Child–Parent Familial Hypercholesterolemia Screening in Primary Care
26 Oct 2016-The New England Journal of Medicine (Massachusetts Medical Society)-Vol. 375, Iss: 17, pp 1628-1637
TL;DR: Child-parent screening was feasible in primary care practices at routine child immunization visits and 8 persons were identified as having positive screening results for familial hypercholesterolemia and were consequently at high risk for cardiovascular disease.
Abstract: BackgroundChild–parent screening for familial hypercholesterolemia has been proposed to identify persons at high risk for inherited premature cardiovascular disease. We assessed the efficacy and feasibility of such screening in primary care practice. MethodsWe obtained capillary blood samples to measure cholesterol levels and to test for familial hypercholesterolemia mutations in 10,095 children 1 to 2 years of age during routine immunization visits. Children were considered to have positive screening results for familial hypercholesterolemia if their cholesterol level was elevated and they had either a familial hypercholesterolemia mutation or a repeat elevated cholesterol level 3 months later. A parent of each child with a positive screening result for familial hypercholesterolemia was considered to have a positive screening result for familial hypercholesterolemia if he or she had the same mutation as the child or, if no mutations were identified, had the higher cholesterol level of the two parents. Re...
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TL;DR: The next generation of scientists and decision-makers will be shaped by the experiences of those who have gone before them and will help shape the future of medicine and science.
3,797 citations
Cardiovascular Institute of the South1, Alfred I. duPont Hospital for Children2, University of Texas Southwestern Medical Center3, Baylor College of Medicine4, Florida Atlantic University5, University of Lisbon6, University of Paris7, University of Pennsylvania8, Boston Children's Hospital9, University of Amsterdam10, Central European Institute of Technology11, Ohio State University12, Queen Mary University of London13, Vanderbilt University14, West Virginia University15, Copenhagen University Hospital16, University of São Paulo17, Erasmus University Rotterdam18, Washington University in St. Louis19, Osaka University20
TL;DR: The Expert Consensus Panel recommends that FH genetic testing become the standard of care for patients with definite or probable FH, as well as for their at-risk relatives, and more accurate risk stratification.
354 citations
Cites background or methods from "Child–Parent Familial Hypercholeste..."
..., $190 mg/dl) missing significant numbers of individuals with FH pathogenic variants, the ability to distinguish those with FH from those with elevated cholesterol levels due to other reasons is complicated by an overlap in LDL-C levels between individuals with and without an FH pathogenic variant (10,36,41)....
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...When the FH proband is a child, this method allows for reverse cascade testing and identification of the affected parent (10), or parents, when affected children have 2 pathogenic variants; affected siblings can also be identified....
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...(10) found that not all children with an FH mutation had hypercholesterolemia at w12 months of age....
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TL;DR: With an overall prevalence of 1:311, FH is among the commonest genetic disorders in the GP, similarly present across different regions of the world, and is more frequent among those with ASCVD.
Abstract: Background: Contemporary studies suggest that familial hypercholesterolemia (FH) is more frequent than previously reported and increasingly recognized as affecting individuals of all ethnicities an...
252 citations
TL;DR: FH prevalence in the general population was similar using genetic versus clinical diagnoses, and FH prevalence is 10-fold higher among those with IHD, 20-fold Higher among thoseWith premature IHD and 23-foldHigher among thosewith severe hypercholesterolemia.
251 citations
TL;DR: The authors' systematic review suggests that FH is a common disorder, affecting 1 in 250 individuals, and underscore the need for early detection and management to decrease CVD risk.
Abstract: Objectives Heterozygous familial hypercholesterolaemia (FH) confers a significant risk for premature cardiovascular disease (CVD). However, the estimated prevalence of FH varies substantially among studies. We aimed to provide a summary estimate of FH prevalence in the general population and assess variations in frequency across different sociodemographic characteristics. Setting, participants and outcome measures We searched MEDLINE, EMBASE, Global Health, the Cochrane Library, PsycINFO and PubMed for peer-reviewed literature using validated strategies. Results were limited to studies published in English between January 1990 and January 2017. Studies were eligible if they determined FH prevalence using clinical criteria or DNA-based analyses. We determined a pooled point prevalence of FH in adults and children and assessed the variation of the pooled frequency by age, sex, geographical location, diagnostic method, study quality and year of publication. Estimates were pooled using random-effects meta-analysis. Differences by study-level characteristics were investigated through subgroups, meta-regression and sensitivity analyses. Results The pooled prevalence of FH from 19 studies including 2 458 456 unique individuals was 0.40% (95% CI 0.29% to 0.52%) which corresponds to a frequency of 1 in 250 individuals. FH prevalence was found to vary by age and geographical location but not by any other covariates. Results were consistent in sensitivity analyses. Conclusions Our systematic review suggests that FH is a common disorder, affecting 1 in 250 individuals. These findings underscore the need for early detection and management to decrease CVD risk.
234 citations
References
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TL;DR: A method for estimating the cholesterol content of the serum low-density lipoprotein fraction (Sf0-20) is presented and comparison of this suggested procedure with the more direct procedure, in which the ultracentrifuge is used, yielded correlation coefficients of .94 to .99.
Abstract: A method for estimating the cholesterol content of the serum low-density lipoprotein fraction (Sf0-20) is presented. The method involves measurements of fasting plasma total cholesterol, triglyceride, and high-density lipoprotein cholesterol concentrations, none of which requires the use of the preparative ultracentrifuge. Comparison of this suggested procedure with the more direct procedure, in which the ultracentrifuge is used, yielded correlation coefficients of .94 to .99, depending on the patient population compared.
30,622 citations
Copenhagen University Hospital1, French Institute of Health and Medical Research2, University College London3, Columbia University4, University of Gothenburg5, University of Western Ontario6, University of the Witwatersrand7, University of Amsterdam8, University of São Paulo9, University of Western Australia10, Ludwig Maximilian University of Munich11, University of Palermo12, University of Milan13, University of Groningen14, University Medical Center15, University of California, Los Angeles16, University of London17, Radboud University Nijmegen18, University of Helsinki19, University of Copenhagen20
TL;DR: There is an urgent worldwide need for diagnostic screening together with early and aggressive treatment of this extremely high-risk condition, familial hypercholesterolaemia.
Abstract: Aims The first aim was to critically evaluate the extent to which familial hypercholesterolaemia (FH) is underdiagnosed and undertreated. The second aim was to provide guidance for screening and treatment of FH, in order to prevent coronary heart disease (CHD).
Methods and results Of the theoretical estimated prevalence of 1/500 for heterozygous FH, <1% are diagnosed in most countries. Recently, direct screening in a Northern European general population diagnosed approximately 1/200 with heterozygous FH. All reported studies document failure to achieve recommended LDL cholesterol targets in a large proportion of individuals with FH, and up to 13-fold increased risk of CHD. Based on prevalences between 1/500 and 1/200, between 14 and 34 million individuals worldwide have FH. We recommend that children, adults, and families should be screened for FH if a person or family member presents with FH, a plasma cholesterol level in an adult ≥8 mmol/L(≥310 mg/dL) or a child ≥6 mmol/L(≥230 mg/dL), premature CHD, tendon xanthomas, or sudden premature cardiac death. In FH, low-density lipoprotein cholesterol targets are <3.5 mmol/L(<135 mg/dL) for children, <2.5 mmol/L(<100 mg/dL) for adults, and <1.8 mmol/L(<70 mg/dL) for adults with known CHD or diabetes. In addition to lifestyle and dietary counselling, treatment priorities are (i) in children, statins, ezetimibe, and bile acid binding resins, and (ii) in adults, maximal potent statin dose, ezetimibe, and bile acid binding resins. Lipoprotein apheresis can be offered in homozygotes and in treatment-resistant heterozygotes with CHD.
Conclusion Owing to severe underdiagnosis and undertreatment of FH, there is an urgent worldwide need for diagnostic screening together with early and aggressive treatment of this extremely high-risk condition.
2,039 citations
TL;DR: The matching criteria were gestation (using an ultrasound crown–rump length or biparietal diameter measurement), duration of storage, and centre, and Screening performance of the individual markers and combinations of markers together with maternal age was assessed.
Abstract: The matching criteria were gestation (using an ultrasound crown–rump length or biparietal diameter measurement), duration of storage, and centre. Screening performance of the individual markers and combinations of markers together with maternal age was assessed using standard methods. In addition pairs of first and second trimester serum samples from 600 controls were tested to secure a larger set in which screening performance could be deter mined using distribution parameters based on dates (time since first day of the last menstrual period).
680 citations
TL;DR: Two years of pravastatin therapy induced a significant regression of carotid atherosclerosis in children with familial hypercholesterolemia, with no adverse effects on growth, sexual maturation, hormone levels, or liver or muscle tissue.
Abstract: ContextChildren with familial hypercholesterolemia have endothelial dysfunction
and increased carotid intima-media thickness (IMT), which herald the premature
atherosclerotic disease they develop later in life. Although intervention
therapy in the causal pathway of this disorder has been available for more
than a decade, the long-term efficacy and safety of cholesterol-lowering medication
have not been evaluated in children.ObjectiveTo determine the 2-year efficacy and safety of pravastatin therapy in
children with familial hypercholesterolemia.DesignRandomized, double-blind, placebo-controlled trial that recruited children
between December 7, 1997, and October 4, 1999, and followed them up for 2
years.Setting and ParticipantsTwo hundred fourteen children with familial hypercholesterolemia, aged
8 to 18 years and recruited from an academic medical referral center in the
Netherlands.InterventionAfter initiation of a fat-restricted diet and encouragement of regular
physical activity, children were randomly assigned to receive treatment with
pravastatin, 20 to 40 mg/d (n = 106), or a placebo tablet (n = 108).Main Outcome MeasuresThe primary efficacy outcome was the change from baseline in mean carotid
IMT compared between the 2 groups over 2 years; the principal safety outcomes
were growth, maturation, and hormone level measurements over 2 years as well
as changes in muscle and liver enzyme levels.ResultsCompared with baseline, carotid IMT showed a trend toward regression
with pravastatin (mean [SD], −0.010 [0.048] mm; P = .049), whereas a trend toward progression was observed in the placebo
group (mean [SD], +0.005 [0.044] mm; P = .28). The
mean (SD) change in IMT compared between the 2 groups (0.014 [0.046] mm) was
significant (P = .02). Also, pravastatin significantly
reduced mean low-density lipoprotein cholesterol levels compared with placebo
(−24.1% vs +0.3%, respectively; P<.001).
No differences were observed for growth, muscle or liver enzymes, endocrine
function parameters, Tanner staging scores, onset of menses, or testicular
volume between the 2 groups.ConclusionTwo years of pravastatin therapy induced a significant regression of
carotid atherosclerosis in children with familial hypercholesterolemia, with
no adverse effects on growth, sexual maturation, hormone levels, or liver
or muscle tissue.
562 citations
TL;DR: The prevalence of familial hypercholesterolemia appears to be higher than commonly perceived in a general population of white Danish individuals, with at least half of affected subjects not receiving cholesterol-lowering medication.
Abstract: Context: The diagnosis of familial hypercholesterolemia (FH) can be made using the Dutch Lipid Clinic Network criteria. This employs the personal and family history of premature coronary artery disease and hypercholesterolemia and the presence of a pathogenic mutation in the low-density lipoprotein receptor (LDLR) and apolipoprotein B (APOB) genes. Objective: We employed this tool to investigate the prevalence of FH and the associations between FH and coronary artery disease and cholesterol-lowering medication in the Copenhagen General Population Study. Setting: The study was of an unselected, community-based population comprising 69,016 participants. Main Outcome Measures: FH (definite/probable) was defined as a Dutch Lipid Clinic Network score higher than 5. Coronary artery disease was myocardial infarction or angina pectoris. Results: The prevalence of FH was 0.73% (one in 137). Of participants with FH, 20% had an LDLR or APOB mutation. The prevalence of coronary artery disease among FH participants wa...
539 citations