Obesity remains a dominant risk factor for cardiovascular disease, yet its classification continues to rely heavily on body mass index (BMI)—a metric that fails to capture individual variability in fat distribution, metabolic health, and cardiometabolic risk. This narrative review analyzes 35 articles published between 2018 and 2025 to explore the limitations of BMI and outlines emerging strategies for obesity redefinition through a precision medicine lens. Drawing from recent advances in imaging, metabolomics, and genomic profiling, we highlight alternative metrics such as visceral adipose tissue (VAT), epicardial adipose tissue (EAT), waist-to-hip ratio (WHR), and multi-omic phenotyping that provide superior predictive value for cardiovascular outcomes. The review synthesizes data on metabolically healthy and unhealthy phenotypes, emphasizes the pathophysiological role of EAT in heart failure and arrhythmogenesis, and discusses the cardioprotective effects of pharmacologic agents such as glucagon-like peptide-1 (GLP-1) receptor agonists. Clinical implications include improved risk stratification, earlier disease detection, and individualized therapeutic targeting. Despite current barriers to widespread implementation—such as imaging cost, access to omics, and lack of guideline integration—this paradigm shift holds promise for refining cardiovascular prevention strategies. Redefining obesity using biologically informed, phenotype-based models is indispensable for aligning clinical practice with the complexities of modern cardiometabolic disease.

Cardiometabolic and cardiovascular risks are commonly assessed using body mass index (BMI) and static measures of adiposity; however, individuals with similar BMI frequently exhibit markedly different metabolic and cardiovascular outcomes. This heterogeneity reflects not only differences in fat distribution but also variation in adipose tissue function and its temporal regulation. Adipose tissue contains intrinsic circadian clocks that coordinate daily rhythms in lipid storage and mobilization, insulin sensitivity, adipokine secretion, and immune activity in alignment with sleep–wake and feeding–fasting cycles. Circadian misalignment, as occurs with shift work, irregular sleep, or mistimed food intake, disrupts this coordination and promotes adipose tissue dysfunction characterized by impaired rhythmic lipid handling, altered endocrine signaling, inflammation, fibrosis, and oxidative stress. Emerging evidence suggests that circadian dysregulation may differentially affect adipose depots, including visceral, epicardial, and perivascular fat, thereby linking chronodisruption to insulin resistance, endothelial dysfunction, atherosclerosis, heart failure phenotypes, and arrhythmia susceptibility. This narrative review synthesizes human, experimental, and translational studies examining adipose tissue circadian regulation as a functional determinant of cardiometabolic and cardiovascular risk beyond BMI. We also discuss the clinical implications of circadian-informed strategies, including chrononutrition and time-restricted eating, as potential tools to improve risk stratification and cardiometabolic health.

Metabolic dysfunction has emerged as a central driver of cardiovascular, renal, hepatic, and endocrine disorders, challenging traditional organ-specific disease models. Increasing evidence indicates that conditions such as obesity, type 2 diabetes, chronic kidney disease, heart failure, and metabolic dysfunction–associated steatotic liver disease frequently develop in parallel, reflecting shared upstream metabolic abnormalities rather than isolated pathologies. This narrative review synthesizes recent clinical, epidemiologic, biomarker, and therapeutic evidence to examine metabolic dysfunction as a unifying framework for multisystem disease, with particular focus on the cardiovascular–renal–hepatic–metabolic (CRHM) model. A targeted literature search of major biomedical databases was conducted to identify relevant studies published between 2020 and 2025, encompassing observational cohorts, randomized trials, and integrative reviews addressing cross-organ metabolic interactions. The reviewed evidence highlights consistent clinical overlap across organ systems, stage-dependent risk amplification and the utility of shared metabolic and inflammatory biomarkers in capturing multisystem vulnerability. In parallel, contemporary metabolic therapies demonstrate coordinated benefits across cardiovascular, renal, and hepatic domains, supporting the concept of common modifiable disease drivers. The reviewed evidence supports a shift from organ-based toward metabolic-centric frameworks for risk stratification and prevention. Viewing metabolic dysfunction as the organizing principle of cardiometabolic disease may improve recognition of multisystem risk, facilitate earlier intervention, and provide a more coherent foundation for precision and preventive medicine, in an era of growing cardiometabolic multimorbidity.

Paragangliomas are rare neuroendocrine tumors that arise from the extra-adrenal autonomic paraganglia, i.e., small organs consisting mainly of neuroendocrine cells that are derived from the embryonic neural crest and have the ability to secrete catecholamines. Paragangliomas can derive from either parasympathetic or sympathetic paraganglia. Most of the parasympathetic ganglia-derived paragangliomas are nonfunctional, and symptoms result from mass effect. Conversely, the sympathetic paragangliomas are functional and produce catecholamine. Although such patients could have symptoms similar to pheochromocytoma, mass effect symptoms, or non-specific symptoms, being benign tumors, they can also present with anemia, specifically iron-deficiency anemia. Considering that neoplastic pathology is chronically accompanied by moderate, normochromic, normocytic anemia, association between paragangliomas that are mostly benign but with a potential degree of malignancy and anemia is not as frequent as expected, with only 12 cases reported in the literature. We report a case of a 54-year-old female patient diagnosed with a paraganglioma of the carotid glomus accompanied by severe normochromic, normocytic anemia, which reached normal limits after excision of the paraganglioma.

Atrial fibrillation (AF) frequently coexists with chronic kidney disease (CKD), and their combination confers a disproportionate risk of both thromboembolic and bleeding events. Conventional anticoagulation strategies rely primarily on creatinine clearance-based dosing, which reflects pharmacokinetic safety but does not fully capture the biological processes underlying thrombohemorrhagic instability. This narrative review synthesizes recent mechanistic and translational evidence regarding the bidirectional cardio–renal axis in AF and CKD, focusing on systemic inflammation, endothelial dysfunction, platelet dysregulation, and altered coagulation. A structured literature search of PubMed/MEDLINE, Scopus, and Web of Science (2018–2026) was performed, complemented by manual review of key references and guidelines. The evidence indicates that inflammatory cytokine activation, oxidative stress, glycocalyx degradation, von Willebrand factor dysregulation, uremic platelet dysfunction, and enhanced thrombin generation converge to create a disrupted vascular interface in which stroke and bleeding arise from shared pathophysiological mechanisms. Renal trajectory and selected circulating biomarkers further highlight the dynamic and heterogeneous nature of risk in advanced CKD. These findings support reframing anticoagulation decision-making in AF with CKD from a static filtration-based model toward a biology-informed approach that integrates renal dynamics, endothelial and platelet phenotype, and clinical context to better align thromboembolic protection with hemorrhagic safety.

Background: Sepsis is a leading cause of morbidity and mortality among patients receiving maintenance hemodialysis (HD), reflecting a unique combination of immunologic dysfunction, comorbidities, and healthcare-related exposures. Despite advances in dialysis technology and infection control, outcomes for septic HD patients remain disproportionately poor. Objective: This review aims to synthesize current evidence on the epidemiology, risk factors, diagnostic challenges, and treatment considerations of sepsis in HD patients, highlighting persistent vulnerabilities and areas for clinical improvement. Methods: A structured narrative review was conducted, focusing on high-quality cohort studies, surveillance data, and pharmacologic analyses published over the past two decades. The literature search was performed using PubMed, Web of Science, and Google Scholar. A total of 37 studies were included in the final synthesis. Key themes were organized around epidemiologic trends, infection sources, risk modifiers, treatment outcomes, and antimicrobial considerations in the dialysis population. Results: The review found that sepsis in HD patients is multifactorial and systemic. Diabetes, advanced age, and central venous catheters remain strong risk factors, while a substantial proportion of infections arise from non-access-related sources. Mortality rates remain high, often due to delays in recognition, inappropriate empiric therapy, and challenges in antimicrobial dosing. Pharmacokinetic alterations in renal replacement therapy complicate treatment, requiring individualized approaches. Despite variations in infection rates across centers, systemic vulnerabilities—rather than dialysis modality alone—drive outcomes. Conclusions: Sepsis in hemodialysis patients is not solely a hardware-related complication but reflects deeper systemic and immunologic challenges. Improving outcomes will require earlier recognition, tailored antimicrobial strategies, standardized infection control protocols, and broader attention to patient-specific risk factors. Future research should focus on ESRD-adapted sepsis diagnostics and interventional models to reduce infection-related mortality in this high-risk group.