Opportunistic screening for familial hypercholesterolaemia via a community laboratory

2012 ◽  
Vol 49 (6) ◽  
pp. 534-537 ◽  
Author(s):  
Damon A Bell ◽  
Amanda J Hooper ◽  
Robert Bender ◽  
Jenny McMahon ◽  
Glenn Edwards ◽  
...  
Keyword(s):  
Ldl Cholesterol ◽  
Familial Hypercholesterolaemia ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Early Death ◽  
Sample Population ◽  
Atherosclerotic Cardiovascular Disease ◽  
Opportunistic Screening ◽  
Lipid Clinic ◽  
One Year

Background Familial hypercholesterolaemia (FH) is an inherited disorder characterized by increased serum low-density lipoprotein (LDL)-cholesterol concentrations and premature atherosclerotic cardiovascular disease. The majority of people with FH are currently undiagnosed. We sought to determine the ability of a community laboratory to screen for individuals with potential FH. Methods Serum LDL-cholesterol concentrations issued by a private community laboratory in Western Australia were reviewed over a one-year period (1 May 2010 to 31 April 2011). We assessed the prevalence of possible FH based on LDL-cholesterol thresholds employed by the Make Early Diagnosis-Prevent Early Death (MED-PED), the Simon Broome Registry and the Dutch Lipid Clinic Network criteria. Results During this period, 84,823 people had 99,467 serum LDL-cholesterol measurements, with 91.8% requested by general practitioners. A secondary cause of hypercholesterolaemia was identified in 8.3% of subjects with an LDL-cholesterol ≥5.0 mmol/L. The prevalence of FH based on an LDL-cholesterol ≥6.5 mmol/L, the 99.75th percentile, was 1:398 in this sample population; similarly, the MED-PED LDL-cholesterol criteria gave a prevalence of 1:482. Conclusions The community laboratory is well placed to screen opportunistically for subjects with potential FH. This may be achieved using either the MED-PED criteria or a serum LDL-cholesterol cut-off point of ≥6.5 mmol/L, irrespective of age. Further investigation is required to determine the most effective method of identifying these individuals and, thereby, ensuring referral to a specialist lipid clinic.

scholarly journals Hokuriku-plus familial hypercholesterolaemia registry study: rationale and study design

BMJ Open ◽  
2020 ◽  
Vol 10 (9) ◽  
pp. e038623
Author(s):  
Hayato Tada ◽  
Hirofumi Okada ◽  
Shohei Yoshida ◽  
Masaya Shimojima ◽  
Akihiro Nomura ◽  
...  
Keyword(s):  
Cardiovascular Risk ◽  
Ldl Cholesterol ◽  
Familial Hypercholesterolaemia ◽  
Human Subjects ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Atherosclerotic Cardiovascular Disease ◽  
Ethical Guidelines ◽  
Clinical Criteria ◽  
Few Data

IntroductionFamilial hypercholesterolaemia (FH) is an autosomal-dominant inherited genetic disease. It carries an extremely high cardiovascular risk associated with significantly elevated low-density lipoprotein (LDL) cholesterol. The diagnostic rate of this disease in some European nations is quite high, due to the presence of multiple prospective registries. On the other hand, few data—and in particular multicentre data—exist regarding this issue among Japanese subjects. Therefore, this study intends to assemble a multicentre registry that aims to comprehensively assess cardiovascular risk among Japanese FH patients while taking into account their genetic backgrounds.Methods and analysisThe Hokuriku-plus FH registry is a prospective, observational, multicentre cohort study, enrolling consecutive FH patients who fulfil the clinical criteria of FH in Japan from 37 participating hospitals mostly in Hokuriku region of Japan from April 2020 to March 2024. A total of 1000 patients will be enrolled into the study, and we plan to follow-up participants over 5 years. We will collect clinical parameters, including lipids, physical findings, genetic backgrounds and clinical events covering atherosclerotic and other important events, such as malignancies. The primary endpoint of this study is new atherosclerotic cardiovascular disease (ASCVD) events. The secondary endpoints are as follows: LDL cholesterol, secondary ASCVD events and the occurrence of other diseases including hypertension, diabetes and malignancies.Ethics and disseminationThis study is being conducted in compliance with the Declaration of Helsinki, the Ethical Guidelines for Medical and Health Research Involving Human Subjects, and all other applicable laws and guidelines in Japan. This study protocol has been approved by the Institutional Review Board at Kanazawa University. We will disseminate the final results at international conferences and in a peer-reviewed journal.Trial registration numberUMIN000038210.

Dyslipidaemia

2019 ◽  
pp. 33-48
Author(s):  
Heinz Drexel
Keyword(s):  
Cardiovascular Disease ◽  
Randomized Clinical Trials ◽  
Ldl Cholesterol ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Hdl Cholesterol ◽  
Epidemiological Studies ◽  
Residual Risk ◽  
Atherosclerotic Cardiovascular Disease ◽  
Cholesterol Levels

Lipid metabolism has gained cardiological interest only after statins were demonstrated to reduce cardiovascular disease in secondary and primary prevention. Therefore, this chapter first introduces the physiological and atherogenic properties of lipoproteins, before focusing on interventions. Both the efficacy and safety of statins have been proven in numerous randomized clinical trials. Because there is a considerable residual risk in statin-treated patients, additional approaches have been investigated. The focus is now on further reductions in low-density lipoprotein (LDL) cholesterol levels. First, high-intensity statin regimens were shown to reduce residual risk. Subsequently, ezetimibe was demonstrated, for the first time, to have a beneficial effect as a non-statin lipid intervention. More recently, inhibitors of the enzyme PCSK9 have demonstrated a very high efficacy in reducing LDL cholesterol levels. Although the causality of LDL for atherosclerotic cardiovascular disease has been proven in epidemiological studies, including Mendelian randomization studies, as well as interventional trials, adherence to statins and other therapies is far from optimal. In contrast, interventions to increase high-density lipoprotein (HDL) cholesterol levels could not proven to have further benefits when combined with statins.

Biological Variability of Lipoproteins and Apolipoproteins in Patients Referred to a Lipid Clinic

1992 ◽  
Vol 38 (6) ◽  
pp. 864-872 ◽  
Author(s):  
S D Kafonek ◽  
C A Derby ◽  
P S Bachorik
Keyword(s):  
Total Cholesterol ◽  
Ldl Cholesterol ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Hdl Cholesterol ◽  
Lipid Clinic ◽  
Physiological Variability ◽  
Coefficients Of Variation ◽  
Baseline Evaluation ◽  
Serial Samples

Abstract We determined the physiological variability of total cholesterol, high- (HDL) and low-density lipoprotein (LDL) cholesterol, triglycerides, and apolipoproteins A-I and B in fasting blood samples from patients referred to the Johns Hopkins Lipid Referral Clinic. Samples were taken on each of three occasions during baseline evaluation visits before the patients were treated. The median physiological coefficients of variation (CVp) were as follows: total cholesterol, 5.0%; triglycerides, 17.8%; HDL cholesterol, 7.1%; LDL cholesterol, calculated from the previous three measurements, 7.8%; and apolipoproteins A-I and B, 7.1% and 6.4%, respectively. There were no significant differences in CVp between children (less than or equal to 18 years) and adults (greater than 18 years) for any of the measurements. On the basis of our findings, single measurements in serial samples taken on three occasions suffice to establish the patients' usual values with the following precisions (+/- 1 CV): total cholesterol, +/- 4%; triglycerides, +/- 11%; HDL cholesterol, +/- 8%; LDL cholesterol, +/- 6%; and apolipoproteins A-I and B, +/- 7%.

scholarly journals Cholesterol Levels in Genetically Determined Familial Hypercholesterolaemia in Russian Karelia

Cholesterol ◽  
2017 ◽  
Vol 2017 ◽  
pp. 1-6 ◽  
Author(s):  
V. A. Korneva ◽  
T. Yu. Kuznetsova ◽  
T. Yu. Bogoslovskaya ◽  
D. S. Polyakov ◽  
V. B. Vasilyev ◽  
...  
Keyword(s):  
Ldl Cholesterol ◽  
Familial Hypercholesterolaemia ◽  
Receptor Gene ◽  
Low Density Lipoprotein ◽  
Ldl Receptor ◽  
Gene Mutations ◽  
Density Lipoprotein ◽  
Single Strand Conformation Polymorphism ◽  
Polymorphism Analysis ◽  
Cholesterol Levels

Familial hypercholesterolaemia (FH) is a rare disease that tends to be diagnosed lately. In Russia, the genetic and phenotypic characteristics of the disease are not well defined. We investigated 102 patients with definite FH. In 52 of these patients (50.9%) genetic analysis was performed, revealing pathogenic mutations of the low density lipoprotein (LDL) receptor gene in 22 patients. We report here five mutations of the LDL receptor gene found in the Karelian FH sample for the first time. The detection rate of mutations in definite FH patients was 42.3%. Two groups of patients with a definite diagnosis of FH according to the Dutch Lipid Clinic Network criteria were compared: the first group had putatively functionally important LDL receptor gene mutations, while in the second group LDL receptor gene mutations were excluded by single-strand conformation polymorphism analysis. Total and LDL cholesterol levels were higher in the group with LDL receptor mutations compared to the mutation-free population. The frequency of mutations in patients with LDL cholesterol > 6.5 mmol/L was more than 3 times higher than that in patients with LDL < 6.5 mmol/L. Total and LDL cholesterol levels and the frequency of coronary heart disease and myocardial infarction were higher in the group with definite FH compared to groups with probable and possible FH. Cholesterol figures in FH patients of different age and sex from the Karelian population were comparable.

scholarly journals Classification of Familial Hypercholesterolaemia Using Ordinal Logistic Regression

2020 ◽  
Vol 28 (4) ◽  
Author(s):  
Muhammad Hamizan Jamaludin ◽  
Yap Bee Wah ◽  
Hapizah Mohd Nawawi ◽  
Chua Yung-An ◽  
Marshima Mohd Rosli ◽  
...  
Keyword(s):  
Logistic Regression ◽  
Familial Hypercholesterolaemia ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Information Criterion ◽  
Physical Symptoms ◽  
Ordinal Logistic Regression ◽  
Link Function ◽  
Lipid Clinic

Familial hypercholesterolaemia (FH) is a genetic disease that causes the elevation of low-density lipoprotein cholesterol (LDL-C), which subsequently leads to premature coronary heart disease (CHD). Features which have been reported to be associated with FH include lipids level, tendon xanthomata, and history of CHD. The Ordinal Logistic Regression model using the classification of FH patients with the Dutch Lipid Clinic Network Criteria (DLCN) as the dependent variable (where 1=Possible, 2=Probable, 3=Definite) was developed and evaluated for different types of link functions. The FH patients (n = 449) were recruited from health screening programmes conducted in hospitals and clinics in Malaysia from 2010 to 2018. Results indicate there is a significant association between FH categories with demographic factors (ethnicity and smoking) and physical symptoms (corneal arcus and xanthomata). The Ordinal Logistic Regression using Cauchit link function has lower Akaike Information Criterion (AIC) value, higher Nagelkerke's R-Square and classification accuracy compared to Probit and Logit link function, diastolic blood pressure, corneal arcus and xanthomata were found to be significant covariates of FH.

Experimental and clinical research findings on the cardiovascular benefits of consuming flaxseed

2009 ◽  
Vol 34 (5) ◽  
pp. 965-974 ◽  
Author(s):  
Chantal M.C. Bassett ◽  
Delfin Rodriguez-Leyva ◽  
Grant N. Pierce
Keyword(s):  
Dietary Fibre ◽  
Dietary Intervention ◽  
Ldl Cholesterol ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Atherosclerotic Cardiovascular Disease ◽  
Omega 3 ◽  
Hypocholesterolemic Action ◽  
Relaxation Responses ◽  
Intervention Trials

Functional foods and nutraceuticals are becoming popular alternatives to pharmacological treatments by providing health benefits and (or) reducing the risk of chronic diseases. Flaxseed is a rich source of 3 components with demonstrated cardioprotective effects: the omega-3 fatty acid α-linolenic acid (ALA), dietary fibre, and phytoestrogen lignans. Multiple clinical dietary intervention trials report that consuming flaxseed daily can modestly reduce circulating total cholesterol (TC) by 6%–11% and low-density lipoprotein (LDL) cholesterol by 9%–18% in normolipemic humans and by 5%–17% for TC and 4%–10% for LDL cholesterol in hypercholesterolemic patients, as well as lower various markers associated with atherosclerotic cardiovascular disease in humans. Evidence to date suggests that the dietary fibre and (or) lignan content of flaxseed provides the hypocholesterolemic action. The omega-3 ALA found in the flaxseed oil fraction also contributes to the antiatherogenic effects of flaxseed via anti-inflammatory and antiproliferative mechanisms. Dietary flaxseed may also protect against ischemic heart disease by improving vascular relaxation responses and by inhibiting the incidence of ventricular fibrillation.

Dyslipidaemia

2019 ◽  
pp. 33-48
Author(s):  
Heinz Drexel
Keyword(s):  
Cardiovascular Disease ◽  
Randomized Clinical Trials ◽  
Ldl Cholesterol ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Hdl Cholesterol ◽  
Epidemiological Studies ◽  
Residual Risk ◽  
Atherosclerotic Cardiovascular Disease ◽  
Cholesterol Levels

Lipid metabolism has gained cardiological interest only after statins were demonstrated to reduce cardiovascular disease in secondary and primary prevention. Therefore, this chapter first introduces the physiological and atherogenic properties of lipoproteins, before focusing on interventions. Both the efficacy and safety of statins have been proven in numerous randomized clinical trials. Because there is a considerable residual risk in statin-treated patients, additional approaches have been investigated. The focus is now on further reductions in low-density lipoprotein (LDL) cholesterol levels. First, high-intensity statin regimens were shown to reduce residual risk. Subsequently, ezetimibe was demonstrated, for the first time, to have a beneficial effect as a non-statin lipid intervention. More recently, inhibitors of the enzyme PCSK9 have demonstrated a very high efficacy in reducing LDL cholesterol levels. Although the causality of LDL for atherosclerotic cardiovascular disease has been proven in epidemiological studies, including Mendelian randomization studies, as well as interventional trials, adherence to statins and other therapies is far from optimal. In contrast, interventions to increase high-density lipoprotein (HDL) cholesterol levels could not proven to have further benefits when combined with statins.

New Horizons in the Pathogenesis, Pathophysiology and Treatment of Familial Hypercholesterolaemia

2019 ◽  
Vol 24 (31) ◽  
pp. 3599-3604 ◽  
Author(s):  
Margus Viigimaa ◽  
Silver Heinsar ◽  
Dragan Lovic ◽  
Alexandra Katsimardou ◽  
Alexia Piperidou ◽  
...  
Keyword(s):  
Clinical Diagnosis ◽  
Familial Hypercholesterolaemia ◽  
Genetic Disorder ◽  
Low Density Lipoprotein ◽  
Ldl Receptor ◽  
Density Lipoprotein ◽  
Public Health Problem ◽  
Atherosclerotic Cardiovascular Disease ◽  
Significant Public Health Problem ◽  
Significant Public Health

Background: Familial Hypercholesterolaemia (FH) is an autosomal-dominant genetic disease and represents the most common genetic disorder: heterozygous 1/250 births, homozygous 1/300, 000 births. FH is characterized by high to very high low-density lipoprotein cholesterol (LDL-C), which is the main cause of increased incidence of premature atherosclerotic Cardiovascular Disease (CVD) or aortic stenosis. Objective: The aim of the review was to investigate the pathogenesis and the pathophysiology of FH. Results: The most common (60-80%) FH cause is mutations of the LDL Receptor (LDLR) protein (6 classes with a different number of receptors and functionality). Moreover, mutations in apolipoprotein B (APOB) (<5%) and gain-of-function mutations of proprotein convertase subtilisin/kexin type 9 genes (PCSK9) (<1%) contribute to its pathogenesis. An Autosomal Recessive Hypercholesterolaemia (ARH) is another cause, very rare (1/2.500 births), mainly in Sardinia. The remaining patients with a clinical diagnosis of monogenic hypercholesterolaemia do not present any known genetic cause. Since FH is a significant public health problem, early diagnosis and treatment are of utmost importance. Recent studies demonstrated the influence of the LDLR mutation type in the FH phenotype, associating a more severe clinical phenotype and worse advanced CVD in patients with null mutation than those with receptor-defective mutations. This analysis completes the adequate clinical diagnosis. Conclusion: Both homozygous and heterozygous FH are related to mutations of LDLR (mainly), APOB, PCSK9, while other rare forms exist. All aberrations lead to the impaired removal of LDL-C from the blood leading to its accumulation and subsequent CVD earlier than in the general population.

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