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Systematic Review/Meta-analysis| Volume 35, ISSUE 10, P1322-1331, October 2019

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Estimating the Prevalence of Familial Hypercholesterolemia in Acute Coronary Syndrome: A Systematic Review and Meta-analysis

  • Adam I. Kramer
    Affiliations
    Faculty of Medicine, University of British Columbia, Centre for Heart and Lung Innovation, Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada
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  • Mark Trinder
    Affiliations
    Faculty of Medicine, University of British Columbia, Centre for Heart and Lung Innovation, Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada
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  • Liam R. Brunham
    Correspondence
    Corresponding author: Dr Liam R. Brunham, University of British Columbia Centre for Heart Lung Innovation, 1081 Burrard Street, Room 166, Vancouver, British Columbia V6Z 1Y6, Canada. Tel.: +1-604-682-2344, ext. 63929; fax: +1-604-806-8351.
    Affiliations
    Faculty of Medicine, University of British Columbia, Centre for Heart and Lung Innovation, Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada
    Search for articles by this author

      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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      Linked Article

      • Finding the Familial Hypercholesterolemia Needle in Acute Coronary Syndrome: The Haystack Is Smaller Than You Think
        Canadian Journal of CardiologyVol. 35Issue 10
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          Familial 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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