competitive and selective inhibition of HMG-CoA reductase. This limits cholesterol formation. Atorvastatin undergoes extensive first-pass metabolism; the first-pass effect is saturable at higher doses. Time to maximum plasma concentration ranges from one to four hours. The plasma elimination half-life is considerably longer than for other statins. Like other statins, atorvastatin reduces low-density-lipoprotein cholesterol (LDL-C) and total cholesterol in patients with hypercholesterolemia. However, the reductions achieved with atorvastatin exceed those for other statins. Atorvastatin recipients are more likely to achieve LDL-C goals and to do so more quickly. Atorvastatin also moderately reduces triglyceride levels in patients with hypertriglyceridemia and may play a role in the management of familial hypercholesterolemia. Adequate lipid control with atorvastatin monotherapy may preclude the need for combination drug therapy in some patients. The adverse effects of atorvastatin include mild gastrointestinal disturbances, increased liver enzyme levels, and myalgia. Drug interactions involving atorvastatin can be expected to parallel those of other statins metabolized via CYP3A4. Atorvastatin has become a popular addition to hospital formularies, even though formal pharmacoeconomic analyses are lacking. Atorvastatin effectively reduces blood lipids and may offer some advantages over other statins, but more studies are needed to clarify its optimal role in pharmacotherapy.