Displaying publications 1 - 20 of 38 in total

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  1. Abdul-Razak S, Rahmat R, Mohd Kasim A, Rahman TA, Muid S, Nasir NM, et al.
    BMC Cardiovasc Disord, 2017 Oct 16;17(1):264.
    PMID: 29037163 DOI: 10.1186/s12872-017-0694-z
    BACKGROUND: Familial hypercholesterolaemia (FH) is a genetic disorder with a high risk of developing premature coronary artery disease that should be diagnosed as early as possible. Several clinical diagnostic criteria for FH are available, with the Dutch Lipid Clinic Criteria (DLCC) being widely used. Information regarding diagnostic performances of the other criteria against the DLCC is scarce. We aimed to examine the diagnostic performance of the Simon-Broom (SB) Register criteria, the US Make Early Diagnosis to Prevent Early Deaths (US MEDPED) and the Japanese FH Management Criteria (JFHMC) compared to the DLCC.

    METHODS: Seven hundered fifty five individuals from specialist clinics and community health screenings with LDL-c level ≥ 4.0 mmol/L were selected and diagnosed as FH using the DLCC, the SB Register criteria, the US MEDPED and the JFHMC. The sensitivity, specificity, efficiency, positive and negative predictive values of individuals screened with the SB register criteria, US MEDPED and JFHMC were assessed against the DLCC.

    RESULTS: We found the SB register criteria identified more individuals with FH compared to the US MEDPED and the JFHMC (212 vs. 105 vs. 195; p 

    Matched MeSH terms: Hyperlipoproteinemia Type II/blood*; Hyperlipoproteinemia Type II/diagnosis; Hyperlipoproteinemia Type II/genetics*
  2. Al-Khateeb A, Al-Talib H, Mohamed MS, Yusof Z, Zilfalil BA
    Adv Clin Exp Med, 2013 Jan-Feb;22(1):57-67.
    PMID: 23468263
    BACKGROUND: Familial hypercholesterolemia and familial defective apo lipoprotein B are genetic disorders caused by defects in the low-density lipoprotein receptor gene and apo lipoprotein B 100 genes, respectively. The clinical phenotype of both diseases is characterized by increased plasma levels of total cholesterol and low density lipoprotein cholesterol, tendinous xanthomata, and premature coronary heart disease.
    OBJECTIVES: The aim of this study is to perform an association study between different gene sequence variants in low-density lipoprotein and apo lipoprotein B 100 genes to the clinical finding and lipid profile parameters of the study subjects.
    MATERIAL AND METHODS: A group of 164 familial hypercholesterolemic patients were recruited. The promoter region, exon 2-15 of the low density lipoprotein gene and parts of exon 26 and 29 of apo lipoprotein B 100 gene were screened by Denaturating Gradient High Performance Liquid Chromatography.
    RESULTS: For the apo lipoprotein B 100 gene, those with apo lipoprotein B 100 gene mutation have a significantly higher frequency of cardiovascular disease (P = 0.045), higher low density lipoprotein cholesterol and total cholesterol: high density lipoprotein cholesterol ratio than those without mutation (P = 0.03 and 0.02, respectively). For the low density lipoprotein gene defect those with frame shift mutation group showed the worst clinical presentation in terms of low density lipoprotein cholesterol level and cardiovascular frequency.
    CONCLUSIONS: There was a statistically significant association between mutations of low density lipoprotein gene and apo lipoprotein B 100 genes and history of cardiovascular disease, younger age of presentation, family history of hyperlipidemia, tendon xanthoma and low density lipoprotein cholesterol level.
    Study site: Cardiology Clinic, Hospital Universiti Sains Malaysia (HUSM), Kelantan, Malaysia
    Matched MeSH terms: Hyperlipoproteinemia Type II/blood; Hyperlipoproteinemia Type II/diagnosis*; Hyperlipoproteinemia Type II/genetics*
  3. Al-Khateeb A, Zahri MK, Mohamed MS, Sasongko TH, Ibrahim S, Yusof Z, et al.
    BMC Med Genet, 2011;12:40.
    PMID: 21418584 DOI: 10.1186/1471-2350-12-40
    Familial hypercholesterolemia is a genetic disorder mainly caused by defects in the low-density lipoprotein receptor gene. Few and limited analyses of familial hypercholesterolemia have been performed in Malaysia, and the underlying mutations therefore remain largely unknown.We studied a group of 154 unrelated FH patients from a northern area of Malaysia (Kelantan). The promoter region and exons 2-15 of the LDLR gene were screened by denaturing high-performance liquid chromatography to detect short deletions and nucleotide substitutions, and by multiplex ligation-dependent probe amplification to detect large rearrangements.
    Matched MeSH terms: Hyperlipoproteinemia Type II/complications; Hyperlipoproteinemia Type II/genetics*; Hyperlipoproteinemia Type II/epidemiology
  4. Al-Khateeb AR, Mohd MS, Yusof Z, Zilfalil BA
    Biochem Genet, 2013 Oct;51(9-10):811-23.
    PMID: 23775634 DOI: 10.1007/s10528-013-9609-6
    Familial ligand-defective apolipoprotein B-100 is characterized by elevated plasma low-density lipoprotein levels and premature heart disease. This study aims to determine apolipoprotein B gene mutations among Malaysians with clinical diagnoses of familial hypercholesterolemia and to compare the phenotype of patients with apolipoprotein B gene mutations to those with a low-density lipoprotein receptor gene mutation. A group of 164 patients with a clinical diagnosis of familial hypercholesterolemia was analyzed. Amplicons in exon 26 and exon 29 of the apolipoprotein B gene were screened for genetic variants using denaturing gradient high-performance liquid chromatography; 10 variants were identified. Five novel mutations were detected (p.Gln2485Arg, p.Thr3526Ala, p.Glu3666Lys, p.Tyr4343CysfsX221, and p.Arg4297His). Those with familial defective apolipoprotein had a less severe phenotype than those with familial hypercholesterolemia. An apolipoprotein gene defect is present among Malaysian familial hypercholesterolemics. Those with both mutations show a more severe phenotype than those with one gene defect.
    Matched MeSH terms: Hyperlipoproteinemia Type II/genetics*
  5. Al-Khateeb, A, Al-Talib, H
    JUMMEC, 2016;19(2):1-11.
    MyJurnal
    Background:
    Familial hypercholesterolaemia (FH) is one of the most frequent inherited metabolic disorders that can lead
    to a risk of premature cardiovascular disease. Publications on FH are mainly from western patients as there is
    little research on Asians, including Malaysians. The aim of this review is to provide an up-to- date information
    on Malaysian studies on FH genotyping and its relation to the phenotype of the affected patients.
    Method:
    A search was conducted for data from online databases on FH in Malaysia.
    Results:
    The mutation spectrum for FH among Malaysian patients was extremely broad. The gene variants were located
    mainly in the low-density lipoprotein receptor (LDLR) and apolipoprotein B-100 (APOB-100) genes rather than
    in the proprotein convertase subtilisin kexin type 9 (PCSK9) gene. The exon 9 and 14 were the hotspots in the
    LDLR gene. The most frequent mutation was p.Cys255Ser, at 12.5%, followed by p.Arg471Gly, at 11%, and the
    most common single nucleotide polymorphism (SNP) was c.1060+7 T>C at 11.7%. The LDLR gene variants were
    more common compared to the APOB-100 gene variants, while variants in the PCSK9 gene were very few.
    Phenotype-genotype associations were identified. Subjects with LDLR and APOB-100 genes mutations had a
    higher frequency of cardiovascular disease, a family history of hyperlipidaemia and tendon xanthoma and a
    higher low-density lipoprotein cholesterol (LDL-C) level than non-carriers.
    Conclusion:
    Research on Malaysian familial hypercholesterolaemic patients by individual groups is encouraging. However,
    more extensive molecular studies on FH on a national scale, with a screening of the disease-causing mutations
    together with a comprehensive genotype-phenotype association study, can lead to a better outcome for
    patients with the disease.
    Matched MeSH terms: Hyperlipoproteinemia Type II
  6. Alex L, Chahil JK, Lye SH, Bagali P, Ler LW
    J Hum Genet, 2012 Jun;57(6):358-62.
    PMID: 22534770 DOI: 10.1038/jhg.2012.34
    Hypercholesterolemia is caused by different interactions of lifestyle and genetic determinants. At the genetic level, it can be attributed to the interactions of multiple polymorphisms, or as in the example of familial hypercholesterolemia (FH), it can be the result of a single mutation. A large number of genetic markers, mostly single nucleotide polymorphisms (SNP) or mutations in three genes, implicated in autosomal dominant hypercholesterolemia (ADH), viz APOB (apolipoprotein B), LDLR (low density lipoprotein receptor) and PCSK9 (proprotein convertase subtilisin/kexin type-9), have been identified and characterized. However, such studies have been insufficiently undertaken specifically in Malaysia and Southeast Asia in general. The main objective of this study was to identify ADH variants, specifically ADH-causing mutations and hypercholesterolemia-associated polymorphisms in multiethnic Malaysian population. We aimed to evaluate published SNPs in ADH causing genes, in this population and to report any unusual trends. We examined a large number of selected SNPs from previous studies of APOB, LDLR, PCSK9 and other genes, in clinically diagnosed ADH patients (n=141) and healthy control subjects (n=111). Selection of SNPs was initiated by searching within genes reported to be associated with ADH from known databases. The important finding was 137 mono-allelic markers (44.1%) and 173 polymorphic markers (55.8%) in both subject groups. By comparing to publicly available data, out of the 137 mono-allelic markers, 23 markers showed significant differences in allele frequency among Malaysians, European Whites, Han Chinese, Yoruba and Gujarati Indians. Our data can serve as reference for others in related fields of study during the planning of their experiments.
    Matched MeSH terms: Hyperlipoproteinemia Type II/genetics*
  7. Alhabib KF, Al-Rasadi K, Almigbal TH, Batais MA, Al-Zakwani I, Al-Allaf FA, et al.
    PLoS One, 2021;16(6):e0251560.
    PMID: 34086694 DOI: 10.1371/journal.pone.0251560
    BACKGROUND AND AIMS: Familial hypercholesterolemia (FH) is a common autosomal dominant disorder that can result in premature atherosclerotic cardiovascular disease (ASCVD). Limited data are available worldwide about the prevalence and management of FH. Here, we aimed to estimate the prevalence and management of patients with FH in five Arabian Gulf countries (Saudi Arabia, Oman, United Arab Emirates, Kuwait, and Bahrain).

    METHODS: The multicentre, multinational Gulf FH registry included adults (≥18 years old) recruited from outpatient clinics in 14 tertiary-care centres across five Arabian Gulf countries over the last five years. The Gulf FH registry had four phases: 1- screening, 2- classification based on the Dutch Lipid Clinic Network, 3- genetic testing, and 4- follow-up.

    RESULTS: Among 34,366 screened patient records, 3713 patients had suspected FH (mean age: 49±15 years; 52% women) and 306 patients had definite or probable FH. Thus, the estimated FH prevalence was 0.9% (1:112). Treatments included high-intensity statin therapy (34%), ezetimibe (10%), and proprotein convertase subtilisin/kexin type 9 inhibitors (0.4%). Targets for low-density lipoprotein cholesterol (LDL-C) and non-high-density lipoprotein cholesterol were achieved by 12% and 30%, respectively, of patients at high ASCVD risk, and by 3% and 6%, respectively, of patients at very high ASCVD risk (p <0.001; for both comparisons).

    CONCLUSIONS: This snap-shot study was the first to show the high estimated prevalence of FH in the Arabian Gulf region (about 3-fold the estimated prevalence worldwide), and is a "call-to-action" for further confirmation in future population studies. The small proportions of patients that achieved target LDL-C values implied that health care policies need to implement nation-wide screening, raise FH awareness, and improve management strategies for FH.

    Matched MeSH terms: Hyperlipoproteinemia Type II/drug therapy; Hyperlipoproteinemia Type II/metabolism; Hyperlipoproteinemia Type II/epidemiology*
  8. Alicezah MK, Razali R, Rahman T, Hoh BP, Suhana NH, Muid S, et al.
    Malays J Pathol, 2014 Aug;36(2):131-7.
    PMID: 25194536 MyJurnal
    We report a rare case of homozygous familial hypercholesterolemia (HoFH), a 22-year-old Malay woman who presented initially with minor soft tissue injury due to a cycling accident. She was then incidentally found to have severe xanthelasma and hypercholesterolemia (serum TC 15.3 mmol/L and LDL-C 13.9 mmol/L). She was referred to the Specialized Lipid Clinic and was diagnosed with familial hypercholesterolemia (FH) based on the Simon Broome (SB) diagnostic criteria. There was a family history of premature coronary heart disease (CHD) in that three siblings had sudden cardiac death, and of consanguineous marriage in that her parents are cousins. DNA screening of LDLR and APOB genes was done by Polymerase Chain Reaction (PCR), followed by Denaturing High Performance Liquid Chromatography (DHPLC). Homozygous mutation C255S in Exon 5 of her LDLR gene was found. There was no mutation was found in Exon 26 and Exon 29 of the APOB gene. This report is to emphasize the importance of identifying patients with FH and cascade screening through established diagnostic criteria and genetic studies in order to ensure early detection and early treatment intervention to minimize the risk of developing CHD and related complications.
    Matched MeSH terms: Hyperlipoproteinemia Type II/genetics*
  9. Azian M, Hapizah MN, Khalid BA, Khalid Y, Rosli A, Jamal R
    Malays J Pathol, 2006 Jun;28(1):7-15.
    PMID: 17694954 MyJurnal
    Familial hypercholesterolaemia (FH) and Familial defective apolipoprotein B100 (FDB) are autosomal dominant inherited diseases of lipid metabolism caused by mutations in the low density lipoprotein (LDL) receptor and apolipoprotein B 100 genes. FH is clinically characterised by elevated concentrations of total cholesterol (TC) and low density lipoprotein cholesterol (LDL-C), presence of xanthomata and premature atherosclerosis. Both conditions are associated with coronary artery disease but may be clinically indistinguishable. Seventy-two (72) FH patients were diagnosed based on the Simon Broome's criteria. Mutational screening was performed by polymerase chain reaction (PCR)-denaturing gradient gel electrophoresis (DGGE). Positive mutations were subjected to DNA sequencing for confirmation of the mutation. We successfully amplified all exons in the LDL receptor and apo B100 genes. DGGE was performed in all exons of the LDL receptor (except for exons 4-3', 18 and promoter region) and apo B100 genes. We have identified four different mutations in the LDL receptor gene but no mutation was detected in the apo B 100 gene. The apo B100 gene mutation was not detected on DGGE screening as sequencing was not performed for negative cases on DGGE technique. To our knowledge, the C234S mutation (exon 5) is a novel mutation worldwide. The D69N mutation (exon 3) has been reported locally while the R385W (exon 9) and R716G (exon 15) mutations have not been reported locally. However, only 4 mutations have been identified among 14/72 patients (19.4%) in 39 FH families. Specificity (1-false positive) of this technique was 44.7% based on the fact that 42/76 (55.3%) samples with band shifts showed normal DNA sequencing results. A more sensitive method needs to be addressed in future studies in order to fully characterise the LDLR and apo B100 genes such as denaturing high performance liquid chromatography. In conclusion, we have developed the DNA analysis for FH patients using PCR-DGGE technique. DNA analysis plays an important role to characterise the type of mutations and forms an adjunct to clinical diagnosis.
    Matched MeSH terms: Hyperlipoproteinemia Type II/genetics*
  10. Azraii AB, Ramli AS, Ismail Z, Abdul-Razak S, Badlishah-Sham SF, Mohd-Kasim NA, et al.
    BMC Cardiovasc Disord, 2021 01 19;21(1):39.
    PMID: 33468051 DOI: 10.1186/s12872-020-01845-y
    BACKGROUND: Primary care physicians (PCP) play an important role in detecting Familial Hypercholesterolaemia (FH) early. However, knowledge, awareness and practice (KAP) regarding FH among Malaysian PCP are not well established, and there was no validated tool to assess their FH KAP. Thus, the aim of this study was to adapt an FH KAP questionnaire and determine its validity and reliability among Malaysian PCP.

    METHODS: This cross-sectional validation study involved Malaysian PCP with ≥ 1-year work experience in the primary care settings. In Phase 1, the original 19-item FH KAP questionnaire underwent content validation and adaptation by 7 experts. The questionnaire was then converted into an online survey instrument and was face validated by 10 PCP. In Phase 2, the adapted questionnaire was disseminated through e-mail to 1500 PCP. Data were collected on their KAP, demography, qualification and work experience. The construct validity was tested using known-groups validation method. The hypothesis was PCP holding postgraduate qualification (PCP-PG-Qual) would have better FH KAP compared with PCP without postgraduate qualification (PCP-noPG-Qual). Internal consistency reliability was calculated using Kuder Richardson formula-20 (KR-20) and test-retest reliability was tested on 26 PCP using kappa statistics.

    RESULTS: During content validation and adaptation, 10 items remained unchanged, 8 items were modified, 1 item was moved to demography and 7 items were added. The adapted questionnaire consisted of 25 items (11 knowledge, 5 awareness and 9 practice items). A total of 130 out of 1500 PCP (response rate: 8.7%) completed the questionnaire. The mean percentage knowledge score was found to be significantly higher in PCP-PG-Qual compared with PCP-noPG-Qual (53.5, SD ± 13.9 vs. 35.9, SD ± 11.79), t(128) = 6.90, p 

    Matched MeSH terms: Hyperlipoproteinemia Type II
  11. Azraii AB, Ramli AS, Ismail Z, Abdul-Razak S, Mohd-Kasim NA, Ali N, et al.
    Atherosclerosis, 2018 10;277:508-516.
    PMID: 30270092 DOI: 10.1016/j.atherosclerosis.2018.08.018
    BACKGROUND AND AIMS: This study aimed to determine knowledge, awareness and practice (KAP) regarding familial hypercholesterolaemia (FH) among Malaysian primary care physicians (PCP), and to compare KAP between PCP with postgraduate qualification (PCP-PG-Qual) and PCP without PG qualification (PCP-noPG-Qual).

    METHODS: This was a cross-sectional study involving PCP with ≥1-year working experience in Malaysian primary care settings. An adapted and validated 25-item FH-KAP questionnaire was disseminated during primary care courses. Total score for each domain was calculated by summing-up the correct responses, converted into percentage scores. Normality distribution was examined and comparisons of mean/median percentage scores were made between the two groups of PCP.

    RESULTS: A total of 372 PCP completed the questionnaire. Regarding knowledge, 77.7% correctly defined FH. However, only 8.3% correctly identified coronary artery disease risk in untreated FH. The mean percentage knowledge score was significantly higher in PCP-PG-Qual compared to PCP-noPG-Qual (48.9, SD ± 13.92 vs. 35.2, SD ± 14.13), t(370) = 8.66, p 

    Matched MeSH terms: Hyperlipoproteinemia Type II/blood; Hyperlipoproteinemia Type II/diagnosis; Hyperlipoproteinemia Type II/genetics; Hyperlipoproteinemia Type II/therapy*
  12. Choong ML, Koay ES, Khoo KL, Khaw MC, Sethi SK
    Clin Chem, 1997 Jun;43(6 Pt 1):916-23.
    PMID: 9191540
    The Arg-to-Trp substitution at codon 3500 in the apolipoprotein (apo) B-100 gene is established as a cause of familial defective apo B-100 (FDB), a functional mutation, resulting in reduced LDL receptor binding and manifest hypercholesterolemia. In a search for similar mutations in 163 Malaysians, we screened the putative receptor-binding region (codons 3456-3553) of the apo B-100 gene by PCR amplification and denaturing gradient-gel electrophoresis. Four single-base mutations were detected and confirmed by DNA sequencing. Two females, a Chinese and a Malay, had the same CGG3500-->TGG mutation, resulting in an Arg3500-to-Trp substitution. This is the second published report of such an independent mutation involving the same codon as the established Arg3500-to-Gln mutation. The two other mutations detected, CTT3517-->CTG and GCC3527-->GCT, resulted in degenerate codons with no amino acid substitutions. All four mutations were associated with a unique apo B haplotype, different from those found in Caucasian FDB patients but concurring with that previously reported for two other Asians with FDB.
    Matched MeSH terms: Hyperlipoproteinemia Type II/blood; Hyperlipoproteinemia Type II/genetics
  13. Chua YA, Razman AZ, Ramli AS, Mohd Kasim NA, Nawawi H
    J Atheroscler Thromb, 2021 Oct 01;28(10):1095-1107.
    PMID: 33455995 DOI: 10.5551/jat.57026
    AIM: Familial hypercholesterolaemia (FH) is the most common autosomal dominant lipid disorder, leading to severe hypercholesterolaemia. Early detection and treatment with lipid-lowering medications may reduce the risk of premature coronary artery disease in FH patients. However, there is scarcity of data on FH prevalence, detection rate, treatment and control with lipid-lowering therapy in the Malaysian community.

    METHODS: Community participants (n=5130) were recruited from all states in Malaysia. Blood samples were collected for lipid profiles and glucose analyses. Personal and family medical histories were collected by means of assisted questionnaire. Physical examination for tendon xanthomata and premature corneal arcus were conducted on-site. FH were clinically screened using Dutch Lipid Clinic Network Criteria.

    RESULTS: Out of 5130 recruited community participants, 55 patients were clinically categorised as potential (Definite and Probable) FH, making the prevalence FH among the community as 1:100. Based on current total population of Malaysia (32 million), the estimated number of FH patients in Malaysia is 320,000, while the detection rates are estimated as 0.5%. Lipid-lowering medications were prescribed to 54.5% and 30.5% of potential and possible FH patients, respectively, but none of them achieved the therapeutic LDL-c target.

    CONCLUSION: Clinically diagnosed FH prevalence in Malaysian population is much higher than most of the populations in the world. At community level, FH patients are clinically under-detected, with majority of them not achieving target LDL-c level for high-risk patients. Therefore, public health measures are warranted for early detection and treatment, to enhance opportunities for premature CAD prevention.

    Matched MeSH terms: Hyperlipoproteinemia Type II/diagnosis; Hyperlipoproteinemia Type II/epidemiology*; Hyperlipoproteinemia Type II/therapy
  14. EAS Familial Hypercholesterolaemia Studies Collaboration, Vallejo-Vaz AJ, Akram A, Kondapally Seshasai SR, Cole D, Watts GF, et al.
    Atheroscler Suppl, 2016 Dec;22:1-32.
    PMID: 27939304 DOI: 10.1016/j.atherosclerosissup.2016.10.001
    The potential for global collaborations to better inform public health policy regarding major non-communicable diseases has been successfully demonstrated by several large-scale international consortia. However, the true public health impact of familial hypercholesterolaemia (FH), a common genetic disorder associated with premature cardiovascular disease, is yet to be reliably ascertained using similar approaches. The European Atherosclerosis Society FH Studies Collaboration (EAS FHSC) is a new initiative of international stakeholders which will help establish a global FH registry to generate large-scale, robust data on the burden of FH worldwide.
    Matched MeSH terms: Hyperlipoproteinemia Type II/diagnosis; Hyperlipoproteinemia Type II/genetics; Hyperlipoproteinemia Type II/mortality; Hyperlipoproteinemia Type II/therapy*
  15. EAS Familial Hypercholesterolaemia Studies Collaboration, Vallejo-Vaz AJ, De Marco M, Stevens CAT, Akram A, Freiberger T, et al.
    Atherosclerosis, 2018 10;277:234-255.
    PMID: 30270054 DOI: 10.1016/j.atherosclerosis.2018.08.051
    BACKGROUND AND AIMS: Management of familial hypercholesterolaemia (FH) may vary across different settings due to factors related to population characteristics, practice, resources and/or policies. We conducted a survey among the worldwide network of EAS FHSC Lead Investigators to provide an overview of FH status in different countries.

    METHODS: Lead Investigators from countries formally involved in the EAS FHSC by mid-May 2018 were invited to provide a brief report on FH status in their countries, including available information, programmes, initiatives, and management.

    RESULTS: 63 countries provided reports. Data on FH prevalence are lacking in most countries. Where available, data tend to align with recent estimates, suggesting a higher frequency than that traditionally considered. Low rates of FH detection are reported across all regions. National registries and education programmes to improve FH awareness/knowledge are a recognised priority, but funding is often lacking. In most countries, diagnosis primarily relies on the Dutch Lipid Clinics Network criteria. Although available in many countries, genetic testing is not widely implemented (frequent cost issues). There are only a few national official government programmes for FH. Under-treatment is an issue. FH therapy is not universally reimbursed. PCSK9-inhibitors are available in ∼2/3 countries. Lipoprotein-apheresis is offered in ∼60% countries, although access is limited.

    CONCLUSIONS: FH is a recognised public health concern. Management varies widely across countries, with overall suboptimal identification and under-treatment. Efforts and initiatives to improve FH knowledge and management are underway, including development of national registries, but support, particularly from health authorities, and better funding are greatly needed.

    Matched MeSH terms: Hyperlipoproteinemia Type II/blood; Hyperlipoproteinemia Type II/diagnosis; Hyperlipoproteinemia Type II/epidemiology; Hyperlipoproteinemia Type II/therapy*
  16. Hagger MS, Hardcastle SJ, Hu M, Kwok S, Lin J, Nawawi HM, et al.
    Eur J Prev Cardiol, 2018 06;25(9):936-943.
    PMID: 29592531 DOI: 10.1177/2047487318766954
    Background High rates of inadequate health literacy are associated with maladaptive health outcomes in chronic disease including increased mortality and morbidity rates, poor treatment adherence and poor health. Adequate health literacy may be an important factor in the effective treatment and management of familial hypercholesterolemia, and may also be implicated in genetic screening for familial hypercholesterolemia among index cases. The present study examined the prevalence and predictors of health literacy in familial hypercholesterolemia patients attending clinics in seven countries. Design Cross-sectional survey. Methods Consecutive FH patients attending clinics in Australia, Brazil, China, Hong Kong, Malaysia, Taiwan and the UK completed measures of demographic variables (age, gender, household income and highest education level) and a brief three-item health literacy scale. Results Rates of inadequate health literacy were lowest in the UK (7.0%), Australia (10.0%), Hong Kong (15.7%) and Taiwan (18.0%) samples, with higher rates in the Brazil (22.0%), Malaysia (25.0%) and China (37.0%) samples. Income was an independent predictor of health literacy levels, accounting for effects of age. Health literacy was also independently related to China national group membership. Conclusions Findings indicate non-trivial levels of inadequate health literacy in samples of familial hypercholesterolemia patients. Consistent with previous research in chronic illness, inadequate health literacy is related to income as an index of health disparities. Chinese familial hypercholesterolemia patients are more likely to have high rates of inadequate health literacy independent of income. Current findings highlight the imperative of education interventions targeting familial hypercholesterolemia patients with inadequate health literacy.
    Matched MeSH terms: Hyperlipoproteinemia Type II/diagnosis; Hyperlipoproteinemia Type II/ethnology*; Hyperlipoproteinemia Type II/psychology; Hyperlipoproteinemia Type II/therapy*
  17. Hagger MS, Hardcastle SJ, Hu M, Kwok S, Lin J, Nawawi HM, et al.
    Atherosclerosis, 2018 10;277:493-501.
    PMID: 30270090 DOI: 10.1016/j.atherosclerosis.2018.06.010
    BACKGROUND AND AIMS: Although familial hypercholesterolemia (FH) can be effectively managed using cholesterol-lowering medication, patients often fall short of complete treatment adherence. Identifying the psychological factors associated with self-regulation of FH medication is important to inform interventions to maximize adherence. The aim of the present study was to test an integrated psychological model in predicting FH patients' intentions to take medication.

    METHODS: FH patients attending clinics in seven countries were invited to participate in a cross-sectional survey study. Consenting patients (N = 551) completed self-report measures of generalized beliefs about medication overuse and harms, beliefs in treatment effectiveness, specific beliefs about taking medication (attitudes, subjective norms, perceived behavioral control), and intentions to take medication. Participants also completed measures of demographic variables (age, gender, education level, income, cardiovascular disease status). Data were analysed using path analysis controlling for country and demographic variables.

    RESULTS: Attitudes (β = .331, p<0.001), subjective norms (β = .121, p=0.009), and beliefs about medication overuse (β = -.160, p<0.001) were significant predictors of intentions to take medication. Treatment beliefs predicted intentions indirectly (β = .088, p<0.001) through attitudes and subjective norms. There was also an indirect effect of beliefs about medication overuse on intentions (β = -.045, p=0.056), but the effect was small compared with the direct effect.

    CONCLUSIONS: The findings indicate the importance among FH patients of specific beliefs about taking medication and generalized beliefs about medication overuse and treatment in predicting medication intentions. When managing patients, clinicians should emphasize the efficacy of taking cholesterol-lowering drugs and the importance of treatment outcomes, and allay concerns about medication overuse.

    Matched MeSH terms: Hyperlipoproteinemia Type II/blood; Hyperlipoproteinemia Type II/diagnosis; Hyperlipoproteinemia Type II/drug therapy*; Hyperlipoproteinemia Type II/psychology
  18. Hagger MS, Hamilton K, Hardcastle SJ, Hu M, Kwok S, Lin J, et al.
    Soc Sci Med, 2019 12;242:112591.
    PMID: 31630009 DOI: 10.1016/j.socscimed.2019.112591
    RATIONALE: Familial Hypercholesterolemia (FH) is a genetic condition that predisposes patients to substantially increased risk of early-onset atherosclerotic cardiovascular disease. FH risks can be minimized through regular participation in three self-management. BEHAVIORS: physical activity, healthy eating, and taking cholesterol lowering medication.

    OBJECTIVE: The present study tested the effectiveness of an integrated social cognition model in predicting intention to participate in the self-management behaviors in FH patients from seven countries.

    METHOD: Consecutive patients in FH clinics from Australia, Hong Kong, Brazil, Malaysia, Taiwan, China, and UK (total N = 726) completed measures of social cognitive beliefs about illness from the common sense model of self-regulation, beliefs about behaviors from the theory of planned behavior, and past behavior for the three self-management behaviors.

    RESULTS: Structural equation models indicated that beliefs about behaviors from the theory of planned behavior, namely, attitudes, subjective norms, and perceived behavioral control, were consistent predictors of intention across samples and behaviors. By comparison, effects of beliefs about illness from the common sense model were smaller and trivial in size. Beliefs partially mediated past behavior effects on intention, although indirect effects of past behavior on intention were larger for physical activity relative to taking medication and healthy eating. Model constructs did not fully account for past behavior effects on intentions. Variability in the strength of the beliefs about behaviors was observed across samples and behaviors.

    CONCLUSION: Current findings outline the importance of beliefs about behaviors as predictors of FH self-management behaviors. Variability in the relative contribution of the beliefs across samples and behaviors highlights the imperative of identifying sample- and behavior-specific correlates of FH self-management behaviors.

    Matched MeSH terms: Hyperlipoproteinemia Type II/complications; Hyperlipoproteinemia Type II/psychology*; Hyperlipoproteinemia Type II/therapy
  19. Khoo KL, Van Acker P, Tan H, Deslypere JP
    Med J Malaysia, 2000 Dec;55(4):409-18.
    PMID: 11221151
    A total of 86 unrelated Malaysian patients with familial hypercholesterolaemia (FH) were studied for mutations in their low-density lipoprotein receptor (LDL-R) gene. Amongst them, 23 had a LDL-R gene mutation, while none having an Apolipoprotein B-3500 (Apo B-3500) mutation. Patients with the LDL-R gene defect appeared to have a higher level of low-density lipoprotein cholesterol (LDL-C), an increased incidence of xanthomas and coronary heart disease (CHD), but no relationships were found between the type of LDL-R gene mutations and their lipid levels or clinical signs of CHD. In contrast to Western data, our findings seemed to indicate a predominance of mutations in the ligand binding domain and an absence of Apo B-3500 gene mutation. The latter finding may offer a genetic basis as to why Asian patients with familial hypercholesterolaemia have lower LDL-C levels and less premature CHD than their Western counterparts.
    Matched MeSH terms: Hyperlipoproteinemia Type II/blood; Hyperlipoproteinemia Type II/genetics*
  20. Khoo KL, van Acker P, Defesche JC, Tan H, van de Kerkhof L, Heijnen-van Eijk SJ, et al.
    Clin Genet, 2000 Aug;58(2):98-105.
    PMID: 11005141 DOI: 10.1034/j.1399-0004.2000.580202.x
    The aim of this study was to detect mutations in the genes coding for the low-density lipoprotein receptor and apolipoprotein B in patients of Southeast Asian origin with clinically diagnosed familial hypercholesterolemia (FH) and to relate these findings with the observed lower incidence of coronary heart disease in this part of the world. A total of 86 unrelated patients with FH were selected on clinical grounds, and complete DNA analysis of the low-density lipoprotein (LDL)-receptor and apolipoprotein B (apoB) genes by DGGE and DNA-sequencing was performed. In the majority (73%) of the cohort studied, no mutations could be detected, even after extensive analysis of the LDL-receptor and apoB genes. However, the 22 patients with a mutation had significantly more xanthomas and a higher incidence of coronary heart disease and levels of low-density lipoproteins were also significantly different. There was no correlation between the type of the mutation and lipoprotein levels or clinical signs of atherosclerosis. The fact that the majority of the FH patients studied had no detectable mutation and that this group had a significant milder phenotype, suggests the presence of a third gene in the Southeast Asian population, predominantly leading to a disorder resembling a milder form of FH. A similar, but less frequent, trait has recently been described in a number of European families.
    Matched MeSH terms: Hyperlipoproteinemia Type II/ethnology; Hyperlipoproteinemia Type II/genetics*
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