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      Familial hypercholesterolaemia and coronary risk factors among patients with angiogram-proven premature coronary artery disease in an Asian cohort

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          Abstract

          Background

          Familial hypercholesterolaemia (FH) patients have elevated levels of low-density lipoprotein cholesterol, rendering them at high risk of premature coronary artery disease (PCAD). However, the FH prevalence among angiogram-proven PCAD (AP-PCAD) patients and their status of coronary risk factors (CRFs) have not been reported in the Asian population.

          Objectives

          This study aimed to (1) determine the prevalence of clinically diagnosed FH among AP-PCAD patients, (2) compare CRFs between AP-PCAD patients with control groups, and (3) identify the independent predictors of PCAD.

          Methods

          AP-PCAD patients and FH patients without PCAD were recruited from Cardiology and Specialist Lipid Clinics. Subjects were divided into AP-PCAD with FH (G1), AP-PCAD without FH (G2), FH without PCAD (G3) and normal controls (G4). Medical records were collected from the clinic database and standardised questionnaires. FH was clinically diagnosed using Dutch Lipid Clinic Network Criteria.

          Results

          A total of 572 subjects were recruited (males:86.4%; mean ±SD age: 55.6±8.5years). The prevalence of Definite, Potential and All FH among AP-PCAD patients were 6%(19/319), 16% (51/319) and 45.5% (145/319) respectively. G1 had higher central obesity, family history of PCAD and family history of hypercholesterolaemia compared to other groups. Among all subjects, diabetes [OR(95% CI): 4.7(2.9,7.7)], hypertension [OR(95% CI): 14.1(7.8,25.6)], FH [OR(95% CI): 2.9(1.5,5.5)] and Potential (Definite and Probable) FH [OR(95% CI): 4.5(2.1,9.6)] were independent predictors for PCAD. Among FH patients, family history of PCAD [OR(95% CI): 3.0(1.4,6.3)] and Definite FH [OR(95% CI): 7.1(1.9,27.4)] were independent predictors for PCAD.

          Conclusion

          Potential FH is common among AP-PCAD patients and contributes greatly to the AP-PCAD. FH-PCAD subjects have greater proportions of various risk factors compared to other groups. Presence of FH, diabetes, hypertension, obesity and family history of PCAD are independent predictors of PCAD. FH with PCAD is in very-high-risk category, hence, early management of modifiable CRFs in these patients are warranted.

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          Most cited references50

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          2019 ESC/EAS Guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk

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            Inflammation, atherosclerosis, and coronary artery disease.

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              Familial hypercholesterolaemia is underdiagnosed and undertreated in the general population: guidance for clinicians to prevent coronary heart disease

              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.
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                Author and article information

                Contributors
                Role: Data curationRole: Formal analysisRole: InvestigationRole: MethodologyRole: VisualizationRole: Writing – original draftRole: Writing – review & editing
                Role: Data curationRole: ValidationRole: Writing – original draftRole: Writing – review & editing
                Role: InvestigationRole: Project administrationRole: ResourcesRole: ValidationRole: Writing – review & editing
                Role: Formal analysisRole: MethodologyRole: Writing – review & editing
                Role: InvestigationRole: ResourcesRole: Writing – review & editing
                Role: InvestigationRole: ResourcesRole: Writing – review & editing
                Role: InvestigationRole: ResourcesRole: Writing – review & editing
                Role: InvestigationRole: ResourcesRole: Writing – review & editing
                Role: ConceptualizationRole: Funding acquisitionRole: MethodologyRole: Project administrationRole: ResourcesRole: SupervisionRole: ValidationRole: Writing – review & editing
                Role: Editor
                Journal
                PLoS One
                PLoS One
                plos
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                2 September 2022
                2022
                : 17
                : 9
                : e0273896
                Affiliations
                [1 ] Laboratory and Forensic Medicine (I-PPerForM), Institute for Pathology, Universiti Teknologi MARA, Selangor, Malaysia
                [2 ] Faculty of Medicine, Universiti Teknologi MARA, Selangor, Malaysia
                [3 ] Institut Jantung Negara (IJN), Kuala Lumpur, Malaysia
                Temple University School of Medicine, UNITED STATES
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Author information
                https://orcid.org/0000-0003-2387-0087
                https://orcid.org/0000-0003-1144-4451
                https://orcid.org/0000-0003-4462-8484
                Article
                PONE-D-21-27710
                10.1371/journal.pone.0273896
                9439256
                36054188
                83abe598-848c-4637-8c7b-0fb5654afa99
                © 2022 Nazli et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 26 August 2021
                : 17 August 2022
                Page count
                Figures: 2, Tables: 5, Pages: 18
                Funding
                Funded by: Ministry of Higher Education Long Term Research Grant Scheme
                Award ID: RMI/ST/LRGS5/3 (2/2011)
                Award Recipient :
                Funded by: funder-id http://dx.doi.org/10.13039/501100013262, Institute of Research Management and Innovation, Universiti Teknologi MARA;
                Award ID: [600-IRMI/MYRA 5/3/MITRA (003/20170)-1]
                Award Recipient :
                Funded by: Ministry of Education Fundamental Research Grant Scheme
                Award ID: 600-IRMI/FRGS 5/3 (067/2019)
                Award Recipient :
                This study was funded by Malaysia Ministry of Higher Education Long Term Research Grant Scheme [RMI/ST/LRGS5/3 (2/2011)], Universiti Teknologi MARA MITRA Grant [600-IRMI/MYRA 5/3/MITRA (003/20170)-1] and Malaysia Ministry of Higher Education Fundamental Research Grant Scheme (FRGS) [600-IRMI/FRGS 5/3 (067/2019)] which were awarded to the corresponding author (HN). The URL of the funders are ( http://mygrants.gov.my/main.php?Content=articles&ArticleID=3&IID=, https://rmc.uitm.edu.my/images/Download/Guidelines/G.Dalaman/G.MITRA/GarisPanduanMitra2017.pdf and http://mygrants.gov.my/main.php?Content=articles&ArticleID=1&IID=; respectively). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Medicine and Health Sciences
                Medical Conditions
                Cardiovascular Diseases
                Coronary Heart Disease
                Medicine and Health Sciences
                Cardiology
                Cardiovascular Medicine
                Cardiovascular Diseases
                Coronary Heart Disease
                Medicine and Health Sciences
                Vascular Medicine
                Coronary Heart Disease
                Biology and Life Sciences
                Physiology
                Physiological Parameters
                Body Weight
                Obesity
                Medicine and Health Sciences
                Epidemiology
                Medical Risk Factors
                Medicine and Health Sciences
                Medical Conditions
                Cardiovascular Diseases
                Cardiovascular Disease Risk
                Medicine and Health Sciences
                Cardiology
                Cardiovascular Medicine
                Cardiovascular Diseases
                Cardiovascular Disease Risk
                Medicine and Health Sciences
                Endocrinology
                Endocrine Disorders
                Diabetes Mellitus
                Medicine and Health Sciences
                Medical Conditions
                Metabolic Disorders
                Diabetes Mellitus
                Biology and Life Sciences
                Biochemistry
                Lipids
                Biology and Life Sciences
                Biochemistry
                Lipids
                Cholesterol
                Biology and Life Sciences
                Biochemistry
                Proteins
                Lipoproteins
                Custom metadata
                We have uploaded the dataset to a public repository site UK Data Service ReShare ( https://reshare.ukdataservice.ac.uk/855685/).

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