Familial Hypercholesterolemia with Bilateral Recurrent Extensor Tendon Xanthomas: A Case Report.

Familial hypercholesterolemia (FH) is a genetic disorder, characterized by high blood cholesterol levels, particularly – very high low-density lipoprotein (LDL) levels, which leads to the development of cardiovascular disease at a young age. Heterozygous FH is diagnosed in the general population in most countries in one of 500 people. Certain phenotypic manifestations of this disease have been identified, namely: tendon xanthomas, lipid arch of the cornea and xanthelasma. Patients with FH are prone to early development of atherosclerosis and clinically manifest forms of cardiovascular diseases, in particular ischemic heart disease. A direct correlation has been established between morbidity, mortality from coronary heart disease and blood cholesterol level. It has also been proven that hypercholesterolemia is the main risk factor for the development of atherosclerosis and its complications. Early diagnosis and modern lipid-lowering therapy play an important role for patients with signs of hereditary lipid metabolism disorders. Patients with heterozygous FH are usually treated by statins, which act by inhibiting an enzyme in the liver. Statins are effective in lowering total cholesterol and LDL levels. Sometimes other drugs are additionally prescribed. The diagnosis of this pathology requires a genetic consultation. All patients with FH require lifelong pharmacological therapy. The use of statins leads to a decrease in coronary mortality by 25–40%, and decrease in the risk of ischemic events – by 26–30%. An observational study of a large British registry noted that mortality in patients with FH began to decline slightly from the early 90s of the XX century, when statins were started to use in treatment. The article presents a clinical case of ischemic heart disease in heterozygous FH patent, considers diagnostic criteria and modern approaches to the management of patients with hereditary disorders of lipid metabolism.

Familial hypercholesterolemia in China requires greater efforts

Funding Acknowledgements Type of funding sources: None. Background Coronary artery calcium (CAC) score has been shown to improve the risk stratification and prediction of Atherosclerotic Cardiovascular Disease (ASCVD) in cohorts of patients with Heterozygous Familial Hypercholesterolaemia (FH) [i]. Objectives We sought to examine the CAC score in patients with FH who are on treatment and correlate to the therapy, Total Cholesterol (TC), Low Density Lipoprotein (LDL) and High-Density Lipoprotein (HDL) levels. Method Retrospective Analysis of patients with established diagnosis of FH from a specialist lipid clinic who underwent CAC for risk stratification. Results The study included 64 patients, of which 33 patients (52%) were males with an average age of 57.4 years. At diagnosis, the mean elevated TC level was 7.40 ±1.60 mmol/l. 37 patients (58%) were on statin, (7 patients were on Rosuvastatin 20 mg, 20 patients were on Atorvastatin 40 mg, 8 patients were on Atorvastatin 20 mg, 2 patients were on Atorvastatin 80 mg), 8 patients (12%) were on a combination of PCSK9 and statins, 3 patients (5%) were on fibrates (fenofibrates) 160 mg, 3 patients (5%) were on Ezetimibe 10 mg, 4 patients (6%) were on Bempedoic Acid 180 mg, 9 patients (15%) were on lifestyle modifications and did not prefer to start on any lipid lowering agents. 71% of patients with TC level of 7.29 ±1.87 mmol/l had a calcium score of less than 100. CAC of >100 was observed in 29% of patients with a TC level of 7.44 ±1.50 mmol/l. (p value of 0.741) CAC score >100 appeared independent of (A) LDL level (27% with a mean LDL level of 4.81±1.81 mmol/l versus 73% with a CAC <100 and a mean LDL level of 4.40 ±1.38mmol/l) (p value of 0.424) and of HDL level (29% of patients with a mean HDL level of 1.45 ±0.64mmol/l versus 71% with a CAC score< 100 with a mean HDL level of 1.44 ±0.61mmol/l) (p value of 0.768). Despite therapy, 45 patients (27 %) had high LDL level with a mean LDL level of 4.5 ±1.50mmol/l though we found no difference in CAC score between the two groups (p value of 0.424). Conclusion In a single centre retrospective analysis of patients with Heterozygous Familial Hypercholesterolaemia on therapy, there appears to be no correlation between the CAC score of more than 100 and baseline therapy, Total Cholesterol, LDL or HDL levels achieved. We postulate that more stringent LDL reduction to ~1.4mmol/l should be adopted with further analysis of Coronary calcium score in the long term.

Familial hypercholesterolemia (FH) is a genetic condition that causes high low-density lipoprotein (LDL) cholesterol (sometimes referred to as bad cholesterol) from birth. FH means high cholesterol that runs in a family. FH is caused by specific DNA changes that are passed on from parents to their children. It is not caused by lifestyle factors such as a high-fat diet or lack of exercise. There are 2 main types of FH, homozygous and heterozygous, that have different symptoms, risks, and treatments. In this Cardiology Patient Page, we focus on heterozygous FH, which we will call FH. FH affects 1 in 200 to 300 people. FH is usually inherited from 1 parent in an autosomal dominant pattern. This means a parent with FH has a 50% chance of passing it on to each child, regardless of sex. This also means all first-degree relatives (parents, siblings, and children) of a person with FH have a 50% chance to have FH, and a 50% chance to not have FH. Healthcare providers and the general public lack awareness about FH. Therefore, it is underdiagnosed and undertreated. A person with FH who is not treated is 20 times more likely to develop coronary artery disease than a person without FH. Coronary artery disease can lead to heart attacks and other major cardiovascular diseases, including stroke and sudden cardiac death. However, early diagnosis with universal lipid screening, cascade screening in families, and appropriate treatment with statins and other medications can reduce this risk. Most people with FH will not have any symptoms until complications of untreated high cholesterol arise years later. Rarely, patients may have visible signs of extremely high cholesterol, such as a corneal arcus or tendon xanthomas. A corneal arcus is a yellowish ring along the edge of the colored part of one or both …

Improved Coronary Risk Assessment With Electron Beam Computed Tomography in an Asymptomatic Female With Familial Hypercholesterolemia

The objective of this study was to evaluate how well high-frequency linear array sonography reveals xanthomas in the Achilles' tendons of individuals with heterozygous familial hypercholesterolemia before the xanthomas enlarge the tendons enough to become palpable. Both Achilles' tendons of 23 individuals (18 female and five male; age range, 16-69 years old) who had heterozygous familial hypercholesterolemia but no clinically apparent Achilles' tendon xanthomas were studied with high-frequency linear array sonography. Hypoechoic areas, consistent with xanthomas, were noted. Xanthomas were revealed in 36 (78%) of 46 tendons and 19 (83%) of 23 individuals. Sonography reveals Achilles' tendon xanthomas in many individuals with heterozygous familial hypercholesterolemia before the xanthomas are clinically apparent. Because tendon xanthomas in a hypercholesterolemic individual are essentially pathognomonic of heterozygous familial hypercholesterolemia and are a mainstay in its diagnosis, our study suggests that sonography is useful in the early diagnosis of heterozygous familial hypercholesterolemia.

Clinical observation and scientific research have established that premature atherosclerotic vascular disease is strongly associated with markedly elevated low-density lipoprotein (LDL) cholesterol levels. Genetic disorders that impair LDL clearance via LDL receptors (LDLRs) are classified into heterozygous and homozygous familial hypercholesterolemia (FH) phenotypes. The heterozygous FH (HeFH) phenotype is characterized by LDL cholesterol levels exceeding 4.9 mmol/L, the presence of tendon xanthomas, and premature heart disease. In contrast, homozygous FH (HoFH) is characterised by LDL cholesterol levels above 13 mmol/L, both cutaneous and tendon xanthomas, and may lead to atherosclerotic vascular disease manifesting in childhood. FH is relatively common and occurs at even higher frequencies in populations founded by small ancestral groups, as documented in South Africa through investigations conducted in tertiary healthcare settings. Despite significant advances in the diagnosis and treatment of lipid and lipoprotein disorders - many of which are part of the differential diagnosis of FH - support for the diagnosis and management of FH has declined. While existing clinical guidelines address most cases of hypercholesterolemia, a subset of individuals with severe dyslipidemias requires more specialized evaluation. Referral criteria are proposed to help identify these patients. Given the high cardiovascular risk associated with severe hypercholesterolemia and the availability of effective treatments, there is an urgent need to strengthen, coordinate, and integrate clinical and laboratory services in South Africa to differentiate among the various causes of these disorders.

Dietary recommendations are a key element in the management of cardiovascular disease. Evidence is mounting that certain dietary patterns can influence cardiovascular health by modifying risk factors such as obesity, dyslipidemia, and hypertension, as well as factors involved in systemic inflammation, insulin sensitivity, oxidative stress, endothelial function, thrombosis, and cardiac rhythm.1,2 In recent years, numerous dietary fads have emerged, in part as a response to the rising prevalence of obesity in the United States.3 In the present study, we review the various dietary portfolios that have emerged in the literature and the major studies that investigated their effectiveness in modifying cardiovascular risk. Currently, the typical American diet is estimated to derive 49% of its calories from carbohydrates, 34% from fat, and 12% to 16% from protein.4 Proposals to alter the proportions and/or types of macronutrients in this diet have been made for weight loss and cardiovascular health (Table 1).5–12 For weight management, for example, the strategy recommended by most medical groups entails the intake of a low-calorie, low-fat diet. The concept of fat restriction for weight management stems from traditional calorimetric measurements, which assign greater energy values to fat (&9 kcal/g) and less to carbohydrate and protein (&4 kcal/g). The low-calorie concept, on the other hand, is an intuitive technique to induce negative energy balance and has been adopted by some commercialized weight loss programs such as Weight Watchers International. View this table: TABLE 1. Various Dietary Patterns, Including Those Popularized Commercially and Those Investigated by Observational Studies and Clinical Trials One alternative proposed for weight loss is the low-carbohydrate diet. This was first described by William Banting13 in the 1860s and recently has received much attention in the form of the Atkins’, Stillman, Protein Power Lifeplan, and Zone diets. The Atkins’ diet begins with a weight-loss …

Background: High level of cholesterol and low physical activity correlate with hypertension. Low physical activity will cause low energy expenditure and as a consequences, calorie intake will be stored as lipid. There were several studies that have been conducted to analyze the relationship between physical activity and cholesterol level. However, the results varied. This study was conducted to analyze the relationship between physical activity and total cholesterol, low density lipoprotein (LDL) and high density lipoprotein (HDL) level in Jatinangor community. Method: An analytical cross-sectional study design involving 120 subjects from ‘Primary and secondary prevention of hypertension in Jatinangor’ research was used in this study. The studied variables consisted of gender, age, body mass index, physical activity, total cholesterol, LDL and HDL levels. The data were analyzed using Spearman's rank-order correlation formula. Result: The result revealed that there was a significant negative relationshipbetween physical activity and total cholesterol and LDL levels, r = −0.302(p = 0.001) and r = −0.288(p = 0.001), respectivelly. Meanwhile, there was no significant relationship between physical activity and HDL cholesterol levels, with r = 0.090 (p = 0.328). Conclusion: Physical activity correlates negatively with total cholesterol and LDL level.

Opposite effects on serum cholesteryl ester transfer protein levels between long-term treatments with pravastatin and probucol in patients with primary hypercholesterolemia and xanthoma

A 4-year trial of simvastatin in the treatment of patients with heterozygous familial hypercholesterolemia

Coronary Computed Tomographic Angiographic Findings in Asymptomatic Patients With Heterozygous Familial Hypercholesterolemia and Null Allele Low-Density Lipoprotein Receptor Mutations

Introduction Familial combined hyperlipidaemia (FCH) was originally described by Goldstein et al. as a new inheritable lipid disorder 182. It is the most common genetic cause of dyslipidaemia, with an estimated prevalence of 0.5-5.7 % in the general population and 10-14% among patients who suffer an early myocardial infarction 184,186,189. Individuals with FCH have a 10-fold higher risk for developing premature coronary artery disease (CAD) 186. It accounts for approximately 100,000 myocardial infarctions per year in the United States and the European Union 187. FCH is characterised by intraindividual and intrafamilial variability of the lipid profile, expressed as periodical increase of triglyceride (TG) and/or total cholesterol (TC) levels, and the presence of premature cardiovascular disease before the age of 60 years 182. Elevated levels of apolipoprotein B (apoB) and small dense low density lipoproteins (sdLDL) are the two most consistent metabolic findings in FCH, while other metabolic disturbances such as insulin resistance, impaired chylomicron (CM) clearance, hypertension, abdominal obesity and low high density lipoprotein levels (HDL) often coexist 186-187. It is estimated that 65% of individuals with FCH fulfil the National Cholesterol Education Program (NCEP) - Adult Treatment Panel III (ATP III) criteria for the diagnosis of the metabolic syndrome (Mets) 121,189. Gene mutations of lipoprotein lipase (LPL), hepatic lipase, apolipoprotein C-II and/or apolipoprotein A5 have been implicated in the pathogenesis of FCH 637. Familial hypercholesterolaemia (FH) is an autosomal, condominant, monogenic disorder of lipoprotein metabolism, characterised by very high levels of low density lipoprotein (LDL), tendon xanthomas and increased risk of premature atherosclerosis. The heterozygote frequency has been reported in most populations as 1:500, while the homozygote frequency as 1/1.000.000 638. FH results from inherited mutations of the LDL receptor (LDLr) gene and to date more than 1000 mutations have been reported 10. Coronary events occur before the age of 65 years in up to 85% of males and 50% of females with untreated heterozygous FH, while in homozygous FH CAD generally appears during the teenage years 14. FH has also been linked to premature valvulopathy and peripheral vascular disease 47,51-52. Postprandial lipaemia is a physiological polygenic metabolic process, following ingestion of dietary fat, mainly characterised by a marked increase in TG rich lipoprotein levels, such as CM, very low density lipoproteins (VLDL) and their remnants 291. The hypertriglyceridaemic state is accompanied by sdLDL particles that are more susceptible to oxidation and low HDL cholesterol levels 191. Hypertriglyceridaemia is also considered as a prothrombotic state, by provoking activation of nuclear factor B, a key mediator of atherosclerosis 639-640. Elevated fasting plasma TG concentrations are well established as an independent risk factor for the development of CAD 276-277. Although it is known that postprandial TG levels can be highly discriminatory between CAD patients and healthy subjects, it is not yet clear whether postprandial lipaemia, itself, is an independent risk factor for atherosclerosis 279. In the present study we evaluated the postprandial TG response in untreated patients with FCH and FH and a group of healthy subjects, as well as among different subgroups of FH and FCH patients, according to their lipid phenotype. ........................................................................................................

Unfavorable lipid profile in women with endometriosis

Aims: Familial hypercholesterolemia (FH) is a genetic disorder characterized by high serum levels of low-density lipoprotein (LDL)-cholesterol (LDL-C), tendon and skin xanthomas, and premature coronary artery disease (CAD). In Japan, detailed information on the current status of drug therapies for patients with FH has not been reported so far, and their efficacy and safety have not been clarified. After the introduction of ezetimibe, which can further reduce serum LDL-C levels on top of statins, the changes of management for FH patients with these drugs are of particular interest. The current study aimed to evaluate the clinical status of FH heterozygotes and homozygotes, especially focusing on the real-world lipid-lowering drug therapy, attained serum LDL-C levels, and cardiovascular events at registration and during the follow-up. Methods: The FAME Study enrolled 762 heterozygous (including 17 newly diagnosed cases) and 7 homozygous FH patients from hospitals and clinics nationwide. Diagnosis of FH was based upon the criteria defined in the Study Report in 2008 of the Research Committee on Primary Hyperlipidemia supported by Grants-in-Aid for Scientific Research from the Japanese Ministry of Health, Labor and Welfare. Data analysis was primarily carried on heterozygous FH patients. Results: Xanthoma or thickening of the Achilles tendon was observed in more than 80% of the patients. CAD was recorded in 23% of patients. Patients with parental and sibling CAD accounted for 47% and 24%, respectively. At baseline, patients without CAD who had LDL-C ＜100 mg/dL accounted for 12.3% and those with CAD who had attained the target (LDL-C ＜70 mg/dL) in the secondary prevention accounted for only 1.8%. In the multiple logistic analysis, male sex, age ＞40, heterozygous FH score ＞20, hypertension, and sibling CAD were significantly and positively associated with prevalent CAD, whereas serum HDL-cholesterol levels showed a significant inverse association with CAD. Patients treated with statin alone, statin＋ezetimibe, statin＋resin, or statin＋probucol accounted for 31.1%, 26.3%, 4.0%, and 3.7%, respectively. Patients treated with three-drug combination (statin＋ezetimibe＋resin or statin＋ezetimibe＋probucol) accounted for 7.5%. Statins and ezetimibe were used in 88.0% and 48.0% at the baseline, respectively. Although high-intensity statins were mainly prescribed, statin doses were much lower than those reported in Western countries. The addition of ezetimibe resulted in ~20% reduction in serum LDL-C. CAD was diagnosed in 17 patients with 21 episodes during follow-up. The Cox hazard model analysis demonstrated that male sex, CAD at the baseline, and parental CAD were related to the development of atherosclerotic cardiovascular disease (ASCVD) events. Furthermore, an increase in serum HDL-C was associated with a significant reduction of ASCVD events, while serum LDL-C and triglyceride levels were not related to ASCVD events. Conclusion: The prevalence of CAD in Japanese patients with heterozygous FH is still very high. In most of the cases, the target level of serum LDL-C was not achieved for primary and secondary prevention of CAD, suggesting that a more aggressive LDL-C lowering and appropriate management of residual risks are necessary.