Lipid clinics worldwide: harmonization and guidance on how to optimally organize and fund. European Atherosclerosis Society consensus statement across 55 countries and more than 500 lipid clinics.

BackgroundAtherosclerotic cardiovascular disease (ASCVD) is a leading cause of morbidity and mortality in the UK, with raised cholesterol contributing to 25%–28% of ASCVD deaths. Despite well-established guidelines, cholesterol levels remain suboptimally managed and can vary based on ethnicity, sex and socioeconomic deprivation, potentially leading to disproportionate cardiovascular risk for those living at these intersections. Pharmacist-led lipid clinics may reduce variation through structured review and continuity of care. This study evaluates whether automating the detection and referral of high-risk patients to a pharmacist-led clinic is associated with improved attainment of low-density lipoprotein cholesterol (LDL-C) among post-acute coronary syndrome patients in a West London borough, and whether outcomes vary by sex, ethnicity and socioeconomic deprivation.MethodsPatients with established ASCVD and residual elevated lipid levels were identified using the International Classification of Diseases, 10th revision and Systematised Nomenclature of Medicine coding and referred to a pharmacist-led review. Sex, ethnicity, age and index of multiple deprivation (IMD) were automatically extracted. The review involved a structured consultation, treatment intensification where required, and follow-up at agreed intervals. The primary outcome was attainment of LDL-C ≤2.0 mmol/L in line with National Institute for Health and Care Excellence recommendations assessed using a pre-post design.ResultsAmong 204 secondary prevention patients, 65% were from ethnically diverse backgrounds and 71% were male. Mean baseline LDL-C was 3.39 mmol/L and 13% were not actively receiving lipid-lowering therapy. Attendance by IMD quintile was 7.4% (most deprived), 34%, 33%, 13% and 12% (least deprived). Following the intervention, mean LDL-C reduced to 1.97 mmol/L with 70.6% achieving targets. Reductions were similar across sex, ethnicity and IMD quintile.ConclusionsA data-driven, pharmacist-led pathway was associated with significant LDL-C reduction. Among those who engaged, target attainment was similar across sex, ethnicity and IMD quintile, although low engagement from the most deprived quintile highlights that equitable reach has not yet been achieved. Further work is required to address upstream barriers and evaluate long-term sustainability.

Familial hypercholesterolemia (FH) is a genetic disorder characterised by elevated low-density lipoprotein cholesterol (LDL-C) and increased risk of premature atherosclerotic cardiovascular disease. In Denmark, general practitioners (GPs) play a key role in identifying and referring patients with suspected FH, yet referral rates remain low. To assess GPs' awareness of FH among patients with LDL-C values above guideline-based thresholds and examine how individual patient factors influence awareness. We conducted a retrospective audit of 304 patient records from 14 general practices in the Central Denmark Region. Audit inclusion criteria were LDL-C ≥5.0 mmol/L, or ≥4.0 mmol/L if aged <40 years, and a recorded consultation in primary care. Full-text medical records were reviewed, and systematic keyword searches identified documentation related to FH. Data was extracted using a structured audit form aligned with national guidelines, capturing demographics, LDL-C levels, treatments, and referral status. The median age was 58 years (IQR 51-65) and 54.6% were females. Median first LDL-C above threshold was 5.3 mmol/L. FH awareness was documented in 29% of records, despite all patients having LDL-C values above guideline-based thresholds. Referral rates to lipid clinics were 18% overall, varying by clinic affiliation. FH awareness rates were higher among patients with higher LDL-C values and younger age at presentation. The first LDL-C value also influenced subsequent statin initiation. GPs' awareness and referral rates for FH were low. FH awareness, LDL-C value, and age influenced management and referral rates, highlighting the need for improved support in identifying FH in primary care.

IntroductionAn affordable heart-healthy dietary approach is essential for the management of familial hypercholesterolaemia (FH); however, the optimal dietary pattern and the role of adjunctive nutrient supplementation remain uncertain. This study aims to evaluate the effects of the Brazilian Cardioprotective Diet (DICA Br), adapted from the Portfolio Diet, with or without phytosterol and/or krill oil supplementation in individuals with probable or definite FH according to the Dutch Lipid Clinic Network (Dutch MEDPED) criteria.Methods and analysisThe DICA-FH study is a national, multicentre, randomised, factorial, parallel-group, superiority, placebo-controlled clinical trial with a 1:1:1:1 allocation ratio. Participants aged ≥16 years receiving age-appropriate lipid-lowering therapy will be randomised into four groups: (1) adapted cardioprotective diet (DICA-FH) plus phytosterol placebo and krill oil placebo; (2) DICA-FH plus phytosterol 2 g/day and krill oil placebo; (3) DICA-FH plus phytosterol placebo and krill oil 2 g/day or (4) DICA-FH plus phytosterol 2 g/day and krill oil 2 g/day. All participants will undergo whole-genome sequencing and receive appropriate genetic counselling. Primary outcomes will be means of low-density lipoprotein cholesterol and lipoprotein(a) levels after 120 days. Secondary outcomes will include additional lipid biomarkers, adherence to protocol and adverse events. The planned sample size is 300 participants. Follow-up is expected to conclude in July 2026.Ethics and disseminationThis study was registered under CAAE 65549622.2.1001.0060 and received ethical approval from the Hcor Research Ethics Committee (approval number 5.805.072) and the Brazilian National Research Ethics Commission (CONEP; approval number 6.864.951). Written informed consent will be obtained from all participants prior to enrolment. The study findings will be disseminated through peer-reviewed publications, scientific conferences and channels aimed at the general public.Trial registration numberNCT06331195.

Familial hypercholesterolaemia (FH) is a common but underdiagnosed genetic condition that leads to high low-density lipoprotein cholesterol and premature cardiovascular disease. Cascade genetic testing remains underutilised as a screening approach. Implementation strategies can increase the diffusion of innovations such as genetic medicine into non-genetic specialty settings more rapidly through dissemination networks. This study aimed to evaluate the success of a multifaceted implementation strategy to increase cascade testing for relatives of a person diagnosed with FH using a primary-tertiary shared care model. A multisite effectiveness-implementation hybrid type III pre-post study was conducted between 2022 and 2024 to compare the implementation of a new shared care model for FH cascade testing in NSW, Australia. During the control period, cascade testing of relatives was offered to FH index cases by a genetic counsellor at the lipid clinic. In the implementation strategy period, FH index cases were offered a cascade testing expression of interest form to provide to their relatives. Relatives were contacted by a genetic counsellor and provided with a pre- and post-cascade testing package, which was also provided to their general practitioner. A total of n = 25 index and n = 6 cascade cases were included in the control period and n = 81 index and n = 56 cascade cases in the implementation period. The number of cascade genetic tests per index case increased significantly from 0.24 in the control period to 0.52 in the implementation strategy period (incident rate ratio = 4.62; 95% CI: 0.39, 8.84; p = 0.032). Among relatives tested, there was no difference in the proportion with a confirmed FH gene change per index case (IRR = 2.15; 95% CI: 0.65, 7.01; p = 0.207). There was no difference in the proportion of index cases with at least one cascade test (OR = 1.49; 95% CI: 0.53, 4.19; p = 0.442). Implementation of our model increased FH cascade testing compared to previous standard care. These findings suggest a greater role for cascade testing in primary care settings. This opens new opportunities for integrating genetic screening into routine general practice, particularly for autosomal dominant conditions such as FH.

Management of autosomal recessive hypercholesterolemia in a patient with an LDLRAP1 mutation.

From identification to implementation: A narrative review of strategies to close the implementation gap in patients with familial hypercholesterolemia.

To evaluate the association between lipid profile, statin use, metabolic syndrome, and clinic. Prostate Enlargement (PE) in adult men attending a urology outpatient clinic. A cross-sectional study was conducted among 1117 men aged 40-years or older. Prostate volume was measured by ultrasonography; a volume ≥ 40 mL was considered the threshold for enlargement. Independent variables included lipid fractions, prescription-based statin use, and components of metabolic syndrome. Multivariate logistic regression models were applied, adjusted for age, hypertension, and medication exposure. The median age was 63-years (IQR: 55-71), and the median prostate volume was 34.0 mL (IQR: 26.0-48.0). Statin use was identified in 36.5% of the sample, and the prevalence of PE was 38.9%. Age was the only factor independently associated with PE (OR = 1.07; 95% CI: 1.05-1.09; p < 0.001). Metabolic syndrome was associated with PE in crude analysis; however, this association lost statistical significance after adjustment for potential confounders. Age was the only independent determinant of prostate enlargement in this metabolically controlled cohort. Lipid parameters and prescription-based statin use showed no adjusted association with prostate volume; however, the lack of detailed statin exposure data warrants cautious interpretation of these findings.

Screening for familial hypercholesterolemia in the era of artificial intelligence: A contemporary narrative review.

Moving beyond clinical risk factors for diagnosis: The necessity of systematic Lp(a) measurement and familial hypercholesterolemia genetic testing.

Familial hypercholesterolemia is a common genetic disorder associated with premature cardiovascular disease. Genetic cascade screening is recommended but remains underused due to privacy laws that prevent clinicians from directly contacting at-risk relatives. To examine whether implementing a web-based communication platform in a patient-mediated genetic cascade screening program for familial hypercholesterolemia increases uptake compared with usual care. This open-label, multicenter, implementation randomized clinical trial (CATCH) was conducted between November 1, 2020, and October 31, 2023, at 7 cardiovascular prevention or lipid clinics across Switzerland, representing French-, German-, and Italian-speaking regions. Adults aged 16 years or older with genetically confirmed familial hypercholesterolemia and at least 1 eligible first-degree relative living in Switzerland participated. A total of 87 index patients with 359 eligible first-degree relatives were randomized by family cluster (1:1) to the intervention or usual care arm. A secure web-based platform allowing participants to send preprepared electronic messages (email or text) to their relatives, linking them directly to participating centers for genetic testing. The primary outcome was cascade screening uptake, defined as the proportion of eligible first-degree relatives undergoing genetic testing within 6 months. The secondary outcome was new cases identified. Among 221 adults screened across multiple families, 87 (39.4%) had genetically confirmed familia hypercholesterolemia (median [IQR] age, 49.2 [16.4-83.7] years; 46 [52.9%] female; median [IQR] highest low-density lipoprotein cholesterol, 289.58 [139.00-498.07] mg/dL); 43 were randomized to the usual care arm, and 44 were randomized to the intervention arm. Among the 359 eligible relatives (median family size, 4), 99 (27.6%) underwent genetic testing. Uptake was higher in the intervention arm (30.4%; 95% CI, 22.0%-40.4%) than in usual care arm (16.7%; 95% CI, 10.1%-26.3%), yielding an odds ratio of 2.18 (95% CI, 1.06-4.51; P = .03). New case identification was also greater (17.0% vs 8.1%; odds ratio, 2.32; 95% CI, 1.07-5.05; P = .03). Newly identified patients were often untreated or had modifiable risk factors. In this randomized clinical trial of patient-mediated genetic cascade screening supported by a web-based platform, participation in genetic testing and detection of familial hypercholesterolemia was increased compared with usual care. These results suggest that the use of digital communication tools enhanced the reach and effectiveness of genetic screening programs within privacy-regulated health systems. ClinicalTrials.gov Identifier: NCT04419090.

Cardiometabolic disorders including hypertension, diabetes mellitus, and dyslipidemia are major contributors to global morbidity, mortality, and healthcare costs. Conventional physician-centered care models often face challenges of accessibility, continuity, and patient engagement, particularly in resource-limited settings. Nurseled interventions have emerged as effective, patient-centered strategies that utilize nurses’ expertise in education, counseling, monitoring, and protocol-driven management. This review synthesizes evidence from randomized controlled trials, systematic reviews, and policy documents published between 2010 and 2025 to evaluate the impact of nurse-led approaches in managing cardiometabolic disorders. Findings indicate that nurse-led interventions significantly improve clinical outcomes. In hypertension, nurse-led clinics, home blood pressure monitoring, and lifestyle counseling reduce blood pressure and enhance adherence. In diabetes care, structured education, dietary counseling, and telehealth follow-up improve glycemic control and self-care behaviors. For dyslipidemia, nurse-managed lipid clinics and lifestyle programs reduce LDL cholesterol and increase patient awareness of cardiovascular risk. Across conditions, nurse-led interventions foster empowerment, satisfaction, and reduced hospital admissions. Their success lies in accessibility, patient-centeredness, and integration with technology. Challenges include variability in training, scope-of-practice regulations, and resource allocation. Nurse-led interventions are effective, scalable, and sustainable strategies that complement physician-led care, strengthen health systems, and should be prioritized in national strategies for cardiometabolic disease management.

Background: In clinical practice, LDL-dominant familial hypercholesterolemia (FH) may overlap phenotypically with triglyceride-dominant or mixed familial dyslipidemia. Rule-based diagnostic approaches like the Dutch Lipid Clinic Network (DLCN) and Simon Broome (SB) criteria are frequently used in countries with limited genetic testing, but their concordance with molecular confirmation is inconsistent. In a large Turkish tertiary-care cohort, we studied phenotype-related discordance between clinical criteria and molecular data and tested whether machine learning (ML) models could improve the prediction of reportable pathogenic/likely pathogenic variant positivity among patients with a clinical FH phenotype. Methods: Patients referred for suspected familial hyperlipidemia underwent targeted next-generation sequencing with a 9-gene panel. For the ML analysis, we focused on FH cases with a definitive molecular status (pathogenic/likely pathogenic vs. no reportable variant; variants of uncertain significance were excluded) and applied an 80/20 stratified split (n = 200; 82 molecular-positive cases). Elastic-net logistic regression, random forest, and XGBoost models trained on routinely available clinical variables were compared with dichotomized SB and DLCN classifications. Results: SB positivity was significantly more frequent in triglyceride-dominant phenotypes than in FH (68.4% vs. 52.3%, p = 0.041), despite the substantially lower molecular positivity (14.0% vs. 36.9%, p = 0.002), indicating FH-like false-positive clinical classification in mixed dyslipidemia. In the FH test set, the ML models showed higher discrimination for reportable pathogenic/likely pathogenic variant positivity than dichotomized rule-based criteria (AUC: XGBoost 0.808; random forest 0.769; elastic-net 0.747 vs. SB 0.639; and DLCN 0.598). Thirteen novel variants absent from gnomAD were identified, predominantly in LDLR. Conclusions: In this real-world Turkish cohort, within clinically defined FH cases, ML models performed better at predicting LP/P variant positivity than dichotomized DLCN and Simon Broome criteria. ML-based risk stratification may support prioritization for genetic testing; however, external validation is warranted.

Improving the clinical diagnosis of familial hypercholesterolemia among patients attending diabetes and cardiology clinics

Dietary and lifestyle habits in patients with hypertriglyceridemia referred to a Danish lipid clinic: a retrospective cross-sectional and follow-up study

Ischemic stroke and intracranial large-artery disease risk in familial hypercholesterolemia: A prospective Japanese study.

PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibition is a potent cholesterol-lowering strategy. This study examined the effects of PCSK9 monoclonal antibodies (mAbs) and high-intensity statins beyond low-density lipoprotein cholesterol reduction, which are not fully defined, particularly in patients with acute myocardial infarction (MI). Proteomic and lipidomic analyses were conducted on plasma from 265 patients with acute MI from the PACMAN-AMI (Effects of the PCSK9 Antibody Alirocumab on Coronary Atherosclerosis in Patients With Acute Myocardial Infarction) randomized, placebo-controlled PCSK9 mAb trial and 34 patients without MI with hyperlipidemia from the Vienna Lipid Clinic registry, also receiving PCSK9 mAbs. Discovery proteomics revealed changes in apolipoproteins and increased PCOLCE (procollagen C-endopeptidase enhancer 1) levels in both the PCSK9 mAb and placebo groups after MI. UK Biobank data confirmed PCOLCE and PCSK9 upregulation as associated with statin use. Hepatoma cell experiments demonstrated a dose-dependent PCOLCE induction on statin treatment. Compared with placebo (statins only), PCSK9 mAb therapy resulted in greater reductions in APOB (apolipoprotein B), APOE (apolipoprotein E), APOC2 (apolipoprotein C2), and APOC3 (apolipoprotein C3), as shown by targeted proteomics. Mediation analysis indicated that these changes were largely explained by low-density lipoprotein cholesterol lowering. Lipidomics identified more pronounced reductions in cholesteryl esters, ceramides, sphingomyelins, phosphatidylcholines, triglycerides, and diglycerides in PCSK9 mAb-treated patients with MI. Results were largely consistent in patients without MI. However, levels of LPA (apolipoprotein[a]), the characteristic protein component of lipoprotein(a), remained unchanged in PCSK9 mAb-treated patients with MI, since a rise of LPA was observed in the placebo group post-MI. Most apolipoprotein changes after PCSK9 mAb therapy following MI were mediated by low-density lipoprotein cholesterol lowering. Statin use is associated with increased circulating PCOLCE, with hepatoma cell experiments supporting a predominant hepatic origin. Combining PCSK9 mAbs with high-intensity statins mitigates post-MI increases in lipoprotein(a). URL: https://www.clinicaltrials.gov; Unique identifier: NCT03067844.

The SLCO1B1 c.521T > C variant, which reduces hepatic statin uptake, has been linked to an increased risk of statin-associated muscle symptoms (SAMS), particularly with simvastatin. This study aimed to assess its association with SAMS and prescription of contemporary lipid-lowering therapy in patients with severe hypercholesterolemia. We included 219 patients with a mean age of 53.9 ± 12.7years who attended our outpatient lipid clinic and were genotyped for the SLCO1B1 c.521T > C variant. Treating physicians and patients were unaware of genotyping results. Six patients (2.7%) were homozygous and 68 patients (31.1%) were heterozygous for the c.521T > C variant. After treatment optimization, the median LDL cholesterol levels were 63 (IQR 40-124) mg/dL and 74 (IQR 43-129) mg/dL in mutation carriers and non-carriers, respectively (p = 0.35). Self-reported SAMS did not differ between mutation carriers and non-carriers (25.7% vs. 27.6%; p = 0.76). In addition, statin usage (70.3% vs. 73.1%; p = 0.66) and prescription rates of proprotein convertase subtilisin/kexin type-9 inhibitors (PCSK9i) (32.4% vs. 31.0%; p = 0.83) did not differ according to mutation status. In patients with severe hypercholesterolemia on contemporary statin therapy, the SLCO1B1 c.521T > C variant was not associated with SAMS, reduced statin use, or increased prescription of PCSK9 inhibitors. The SLCO1B1 c.521T > C variant appears to have no clear clinical relevance, but testing for it may potentially be harmful, as fear of side effects could result in statin undertreatment.

Cascade screening can identify individuals with elevated lipoprotein(a) [Lp(a)], a causal risk factor for atherosclerotic cardiovascular disease (ASCVD). The aim of this study is to explore the effectiveness of cascade screening with asymptomatic children as index cases to identify family members with elevated Lp(a). In this retrospective study we used our database consisting of all children referred for a tentative diagnosis of hereditary dyslipidemia to the Amsterdam University Medical Centers pediatric lipid clinic (1989-2023). Elevated Lp(a) was defined as ≥30 mg/dL or ≥75 nmol/L. We evaluated two cascade screening approaches (opportunistic and systematic), calculated the number needed to screen (NNS) and repeated the analysis exclusively in children with FH as subgroup with particularly high cardiovascular risk. A total of 1,931 children were included (732 indexes, mean age (SD) 11.7 (4.5) years; 1,199 relatives, mean age (SD) 10.1 (4.4) years). In total, 480 (25%) of all children had elevated Lp(a) concentrations (≥30 mg/dL or ≥75 nmol/L). Both opportunistic (732 indexes) and systematic (316 indexes) cascade screening identified relatives with elevated Lp(a). The NNS was of 3.7 (95% CI 3.3-4.3) for the systematic approach and 4.1 (95% CI 3.8-4.6) for the opportunistic approach. In the FH subgroup, NNS were 3.9 (95% CI 3.4-4.5) and 4.3 (95% CI 3.9-4.8), respectively. Our findings suggest that cascade screening using children as index cases is an effective strategy to identify asymptomatic relatives at risk. Cardiovascular risk assessment should include Lp(a), especially in patients with FH who face an even higher cardiovascular risk. Until effective therapies become available, management should focus on modifiable risk factors.

ABSTRACT Objectives Familial hypercholesterolemia (FH) markedly increases the risk of premature atherosclerotic cardiovascular disease (ASCVD). Despite available therapies, FH remains underdiagnosed and undertreated. The aim of this study is to characterize FH patients and to evaluate treatment response specifically in those with a confirmed pathogenic mutation. Methods We retrospectively analysed 189 adults with clinical suspicion of FH seen at a cardiology department of a Belgian hospital between 2018 and 2024. Clinical, biochemical, and treatment data were retrieved from electronic records, and the Dutch Lipid Clinic Network (DLCN) score was calculated. Genetic testing was performed in 181 patients. Patients were stratified into primary and secondary prevention groups. Results The cohort comprised 116 patients (61%) in primary prevention and 73 (39%) in secondary prevention; the latter were older, predominantly male, and had more comorbidities. Genetic mutations were identified in 91 patients, most frequently in the LDL receptor gene (74%), followed by the ApoB gene (19%). Twenty-one patients had a DLCN score > 8, of whom four had no detectable pathogenic mutation. In genetically confirmed FH, mean LDL-cholesterol decreased from 267 ± 82 mg/dL at baseline to 100 ± 57 mg/dL at last follow-up, with greater reductions in secondary prevention. PCSK9 inhibitor use increased significantly during follow-up. Nevertheless, only 43% of secondary prevention patients achieved LDL-C < 55 mg/dL, and 24% of primary prevention patients reached < 70 mg/dL. Conclusion FH lipid management in this real-world cohort achieved substantial LDL-C reductions, but target attainment remained suboptimal.