BACKGROUND: The association between low-density lipoprotein to high-density lipoprotein (LDL/HDL) ratio and incident stroke among individuals with cardiovascular-kidney-metabolic (CKM) syndrome stages 0 to 3 remains uncl...BACKGROUND: The association between low-density lipoprotein to high-density lipoprotein (LDL/HDL) ratio and incident stroke among individuals with cardiovascular-kidney-metabolic (CKM) syndrome stages 0 to 3 remains unclear. OBJECTIVE: To examine the relationship of baseline and cumulative LDL/HDL ratio with new-onset stroke in CKM stages 0 to 3. METHODS: Data were obtained from the China Health and Retirement Longitudinal Study between 2011 and 2020. Individuals with CKM syndrome stages 0 to 3 were included to evaluate the relationship between baseline and cumulative LDL/HDL ratio and new-onset stroke. RESULTS: A total of 7867 participants were included. During follow-up, 501 individuals (6.4%) developed incident stroke. Stroke incidence increased progressively across LDL/HDL quartiles (Q1-Q4: 4.5%, 5.5%, 7.5%, and 7.9%, respectively; P < 0.001). Multivariate Cox regression demonstrated significantly elevated new-onset stroke risk in higher quartiles (Q3 vs. Q1: hazard ratio [HR] = 1.456, 95% CI 1.110-1.910, P = 0.007; Q4 vs. Q1: HR = 1.373, 95% CI 1.044-1.805, P = 0.023). Subgroup analyses confirmed the consistency of these associations. Mediation analyses indicated that systolic blood pressure (17.53%), glucose (6.67%), waist circumference (26.30%), and body mass index (20.60%) partially mediated the relationship. Additionally, a higher cumulative LDL/HDL ratio was associated with increased stroke risk (Q4 vs. Q1: HR =1.540, 95% CI 1.127-2.104, P = 0.007). CONCLUSION: Both baseline and cumulative LDL/HDL ratios were significantly correlated with an increased risk of new-onset stroke. Early identification and intervention of elevated LDL/HDL ratios may mitigate new-onset stroke risk in individuals with CKM syndrome.
BACKGROUND: Familial chylomicronemia syndrome (FCS) is a rare genetic form of primary hypertriglyceridemia with an increased risk of acute pancreatitis (AP). Apolipoprotein C-III (apoC-III) inhibitors, olezarsen and ploz...BACKGROUND: Familial chylomicronemia syndrome (FCS) is a rare genetic form of primary hypertriglyceridemia with an increased risk of acute pancreatitis (AP). Apolipoprotein C-III (apoC-III) inhibitors, olezarsen and plozasiran, provide therapeutic approaches to reduce triglycerides in patients with FCS. OBJECTIVE: To compare the efficacy and safety of olezarsen (Balance) with plozasiran (PALISADE) in FCS. METHODS: An anchored matching-adjusted indirect comparison was conducted. Outcome analyses included only the approved dosages of study therapies, while the AP analysis also pooled high- and low-dose regimens. RESULTS: Analyses showed no statistically significant differences in 52-week efficacy or safety. Mean differences (olezarsen vs plozasiran) in triglycerides and apoC-III reduction were -15.5% (95% CI: -76.2, 45.2) and -8.4% (95% CI: -69.7, 53.0). Relative risks of AP, treatment-emergent, and serious adverse events were 0.70 (95% CI: 0.07, 6.66), 0.81 (95% CI: 0.58, 1.13), and 0.50 (95% CI: 0.10, 2.58). CONCLUSION: Overall, there was no evidence of differences in efficacy or safety between olezarsen and plozasiran in the treatment of patients with FCS.
Severe hypertriglyceridemia in children is uncommon and typically results from a combination of acquired and genetic factors. We report the case of an 11-year-old boy with triglyceride levels exceeding 1700 mg/dL seconda...Severe hypertriglyceridemia in children is uncommon and typically results from a combination of acquired and genetic factors. We report the case of an 11-year-old boy with triglyceride levels exceeding 1700 mg/dL secondary to obesity, medication effects, and rare genetic variants. This case highlights the importance of early recognition, comprehensive evaluation, and evidence-based management to prevent acute complications such as pancreatitis and, in adulthood, premature cardiovascular disease.
BACKGROUND: Despite guideline recommendations, low-density lipoprotein cholesterol (LDL-C) target attainment remains suboptimal, particularly in China, where only 26.6% of high-risk patients attain goals. Given the estab...BACKGROUND: Despite guideline recommendations, low-density lipoprotein cholesterol (LDL-C) target attainment remains suboptimal, particularly in China, where only 26.6% of high-risk patients attain goals. Given the established role of pharmacists in lipid management and the current lack of a standardized intervention, we developed a comprehensive pharmacist-led intervention framework to improve patients' LDL-C goal attainment. OBJECTIVE: To evaluate the effectiveness of a pharmacist-led intervention framework in improving LDL-C target attainment compared with usual care. METHODS: An open-label, randomized controlled trial (RCT, January 2024-June 2025) was conducted. A total of 123 adults with above-target LDL-C were randomly assigned 1:1 to a 4-step pharmacist-led intervention or usual care. The primary endpoint was LDL-C target achievement at 12 months. RESULTS: Of 123 randomized participants, 109 (88.6%) completed follow-up. The intervention group achieved higher LDL-C goal attainment [45.5% vs. 25.9%; relative risk (RR) = 2.381, 95% confidence interval (CI) 1.062-5.339, P = .033] and greater LDL-C reduction (-0.67 mmol/L [IQR: -1.21 to -0.12] vs. -0.08 mmol/L [IQR: -0.53 to 0.29], P < .001) than the control group. At 1-year follow-up, the adoption rate of lipid-lowering drugs showed significant differences between the two groups (80.0% vs. 59.3%, RR = 2.750, 95% CI 1.169-6.467, P = .018); especially, the nonstatin agent adoption rate was 5-fold higher with shared decision-making (20.0% vs. 3.7%). CONCLUSION: The proposed pharmacist-led intervention framework significantly improved LDL-C target attainment and facilitated adoption of nonstatin therapies in high-risk patients. This intervention provides an immediately implementable, scalable template for integrating pharmacists into multidisciplinary cardiovascular care. TRIAL REGISTRATION: This study was registered at the Chinese Clinical Trial Registry (http://www.chictr.org.cn, ChiCTR2300079223; Registration Date: December 27, 2023).
Sampietro T, Sbrana F, Dal Pino B
… +10 more, Migliori M, Bruno S, Grange C, Bussolati B, Camussi G, Grossini E, Bigazzi F, Viacava P, Panichi V, Cantaluppi V
BACKGROUND: Lipoprotein glomerulopathy (LPG) is a rare disease affecting the kidney, clinically characterized by type III hyperlipoproteinemia, mutated apolipoprotein E (ApoE), the presence of glomerular lipoprotein thro...BACKGROUND: Lipoprotein glomerulopathy (LPG) is a rare disease affecting the kidney, clinically characterized by type III hyperlipoproteinemia, mutated apolipoprotein E (ApoE), the presence of glomerular lipoprotein thrombi, proteinuria in the nephrotic range, and progression toward chronic kidney disease (CKD). OBJECTIVE: Evaluate the role of lipoprotein apheresis (LA) as rescue therapy in LPG. METHODS: Since 2011, we have identified 6 unrelated patients living in the same geographical area of Central Italy (Tuscany Region) who share the same rare ApoE mutation. RESULTS: Four patients, due to nephrotic syndrome associated with biopsy-proven LPG, underwent LA. LA was able to stabilize renal function even for years in three of these subjects: of note, a better prognosis was reported when less impairment of renal function was present.LA was associated with a significant decrease of the number of plasmatic extracellular vesicles (EV) released from activated and/or damaged cells. In vitro studies showed that EV isolated from plasma of LPG patients induced human glomerular endothelial cell and podocyte alterations potentially responsible for the development of nephrotic syndrome and tissue injury. CONCLUSION: In conclusion, we demonstrated, in unrelated LPG patients with LPG carrying the same ApoE mutation, a protective role of LA on proteinuria and progression toward CKD. This LA-associated protective effect may be at least in part related to the modulation of biologically active EVs in patients' plasma.
BACKGROUND: Sitosterolemia is a rare autosomal recessive disorder caused by pathogenic variants in ABCG5 or ABCG8, leading to plant sterol buildup and variable low-density lipoprotein cholesterol levels. Its symptoms oft...BACKGROUND: Sitosterolemia is a rare autosomal recessive disorder caused by pathogenic variants in ABCG5 or ABCG8, leading to plant sterol buildup and variable low-density lipoprotein cholesterol levels. Its symptoms often mimic familial hypercholesterolemia (FH), making diagnosis difficult since standard lipid panels do not measure plant sterols. OBJECTIVE: We aimed to estimate the genetic burden of sitosterolemia in Qatar using pathogenic ABCG5/ABCG8 variants METHODS: We interrogated the ABCG5/ABCG8 variation in 14,060 Qatar Genome Program participants linked to Qatar Biobank phenotypes. Variants were annotated using ClinVar and gnomADv4.1 and classified according to American College of Medical Genetics and Genomics criteria. The carrier frequency was estimated in 5385 unrelated Qataris, incorporating a recessive disease burden model that accounted for inbreeding. RESULTS: We observed 7 pathogenic/likely pathogenic variants (3 in ABCG5; 4 in ABCG8) and identified 4 novel predicted loss‑of‑function variants in ABCG8. Estimated carrier frequencies were ∼1:215 (ABCG5) and ∼1:192 (ABCG8), yielding a combined ∼1:102 and an overall disease burden of ∼1:7509 in Qatar, markedly exceeding gnomAD estimates (∼1:251 carrier frequency; ∼1:383,744 disease burden). Several variants had homozygous individuals with abnormal lipid profiles and self‑reported hypercholesterolemia, suggestive of a potential FH-like phenotype. CONCLUSION: ABCG5/ABCG8 variants are enriched in Qatar relative to global datasets, consistent with population structure and consanguinity. Given the phenotypic overlap with FH but distinct therapeutic implications (notably superior response to ezetimibe and dietary sterol restriction), we propose integrating ABCG5/ABCG8 into dyslipidemia diagnostic workflows, especially in FH clinics, pediatrics, and ancestry-informed screening programs in the Middle-East and North Africa (MENA) region. These data highlight the potential value of plant-sterol testing and ABCG5/ABCG8 screening to reduce misdiagnosis, guide treatment, and enable cascade testing.
BACKGROUND: Hypertriglyceridemia remains prevalent among individuals with diabetes mellitus despite lipid-lowering treatments; however, evidence in Asian populations, particularly Koreans, is limited. OBJECTIVE: To evalu...BACKGROUND: Hypertriglyceridemia remains prevalent among individuals with diabetes mellitus despite lipid-lowering treatments; however, evidence in Asian populations, particularly Koreans, is limited. OBJECTIVE: To evaluate the prevalence and determinants of hypertriglyceridemia according to low-density lipoprotein cholesterol (LDL-C) levels and lipid-lowering therapy among Korean adults with diabetes mellitus, and to compare findings with U.S. METHODS: Data from 7713 Korean adults with diabetes mellitus in the 2011-2021 Korea National Health and Nutrition Examination Survey (NHANES) were analyzed. Hypertriglyceridemia prevalence (≥150 mg/dL and ≥200 mg/dL) was assessed by LDL-C levels and lipid-lowering medication use. Multivariable logistic regression identified risk factors, and results were compared with U.S. NHANES data. RESULTS: Among individuals with diabetes mellitus, the prevalence of hypertriglyceridemia was 43.3% (≥150 mg/dL) and 24.6% (≥200 mg/dL). Even in those achieving LDL-C <70 mg/dL with lipid-lowering medications, 37.8% had triglyceride levels ≥150 mg/dL and 19.3% had levels ≥200 mg/dL. Male sex (adjusted odds ratio [OR] 1.39, 95% CI 1.03-1.88) and higher LDL-C were positively associated with hypertriglyceridemia, whereas older age (OR 0.97 per year, 95% CI 0.96-0.99) and higher high-density lipoprotein cholesterol were inversely associated. Smoking was a significant risk factor for hypertriglyceridemia among women, and heavy alcohol consumption was a risk factor in both sexes. Compared with NHANES data, prevalence was similar, but associations with younger age, male sex, and elevated LDL-C were stronger among Koreans. CONCLUSION: Hypertriglyceridemia is highly prevalent among Korean adults with diabetes mellitus, including those achieving LDL-C targets. Younger age, male, elevated LDL-C levels, and adverse lifestyle factors were key determinants, highlighting the need for comprehensive lipid management strategies beyond LDL-C control.
BACKGROUND: The prevalence of dyslipidemia among adolescents and young adults is rising, increasing lifetime atherosclerotic cardiovascular disease (ASCVD) risk. Identifying dyslipidemia requires age-appropriate referenc...BACKGROUND: The prevalence of dyslipidemia among adolescents and young adults is rising, increasing lifetime atherosclerotic cardiovascular disease (ASCVD) risk. Identifying dyslipidemia requires age-appropriate reference ranges. OBJECTIVE: To describe lipid distributions, determine dyslipidemia prevalence, and identify associated factors in a cohort of Asian males. METHODS: This retrospective study included 19,130 males aged 16 to 25 years who underwent pre-enlistment medical screening. As military service is mandatory in Singapore, the cohort represented a nationwide sample of young males. Demographics, anthropometrics, and clinical measurements were collected using standardized protocols. Nonfasted blood samples were analyzed for total cholesterol (TC), triglycerides (TG), and high-density lipoprotein cholesterol (HDL-C). Low-density lipoprotein cholesterol (LDL-C) was estimated using the Martin/Hopkins equation. Dyslipidemia was defined using local cutoffs aligned with the National Cholesterol Education Program Adult Treatment Panel III criteria. Individuals with significantly elevated cholesterol levels were referred for familial hypercholesterolemia (FH) assessment. RESULTS: Mean lipid values were TC 169 ± 31 mg/dL, TG 109 ± 65 mg/dL, HDL-C 53 ± 11 mg/dL, and LDL-C 95 ± 28 mg/dL, and 44.3% of participants were overweight or obese. Dyslipidemia was present in 13.1%, including a substantial proportion without obesity. Severe hypercholesterolemia (LDL-C ≥190 mg/dL) was observed in 0.6%, and FH was diagnosed in 0.3%. Hypercholesterolemia was associated with older age, higher body fat, and grade 1 hypertension; hypertriglyceridemia and low HDL-C were associated with higher body fat, overweight or obesity, and grade 1 hypertension. CONCLUSION: The high dyslipidemia prevalence highlights the importance of early detection and preventive interventions to reduce ASCVD risk.
BACKGROUND: Residual cardiovascular risk persists in stable coronary artery disease despite improved low-density lipoprotein cholesterol (LDL-C) control. OBJECTIVE: We aimed to identify lipid phenotypes using multidimens...BACKGROUND: Residual cardiovascular risk persists in stable coronary artery disease despite improved low-density lipoprotein cholesterol (LDL-C) control. OBJECTIVE: We aimed to identify lipid phenotypes using multidimensional lipid profiling and to evaluate phenotype-dependent associations of fatty acid balance and lipoprotein(a) [Lp(a)] with major adverse cardiovascular events (MACE). METHODS: This retrospective study included patients undergoing elective percutaneous coronary intervention or coronary angiography. The day after the procedure, LDL-C, triglycerides (TG), remnant-like particle cholesterol (RLP-C), fatty acids (eicosapentaenoic acid [EPA], docosahexaenoic acid [DHA], arachidonic acid [AA], dihomo-γ-linolenic acid [DGLA]), malondialdehyde-modified low-density lipoprotein (MDA-LDL), and Lp(a) were measured; clustering using lipid parameters, including EPA/AA, DHA/AA, and DGLA/AA, identified lipid phenotypes. The primary endpoint was MACE (cardiovascular death, myocardial infarction, or stroke); the secondary endpoint was ischemia-driven repeat revascularization. RESULTS: Two phenotypes were identified: Cluster 1 (TG/RLP-C/MDA-LDL dominant phenotype) and Cluster 2 (higher EPA/AA lipid phenotype). During a median follow-up of 1356 days, a total of 86 MACE events occurred. Events were more frequent in Cluster 2 in unadjusted analysis (log-rank P = .036), but the association was attenuated after adjustment. Repeat revascularization did not differ between phenotypes. A higher EPA/AA ratio was independently associated with lower MACE risk only in Cluster 2 (HR 0.63, 95% CI 0.47-0.83; P = .001), with a significant interaction (likelihood ratio P = .012). Lp(a) showed a phenotype-specific, time-dependent association with early MACE only in Cluster 2. CONCLUSION: Fatty acid balance may have phenotype-dependent prognostic relevance. These findings support further investigation of multidimensional lipid phenotyping in residual cardiovascular risk assessment, although they should be interpreted as exploratory.
The recent 2026 American College of Cardiology/American Heart Association Multisociety Guideline on the Management of Dyslipidemia joins the growing international consensus that lipoprotein(a) [Lp(a)] should be tested at...The recent 2026 American College of Cardiology/American Heart Association Multisociety Guideline on the Management of Dyslipidemia joins the growing international consensus that lipoprotein(a) [Lp(a)] should be tested at least once in all adults. Despite the estimation that approximately 1 in 5 individuals have Lp(a) levels at or above those that are clearly associated with an increased risk for atherosclerotic cardiovascular disease and calcific aortic valve stenosis (≥50 mg/dL or ≥125 nmol/L), data from recent studies reveal very low testing rates across the general population. Thus, expanded Lp(a) testing is urgently needed. Along with guidance to test all adults for Lp(a), solutions are needed to help address remaining knowledge gaps, barriers to testing, and nuances in the clinical use of Lp(a). Studies designed to address these unmet needs should be prioritized as we enter the era of universal Lp(a) testing in adults.
BACKGROUND: Lipid-lowering therapies may attenuate kidney disease progression; however, whether specific lipid-lowering drug targets exert causal effects on albuminuria, which is an early marker of kidney injury, remains...BACKGROUND: Lipid-lowering therapies may attenuate kidney disease progression; however, whether specific lipid-lowering drug targets exert causal effects on albuminuria, which is an early marker of kidney injury, remains unclear. OBJECTIVE: To assess whether lipid-lowering drugs causally influence albuminuria risk and explore potential mediating pathways. METHODS: We conducted drug-target Mendelian randomization (MR) for 4 targets (lipoprotein lipase [LPL], peroxisome proliferator-activated receptor alpha [PPARA], 3-hydroxy-3-methylglutaryl-coenzyme A reductase [HMGCR], proprotein convertase subtilisin/kexin type 9 [PCSK9]) using 2 complementary approaches. Summary data-based MR (SMR) leveraged cis-expression quantitative trait loci to proxy target-gene expression, whereas cis-MR used lipid-associated cis variants to proxy target perturbation. Albuminuria summary statistics were obtained from CKDGen (cases: urinary albumin-to-creatinine ratio [UACR] >30 mg/g; controls: UACR <10 mg/g). Colocalization and 2-step MR evaluated shared genetic signals and potential mediation. RESULTS: SMR suggested that higher LPL expression was associated with lower albuminuria risk (odds ratio [OR], 0.987; 95% CI, 0.979-0.995; P = 9.68 × 10). In cis-MR, a genetically predicted 1 mmol/L triglyceride (TG) decrease attributable to LPL was associated with reduced albuminuria risk (OR, 0.880; 95% CI, 0.832-0.931; P = 8.04 × 10). No significant effects were observed for LDL-C-lowering targets (HMGCR, PCSK9) or PPARA. Colocalization supported a possible shared signal between whole-blood LPL expression and albuminuria (posterior probability for hypothesis 4 = 0.657). Two-step MR suggested partial mediation via type 2 diabetes (mediated proportion 11.88%; 95% CI, 5.32%-18.45%), atrial fibrillation (4.49%; 95% CI, 1.25%-7.72%), and visceral adipose tissue (4.69%; 95% CI, 1.27%-8.11%). CONCLUSION: Our genetic study suggests that genetically proxied LPL activation is associated with lower albuminuria risk, consistent with TG lowering and partial mediation through cardiometabolic pathways.
Phytosterolemia (MIM#210250, Orpha:2882) is a rare inherited disorder characterized by the accumulation of plant sterols. Typical clinical manifestations include cutaneous and tendon xanthomas, premature coronary artery...Phytosterolemia (MIM#210250, Orpha:2882) is a rare inherited disorder characterized by the accumulation of plant sterols. Typical clinical manifestations include cutaneous and tendon xanthomas, premature coronary artery disease, thrombocytopenia, anemia, and arthralgia. We describe a 30-year-old male patient with notable dyslipidemia who presented with signs and symptoms mimicking both Takayasu arteritis and a histiocytic tumor. The diagnosis of phytosterolemia was confirmed by detecting a pathogenic homozygous variant, c.1083G>A (p.Trp361Ter), in the ABCG8 gene. A coinciding systemic inflammatory process, histiocytosis, and phytosterolemia were considered to be interconnected. During the diagnostic process, significant coronary artery disease with ischemic sequelae was identified and routinely treated. Avoiding dietary plant sterols, in combination with ezetimibe and rosuvastatin, effectively corrected dyslipidemia. Despite targeted treatments, C-reactive protein and the erythrocyte sedimentation rate remained elevated, and the patient felt subjectively ill without a considerable prednisolone dose until treatment with interleukin-6 receptor antagonist tocilizumab was initiated. This case suggests that an extreme plant sterol excess may trigger severe, life-threatening inflammation, and highlights the importance of considering phytosterolemia in young patients with unexplained dyslipidemia and systemic inflammatory disease.
Capece U, Iacomini C, Morciano C
… +14 more, Gugliandolo S, Splendore A, Cesario A, Masciocchi C, Di Giuseppe G, Ciccarelli G, Avolio A, Brunetti M, Soldovieri L, Cinti F, Mezza T, Patarnello S, Giaccari A, Di Giorgi N
BACKGROUND: In diabetes, there is a lower concordance between estimated and directly measured low-density lipoprotein cholesterol (LDL-C) values. In previous studies, the Martin-Hopkins (MH) and the modified Sampson (mS)...BACKGROUND: In diabetes, there is a lower concordance between estimated and directly measured low-density lipoprotein cholesterol (LDL-C) values. In previous studies, the Martin-Hopkins (MH) and the modified Sampson (mS) equations emerged as novel LDL-C estimating methods with a higher concordance with direct measurement than the Friedewald (F) equation. OBJECTIVE: Our prior analysis of an entire population of inpatients showed a progressive decline in LDL-C target attainment from low to higher-risk categories, with only 32.5% of patients with diabetes reaching the target. This analysis aimed to compare LDL-C levels calculated using the F, MH, and mS equations in this population, and to evaluate the clinical implications of adopting these approaches on cardiovascular risk categorization - both in the overall cohort and within diabetes and non-diabetes subgroups. METHODS: Retrospective real-world data were extracted from the Hospital Information System using automated data extraction strategies and stored in a patient-centered repository (the Dyslipidaemia Data Mart). LDL-C was calculated using the F, MH, and mS equations. Goal achievement for LDL-C was evaluated using the 3 equations, overall and for diabetic and nondiabetic subgroups. We then assessed the effect of the switch from the traditional method to these novel approaches on patient risk categorization. RESULTS: A total of 13,834 patients were included. Overall, patients at goal were 35.8% with MH and 32.6% with mS, both lower compared with F (38.9%). The percentage of patients at goal (according to F) who were reclassified as not at goal (according to MH and mS) was significantly higher in diabetes compared with nondiabetes (5.1% vs 2.8% for reclassification from F to MH, P < .001; 8.3% vs 5.3% for reclassification from F to mS, P < .001). Distance to target was also higher with MH and mS, particularly among patients with diabetes. CONCLUSION: Accurate LDL-C estimation is critical for the cardiovascular risk management of people with diabetes. The choice of calculation method can significantly influence both target achievement and therapeutic decisions, with the MH and mS equations identifying a larger proportion of patients with diabetes as not at goal compared with the F equation.