OBJECTIVES: The objective of this study was to present the first experiences with LA in Malaysia, between 2004 and 2014.
METHODS: We retrospectively collected data from patient records to assess the effectiveness, adverse effects, patient quality of life, and costs associated with an LA service for genetically confirmed homozygous and heterozygous FH.
RESULTS: We treated 13 women and 2 men aged 6 to 59 years, 10 with homozygous and 5 with heterozygous FH, all on maximally tolerated cholesterol-lowering drug therapy, for a total of 65 patient-years. Acute lowering of low-density lipoprotein cholesterol post apheresis was 56.3 ± 7.2%, with time-averaged mean lowering of 34.9 ± 13.9%. No patients experienced any cardiovascular events during the period of receiving LA. Patients receiving LA experienced few side effects and enjoyed reasonable quality of life, but inability to continue treatment was frequent because of cost.
CONCLUSION: LA for severe FH can be delivered effectively in the short term in developing nations, but costs are a major barrier to sustaining this mode of treatment for this high-risk group of patients. New drug therapies for FH, such as the proprotein convertase subtilisin/kexin type 9 inhibitors, microsomal triglyceride transfer protein inhibitors, and apolipoprotein-B100 antisense oligonucleotides may allow improved care for these patients, but costs and long-term safety remain as issues to be addressed.
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
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.
METHODS: One hundred thirty-one FH patients, 68 RUC and 214 matched NC were recruited. Fasting lipid profile, biomarkers of inflammation (hsCRP), endothelial activation (sICAM-1 and E-selectin) and oxidative stress [oxidized LDL (oxLDL), malondialdehyde (MDA) and F2-isoprostanes (ISP)] were analyzed and independent predictor was determined using binary logistic regression analysis.
RESULTS: hsCRP was higher in FH and RUC compared to NC (mean ± SD = 1.53 ± 1.24 mg/L and mean ± SD = 2.54 ± 2.30 vs 1.10 ± 0.89 mg/L, p 0.05). FH was an independent predictor for sICAM-1 (p = 0.007), ox-LDL (p
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
OBJECTIVE: The objective of this study was to compare the health care of FH in countries of the Asia-Pacific region and Southern Hemisphere.
METHODS: A series of questionnaires were completed by key opinion leaders from selected specialist centers in 12 countries concerning aspects of the care of FH, including screening, diagnosis, risk assessment, treatment, teaching/training, and research; the United Kingdom (UK) was used as the international benchmark.
RESULTS: The estimated percentage of patients diagnosed with the condition was low (overall <3%) in all countries, compared with ∼15% in the UK. Underdetection of FH was associated with government expenditure on health care (ϰ = 0.667, P type 9 inhibitors. A deficit of FH registries, training programs, and publications were identified in less economically developed countries. The demonstration of cost-effectiveness for cascade screening, genetic testing, and specialized treatments were significantly associated with the availability of subsidies from the health care system (ϰ = 0.571-0.800, P
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.
OBJECTIVES: The authors sought to assess the LDL-C efficacy of rosuvastatin versus placebo in HoFH children, and the relationship with underlying genetic mutations.
METHODS: This was a randomized, double-blind, 12-week, crossover study of rosuvastatin 20 mg versus placebo, followed by 12 weeks of open-label rosuvastatin. Patients discontinued all lipid-lowering treatment except ezetimibe and/or apheresis. Clinical and laboratory assessments were performed every 6 weeks. The relationship between LDL-C response and genetic mutations was assessed by adding children and adults from a prior HoFH rosuvastatin trial.
RESULTS: Twenty patients were screened, 14 randomized, and 13 completed the study. The mean age was 10.9 years; 8 patients were on ezetimibe and 7 on apheresis. Mean LDL-C was 481 mg/dl (range: 229 to 742 mg/dl) on placebo and 396 mg/dl (range: 130 to 700 mg/dl) on rosuvastatin, producing a mean 85.4 mg/dl (22.3%) difference (p = 0.005). Efficacy was similar regardless of age or use of ezetimibe or apheresis, and was maintained for 12 weeks. Adverse events were few and not serious. Patients with 2 defective versus 2 negative LDL receptor mutations had mean LDL-C reductions of 23.5% (p = 0.0044) and 14% (p = 0.038), respectively.
CONCLUSIONS: This first-ever pediatric HoFH statin trial demonstrated safe and effective LDL-C reduction with rosuvastatin 20 mg alone or added to ezetimibe and/or apheresis. The LDL-C response in children and adults was related to underlying genetic mutations. (A Study to Evaluate the Efficacy and Safety of Rosuvastatin in Children and Adolescents With Homozygous Familial Hypercholesterolemia [HYDRA]; NCT02226198).
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.