Systematic Identification of Familial Hypercholesterolaemia in Primary Care—A Systematic Review

Familial hypercholesterolaemia (FH) is a common inherited cause of premature cardiovascular disease, but the majority of patients remain undiagnosed. The aim of this systematic review was to assess the effectiveness of interventions to systematically identify FH in primary care. No randomised, controlled studies were identified; however, three non-randomised intervention studies were eligible for inclusion. All three studies systematically identified FH using reminders (on-screen prompts) in electronic health records. There was insufficient evidence that providing comments on laboratory test results increased the identification of FH using the Dutch Lipid Clinic Network (DLCN) criteria. Similarly, using prompts combined with postal invitation demonstrated no significant increase in definite FH identification using Simon-Broome (SB) criteria; however, the identification of possible FH increased by 25.4% (CI 17.75 to 33.97%). Using on-screen prompts alone demonstrated a small increase of 0.05% (95% CI 0.03 to 0.07%) in identifying definite FH using SB criteria; however, when the intervention was combined with an outreach FH nurse assessment, the result was no significant increase in FH identification using a combination of SB and DLCN criteria. None of the included studies reported adverse effects associated with the interventions. Currently, there is insufficient evidence to determine which is the most effective method of systematically identifying FH in non-specialist settings

Cost-Effectiveness of Screening Algorithms for Familial Hypercholesterolaemia in Primary Care

Although familial hypercholesterolemia (FH) screening within primary care is considered cost-effective, which screening approach is cost-effective has not been established. This study determines the cost-effectiveness of six case-finding strategies for screening of electronic health records to identify index patients who have genetically confirmed monogenic FH in English primary care. A decision tree was constructed to represent pathways of care for each approach (FH Case Identification Tool (FAMCAT) versions 1 and 2, cholesterol screening, Dutch Lipid Clinic Network (DLCN), Simon Broome criteria, no active screening). Clinical effectiveness was measured as the number of monogenic FH cases identified. Healthcare costs for each algorithm were evaluated from an NHS England perspective over a 12 week time horizon. The primary outcome was the incremental cost per additional monogenic FH case identified (ICER). FAMCAT2 was found to dominate (cheaper and more effective) cholesterol and FAMCAT1 algorithms, and extendedly dominate DLCN. The ICER for FAMCAT2 vs. no active screening was 8111 GBP (95% CI: 4088 to 14,865), and for Simon Broome vs. FAMCAT2 was 74,059 GBP (95% CI: −1,113,172 to 1,697,142). Simon Broome found the largest number of FH cases yet required 102 genetic tests to identify one FH patient. FAMCAT2 identified fewer, but only required 23 genetic tests

A case report of heterozygous familial hypercholesterolaemia with LDLR gene mutation complicated by premature coronary artery disease detected in primary care

BackgroundFamilial Hypercholesterolemia (FH) is an autosomal dominant genetic condition predominantly caused by the low-density lipoprotein receptor (LDLR) gene mutation.Case SummaryThis is the case of a 54-year-old Malay woman with genetically confirmed FH complicated by premature coronary artery disease (PCAD). She was clinically diagnosed in primary care at 52 years old, fulfilling the Simon Broome Criteria (possible FH), Dutch Lipid Clinic Criteria (score of 8: probable FH) and Familial Hypercholesterolemia Case Ascertainment Tool (FAMCAT relative risk score of 9.51). Subsequently, she was confirmed to have a heterozygous LDLR c.190+4A>T intron 2 pathogenic variant at the age of 53 years. She was known to have hypercholesterolemia and was treated with statin since the age of 25. However, the lipid-lowering agent was not intensified to achieve the recommended treatment target. The delayed FH diagnosis has caused this patient to have PCAD and percutaneous coronary intervention (PCI) at the age of 29 years and a second PCI at the age of 49 years. She also has a very strong family history of hypercholesterolemia and PCAD, where seven out of eight of her siblings were affected. Despite this, FH was not diagnosed early and cascade screening of family members was not conducted, resulting in a missed opportunity to prevent PCAD.DiscussionFH can be clinically diagnosed in primary care to identify those who may require genetic testing. Multidisciplinary care focuses on improving identification, cascade screening and management of FH is vital to improving prognosis and ultimately preventing PCAD

Case-finding and genetic testing for familial hypercholesterolaemia in primary care

Objective: Familial Hypercholesterolaemia (FH) is a common inherited disorder causing premature heart disease and death. We have developed novel case-finding algorithms (FAMCAT version 1 & 2) for application in primary care, to improve detection of FH and have evaluated their performance, at 95% specificity, to detect genetically-confirmed FH in the general population. We also compared these algorithms to established clinical case-finding criteria. Methods: Prospective validation study, in 14 general practices, recruiting participants from the general adult population with cholesterol documented. For 260 participants with available health records, we determined possible FH cases based on FAMCAT thresholds, Dutch Lipid Clinic Network (DLCN) score, Simon-Broome criteria and national recommended cholesterol thresholds (total cholesterol > 9.0 mmol/L if ≥30 years or > 7.5 mmol/L i

Acute oral toxicity study of root methanol extract of Goniothalamus lanceolatus miq. and its isolated bioactive compound (parvistone D) in murine model

Goniothalamus lanceolatus Miq. is widely used by the indigenous people of Sarawak, Malaysia as a folk remedy to treat various ailments including skin diseases, cold, and fever. A previous study reported that the root methanol extract, and parvistone D, an active compound of the plant, showed promising in vitro antiplasmodial activity against Plasmodium parasites. However, there is limited data reporting on its toxicological profile. Thus, this study aims to evaluate the potential toxicity of root methanol extract and parvistone D of G. lanceolatus in mice. The acute oral toxicity of the extract and compound was assessed at a single dose of 2000 and 500 mg/kg body weight, respectively. The animals were observed for any mortality, behavioral, motor-neuronal abnormalities, and body weight changes for 14 days. At the end of the experiment, relative organ weights were measured, and gross examination, as well as histopathological analysis, were performed. There was no sign of toxicity, and mortality seen in mice treated with G. lanceolatus root methanol extract, and parvistone D at the administered doses. In addition, no significant differences were observed in the body and relative organ weights between the control and treated groups. Gross and histopathological examinations showed normal appearance of the liver, spleen, kidneys, heart, and lungs as compared to their respective control groups. In conclusion, oral administration of root methanol extract, and parvistone D of G. lanceolatus are safe at the studied dosage levels and cause no acute toxicity in mice

Prevalence and distributions of severely elevated low-density lipoprotein cholesterol (LDL-c) according to age, gender and clinic location among patients in the Malaysian primary care

BackgroundAdults with severely elevated low-density lipoprotein cholesterol (LDL-c) may have familial hypercholesterolaemia (FH) and are at high risk of atherosclerotic cardiovascular disease (ASCVD). The prevalence of elevated LDL-c in primary care clinics in Malaysia is not known. Therefore, this study aimed to determine the prevalence and distributions of severely elevated LDL-c among adult patients attending public primary care clinics in Malaysia.MethodsA cross-sectional study was conducted at 11 public primary care clinics in the central states of Malaysia, among adults ≥18 years old with LDL-c recorded in the electronic medical record. Sociodemographic and LDL-c data from 2018 to 2020 were extracted. Severely elevated LDL-c was defined as ≥4 mmol/L, which were further classified into: 4.0–4.9, 5.0–5.9, 6.0–6.9 and ≥ 7 mmol/L.ResultsOut of 139,702 patients, 44,374 (31.8 %) had severely elevated LDL-c of ≥4 mmol/L of which the majority were females (56.7 %). The mean (±SD) age of patients with severely elevated LDL-c was younger at 56.3 (±13.2) years compared to those with LDL-c of <4.0 mmol/L at 59.3 (±14.5) years. In terms of LDL-c levels, 30,751 (69.3 %), 10,412 (23.5 %), 2,499 (5.6 %) and 712 (1.6 %) were in the 4.0–4.9, 5.0–5.9, 6.0–6.9 and ≥ 7 mmol/L categories, respectively.ConclusionThe prevalence of severely elevated LDL-c of ≥4.0 mmol/L among adult patients in public primary care clinics was high. These patients need to be further investigated for secondary and inherited causes such as FH. Therapeutic lifestyle modification and pharmacological management are pivotal to prevent ASCVD in these patients

Strategies for screening for familial hypercholesterolaemia in primary care and other community settings (Review)

Background: Familial hypercholesterolaemia is a common inherited condition that is associated with premature cardiovascular disease. The increased cardiovascular morbidity and mortality, resulting from high levels of cholesterol since birth, can be prevented by starting lipid‐lowering therapy. However, the majority of patients in the UK and worldwide remain undiagnosed. Established diagnostic criteria in current clinical practice are the Simon‐Broome and Dutch Lipid Clinical network criteria and patients are classified as having probable, possible or definite familial hypercholesterolaemia.Objectives: To assess the effectiveness of healthcare interventions strategies to systematically improve identification of familial hypercholesterolaemia in primary care and other community settings compared to usual care (incidental approaches to identify familial hypercholesterolaemia in primary care and other community settings).Search methods: We searched the Cochrane Inborn Errors of Metabolism Trials Register. Date of last search: 13 September 2021.We also searched databases (Cochrane Central Register of Controlled Trials (CENTRAL), Ovid MEDLINE, PubMed, Embase, CINAHL, Web of Science, and SCOPUS) as well as handsearching relevant conference proceedings, reference lists of included articles, and the grey literature. Date of last searches: 05 March 2020. Selection criteria: As per the Effective Practice and Organisation of Care (EPOC) Group guidelines, we planned to include randomised controlled trials (RCTs), cluster‐RCTs and non‐randomised studies of interventions (NRSI). Eligible NRSI were non‐randomised controlled trials, prospective cohort studies, controlled before‐and‐after studies, and interrupted‐time‐series studies.We planned to selected studies with healthcare interventions strategies that aimed to systematically identify people with possible or definite clinical familial hypercholesterolaemia, in primary care and other community settings. These strategies would be compared with usual care or no intervention.We considered participants of any age from the general population who access primary care and other community settings.Data collection and analysis: Two authors planned to independently select studies according to the inclusion criteria, to extract data and assess for risk of bias and the certainty of the evidence (according to the GRADE criteria). We contacted corresponding study authors in order to obtain further information for all the studies considered in the review.Main results: No eligible RCTs or NRSIs were identified for inclusion, however, we excluded 28 studies.Authors' conclusions: Currently, there are no RCTs or controlled NRSI evidence to determine the most appropriate healthcare strategy to systematically identify possible or definite clinical familial hypercholesterolaemia in primary care or other community settings. Uncontrolled before‐and‐after studies were identified, but were not eligible for inclusion. Further studies assessing healthcare strategies of systematic identification of familial hypercholesterolaemia need to be conducted with diagnosis confirmed by genetic testing or validated through clinical phenotype (or both)