Abstract
Background
Heterozygous familial hypercholesterolemia (FH) is one of the most common monogenic
conditions but remains substantially underdiagnosed. One method for increasing the
diagnosis is via opportunistic screening of individuals presenting with acute coronary
syndrome (ACS). The prevalence of FH in the ACS population has been assessed in numerous
studies using various diagnostic criteria, resulting in wide variability of prevalence
estimates. The purpose of this study was to perform a systematic review and meta-analysis
to provide a more robust estimate.
Methods
We searched MEDLINE, EMBASE, Pubmed, Cochrane Central Register of Controlled Trials,
and Cochrane Database of Systematic Reviews to identify peer-reviewed articles reporting
the prevalence of FH in ACS. We calculated pooled prevalence using a random-effects
model. When multiple diagnostic criteria were used in a single study, we gave priority
to DNA-based criteria, followed by Dutch Lipid Clinic Network (DLCN) criteria. We
also investigated the prevalence in subanalyses according to age and diagnostic criteria.
Results
The overall pooled prevalence of FH in ACS, derived from 22 studies, was 4.7% (95%
confidence interval [CI], 3.0-7.3). DNA-based criteria and DLCN criteria provided
similar estimates of 5.0% (95% CI, 2.6-9.3) and 5.5% (95% CI, 3.0-10.0), respectively.
The prevalence was 7.3% (95% CI, 5.3-10.0) for patients aged ≤ 60 years and increased
to 13.7% (95% CI, 8.2-22.1) for those aged ≤45 years.
Conclusions
Approximately 1 in 21 patients with ACS has FH, and this increases to 1 in 7 among
those ≤45 years. These results reinforce the importance of screening for FH in the
ACS population.
Résumé
Contexte
L’hypercholestérolémie familiale hétérozygote est l’une des affections monogéniques
les plus fréquentes, mais elle demeure nettement sous-diagnostiquée. L’une des méthodes
permettant de favoriser son diagnostic est le dépistage opportuniste des personnes
consultant pour un syndrome coronarien aigu (SCA). La prévalence de l’hypercholestérolémie
familiale hétérozygote chez la population présentant un SCA a été évaluée dans de
nombreuses études à l’aide de divers critères diagnostiques, donnant lieu à une importante
variabilité de la prévalence estimée. L’objectif de cette étude était de réaliser
un examen systématique et une méta-analyse afin d’obtenir une estimation plus solide.
Méthodologie
Nous avons mené des recherches dans les bases de données MEDLINE, EMBASE, Pubmed,
Cochrane Central Register of Controlled Trials et Cochrane Database of Systematic
Reviews afin d’y trouver des articles révisés par des pairs indiquant la prévalence
de l’hypercholestérolémie familiale hétérozygote en présence d’un SCA. À l’aide d’un
modèle à effets aléatoires, nous avons calculé la prévalence à partir des données
groupées. Lorsque plusieurs critères diagnostiques étaient utilisés dans la même étude,
nous avons privilégié les critères fondés sur l’ADN, puis les critères du Dutch Lipid
Clinic Network (DLCN). Nous avons aussi évalué la prévalence dans des sous-analyses
effectuées en fonction de l’âge et des critères diagnostiques.
Résultats
La prévalence globale de l’hypercholestérolémie familiale hétérozygote en présence
d’un SCA selon les données groupées de 22 études a été de 4,7 % (intervalle de confiance
[IC] à 95 % : de 3,0 à 7,3). Les critères fondés sur l’ADN et les critères du DLCN
ont donné des estimations similaires, soit 5,0 % (IC à 95 % : de 2,6 à 9,3) et 5,5
% (IC à 95 % : de 3,0 à 10,0), respectivement. La prévalence était de 7,3 % (IC à
95 % : de 5,3 à 10,0) chez les patients âgés de ≤ 60 ans et passait à 13,7 % (IC à
95 % : de 8,2 à 22,1) chez les patients âgés de ≤ 45 ans.
Conclusion
Environ 1 patient sur 21 présentant un SCA était atteint d’hypercholestérolémie familiale
hétérozygote, cette prévalence passait à 1 sur 7 chez les patients de ≤ 45 ans. Ces
résultats soulignent l’importance du dépistage de l’hypercholestérolémie familiale
hétérozygote chez la population présentant un SCA.
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References
- The complex molecular genetics of familial hypercholesterolaemia.Nat Rev Cardiol. 2019; 16: 9-20
- Estimating the prevalence of heterozygous familial hypercholesterolaemia: a systematic review and meta-analysis.BMJ Open. 2017; 7e016461
- Familial hypercholesterolaemia is underdiagnosed and undertreated in the general population: guidance for clinicians to prevent coronary heart disease: consensus statement of the European Atherosclerosis Society.Eur Heart J. 2013; 34 (3478-90a)
- Treatment of adults with familial hypercholesterolemia and evidence for treatment: recommendations from the National Lipid Association Expert Panel on familial hypercholesterolemia.J Clin Lipidol. 2011; 5: S18-S29
- Identifying familial hypercholesterolemia in acute coronary syndrome.Curr Opin Lipidol. 2016; 27: 375-381
- Familial hypercholesterolemia among young adults with myocardial infarction.J Am Coll Cardiol. 2019; 73: 2439-2450
- Familial Hypercholesterolemia: Report of a Second WHO Consultation.World Health Organization, Geneva, Switzerland1999
- Risk of fatal coronary heart disease in familial hypercholesterolaemia: Scientific Steering Committee on behalf of the Simon Broome Register Group.BMJ. 1991; 303: 893-896
- Diagnosing heterozygous familial hypercholesterolemia using new practical criteria validated by molecular genetics.Am J Cardiol. 1993; 72: 171-176
- The agenda for familial hypercholesterolemia: a scientific statement from the American Heart Association.Circulation. 2015; 132: 2167-2192
- Simplified Canadian definition for familial hypercholesterolemia.Can J Cardiol. 2018; 34: 1210-1214
- Guidelines for the management of familial hypercholesterolemia.J Atheroscler Thromb. 2012; 19: 1043-1060
- Meta: an R package for meta-analysis.R News. 2007; 7: 40-45
- Metaprop: a Stata command to perform meta-analysis of binomial data.Arch Public Health. 2014; 72: 39
- Meta-analysis in clinical trials.Control Clin Trials. 1986; 7: 177-188
- Conducting meta-analyses in R with the Metafor package.J Stat Softw. 2010; 36: 1-48
- Improved tests for a random effects meta-regression with a single covariate.Statist Med. 2003; 22: 2693-2710
- Bias in meta-analysis detected by a simple, graphical test.BMJ. 1997; 315: 629-634
- Assessing risk of bias in prevalence studies: modification of an existing tool and evidence of interrater agreement.J Clin Epidemiol. 2012; 65: 934-939
- Prevalence, management, and outcomes of familial hypercholesterolemia in patients with acute coronary syndromes in the Arabian Gulf.J Clin Lipidol. 2018; 12: 685-692
- Genetically confirmed familial hypercholesterolemia in patients with acute coronary syndrome.J Am Coll Cardiol. 2017; 70: 1732-1740
- Familial hypercholesterolemia in Chinese patients with premature ST-segment-elevation myocardial infarction: prevalence, lipid management and 1-year follow-up.PLoS ONE. 2017; 12e0186815
- Genetic testing for familial hypercholesterolemia among survivors of acute coronary syndrome.J Intern Med. 2018; 284: 674-684
- Prevalence and management of familial hypercholesterolemia in patients with coronary artery disease: the heredity survey.Int J Cardiol. 2018; 252: 193-198
- Prevalence of familial hypercholesterolemia in patients with acute coronary syndrome in Japan: results of the EXPLORE-J study.Atherosclerosis. 2018; 277: 362-368
- Characterization of coronary artery disease in young adults and assessment of long-term outcomes.Isr Med Assoc J. 2018; 20: 613-618
- Prevalence of familial hypercholesterolemia among young north Karelian patients with coronary heart disease: a study based on diagnosis by polymerase chain reaction.J Lipid Res. 1993; 34: 269-277
- Identification of familial hypercholesterolemia in patients with myocardial infarction: a Chinese cohort study.J Clin Lipidol. 2016; 10: 1344-1352
- Familial hypercholesterolemia among unselected contemporary patients presenting with first myocardial infarction: prevalence, risk factor burden, and impact on age at presentation.J Clin Lipidol. 2016; 10: 1145-1152
- Prevalence and management of familial hypercholesterolaemia in patients with acute coronary syndromes.Eur Heart J. 2015; 36: 2438-2445
- Estimated prevalence of heterozygous familial hypercholesterolemia in patients with acute coronary syndrome.Int Heart J. 2017; 58: 88-94
- Frequency of familial hypercholesterolemia in patients with early-onset coronary artery disease admitted to a coronary care unit.J Clin Lipidol. 2015; 9: 703-708
- Elevated Lp(a) is the most frequent familial lipoprotein disorder leading to premature myocardial infarction in a country with low cholesterol levels.Int J Cardiol. 1997; 60: 301-305
- Prevalence of heterozygous familial hypercholesterolaemia and its impact on long-term prognosis in patients with very early ST-segment elevation myocardial infarction in the era of statins.Atherosclerosis. 2016; 249: 17-21
- The prevalence and prognostic importance of possible familial hypercholesterolemia in patients with myocardial infarction.Am Heart J. 2016; 181: 35-42
- Post mortem molecularly defined familial hypercholesterolemia and sudden cardiac death of young men.Forensic Sci Int. 1999; 106: 87-92
- Prevalence of DNA-confirmed familial hypercholesterolaemia in young patients with myocardial infarction.Eur J Intern Med. 2015; 26: 127-130
- Familial-combined hyperlipidaemia in very young myocardial infarction survivors (< or = 40 years of age).Eur Heart J. 2009; 30: 1073-1079
- Prevalence of hypercholesterolaemia in young Afrikaners with myocardial infarction: ischaemic heart disease risk factors.S Afr Med J. 1987; 71: 139-142
- Suboptimal consideration and management of potential familial hypercholesterolaemia in patients with suspected premature coronary artery disease.Singapore Med J. 2012; 53: 174-178
- Long-term risk of atherosclerotic cardiovascular disease in US adults with the familial hypercholesterolemia phenotype.Circulation. 2016; 134: 9-19
- Familial hypercholesterolemia in the Danish general population: prevalence, coronary artery disease, and cholesterol-lowering medication.J Clin Endocrinol Metab. 2012; 97: 3956-3964
- Alirocumab and cardiovascular outcomes after acute coronary syndrome.N Engl J Med. 2018; 379: 2097-2107
- The cardiovascular burden of undiagnosed familial hypercholesterolemia: need to modify guidelines to encourage earlier diagnosis and therapy.Can J Cardiol. 2018; 34: 1112-1113
- Canadian Cardiovascular Society position statement on familial hypercholesterolemia: update 2018.Can J Cardiol. 2018; 34: 1553-1563
Article info
Publication history
Published online: June 24, 2019
Accepted:
June 19,
2019
Received:
May 13,
2019
Footnotes
See editorial by Gupta, pages 1270–1271 of this issue.
See page 1330 for disclosure information.
Identification
Copyright
© 2019 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.
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Access this article on ScienceDirectLinked Article
- Finding the Familial Hypercholesterolemia Needle in Acute Coronary Syndrome: The Haystack Is Smaller Than You ThinkCanadian Journal of CardiologyVol. 35Issue 10
- PreviewFamilial hypercholesterolemia (FH), in its heterozygous form, is considered to be the most common autosomal genetic disorder in humans, with a prevalence in the general population of 0.4%, or 1 in 250.1 Through genetic mutations in proteins ultimately involved in low-density lipoprotein (LDL)–cholesterol production or regulation, FH results in a lifelong increase in LDL-cholesterol concentrations, leading to a multifold increase in the risk of atherosclerotic cardiovascular disease (ASCVD), particularly with premature onset.
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