Cardiometabolic diseases-principally cardiovascular disease, type 2 diabetes, and obesity-remain leading global drivers of premature mortality, disability, and healthcare expenditure, despite substantial advances in their biological understanding, risk assessment, and treatment. This narrative review critically examines why increasingly effective preventive interventions have failed to yield a commensurate reduction in population-level disease burden, identifying the biological, clinical, organizational, economic, and social factors that sustain this evidence-to-practice gap. It integrates evidence across three complementary dimensions: (1) The biological continuum, linking metabolic dysfunction, chronic low-grade inflammation, and cumulative exposure to apolipoprotein B (ApoB)-containing lipoproteins with atherosclerotic cardiovascular disease; (2) The clinical continuum, extending from early risk recognition and targeted diagnostic evaluation to individualized intervention and longitudinal reassessment; and (3) The organizational continuum, required to deliver coordinated, multidisciplinary prevention across health systems. Particular attention is given to total and lifetime cardiovascular risk, the clinical application and limitations of SCORE2 and SCORE2-OP, and the diagnostic challenges of identifying younger or apparently healthy individuals whose low short-term risk masks significant cumulative lifetime exposure. The review critically evaluates the causal role and clinical interpretation of ApoB-containing lipoproteins, including lipoprotein(a) [Lp(a)], and the complementary role of emerging biomarkers and subclinical atherosclerosis imaging, while carefully distinguishing enhanced risk prediction from demonstrated improvements in hard clinical outcomes. An educational and translational clinical vignette illustrates how the longitudinal interpretation of routine clinical and laboratory data supports proportionate assessment of persistent dyslipidemia, treatment response, and plausible primary and secondary contributors to cardiometabolic risk well before symptom onset. Rather than attributing borderline abnormalities to a single occult disorder, the vignette demonstrates how standardized confirmation, verification of medication exposure, etiological assessment, targeted referral, and structured reassessment can translate routine data into actionable preventive pathways. Ultimately, this analysis indicates that cardiometabolic prevention is constrained less by a lack of scientific evidence or effective pharmacotherapies than by delayed risk recognition, therapeutic inertia, poor treatment adherence, fragmented care pathways, limited multidisciplinary coordination, structural health inequalities, and the incomplete integration of clinical, laboratory, behavioral, environmental, and patient-reported data. Improving outcomes therefore demands a systemic shift from episodic, disease-specific management toward early, lifelong, proportionate, coordinated, equitable, and patient-centered cardiometabolic prevention-underpinned by implementation science, precision prevention, digital health solutions, health-economic evaluations, patient-reported outcome measures (PROMs), and patient-reported experience measures (PREMs).

Background Pancreatic duct stones are a frequent structural complication of chronic pancreatitis and may contribute to recurrent attacks and progressive pancreatic damage. Dyslipidemia is associated with metabolic dysfunction and may influence the clinical course of pancreatic disease. However, the relationship between dyslipidemia and clinical outcomes among patients with chronic pancreatitis complicated by pancreatic duct stones remains incompletely defined. This study evaluated the association between dyslipidemia and clinical characteristics and short-term outcomes in these patients. Methodology This prospective observational study was conducted in the Department of Surgery, Dhaka Medical College Hospital (DMCH), Dhaka, Bangladesh, over a 24-month period from January 2021 to December 2022 and included 73 adults with established chronic pancreatitis and radiologically confirmed pancreatic duct stones. Patients with acute pancreatitis without established chronic pancreatic disease, alcohol-induced pancreatitis, gallstone pancreatitis, pancreatic malignancy, and other predefined exclusion criteria were excluded. Dyslipidemia was defined as the presence of at least one abnormal lipid parameter: triglycerides >150 mg/dL, total cholesterol >200 mg/dL, low-density lipoprotein cholesterol >130 mg/dL, or high-density lipoprotein cholesterol <40 mg/dL in men and <50 mg/dL in women. Patients were categorized into dyslipidemia (n = 47) and non-dyslipidemia (n = 26) groups. Clinical characteristics, pancreatitis severity, pancreatic duct stone characteristics, length of hospital stay, and 30-day clinical outcomes were compared between the two groups. Results The mean age of the study population was 46.8 ± 12.5 years, and 55 (75.3%) patients were male. Patients with dyslipidemia had a higher mean body mass index than those without dyslipidemia (26.7 ± 3.9 vs. 24.2 ± 3.4 kg/m², p = 0.006). Recurrent pancreatitis occurred in 30/47 (63.8%) patients with dyslipidemia compared with 9/26 (34.6%) without dyslipidemia (p = 0.017). Moderate-to-severe pancreatitis was more frequent in the dyslipidemia group (27/47 (57.4%) vs. 7/26 (26.9%), p = 0.012). Patients with dyslipidemia also had a greater mean number of previous pancreatitis episodes (3.2 ± 1.4 vs. 1.8 ± 0.9, p < 0.001) and a longer hospital stay (8.6 ± 3.4 vs. 5.2 ± 2.1 days, p < 0.001). No statistically significant association was observed between dyslipidemia and multiple pancreatic duct stones or stone diameter >5 mm. Conclusions In this prospective observational cohort of patients with chronic pancreatitis and pancreatic duct stones, dyslipidemia was associated with recurrent pancreatitis, greater previous attack frequency, moderate-to-severe pancreatitis, and prolonged hospitalization. These findings indicate a clinically relevant association between dyslipidemia and disease burden; however, they do not establish causality or an independent predictive effect. Reverse causality and residual confounding cannot be excluded. Larger multicenter studies with longer follow-up are needed to clarify the temporal and causal relationship between dyslipidemia and the progression of chronic pancreatitis.

Cardiovascular-kidney-metabolic (CKM) syndrome is driven by the interplay of visceral adiposity, insulin resistance, chronic inflammation, oxidative stress, and progressive kidney dysfunction. These mechanisms generate a distinct atherogenic dyslipidaemic phenotype characterised by elevated triglycerides (TG), reduced high-density lipoprotein-cholesterol (HDL-C), increased apolipoprotein B (apoB)-containing lipoproteins, remnant cholesterol (RC) accumulation, small dense low-density lipoprotein (LDL) particles, and frequently elevated lipoprotein(a) [Lp(a)]. Such lipid abnormalities contribute to accelerated atherosclerosis and early renal deterioration. In turn, kidney dysfunction further amplifies lipid abnormalities. These pathways underscore the need for a timely and comprehensive lipid assessment using apoB, non-HDL-C, RC, and Lp(a) within the CKM framework. Effective lipid management is crucial for CKM syndrome treatment, with the potential to reduce residual cardiovascular and renal risk and improve long-term clinical outcomes. In this narrative review, we examine current evidence on the pathophysiological mechanisms underlying CKM-related dyslipidaemia and provide a practical framework for its assessment and management. Management requires a multimodal approach tailored to the patient's lipid phenotype and overall cardiovascular risk, incorporating a range of lipid-lowering strategies including statins, ezetimibe, PCSK9 inhibitors, bempedoic acid, fibrates, icosapent ethyl, and emerging therapies targeting apoC-III, ANGPTL3, and Lp(a). Beyond lipid lowering, lifestyle interventions and cardiometabolic therapies such as glucagon-like peptide-1 receptor agonists, sodium-glucose cotransporter 2 inhibitors, and finerenone may provide complementary cardiometabolic and renal protection.

Metabolic syndrome (MetS), characterized by a cluster of interrelated metabolic abnormalities including central obesity, elevated blood pressure, dysglycemia, hypertriglyceridemia, and reduced high-density lipoprotein cholesterol (HDL-C), substantially increases type 2 diabetes and cardiovascular disease risk. Conventional genome-wide association studies (GWASs) analyze individual traits or a dichotomized MetS status, only partially capturing its heritability and potentially overlooking variants with shared (pleiotropic) effects across correlated traits. Here, we performed a multiple-trait GWAS using data from the Korean Genome and Epidemiology Study. Using the Korea Biobank Array (K-Chip), we analyzed a discovery cohort from the Ansan and Ansung studies (1490 cases and 3856 controls) and validated the findings in CAVAS (3620 cases and 4461 controls) and HEXA (15,257 cases and 41,807 controls) cohorts. We jointly modeled six MetS-related traits using the complementary multivariate frameworks Multiple Phenotype Association Tests and Genome-wide Efficient Mixed Model Association, alongside a baseline logistic regression. Whereas logistic regression detected 2 APOA5 variants (rs662799 and rs2075291), the multivariate analyses identified 79 significant single-nucleotide polymorphisms; all were replicated in the HEXA cohort. Functional annotation prioritized 27 high-risk variants mapping to 12 genes, whereas pathway analysis (DAVID) implicated eight Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathways related to lipid metabolism. Our findings demonstrate that multivariate analysis substantially improves the identification of pleiotropic susceptibility loci for MetS in the Korean population and indicates candidate genes for early detection and management.

Background/Objectives: To evaluate systemic and ocular factors associated with glaucoma in young adults using data from a large health screening cohort. Methods: This cross-sectional observational study analyzed baseline data from 16,002 Korean adults younger than 40 years (range, 18-39 years) in the Gangnam Eye Cohort. Participants underwent comprehensive health screening examinations, including standardized ophthalmic evaluation and fundus photography. Glaucoma was defined by structural glaucomatous changes on fundus photographs, and retinal arteriosclerosis was graded using a modified Scheie classification. Univariable and multivariable logistic regression models were used to identify factors associated with glaucoma. Results: Among 16,002 participants, 257 (1.61%) were classified as having glaucoma; 186 of these participants (72.4%) had unilateral glaucoma. In multivariable logistic regression analysis, retinal arteriosclerosis showed the strongest association with glaucoma (OR, 6.033; 95% CI, 4.417-8.240; p < 0.001). Older age, male sex, higher intraocular pressure, and higher low-density lipoprotein cholesterol level were also independently associated with glaucoma. A graded relationship was observed between retinal arteriosclerosis severity and glaucoma, with adjusted ORs of 5.51 (95% CI, 3.96-7.66) for grade 1 and 13.15 (95% CI, 6.41-26.99) for grade ≥ 2. Conclusions: In young adults, retinal arteriosclerosis was strongly and dose-dependently associated with glaucoma. These findings suggest that retinal microvascular abnormalities visible on routine fundus photographs may provide clinically accessible information for identifying young adults with structural features of glaucomatous optic neuropathy in health screening settings.

Background Dyslipidemia is a frequent metabolic disorder, common in type 2 diabetes mellitus. Serum lipid parameters have increasingly become the focus of interest as potentially modifiable risk factors for the development and progression of diabetic retinopathy. Hence, the present study was designed to assess the association between serum lipid parameters and the severity of diabetic retinopathy among adults with type 2 diabetes mellitus attending a tertiary care center. Methods A cross-sectional study was conducted among 98 adults with type 2 diabetes mellitus. Diabetic retinopathy was classified using the Early Treatment Diabetic Retinopathy Study (ETDRS) classification. Fasting blood glucose, postprandial blood glucose, and serum lipid profile were estimated. Association of serum lipid parameters with severity of diabetic retinopathy was assessed, and logistic regression was performed to determine the factors independently associated with diabetic retinopathy. Results Serum lipid abnormalities were significantly related to diabetic retinopathy severity. Triglycerides had the highest association with disease severity, and total cholesterol, high-density lipoprotein (HDL) cholesterol, and low-density lipoprotein (LDL) cholesterol also differed significantly between retinopathy grades. Hypercholesterolemia and hypertriglyceridemia were significant on univariate analysis, while hypertriglyceridemia was the only independent risk factor after multivariable adjustment. Conclusion Serum lipid abnormalities were associated with the severity of diabetic retinopathy in adults with type 2 diabetes mellitus. Higher triglyceride and total cholesterol levels were observed across categories of diabetic retinopathy, and hypertriglyceridemia remained independently associated with the presence of diabetic retinopathy in multivariable analysis. These findings support further prospective studies to clarify the temporal and potentially modifiable relationship between dyslipidemia and diabetic retinopathy.