Search Results (200)

Background and Aim: Familial hypercholesterolemia (FH) is a genetic disorder leading to severely elevated LDL-C and premature atherosclerotic cardiovascular disease (ASCVD). This study, the GRegistry-FH, provides the first population-based estimation of heterozygous FH (HeFH) prevalence and the clinical profile of affected individuals in Greece. Methods: A cross-sectional, questionnaire-based study was conducted on a representative sample of 7704 adults across 22 Greek regions. HeFH was assessed using the Simon Broome and Dutch Lipid Clinic Network (DLCN) criteria. Clinical characteristics and lipid-lowering therapy (LLT) attainment were compared between individuals with the HeFH phenotype and the general population. Results: The prevalence of HeFH was estimated at 1 in 188 individuals (Simon Broome) and 1 in 183 (DLCN). Individuals with the HeFH phenotype were significantly older and exhibited a much higher prevalence of hypertension (48.8% vs. 23.9%). Notably, individuals with the HeFH phenotype experienced myocardial infarction an average of 14 years earlier than non-FH individuals. Although 80.5% of individuals with the HeFH phenotype were on LLT, only 18.2% achieved LDL-C goals. None of the individuals with the HeFH phenotype with established ASCVD reached the target LDL-C of <1.4 mmol/L (55 mg/dL). Conclusions: HeFH is highly prevalent in Greece but remains largely underdiagnosed in younger ages and suboptimally treated. Despite high treatment rates, the vast majority of individuals with the HeFH phenotype fail to reach protective LDL-C targets. These findings emphasize the need for earlier identification and more aggressive combination lipid-lowering strategies. Full article

Familial hypercholesterolemia (FH) and familial hypertriglyceridemia (FHTG) represent a spectrum of inherited conditions with profoundly different etiologies, risk profiles, and therapeutic implications. Despite decades of clinical experience, their formal diagnostic definitions remain rooted in frameworks developed before the genomic era (the Dutch Lipid Clinic Network (DLCN) score), leading to substantial gaps in diagnostic accuracy. This review traces the historical evolution of diagnostic criteria for FH and FHTG from early phenotypic observation to contemporary genomic and biomarker-driven models. It systematically evaluates the major limitations of current criteria, including the (DLCN) score, and integrates evidence from landmark Mendelian randomization (MR) studies to identify persistent gaps. A narrative synthesis of landmark clinical, epidemiological, and genetic studies was performed, encompassing the original discovery of the low-density lipoprotein cholesterol (LDL-C) receptor pathway, the development of international diagnostic criteria, and contemporary mendelian randomization (MR) evidence on the causal roles of LDL-C, lipoprotein (a) [Lp(a)], triglyceride-rich lipoprotein remnants, and apolipoprotein B (ApoB). Current diagnostic frameworks suffer from age-dependent confounding of LDL-C measurements, failure to account for Lp(a)-mediated phenocopies, inadequate discrimination between monogenic and polygenic etiologies, sex differences, ethnicity, and inapplicability to pediatric populations. MR data reveal that the causal architecture of cardiovascular risk in these disorders is particle-centric (ApoB) rather than LDL-C-centric, and that remnant cholesterol, not triglyceride per se, drives atherosclerotic cardiovascular disease risk in FHTG. We evidenced the evolution of treatment options and the morbidity and mortality rates for FH and FHTG from the 1970s until the 2020s. Future diagnostic paradigms should integrate lifetime Lp(a) measurement, polygenic risk scoring, ApoB quantification, and cascade genomic testing to replace phenotype-only approaches. This review concludes by proposing a four-step integrated diagnostic algorithm for FH and FHTG. Full article

Background: This randomized controlled trial aimed to evaluate the effects of a school physician-led counseling intervention on total cholesterol (TC) levels, adherence to the Mediterranean diet, physical activity, and sedentary behavior in children aged 6–7 years with elevated cholesterol levels in a Mediterranean setting. Methods: A one-year randomized controlled study was conducted among children aged 6–7 years with elevated TC levels, excluding those with familial hypercholesterolemia (FH). Participants were randomly assigned to either a control group (n = 38) or an intervention group (n = 39). All participants received standard care consisting of educational materials and baseline counseling, while the intervention group additionally participated in three structured follow-up counseling sessions conducted by school physicians during the one-year study period. Counseling focused on Mediterranean dietary habits, implementation of basic dietary principles in cases of elevated TC levels, promotion of physical activity, and reduction in sedentary behavior. TC levels were measured at baseline and at the end of the study. Dietary habits, physical activity, and sedentary behavior were assessed using validated questionnaires. For the primary outcome, a descriptive change-from-baseline analysis, unadjusted mean difference, the approximate 95% confidence interval, and Cohen’s d effect size were calculated. Results: At baseline, no significant differences in TC levels were observed between groups (p = 0.852). After the intervention, mean TC levels were lower in the intervention group than in the control group (4.977 ± 0.414 mmol/L vs. 5.137 ± 0.410 mmol/L); however, the between-group difference did not reach statistical significance (p = 0.089). The unadjusted mean difference at follow-up was −0.160 mmol/L, with an approximate 95% confidence interval from −0.35 to 0.03 and a small-to-moderate effect size in favor of the intervention group (Cohen’s d = −0.39). Descriptive change-from-baseline analysis showed a greater mean reduction in TC in the intervention group than in the control group (−0.364 mmol/L vs. −0.195 mmol/L). A statistically significant improvement in adherence to the Mediterranean diet was observed in the intervention group compared with the control group (p < 0.001). Favorable changes were also observed in several physical activity and sedentary behavior variables, including participation in organized physical activity, walking and running activities, and reduced television viewing and video gaming time. Given the exploratory nature of behavioral analyses and the number of physical activity and sedentary behavior outcomes examined, these findings should be interpreted cautiously. Conclusions: The school physician-led counseling intervention did not result in a statistically significant between-group difference in TC levels after one year, although the direction and magnitude of change favored the intervention group. The intervention was associated with improved adherence to the Mediterranean diet and favorable exploratory lifestyle-related behavioral changes. Nevertheless, the findings should be interpreted cautiously in light of the relatively small sample size, non-significant primary outcome, and exploratory nature of behavioral analyses. Full article

High levels of low-density lipoprotein cholesterol (LDL-c) have been recognized as the main causal factor of atherosclerotic cardiovascular disease (ASCVD) and are influenced by both genetic and environmental factors. Among genetic determinants, Familial Hypercholesterolemia (FH) is the most common monogenic disorder, caused by rare high-impact variants in genes involved in LDL uptake. Other monogenic causes of hypercholesterolemia include sitosterolemia, cerebrotendinous xanthomatosis and lysosomal acid lipase deficiency (LALD). However, monogenic disorders only account for a small proportion of inherited hypercholesterolemia. In many individuals, increased LDL-c levels are caused by the contemporary presence of different single-nucleotide polymorphisms (SNPs) with a moderate/low impact. These SNPs could be summarized through polygenic risk scores (PRS) that attribute relative weight to each of these. Another genetic determinant of hypercholesterolemic phenotypes is high levels of lipoprotein(a)—Lp(a). Lp(a) is an LDL particle modified by the binding of apolipoprotein(a)—apo(a)—which represents an independent risk factor for ASCVD. Lp(a) levels are mainly genetically determined by variation in the number of kringle IV type 2 (K-IV₂) repeats, as well as by several SNPs, and remain stable throughout life. The aim of this narrative review is to report an updated overview of the genetic mechanisms underlying hypercholesterolemia, including monogenic disorders, PRS and Lp(a), focusing on their potential repercussion in clinical practice by the integration into cardiovascular risk stratification beyond traditional clinical assessment. This integration could lead to a more comprehensive and individualized approach to cardiovascular prevention, with emerging perspectives including the possible use of artificial intelligence (AI). Full article

Background/Objectives: Dyslipidemia is increasingly linked to retinal microvascular changes, yet its impact in pediatric populations remains unclear. Given the retina’s role as a microvascular model, this review evaluates the association between dyslipidemia and retinal vascular alterations in children and adolescents. Methods: We conducted a systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines to evaluate the association between lipid profiles, body composition, and retinal vascular parameters in individuals younger than 19 years. Four eligible studies were found. Results: Triglyceride (TG) levels, total cholesterol (TC) levels, low-density lipoprotein cholesterol (LDL-C), and apolipoprotein B (apoB) levels were associated with smaller retinal arteriole diameters (CRAE), whereas there was no consistent association between venular diameter (CRVE) and lipid levels. In addition, families with familial hypercholesterolemia (FH) had lower capillary densities and larger foveal avascular zone areas detected by optical coherence tomography angiography (OCT-A) compared to control subjects. The presence of both obesity and dyslipidemia resulted in greater degrees of arteriolar narrowing. Conclusions: These findings suggest that adverse metabolic profiles in childhood may be linked to early microvascular alterations. However, the limited number of heterogeneous studies highlights the need for larger longitudinal investigations. Full article

Background: Heterozygous familial hypercholesterolemia (HeFH) is characterized by elevated low-density lipoprotein cholesterol (LDL-C) and increased cardiovascular risk, making early diagnosis essential; however, the diagnostic performance of pediatric criteria is heterogeneous. This study evaluated the effectiveness of different diagnostic criteria and scoring systems to select children for genetic testing. Materials and methods: A total of 214 pediatric subjects with suspected HeFH were included, recruited from patients followed at a tertiary care center, based on LDL-C levels ≥ 95th age- and sex-specific percentile in both the proband and one biological parent. All subjects underwent genetic analysis of the main FH-associated genes (LDLR, APOB, PCSK9). The following diagnostic criteria and scoring systems were retrospectively evaluated and compared with genetic findings: Simon Broome Register (SBR), Dutch Lipid Clinic Network (DLCN), European Atherosclerosis Society (EAS), American Heart Association (AHA), Familial Hypercholesterolemia Canada Network (FH-CAN), Japanese Atherosclerosis Society (JAS), Lipid TransPort Disorders Italian Genetic Network for Italian pediatric patients (LIPIGEN-FH-PED), and the Familial Hypercholesterolemia Pediatric Diagnostic Score (FH-PeDS). Results: Pathogenic variants were identified in 91.8% of subjects. Approaches using lower LDL-C thresholds minimized the loss of variant-positive individuals (particularly JAS and FH-PeDS, with a missed diagnoses rate of 1.6%), whereas more restrictive definitions excluded a substantial proportion of affected patients (10.5% SBR, 56.3% DLCN, 6.3% EAS, 6.3% AHA, 7.4% FH-CAN, and 6.3% LIPIGEN-FH-PED). The mutation detection rate (MDR) was >91% for all examined criteria. Conclusions: Several current diagnostic criteria may underestimate the true number of children carrying FH-associated variants. Less selective criteria enable the identification of a greater number of FH-positive individuals while maintaining a high MDR, thus supporting the prioritization of identifying as many affected children as possible in the pediatric setting. This cohort reflects a tertiary referral population rather than the general population; therefore, further studies are needed to evaluate the applicability of our findings to broader public health contexts and screening settings. Full article

Introduction/Objectives: Although contemporary cardiovascular guidelines endorse intensive low-density lipoprotein cholesterol (LDL-C) lowering and advanced lipid biomarkers for refined risk stratification, important gaps in knowledge and implementation persist. This study evaluated clinician familiarity with novel lipid-lowering therapies, approaches to residual cardiovascular risk, confidence in identifying familial hypercholesterolemia (FH), and perceived usefulness of digital decision-support tools. Methods: A multispecialty, cross-sectional online survey (October 2025) of physicians involved in dyslipidemia care was conducted. The questionnaire assessed familiarity, accessibility, and barriers regarding proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, inclisiran, and bempedoic acid; confidence and practice in managing complex populations and residual risk; confidence in detecting FH and expectations for lipoprotein(a) [Lp(a)]; and perceived value of digital decision-support and automated risk alerts. Descriptive statistics and chi-square tests were performed. Results: Ninety-five clinicians completed the survey, with the largest group (41.1%) being general practitioners. Of them, 20.0% reported familiarity with all three novel therapies, and 49.5% reported restricted access due to cost and reimbursement constraints. Overall confidence in managing dyslipidemia in complex populations was moderate. Of note, 31.6% did not routinely assess residual risk after achieving LDL-C targets. Among those who did, imaging-based evaluation of subclinical atherosclerosis was the most frequently selected approach, followed by Lp(a) and triglycerides, hs-CRP, and apoB. Confidence in recognizing FH was modest, and expectations regarding future Lp(a) testing differed across specialties. Most respondents endorsed integrated decision-support tools and automated risk-alert prompts. Conclusions: Implementation gaps persist in dyslipidemia care, while strong receptiveness to digital decision-support highlights an opportunity to align practice more closely with evidence-based recommendations. Full article

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. Full article

Despite the availability of numerous lipid-lowering agents, the treatment of lipid disorders remains a public health challenge. A substantial portion of patients, especially those with severe dyslipidemia or familial hypercholesterolemia (FH), fail to achieve the LDL-C goal. The leading causes of suboptimal LDL-C control include underprescription and poor adherence; however, in rare cases, it may result from an unusual biological response to treatment. In the presented case, a 78-year-old female with a history of transient ischemic attack and myocardial infarction was diagnosed with a heterozygous variant of FH and true statin intolerance following trials of simvastatin, rosuvastatin and pitavastatin. Initially, inclisiran was added to ezetimibe, leading to an unexpected increase in LDL-C. Due to the patient’s refusal of another statin re-challenge and the unavailability of bempedoic acid, nutraceuticals were introduced. After 6 months, inclisiran was discontinued because only a 22% reduction in LDL-C was achieved, likely attributable to the nutraceutical’s effect. Another PCSK9 inhibitor, evolocumab, was subsequently initiated. Shortly after the treatment onset, the patient complained of paraesthesia in the upper extremities and discontinued therapy. LDL-C levels increased by 7% after one month of treatment with evolocumab. The patient refused treatment with lipid apheresis. Possible causes of poor response to PCSK9 inhibitors include elevated lipoprotein(a) and FH. Full article

Background/Objectives: An intensive lipid-lowering therapy is needed in familial hypercholesterolemia (FH) subjects; however, the adherence to the Mediterranean diet (MD) and its effects have not been fully evaluated in FH subjects. This study aimed to evaluate the impact of the MD on metabolic and vascular profiles in FH subjects. Methods: In this cross-sectional study 253 genetically confirmed FH subjects were included. Adherence to MD was assessed by the validated Pyramid-based MD Score (PyrMDS) and FH subjects were stratified according to the tertiles of PyrMDSs (low, intermediate, and high), with a higher score indicating higher adherence to MD. The lipid profile as well as the subendocardial viability ratio (SEVR), an indirect measure of myocardial perfusion, were assessed in all FH subjects. Results: Compared to the low-PyrMDS group, FH subjects with a high MD adherence showed lower levels of low-density lipoprotein cholesterol (LDL-C) (149.7 ± 71.4 vs. 176.7 ± 77.4 mg/dL, p = 0.006). After accounting for lipid-lowering therapies, smoking habit, and arterial hypertension, individuals in the high-PyrMDS group showed higher SEVR than those in the intermediate- and low-PyrMDS groups (167 ± 3.51 [standard error—SE] vs. 150 ± 5.03 [SE] vs. 148 ± 3.75 [SE], all p < 0.01). After adjusting for age, sex, and lipid-lowering therapies, PyrMDS was independently associated with LDL-C (β = −0.11, p = 0.03). Conclusions: Greater adherence to the MD was associated with more favorable metabolic and vascular profiles in FH subjects independent of lipid-lowering therapies. This suggests that MD adherence should be actively promoted in clinical practice alongside pharmacological interventions. Full article

Background: Early diagnosis of familial hypercholesterolemia (FH) is crucial to improve long-term outcomes. FH diagnosis relies on elevated low-density lipoprotein cholesterol (LDL-C) levels, familial clinical characteristics, and identification of pathogenic variants in FH-related genes. Secondary factors, such as overweight and obesity, are known to influence lipid profiles in the general population. More recently, polygenic risk scores based on single-nucleotide polymorphisms (SNPs) have been proposed as additional determinants of LDL-C levels. Methods: We enrolled 214 pediatric subjects with LDL-C levels ≥95th percentile (after 6 months of dietary intervention) and with at least one parent with LDL-C levels ≥ 95th percentile. All participants underwent biochemical and auxological assessment and genetic testing for FH. In a subgroup of 60 subjects, LDL-C polygenic scores based on 6- and 12-SNPs were calculated. Results: Pathogenic variants confirming heterozygous FH were identified in 190 subjects (variant-positive, V+); 17 were variant-negative (V−), yielding a mutation detection rate of 91.8%. An additional seven patients carrying variants of uncertain significance were excluded from the primary analysis. LDL-C was modestly higher in V+ than V− subjects using both Friedewald (212 vs. 188 mg/dL; p = 0.035) and Martin–Hopkins formulas (208 vs. 187 mg/dL; p = 0.041), while the other main clinical and laboratory parameters were similar. In V+, LDL-C was higher in subjects with null variants, compared to those with defective variants. Body mass index (BMI SDS) was inversely correlated with HDL-C (p < 0.001), and obesity (BMI z-score > 2 SDS) was associated with lower HDL-C and higher LDL-C, non-HDL-C, and ApoB. With regard to the polygenic scores, 12- and 6-SNP scores showed overlap between V+ and V−, and published cut-offs did not discriminate lipid severity in our population; however, in V+ subjects, the 12-SNP score acted as a phenotype modifier, being independently associated with higher LDL-C and non-HDL-C levels after adjustment for age, sex, and BMI SDS. Conclusions: In children selected by LDL-C ≥ 95th percentile, together with autosomal dominant familial hypercholesterolemia, genetic confirmation of FH is achieved in the vast majority of cases. Variant type (null vs. defective), BMI, and polygenic background contribute to phenotypic heterogeneity, supporting the need to address other factors alongside genetic diagnosis. Further validation is needed before polygenic scores can be implemented in routine clinical practice. Full article

The aim of the study was to characterize the prevalence of comorbidities and molecular genetic status in patients with familial hypercholesterolemia (FH) and non-familial hypercholesterolemia (non-FH). This cross-sectional observational study included 323 patients. Assessments comprised personal and family histories, physical examination, fasting lipid profiling, and molecular genetic testing. Patients with FH were not characterized by an increased prevalence of type 2 diabetes mellitus. In contrast, the non-FH group demonstrated a pronounced cardiometabolic comorbidity profile with a high prevalence of recurrent chronic pancreatitis. Patients with probable or definite FH had a higher prevalence of coronary heart disease and peripheral atherosclerosis, whereas myocardial infarction (MI) was common across all studied groups. Among patients with definite and probable FH, pathogenetic variants were identified in 78.2% and 71.4%, respectively, predominantly in the LDLR gene, with one variant in the APOB gene. In the possible FH group, pathogenic variants were identified in 46.7% of cases (LDLR gene in 64.3% and APOB gene in 28.6%). Patients with FH were characterized by a lower prevalence of concomitant cardiometabolic diseases. The high diagnostic yield of genetic testing in the possible FH category (figured Clinic Network score 3–5) suggests that expanding indications for molecular genetic testing to include this patient group should be considered. Full article

Apolipoprotein B (APOB) is a key structural component of atherogenic lipoproteins and one of the principal genes implicated in familial hypercholesterolemia (FH). However, APOB genetic variation remains poorly characterized in Latin American and admixed populations. In this study, we performed a descriptive analysis of APOB variants in 60 Ecuadorian mestizo patients with inherited cardiac conditions using next-generation sequencing (NGS) and genetic ancestry inference. A total of 227 APOB variants were identified, the majority of which were classified as benign (n = 220) or likely benign (n = 3) according to ACMG criteria, while three variants were classified as variants of uncertain significance (VUS). The most frequently observed variants included rs1042034, rs679899, rs676210, and rs1367117. Comparative allele-frequency analyses using ALFA and PAGE Latin American reference datasets demonstrated that the APOB variant frequencies observed in the cohort were comparable to those reported in other Latin American populations, reflecting the admixed genetic background of Ecuadorian mestizos, predominantly of Native American and European ancestry. No pathogenic APOB variants were detected. Although lipid measurements were not available and genotype–phenotype associations could not be assessed, this study provides the first comprehensive overview of APOB variation in Ecuadorian mestizo individuals. These findings expand population-specific genomic data for an underrepresented group and underscore the importance of regional reference datasets for accurate variant interpretation in admixed populations. Full article

Background/Objectives: Familial hypercholesterolemia (FH) is an autosomal dominant inherited disease characterised by lifelong LDL cholesterol levels and premature presentation of cardiovascular disease if left untreated. Whether fatty acid (FA) composition in lipoproteins is modified in FH patients is not known. This study aimed to identify FA differences in low- and high-density lipoprotein (LDL and HDL, respectively) among young Spanish individuals with FH, treated as per guidelines recommendations, compared to their unaffected relatives with similar LDL concentrations in plasma. We also evaluated associations between the occurrence of cardiovascular event (CVE), dietary patterns, and the lipoprotein FA profile in FH. Methods: Lipoprotein FA profiles were determined by liquid chromatography/mass spectrometry/mass spectrometry (LC/MS/MS). Results: In comparison to their non-FH relatives, FH patients showed changes in the FA profile, predominantly in LDL particles while HDL particles were only modestly changed. FH individuals exhibited higher concentrations of poly- and monounsaturated FAs, oleic, γ-linoleic, α-linoleic, arachidonic, and eicosapentaenoic acids (p < 0.05). Interestingly, FH individuals showed greater adherence to the Mediterranean diet than their non-FH relatives, with no significant differences between those with and without previous CVE. The most pronounced changes in FA profile were observed in FH patients with a history of CVE, although the event itself did not significantly modify lipoprotein FA profiles. Conclusions: Well treated FH patients showed a FA profile that responded to a healthier diet than their relatives with similar plasma LDL levels. The strict lifestyle and pharmacological treatment affected positively the lipoproteins of FH patients and needs to be recommended. Full article

Background: This systematic review and meta-analysis aimed to assess the burden of carotid atherosclerosis, including the prevalence of carotid plaques and stenosis, among individuals with familial hypercholesterolemia (FH). Methods: PubMed, Embase, and Scopus were searched up to 3 August 2025 to identify full-text, peer-reviewed articles published in English reporting the prevalence of carotid atherosclerotic plaques and/or stenosis in adult (≥18 years) patients with either a clinical or genetic diagnosis of FH. The methodological quality of the included studies was assessed using the Mixed Methods Appraisal Tool. Results were synthesized using random-effects meta-analysis and presented as pooled prevalence estimates with 95% confidence intervals (95% CI) displayed in forest plots. Publication bias was assessed using the Doi plot and the Luis Furuya-Kanamori index. Results: For the analysis of carotid plaque prevalence, seventeen studies including a total of 2870 patients were included (weighted age 47.2 ± 13.4 years, 47.3% male). No statistical difference in the pooled prevalence of carotid plaques was observed between clinically and genetically diagnosed FH (both 53%; 95% CI: 40–65%), however sub-analyses suggested a higher plaque burden in genetic FH. For the analysis of carotid stenosis prevalence, four studies comprising 704 participants were included; however, the available data were less consistent, yielding a pooled prevalence of 9% (95% CI: 0–40%). In conclusion, the results should be interpreted with caution due to several limitations, including the relatively low quality of the included studies, potential publication bias, considerable heterogeneity between the studies, and low to moderate certainty of evidence for the pooled estimates. These findings further emphasize the need for large-scale, standardized, multicenter studies to better characterize the burden of carotid atherosclerosis in this population. Full article