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.
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
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.
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
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
CASE PRESENTATION: This is a rare case of a pair of 8-year-old monochorionic diamniotic identical twin, who on family cascade screening were diagnosed as definite FH, according to the Dutch Lipid Clinic Criteria (DLCC) with a score of 10. There were no lipid stigmata noted. Baseline lipid profiles revealed severe hypercholesterolaemia, (TC = 10.5 mmol/L, 10.6 mmol/L; LDL-c = 8.8 mmol/L, 8.6 mmol/L respectively). Their father is the index case who initially presented with premature CAD, and subsequently diagnosed as FH. Family cascade screening identified clinical FH in other family members including their paternal grandfather who also had premature CAD, and another elder brother, aged 10 years. Genetic analysis by targeted next-generation sequencing using MiSeq platform (Illumina) was performed to detect mutations in LDLR, APOB100, PCSK9, ABCG5, ABCG8, APOE and LDLRAP1 genes. Results revealed that the twin, their elder brother, father and grandfather are heterozygous for a missense mutation (c.530C > T) in LDLR that was previously reported as a pathogenic mutation. In addition, the twin has heterozygous ABCG8 gene mutation (c.55G > C). Their eldest brother aged 12 years and their mother both had normal lipid profiles with absence of LDLR gene mutation.
CONCLUSION: A rare case of Asian monochorionic diamniotic identical twin, with clinically diagnosed and molecularly confirmed heterozygous FH, due to LDLR and ABCG8 gene mutations have been reported. Childhood FH may not present with the classical physical manifestations including the pathognomonic lipid stigmata as in adults. Therefore, childhood FH can be diagnosed early using a combination of clinical criteria and molecular analyses.
SETTING: A formal questionnaire was anonymously completed by physicians from different countries/regions in the Asia-Pacific. The survey sought responses relating to general familiarity, awareness of management guidelines, identification (clinical characteristics and lipid profile), prevalence and inheritance, extent of elevation in risk of cardiovascular disease (CVD) and practice on screening and treatment.
PARTICIPANTS: Practising community physicians from Australia, Japan, Malaysia, South Korea, Philippines, Hong Kong, China, Vietnam and Taiwan were recruited to complete the questionnaire, with the UK as the international benchmark.
PRIMARY OUTCOME: An assessment and comparison of the knowledge, awareness and preferences of FH among physicians in 10 different countries/regions.
RESULTS: 1078 physicians completed the questionnaire from the Asia-Pacific region; only 34% considered themselves to be familiar with FH. 72% correctly described FH and 65% identified the typical lipid profile, with a higher proportion of physicians from Japan and China selecting the correct FH definition and lipid profile compared with those from Vietnam and Philippines. However, less than half of the physician were aware of national or international management guidelines; this was significantly worse than physicians from the UK (35% vs 61%, p<0.001). Knowledge of prevalence (24%), inheritability (41%) and CVD risk (9%) of FH were also suboptimal. The majority of the physicians considered laboratory interpretative commenting as being useful (81%) and statin therapy as an appropriate cholesterol-lowering therapy (89%) for FH management.
CONCLUSIONS: The study identified important gaps, which are readily addressable, in the awareness and knowledge of FH among physicians in the region. Implementation of country-specific guidelines and extensive work in FH education and awareness programmes are imperative to improve the care of FH in the region.
RECENT FINDINGS: Genetic testing for familial hypercholesterolaemia is valuable to enhance diagnostic precision, cascade testing, risk prediction and the use of new medications. Hypertriglyceridaemia may be caused by rare recessive monogenic, or by polygenic, gene variants; genetic testing may be useful in the former, for which antisense therapy targeting apoC-III has been approved. Familial high-density lipoprotein deficiency is caused by specific genetic mutations, but there is no effective therapy. Familial combined hyperlipidaemia (FCHL) is caused by polygenic variants for which there is no specific gene testing panel. Familial dysbetalipoproteinaemia is less frequent and commonly caused by APOE ε2ε2 homozygosity; as with FCHL, it is responsive to lifestyle modifications and statins or/and fibrates. Elevated lipoprotein(a) is a quantitative genetic trait whose value in risk prediction over-rides genetic testing; treatment relies on RNA therapeutics.
SUMMARY: Genetic testing is not at present commonly available for managing dyslipidaemias. Rapidly advancing technology may presage wider use, but its worth will require demonstration of cost-effectiveness and a healthcare workforce trained in genomic medicine.
METHODS: In 14 Central England general practices, a novel case-finding tool (Familial Hypercholetserolaemia Case Ascertainment Tool, FAMCAT1) was applied to the electronic health records of 86 219 patients with cholesterol readings (44.5% of total practices' population), identifying 3375 at increased risk of FH. Of these, a cohort of 336 consenting to completing Family History Questionnaire and detailed review of their clinical data, were offered FH genetic testing in primary care.
RESULTS: Genetic testing was completed by 283 patients, newly identifying 16 with genetically confirmed FH and 10 with variants of unknown significance. All 26 (9%) were recommended for referral and 19 attended specialist assessment. In a further 153 (54%) patients, the test suggested polygenic hypercholesterolaemia who were managed in primary care. Total cholesterol and low-density lipoprotein-cholesterol levels were higher in those patients with FH-causing variants than those with other genetic test results (p=0.010 and p=0.002).
CONCLUSION: Electronic case-finding and genetic testing in primary care could improve identification of FH; and the better targeting of patients for specialist assessment. A significant proportion of patients identified at risk of FH are likely to have polygenic hypercholesterolaemia. There needs to be a clearer management plan for these individuals in primary care.
TRIAL REGISTRATION NUMBER: NCT03934320.