BACKGROUND: Homozygous familial hypercholesterolemia (HoFH) is a leading cause of premature atherosclerotic cardiovascular disease (ASCVD) and early mortality if left untreated or inadequately treated. OBJECTIVE: This st...BACKGROUND: Homozygous familial hypercholesterolemia (HoFH) is a leading cause of premature atherosclerotic cardiovascular disease (ASCVD) and early mortality if left untreated or inadequately treated. OBJECTIVE: This study presents 2 pediatric cases of early death from Pakistan due to familial hypercholesterolemia (FH) and provides a systematic review of similar cases reported globally. METHODS: Genetic analysis was conducted using next-generation sequencing to confirm pathogenic variants. For the systematic review, published reports of individuals with FH who died before the age of 18 years were identified. Data were extracted on demographic features, personal and family history, genetic variants, treatment given, and cause of death. RESULTS: Both patients, born to consanguineous families, presented with markedly elevated low-density lipoprotein cholesterol (LDL-C) levels (792 mg/dL [20.48 mmol/L] and 896 mg/dL [23 mmol/L], respectively), multiple xanthomas, and early-onset myocardial infarction, and died at the ages of 5 and 7 years, respectively. Their genetic analysis revealed a pathogenic frameshift variant in the LDLR gene: NM_000527.5: c.2416dupG (p.Val806GlyfsTer11). The systematic review included 12 studies reporting pediatric FH-related mortality. Common clinical features included tendon xanthomas, elevated LDL-C levels, family history, and early-onset ASCVD. Genetic testing was performed in a few cases, which revealed pathogenic variations in the LDLR gene. Most of the patients received inadequate lipid-lowering therapy. The most common causes of death were severe coronary artery disease, myocardial infarction, and sudden cardiac arrest. CONCLUSION: Our 2 cases and the accompanying systematic review identified additional cases of premature mortality. Collectively, these findings highlight diagnostic delays and inadequate treatment as common factors among patients who died prematurely.
BACKGROUND AND OBJECTIVES: Hypertriglyceridemia (HTG) may result from various etiologies, including the rare autosomal recessive disorder of chylomicron metabolism known as Familial Chylomicronemia Syndrome (FCS). Due to...BACKGROUND AND OBJECTIVES: Hypertriglyceridemia (HTG) may result from various etiologies, including the rare autosomal recessive disorder of chylomicron metabolism known as Familial Chylomicronemia Syndrome (FCS). Due to the risk of recurrent acute pancreatitis and subsequent pancreatic insufficiency, early and accurate diagnosis of FCS is clinically critical. Although genetic testing is considered the gold standard for diagnosis, access remains limited in many settings. To address this gap, the North American Familial Chylomicronemia Syndrome score (NAFCS Score) has been developed as a clinical tool incorporating readily available clinical and biochemical parameters. This study aimed to evaluate the performance of the NAFCS score in a cohort of genetically confirmed FCS patients. METHODS: A total of 38 patients with genetically confirmed biallelic mutations causing FCS were evaluated retrospectively. Data on demographics, comorbidities, laboratory values, and pancreatitis history were collected. NAFCS was applied to each patient, and concordance between the score categories and the genetic diagnosis was assessed descriptively. RESULTS: Among 38 genetically confirmed FCS patients, 52.6% were female. The median age was 35 years (IQR: 27-48 years). Acute pancreatitis had occurred in 86.8% of cases. The median triglyceride level was 3523 mg/dL (IQR: 2553-4470 mg/dL), and the median NAFCS was 65 (IQR: 52-81); 65.8% scored ≥60, 18.4% scored 45 to 59, and 15.8% scored <45. CONCLUSION: The use of the NAFCS may serve as a useful tool in the differential diagnosis of patients with limited access to genetic testing. In this cohort, 84.2% of patients scored ≥45, the proposed threshold suggestive of a likely or definite diagnosis of FCS. This highlights the clinical utility of the scoring system in cases with HTG.
BACKGROUND: Desmosterolosis is a ultra-rare autosomal recessive disorder caused by biallelic variants in the DHCR24 gene, which encodes 3-beta-hydroxysterol delta-24-reductase-an enzyme involved in the final step of chol...BACKGROUND: Desmosterolosis is a ultra-rare autosomal recessive disorder caused by biallelic variants in the DHCR24 gene, which encodes 3-beta-hydroxysterol delta-24-reductase-an enzyme involved in the final step of cholesterol biosynthesis. Here, we report a 3.5-year-old female with previously unreported compound heterozygous DHCR24 variants: c.1412A>G (p.Tyr471Cys), and c.275C>T (p.Thr92Met). CASE PRESENTATION: The patient presented with agenesis of the corpus callosum, hypotonia, developmental delay, and dysmorphic facial features. METHOD AND RESULTS: Trio-clinical exome sequencing confirmed the trans configuration of the variants. Plasma desmosterol levels were elevated >50-fold (134 ng/L; reference ≤2.5 ng/L), supporting the diagnosis. In silico 3D protein modeling demonstrated structural alterations associated with both variants. CONCLUSION: A review of reported cases revealed consistent findings of corpus callosum agenesis, developmental delay, and ocular abnormalities. Our case contributes to the limited body of literature on DHCR24-related desmosterolosis and expands the variant spectrum, emphasizing the importance of integrating clinical, biochemical, and computational approaches in diagnosing rare metabolic disorders.
BACKGROUND: Severe hypertriglyceridemia is a major risk factor for cardiovascular disease and acute pancreatitis, where effective and well-tolerated treatments remain limited. MND-21, a highly purified form of ethyl icos...BACKGROUND: Severe hypertriglyceridemia is a major risk factor for cardiovascular disease and acute pancreatitis, where effective and well-tolerated treatments remain limited. MND-21, a highly purified form of ethyl icosapentate with a smaller capsule diameter than currently available products, has not yet been approved for the treatment of severe hypertriglyceridemia, highlighting the need for additional clinical evidence. OBJECTIVE: To evaluate the efficacy and safety of MND-21 for the treatment of severe hypertriglyceridemia. METHODS: In this multicenter, 12-week, double-blind, parallel, placebo-controlled study, participants with severe hypertriglyceridemia (triglyceride [TG] levels between ≥5.65 mmol/L [500 mg/dL] and <22.60 mmol/L [2000 mg/dL]) undergoing lifestyle modification were randomized to receive MND-21 1800 mg/d, MND-21 3600 mg/d, or placebo. The primary endpoint was the percentage change in TG levels from the baseline. This trial was registered at ClinicalTrials.gov (NCT04239950) and ChinaDrugTrials.org (CTR20191474). RESULTS: The mean percentage changes in TG levels from the baseline to the end of treatment were -8.11, -13.88, and -18.38% in the placebo, MND-21 1800 mg, and MND-21 3600 mg groups, respectively. The MND-21 3600 mg group exhibited a significantly greater reduction in TG levels compared with the placebo group (P = .049). Both MND-21 1800 mg/d and MND-21 3600 mg/d were well tolerated, and no substantial differences in safety profiles were observed between the placebo group and either MND-21 dosage. CONCLUSION: The superiority of MND-21 3600 mg/d over the placebo was observed, and MND-21 was safe and well tolerated.
BACKGROUND: Lipoprotein(a) (Lp[a]), is a significant risk factor for cardiovascular disease, yet is infrequently measured. OBJECTIVE: A qualitative investigation was designed to better understand the barriers and facilit...BACKGROUND: Lipoprotein(a) (Lp[a]), is a significant risk factor for cardiovascular disease, yet is infrequently measured. OBJECTIVE: A qualitative investigation was designed to better understand the barriers and facilitators to Lp(a) testing. METHODS: Focus groups were held with clinicians (n = 26) and at-risk individuals (n = 24). Transcripts were thematically analyzed, guided by the Integrated Screening Action Model (I-SAM). Consistent with the I-SAM, barriers and facilitators of Lp(a) measurement were categorized as motivational, capability, and opportunity factors. RESULTS: Facilitators identified included perceived clinical utility, emotional reassurance associated with a newfound understanding of prior events, the ability to use Lp(a) knowledge to better prepare for the future, as well as active requests for testing. Barriers identified included a lack of perceived clinical utility and the potential to cause emotional distress with results, uncertainty and knowledge limitations around Lp(a), cost-related concerns, low expectations for testing, and clinician reluctance to test. CONCLUSIONS: This analysis highlights that Lp(a) testing decisions are multifactorial, providing multiple opportunities for intervention and improvement. Strategies to convey how Lp(a) measurement can inform risk assessment and treatment approaches may be foundational to encouraging more widespread testing.
BACKGROUND: Rheumatoid arthritis (RA) is a systemic autoimmune disease associated with a markedly increased risk of cardiovascular disease (CVD) that is not fully explained by traditional risk factors. Lipoprotein(a) [Lp...BACKGROUND: Rheumatoid arthritis (RA) is a systemic autoimmune disease associated with a markedly increased risk of cardiovascular disease (CVD) that is not fully explained by traditional risk factors. Lipoprotein(a) [Lp(a)], a genetically determined lipoprotein with proatherogenic, prothrombotic, and proinflammatory properties, has emerged as a potential contributor to this excess cardiovascular burden. Growing evidence suggests that Lp(a) may represent a mechanistic link between chronic inflammation, immune dysregulation, and accelerated atherosclerosis in RA. SOURCES OF MATERIAL: This narrative review synthesizes evidence from observational studies, mechanistic research, genetic analyses, biomarker investigations, and emerging therapeutic trials examining Lp(a) in RA. Relevant literature was identified through comprehensive searches of major biomedical databases, with emphasis on studies addressing pathophysiology, cardiovascular outcomes, disease activity, and treatment effects on Lp(a). ABSTRACT OF FINDINGS: RA patients frequently exhibit elevated Lp(a) levels, particularly in the presence of active systemic inflammation. Lp(a) contributes to vascular injury through enhanced arterial wall retention, carriage of oxidized phospholipids, endothelial activation, and impaired fibrinolysis. Clinical studies associate elevated Lp(a) with subclinical atherosclerosis, arterial stiffness, and increased cardiovascular events in RA, independent of conventional lipid parameters. Inflammatory cytokines, particularly interleukin-6 (IL-6), appear to modulate Lp(a) metabolism, providing a biological rationale for the Lp(a)-lowering effects observed with IL-6 receptor blockade. Advances in standardized assays, genetic insights into LPA polymorphisms, and novel RNA-based therapies have revitalized interest in Lp(a) as both a biomarker and therapeutic target in RA. CONCLUSION: Lp(a) occupies a critical intersection between inflammation and atherosclerosis in RA. Incorporating Lp(a) into cardiovascular risk stratification and exploring targeted therapies may enable more precise, integrated management of cardiovascular risk in RA patients, warranting dedicated prospective studies.
BACKGROUND: A large evidence base supports lipid lowering to reduce atherosclerotic cardiovascular disease (ASCVD) morbidity and mortality. Despite guideline-recommended lipid-lowering therapies (LLT), gender-based dispa...BACKGROUND: A large evidence base supports lipid lowering to reduce atherosclerotic cardiovascular disease (ASCVD) morbidity and mortality. Despite guideline-recommended lipid-lowering therapies (LLT), gender-based disparities in lipid management persist, with women less likely to be treated aggressively and achieve optimal low-density lipoprotein cholesterol (LDL-C) levels. OBJECTIVE: We aimed to investigate whether provider gender impacted lipid treatment gaps. METHODS: We conducted a retrospective chart review of 364,021 adults within a large health system who underwent lipid testing between 2022 and 2023. Demographic, clinical, and prescribing data were abstracted from electronic health records. Optimal LDL-C was defined based on ASCVD risk. RESULTS: Women had higher mean LDL-C (108 vs 102 mg/dL, P < .0001) and were less likely to achieve an LDL-C of <100 mg/dL (41% vs 47%, P < .0001) compared to men. Among those with ASCVD, only 31% of women vs 47% of men achieved an LDL-C <70 mg/dL (P < .0001). Women were less likely to be prescribed statins (26% vs 33%, P < .0001) in the overall population and high-intensity statins (23% vs 31%, P < .0001) in the ASCVD population than men. No prescribing difference was noted between male and female providers across specialties. CONCLUSION: Women with or at risk for ASCVD experience lower rates of LLT prescription and LDL-C goal attainment compared to men. These disparities underscore the need for targeted interventions to improve LDL-C goal attainment in women.
BACKGROUND: Chronic vascular inflammation may persist after Kawasaki disease (KD), but the long-term cardio-cerebrovascular prognosis remains unclear. This study aimed to investigate the association between childhood KD...BACKGROUND: Chronic vascular inflammation may persist after Kawasaki disease (KD), but the long-term cardio-cerebrovascular prognosis remains unclear. This study aimed to investigate the association between childhood KD and subsequent cardio-cerebrovascular risks. METHODS: A meta-analysis was performed on observational studies from PubMed, Embase, and Web of Science that compared individuals with and without a history of KD, assessing outcomes including lipid profiles, vascular ultrasound indices, and cardio-cerebrovascular events using a random-effects model. RESULTS: Fifty-one articles were meta-analyzed (46 on lipid and vascular markers, 5 on cardio-cerebrovascular events). Pooled analysis revealed reduced high-density lipoprotein cholesterol (HDLC) (weighted mean difference [WMD], 95% CI: -2.54, -4.31 to -0.77), impaired flow-mediated dilation (FMD) (WMD, 95% CI: -3.98, -5.78 to -2.17), increased carotid intima-media thickness (CIMT) (WMD, 95% CI: 0.03, 0.01-0.04), elevated ankle-brachial pulse wave velocity (BaPWV) (WMD, 95% CI: 46.00, 9.21-82.79), and a 4.4-fold increased risk (relative risk, 95% CI: 4.41, 4.02- 4.85) of cardio-cerebrovascular events vs controls. Subgroup analysis demonstrated reduced HDLC levels in patients with coronary artery lesions (CAL) (WMD, 95% CI: -3.70, -6.90 to -0.50) and Asian populations (WMD, 95% CI: -4.17, -6.86 to -1.47), along with FMD (with CAL: WMD, 95% CI: -7.01, -8.99 to -5.04; Asia: WMD, 95% CI: -5.60, -7.18 to -4.01) and increased CIMT (with CAL: WMD, 95% CI: 0.01, 0.00-0.02; Asia: WMD, 95% CI: 0.02, 0.01-0.03). Notably, reductions in both HDLC (WMD, 95% CI: -1.90, -2.39 to -1.40) and FMD (WMD, 95% CI: -5.29, -8.15 to -2.44) persisted in individuals over 10 years after KD. CONCLUSION: This meta-analysis highlights that prior KD, regardless of CAL status, may confer lasting impairments in vascular homeostasis and dyslipidemia, potentially increasing the lifetime risk of developing cardio-cerebrovascular diseases.
BACKGROUND: Heart transplantation represents an increasingly utilized procedure for end-stage heart failure patients. CURRENT EVIDENCE: Cardiac allograft vasculopathy (CAV) is a post-transplant complication of pathologic...BACKGROUND: Heart transplantation represents an increasingly utilized procedure for end-stage heart failure patients. CURRENT EVIDENCE: Cardiac allograft vasculopathy (CAV) is a post-transplant complication of pathological vasculature remodeling and remains an important cause for long-term graft failure and mortality. Current preventive strategies for CAV include optimization of vascular risk factors and pharmacotherapy with statins and immunosuppressants. CONCLUSION: Despite demonstrated post-transplant mortality benefit and reduction in CAV with statins, the role of other pharmacotherapies on CAV reduction through low-density lipoprotein cholesterol (LDL-C) lowering remains less established. This review explores established evidence as well as evolving pathways for LDL-C lowering strategies to prevent CAV.
BACKGROUND: Rare variants in SCARB1, which encodes the high-density lipoprotein (HDL) receptor scavenger receptor class B type 1 (SR-B1), are hypothesized to drive unexplained extreme levels of plasma HDL cholesterol (HD...BACKGROUND: Rare variants in SCARB1, which encodes the high-density lipoprotein (HDL) receptor scavenger receptor class B type 1 (SR-B1), are hypothesized to drive unexplained extreme levels of plasma HDL cholesterol (HDL-C). OBJECTIVE: We sequenced and phenotypically correlated SCARB1 by analyzing individuals with extreme HDL-C levels and characterizing the functional consequences of rare identified variants. METHODS: SCARB1 was Sanger-sequenced in 96 unrelated participants with extreme HDL-C levels. Clinical, biochemical, and anthropometric data were compared between groups. Bioinformatic tools were used to predict the functional impact of all detected variants. Familial analyses of predicted damaging in silico or not previously described variants was assessed, and HDL uptake was quantified by flow cytometry in HEK293 cells expressing rare SCARB1 variants showing a suggestive pattern of familial segregation. RESULTS: Compared with the high-HDL-C group, low-HDL-C subjects exhibited lower low-density lipoprotein cholesterol and total cholesterol but higher triglycerides, higher body mass index, and a greater frequency of atherosclerotic cardiovascular disease events. Twenty-five SCARB1 variants were identified; 4 of them, c.-177G>T, p.(Thr118Ser), c.843-982G>A and p.(Thr378Met), were predicted to be deleterious. The missense changes p.(Thr118Ser) and p.(Thr378Met) showed a suggestive pattern of segregation with high HDL-C in available pedigrees. Cells expressing p.(Thr378Met) SCARB1 variant showed a reduction in HDL uptake vs wild-type. CONCLUSION: Rare predicted damaging in silico variant in SCARB1, p.(Thr378Met), impairs SR-B1-mediated HDL uptake and associates with high HDL-C levels, highlighting SCARB1 as a candidate gene for genetic screening in dyslipidemic patients.
Bassole Epse Brou MAM, Fujiyoshi A, Higashiyama A
… +17 more, Okami Y, Kita Y, Miura K, Ikezaki H, Furukawa T, Tamura T, Nishimoto D, Nishiyama T, Takashima N, Kuriki K, Ishizu M, Lin Y, Kasugai Y, Koyanagi YN, Oze I, Matsuo K, J-MICC Study Group
BACKGROUND: While cholesterol-lowering trials have consistently demonstrated cardiovascular disease (CVD) benefits, some observational studies showed an elevated mortality risk from all-cause, CVD, and cancer in those wi...BACKGROUND: While cholesterol-lowering trials have consistently demonstrated cardiovascular disease (CVD) benefits, some observational studies showed an elevated mortality risk from all-cause, CVD, and cancer in those with low total cholesterol (TC). This inconsistency is likely due to confounding. OBJECTIVE: We explored potential confounders through various analytical approaches such as exclusion and adjustment. METHODS: Using data from the Japan Multi-Institutional Collaborative Cohort (J-MICC) study, we analyzed all-cause, CVD, and cancer mortality in individuals aged 35 to 69, not on cholesterol-lowering medication at baseline. We applied cohort-stratified Cox proportional hazards models to estimate the hazard ratio (HR) and 95% CI of the lowest TC group (<160 mg/dL) in reference to 160 to <200 mg/dL, after excluding self-reported CVD and cancer at baseline. RESULTS: A total of 55,677 participants were followed over 10.1 years. Initially, the lowest TC group, compared to the reference group, had significantly elevated risks for all-cause and cancer mortality. Excluding liver diseases and adjusting for serum albumin at baseline attenuated the association to non-significant; HR (95% CI) of all-cause, cancer mortality in men: 1.37 (0.99-1.87), 1.06 (0.66-1.71), respectively. The corresponding values for women were 0.96 (0.46-2.02), 1.39 (0.58-3.34). For CVD mortality, the HR in men with low TC remained elevated, while women were nonsignificant regardless of liver diseases exclusion and albumin-adjustment. CONCLUSION: Elevated all-cause and cancer mortality in low TC individuals was likely confounded by baseline liver diseases and serum albumin. Further research is needed to identify additional confounders.
BACKGROUND: Cardiometabolic multimorbidity (CMM) is an emerging public health challenge in China, yet no nationwide study has examined its patterns and associations with combined unhealthy behaviors using nationally repr...BACKGROUND: Cardiometabolic multimorbidity (CMM) is an emerging public health challenge in China, yet no nationwide study has examined its patterns and associations with combined unhealthy behaviors using nationally representative data. OBJECTIVE: (1) to assess the prevalence, patterns, and geographical distribution of CMM among Chinese adults, (2) to investigate the association between individual and combined unhealthy behaviors and the risk of CMM, and (3) to examine the clustering role of individual cardiometabolic diseases, particularly dyslipidemia, within multimorbidity patterns. METHODS: This study used secondary data from the 2015 China National Nutrition Health Survey involving 118,489 adults aged ≥18 years. We determined the prevalence and geographical distribution of CMM, identified patterns using association rule mining (ARM), and analyzed the relationships between unhealthy behaviors and CMM using multivariable logistic regression. RESULTS: The prevalence of CMM was 16.2% among Chinese adults (n = 19,840). ARM revealed dyslipidemia as a key clustering component, appearing in 56.8% of multimorbid cases despite representing only 16.1% individual prevalence. The most common dyad was dyslipidemia-hypertension (9.3% of the total population), followed by hypertension-diabetes (7.3%). Dyslipidemia showed strong bidirectional associations with diabetes (lift = 2.10), while hypertension was central to 80% of multimorbidity clusters. Geographic analysis showed that CMM prevalence peaked in northeastern provinces and was lowest in southern and western regions. Unhealthy behaviors showed dose-dependent associations with CMM risk: daily alcohol use (adjusted odds ratios [aOR] = 1.44), smoking (aOR = 2.58), and poor diet (aOR = 1.29). Combined unhealthy behaviors demonstrated progressive associations with multimorbidity development. CONCLUSION: This nationally representative study revealed dyslipidemia as a central clustering component in CMM, suggesting targeted lipid management could help prevent multimorbidity progression.
BACKGROUND: Patients experiencing premature cardiovascular events (males: <55 years; females: <65 years) represent a high-risk subgroup within the atherosclerotic cardiovascular disease (ASCVD) population. Elevated lipop...BACKGROUND: Patients experiencing premature cardiovascular events (males: <55 years; females: <65 years) represent a high-risk subgroup within the atherosclerotic cardiovascular disease (ASCVD) population. Elevated lipoprotein(a) (Lp[a]) is an independent, genetic, causal risk factor for ASCVD. Lp(a) distribution among patients with premature ASCVD is poorly characterized. OBJECTIVE: This study aimed to describe Lp(a) distribution and baseline characteristics in a large real-world sample of patients with premature ASCVD. METHODS: We identified 17,594 patients with premature ASCVD who had Lp(a) values from US Medicare, Medicaid, and commercial plans between January 2016-September 2022. RESULTS: Mean age (SD) was 50.9 (10.1) years, most patients were female (68.9%), and half (52.2%) were not prescribed lipid-lowering therapy. Lp(a) levels ≥125, ≥175, and ≥225 nmol/L occurred in 26.8%, 18.8%, and 11.5%, respectively. Black patients had higher median (Q1-Q3) Lp(a) levels (111.0 [51.1-206.0] nmol/L) than Asian (35.0 [14.4-100.0] nmol/L), Hispanic (31.0 [10.9-95.0] nmol/L), or White patients (31.0 [10.7-110] nmol/L). CONCLUSION: In one of the largest studies in the US investigating Lp(a) distribution in premature ASCVD, we found over a quarter of patients had elevated Lp(a) (≥125 nmol/L).
BACKGROUND: Epicardial adipose tissue (EAT), a visceral fat depot with metabolic and inflammatory properties, has been increasingly recognized as a potential marker for coronary artery disease (CAD). However, its clinica...BACKGROUND: Epicardial adipose tissue (EAT), a visceral fat depot with metabolic and inflammatory properties, has been increasingly recognized as a potential marker for coronary artery disease (CAD). However, its clinical utility and optimal cut-off values remain under investigation. OBJECTIVE: To assess the association between 2D echocardiographic EAT thickness and the presence and severity of obstructive CAD, and to determine optimal EAT thresholds for predicting significant CAD. METHODS: This cross-sectional study included 120 patients undergoing coronary angiography at a single tertiary center in Tunisia. EAT thickness was measured echocardiographically at end-systole and end-diastole in parasternal long- and short-axis views. CAD severity was evaluated using Syntax and Gensini scores. Patients were stratified into obstructive and non-obstructive CAD groups and further divided into tertiles based on EAT thickness. RESULTS: Obstructive CAD was identified in 66.7% of patients. EAT thickness was significantly higher in those with obstructive CAD (diastolic: 3.29 ± 0.99 mm vs 2.15 ± 1.38 mm; systolic: 5.68 ± 1.36 mm vs 4.05 ± 1.88 mm; P < .001 for both). Diastolic EAT > 2.45 mm and systolic EAT > 4.4 mm were independent predictors of obstructive CAD (odds ratio = 3.37 and 10.57, respectively), with strong diagnostic performance (area under the curve: 0.83 and 0.82). EAT thickness also correlated positively with Gensini and Syntax scores (r ≈ 0.5, P < .001), and higher tertiles were associated with multivessel disease and calcification. CONCLUSION: Echocardiographic EAT thickness is a reliable, noninvasive predictor of obstructive CAD and correlates with disease complexity. Given its simplicity and predictive value, it may serve as a useful screening tool for CAD severity stratification. Further large-scale studies are warranted to validate cut-off values and standardize assessment protocols.
BACKGROUD: As the burden of atherosclerotic cardiovascular disease (ASCVD) continues to rise, knowing the prevalence of its subclinical form is essential for early risk stratification and prevention. This review investig...BACKGROUD: As the burden of atherosclerotic cardiovascular disease (ASCVD) continues to rise, knowing the prevalence of its subclinical form is essential for early risk stratification and prevention. This review investigated the prevalence of carotid subclinical atherosclerosis, defined by the presence of plaque detected by ultrasound of the carotid arteries, as it varies with age in the asymptomatic young to middle-aged general population. SOURCES OF MATERIAL: We searched MEDLINE, EMBASE, PubMed, and CENTRAL (2005-2023) databases for observational and experimental studies assessing a population of asymptomatic (ie, no known cardiovascular disease), individuals (aged 18-65 years) who underwent carotid artery ultrasound imaging. Prevalence of plaque was calculated from each included study, as well as based on age and sex subgroups, and Freeman-Tukey double-arcsine-transformed prevalence measures were computed for each study. Pooled measures were generated with a random-effects meta-analysis model. ABSTRACT OF FINDINGS: A total of 92 studies comprising 204,997 subjects were included in this review (median sample size: 859). The median age of the study sample was 49.5 years (range: 26.6-64 years). The overall pooled prevalence of carotid atherosclerosis across all studies was 23% (95% CI: 19.1%-27.1%). The prevalence of carotid plaque increased according to age, ranging from a pooled prevalence of 5.2% (95% CI: 2.4%-8.9%) in adults aged 18 to 45 years to 30.3% (95% CI: 21.8%-39.4%) in those aged 50 to 65 years. CONCLUSION: Subclinical carotid atherosclerosis is prevalent among young to middle-aged healthy adults, free of known CVD, from the general population. The findings suggest that a significant proportion of low-risk individuals may have undetected plaque, justifying reconsideration of early screening strategies.
BACKGROUND: South Asians experience a disproportionately high burden of atherosclerotic cardiovascular disease at younger ages and at lower body mass index compared with other populations, a pattern that is not adequatel...BACKGROUND: South Asians experience a disproportionately high burden of atherosclerotic cardiovascular disease at younger ages and at lower body mass index compared with other populations, a pattern that is not adequately explained by traditional risk assessment models. An inflammation centered framework explains this excess risk, with visceral adiposity and insulin resistance amplifying inflammatory tone and lipoprotein(a) acting as fuel. OBJECTIVE: The objective of this review is to synthesize current evidence supporting an inflammation-centered framework for cardiometabolic disease in South Asians and to translate these biological insights into population-specific strategies for risk assessment and clinical management. METHODS: Evidence is drawn from population-based cohorts, biobank analyses, pooled studies of inflammatory biomarkers, randomized trials of anti-inflammatory therapies, and mechanistic research in adipose immunobiology. RESULTS: Across sources, South Asians carry more visceral fat at a given body mass, display higher high-sensitivity C-reactive protein and interleukin-6, and experience earlier atherosclerotic events. Mendelian and interventional data support causal inflammatory pathways, and residual inflammatory risk often persists despite attainment of low-density lipoprotein cholesterol targets. CONCLUSION: A pragmatic schema follows applying ethnicity aware adiposity thresholds, measuring lipoprotein(a) once in adulthood, pairing culturally familiar fiber-rich dietary patterns with guideline directed lipid lowering, and considering selective anti-inflammatory strategies such as low dose colchicine or cytokine inhibition in high-risk secondary prevention. Gaps remain for population-specific biomarker thresholds, equitable representation in trials, and implementation strategies tailored to diaspora communities. Framing prevention through inflammation, while addressing lipoprotein(a) as an accelerant, offers a clear path to narrow outcome gaps in cardiometabolic disease among South Asians.