Search Results (11,279)

Background/Objectives: Conventional lipid parameters incompletely reflect coronary atherosclerotic burden, particularly in the setting of metabolic heterogeneity and residual cardiovascular risk. Composite indices such as the atherogenic index of plasma (AIP) and the triglyceride–glucose (TyG) index have emerged as integrative markers. Fatty acid desaturases regulate key pathways of lipid metabolism, and estimated desaturase activity indices (SCD-16, SCD-18, D5D, and D6D) may provide complementary information on the metabolic pathways underlying AIP and the TyG index. However, the relationships among composite atherogenic indices, plasma fatty acid composition, estimated desaturase activity indices, and coronary artery disease (CAD) severity remain incompletely understood. Methods: In this cross-sectional study, 61 patients undergoing coronary angiography for suspected CAD were evaluated. Coronary atherosclerotic burden was quantified using the Gensini score. AIP and the TyG index were calculated from fasting biochemical parameters. Plasma fatty acid composition was analyzed using gas chromatography–mass spectrometry, and estimated desaturase activity indices were calculated using product-to-precursor ratios. Results: AIP was independently associated with Gensini score (β = 37.020, p < 0.001), whereas the TyG index was not independently associated after adjustment for potential confounders (p = 0.101). In correlation analyses, AIP was positively correlated with HOMA-IR (ρ = 0.352, p < 0.05). Myristic acid was positively correlated with AIP, the TyG index, and VLDL (ρ = 0.297, 0.288, and 0.325, respectively; all p < 0.05), whereas n-6 polyunsaturated fatty acids were positively correlated with LDL (ρ = 0.276, p = 0.031). Among the estimated desaturase activity indices, D6D was positively correlated with AIP, BMI, insulin, and VLDL (ρ = 0.262, 0.376, 0.340, and 0.266, respectively; all p < 0.05), whereas D5D was inversely correlated with BMI and VLDL (ρ = −0.319 and −0.266, respectively; both p < 0.05). No significant associations were observed for SCD-16 or SCD-18. Conclusions: The observed associations between AIP, angiographic CAD severity, selected fatty acid species, and estimated desaturase activity indices suggest that AIP may provide complementary information regarding metabolic alterations associated with coronary atherosclerosis. These findings provide a basis for future studies exploring the relationship between composite atherogenic indices and fatty acid metabolism. Full article

Obesity is an increasingly important and modifiable driver of chronic kidney disease (CKD), with effects that extend well beyond its associations with type 2 diabetes, hypertension, and dyslipidemia. To synthesize the evidence that excess adiposity is a causal and modifiable determinant of kidney disease, and to examine how specific adipose depots injure the glomerulus and the tubulointerstitium, and then map these mechanisms onto established and emerging therapies. Throughout, obesity-related kidney disease (ORKD) denotes the full spectrum of diposity-driven renal injury, whereas obesity-related glomerulopathy (ORG) is reserved for the biopsy-defined glomerular lesion. Central, visceral, perirenal and renal-sinus adiposity act first through structural and haemodynamic mechanisms, promoting glomerular hyperfiltration, mechanical renal compression and activation of the adipose-derived renin–angiotensin–aldosterone system (RAAS). In parallel, these depots drive cellular and metabolic injury through lipotoxicity, adipokine imbalance, sterile inflammation, oxidative stress, gut dysbiosis, mitochondrial dysfunction, epigenetic remodelling and cellular senescence. Ectopic lipid accumulation within the renal parenchyma—fatty kidney—offers a unifying description of these changes and is most marked in type 2 diabetes mellitus. These interacting processes converge on podocyte stress, tubular metabolic failure, endothelial dysfunction and interstitial fibrosis, producing a phenotypic continuum that ranges from early albuminuria to obesity-related glomerulopathy and progressive CKD. Within the RAAS limb we highlight two comparatively underappreciated, adiposity-linked routes to injury: adipocyte-derived leptin directly upregulates adrenal aldosterone synthase (CYP11B2), and mast-cell chymase generates angiotensin II independently of angiotensin-converting enzyme, together reinforcing aldosterone- and angiotensin II–mediated damage that conventional RAAS blockade only partially interrupts. We further consider the counter-regulatory ghrelin–leptin axis, in which the suppression of ghrelin that accompanies obesity may withdraw an antioxidant, anti-inflammatory and podocyte-protective signal precisely as leptin-driven glomerular injury intensifies, positioning ghrelin as a plausible modulator and candidate biomarker of obesity-related kidney injury. We also examine how obesity complicates renal risk assessment, drug dosing, dialysis delivery and transplant access. Emerging, mechanism-matched therapies—SGLT2 inhibitors, GLP-1 receptor agonists, finerenone, structured lifestyle intervention, metabolic-bariatric surgery and, most recently, aldosterone synthase inhibitors that suppress the chymase- and leptin-driven aldosterone escaping receptor blockade—now enable a precision cardiovascular-kidney-metabolic framework that aligns adipose-depot biology, biomarkers, histology and treatment response to guide mechanism-based care in ORKD. Full article

Bruton tyrosine kinase inhibitors have transformed the management of chronic lymphocytic leukemia and other B-cell malignancies, but their clinical use is increasingly influenced by cardiovascular safety. In contemporary practice, patients receiving these therapies are typically older and characterized by a high burden of comorbidities, including cardiovascular disease, metabolic disorders, and renal impairment. In this setting, cardiovascular complications should not be interpreted as isolated adverse events, but rather as clinical expressions of underlying patient vulnerability and frailty. Atrial fibrillation and arterial hypertension represent the most frequent complications, while heart failure, ventricular arrhythmias, and bleeding, although less common, may carry significant prognostic implications. Importantly, these events often arise from the interaction between drug exposure and pre-existing comorbidities, and may lead to treatment interruption, dose reduction, or discontinuation, ultimately compromising the long-term benefit of otherwise highly effective therapies. This review provides a comprehensive overview of the clinical burden, mechanisms, and management of cardiovascular complications associated with these agents, and proposes a practical, patient-centered framework to guide clinical decision-making. A structured approach based on risk assessment, early detection, and proactive management is essential to prevent complications, optimize treatment continuity, and preserve the long-term benefit of therapy in a complex and vulnerable population. Full article

Metabolic syndrome (MetS) is a complex multisystem disorder characterized by insulin resistance, central obesity, dyslipidemia, hypertension, and chronic low-grade inflammation, all of which substantially increase the risk of type 2 diabetes mellitus and cardiovascular disease. The aim of this narrative review is to examine the role of vitamin D in the pathophysiology of MetS from a multisystem perspective. Specifically, it synthesizes current evidence on the molecular mechanisms through which vitamin D may influence inter-organ communication, insulin resistance, adipose tissue dysfunction, hepatic metabolism, skeletal muscle function, chronic inflammation, oxidative stress, and mitochondrial homeostasis, highlighting its potential contribution to the prevention and management of MetS. Current evidence indicates that MetS should not be regarded merely as a cluster of isolated metabolic abnormalities but rather as a disorder characterized by disrupted molecular signaling and impaired communication among metabolically active organs. In this context, experimental and preclinical evidence suggests that vitamin D, through activation of the vitamin D receptor (VDR), modulates key signaling pathways, including AMP-activated protein kinase (AMPK), the mechanistic target of rapamycin (mTOR), nuclear factor kappa B (NF-κB), and peroxisome proliferator-activated receptor gamma (PPAR-γ), thereby influencing insulin sensitivity, inflammation, oxidative stress, mitochondrial function, and metabolic homeostasis. Nevertheless, clinical evidence remains heterogeneous due, in part, to the lack of consensus regarding serum 25-hydroxyvitamin D thresholds for defining vitamin D status, as well as differences in baseline vitamin D concentrations, supplementation regimens, study populations, and methodological designs. Overall, the available evidence suggests that vitamin D should be considered an adjunct to lifestyle-based interventions rather than a stand-alone therapeutic strategy. Future research is warranted to clarify its clinical utility in the prevention and management of MetS. Full article

Introduction: Kawasaki disease (KD) is an acute systemic vasculitis and the leading cause of acquired pediatric heart disease in high-income countries. Coronary artery aneurysms (CAA) represent the most severe complication and drive long-term cardiovascular risk. Despite improved outcomes with early intravenous immunoglobulin therapy, follow-up strategies remain heterogeneous, particularly for patients showing CAA regression. Dynamic risk stratification based on coronary Z-scores has been proposed, but long-term real-world data are still needed to optimize surveillance. Methods: We conducted a single-center, retrospective study including pediatric patients (age 1 month–18 years) with KD complicated by CAA, followed at Bambino Gesù Children’s Hospital (Rome) between 1999 and 2024. Coronary involvement was assessed using Boston Z-scores of the right coronary artery, left main coronary artery, and left anterior descending artery. CAA severity over time was analyzed using a composite MAX SCORE (highest Z-score among coronary branches) along with the 1-YEAR MAX SCORE (highest MAX SCORE reached within the 1 year of disease). The distribution and timing of cardiac computed tomography angiography (CCTA) and exercise stress testing (EST) during follow-up were analyzed in relation to coronary severity. Results: Among 502 KD patients, 122 (24.3%) developed CAA; 113 were included in the analysis. Mean age at diagnosis was 24.6 months (M/F 3.5:1). Multivessel involvement was observed in 72%, most frequently affecting the left anterior descending artery. Long-term follow-up ≥10 years was available for 31.9% of patients. Most changes in coronary severity occurred within the first year after disease onset, with complete CAA regression in 76.1% of patients. Conversely, 53% of patients affected by giant aneurysms at 12 months showed persistent severe disease at last follow-up. EST (164 tests in 40 patients) was almost universally negative for inducible ischemia (163/164), whereas CCTA (47 exams in 35 patients) was preferentially performed early and in higher-risk patients. Test prescription correlated more closely with 1-YEAR MAX SCORE than with contemporaneous severity. Echocardiography showed systematic differences compared with CCTA for right coronary and left anterior descending artery Z-scores. Discussion: In our experience, early coronary status was closely associated with the intensity of long-term surveillance strategies in KD. The 1-YEAR MAX SCORE was associated with subsequent patterns of coronary evolution, and the continuous 1-year Maximum Z-score showed good discriminatory ability for persistent CAA on ROC analysis, pending external validation. While the low rate of positive findings on EST raises questions about its diagnostic yield in real-world practice, CCTA provided detailed anatomical characterization. Overall, these findings suggest that early coronary severity may help inform individualized, severity-driven follow-up strategies, warranting confirmation in prospective multicenter studies. Full article

High-sensitivity cardiac troponin has made the diagnosis of myocardial infarction (MI) faster and more precise, but it does not measure the broader biological vulnerability that often determines the outcome after an acute coronary syndrome (ACS). Growth differentiation factor-15 (GDF-15) is induced by ischemic stress, inflammation, oxidative injury, renal dysfunction, metabolic disease, and ageing. This biology explains its appeal in ACS, but also its diagnostic limitation: GDF-15 is not cardiac-specific and should not be used as an alternative to electrocardiography and high-sensitivity troponin algorithms for early MI diagnosis. Its better supported role is prognostic. Across emergency department chest pain cohorts, non-ST elevation MI, ST elevation MI, post-ACS trial populations, and serial biomarker studies, higher GDF-15 concentrations are most consistently associated with all-cause mortality, cardiovascular mortality, heart failure, and major bleeding, while associations with recurrent ischemic events alone are less specific. The key unresolved issue is incremental clinical value. GDF-15 may improve discrimination and reclassification beyond clinical predictors, troponin, natriuretic peptides, renal function and GRACE or GRACE 2.0 in selected settings, but statistical association is not equivalent to clinical utility. Its possible role in bleeding risk estimation and antithrombotic benefit–risk assessment is clinically important, especially after the PLATO biomarker analyses, yet routine GDF-15-guided dual antiplatelet therapy decisions remain unsupported. Future implementation requires validated thresholds, calibration, decision curve evidence, health economic evaluation, and trials in which GDF-15-guided management changes care and improves outcomes. Full article

Introduction: Evidence linking Mediterranean dietary patterns and physical activity to mortality and major adverse cardiovascular events (MACEs) after coronary heart disease (CHD) diagnosis remains inconclusive. Methods: The search covered PubMed, MEDLINE, Scopus, Embase, and CENTRAL from January 2015 through 15 June 2026. Comparable hazard ratios (HRs) were pooled using random-effects models; non-equivalent estimands were reported separately. Risk of bias was evaluated with design-appropriate tools and certainty with GRADE. Results: The 40 reports represented 34 data sources and at least 260,354 unique patients, comprising six randomized trials, 30 observational reports, and four comparative nonrandomized studies. In one randomized comparison of Mediterranean and low-fat diets, the HR for MACE was 0.72 (95% CI 0.54 to 0.96; moderate certainty). Observational findings supported inverse associations of closer dietary adherence with all-cause mortality (HR 0.74, 95% CI 0.60 to 0.90; I² = 44%) and MACE, whereas cardiovascular mortality remained uncertain. HRs for maintained or continued physical activity relative to persistent inactivity were 0.64 for all-cause mortality (95% CI 0.55 to 0.74; I² = 29%) and 0.42 for cardiovascular mortality (95% CI 0.28 to 0.64; I² = 72%). MACE findings for diet adherence and habitual physical activity generally favored lower risk. Randomized evidence on exercise or combined dietary and activity programs was sparse. Conclusions: Greater Mediterranean diet adherence and habitual physical activity were associated with more favorable CHD outcomes. Standardized, adequately powered trials are needed, especially for exercise and combined strategies. Full article

Introduction: Sarcopenia and frailty are emerging independent risk factors for cardiovascular disease. Sarcopenia represents a decline in function associated with reduced muscle mass. Frailty, defined as a phenotype or the multiple stress model, is associated with weakness and a decline in organ reserve with vulnerability to disease. Frailty and sarcopenia may overlap and have shared clinical risk factors including age and malnutrition. Methods: We performed a literature review of published studies on frailty and sarcopenia with respect to cardiovascular risk factors and body composition. Results: Studies demonstrated that obese sarcopenic or obese frail subjects had a higher prevalence of cardiovascular risk factors such as hypertension, diabetes mellitus, dyslipidaemia, smoking and sedentary lifestyle, which was highly associated with cardiovascular disease. On the other hand, anorexic malnourished frail participants with unintentional weight loss or sarcopenic subjects without obesity had a low prevalence of cardiovascular risk factors, which was less associated with cardiovascular disease. Conclusions: Obesity appears to play a crucial role in mediating the cardiovascular risk of both sarcopenic and frail patients. Full article

Objectives: Coronary artery disease (CAD) remains a leading cause of morbidity and mortality worldwide, yet population-specific evidence regarding the contribution of MIA3 genetic variation in Middle Eastern populations remains limited. This study investigated the association of the MIA3 rs17465637 polymorphism with CAD susceptibility and its relationship with lipid-related phenotypes in a Saudi population. Methods: A case–control study was conducted between June 2020 and August 2022, including 200 patients with angiographically confirmed CAD and 200 age- and sex-matched healthy Saudi controls. Genotyping of rs17465637 was performed using a TaqMan real-time polymerase chain reaction assay. Genotype distributions were evaluated using chi-square analysis under multiple inheritance models. Multivariable logistic regression was subsequently performed to estimate adjusted odds ratios after controlling age, BMI, smoking, physical inactivity, systolic BP, diastolic BP, blood glucose, triglycerides, total cholesterol, LDL-C, and HDL-C. Associations between rs17465637 genotypes and serum lipid parameters were also examined. Results: Genotype frequencies of rs17465637 differed modestly between cases and controls; however, unadjusted comparisons under codominant, dominant, recessive, and allelic inheritance models did not reach statistical significance, and none remained significant after Bonferroni correction. In contrast, multivariable logistic regression demonstrated an independent association between the rs17465637 C allele and CAD after adjustment for conventional cardiovascular risk factors. In genotype–phenotype analyses, carriers of the C allele exhibited higher association with low-density lipoprotein cholesterol concentrations and less favorable lipid profiles than AA homozygotes, supporting a relationship between the variant and lipid metabolism. These findings are consistent with a potential contribution of rs17465637 to CAD susceptibility through lipid-related pathways. Conclusions: Although unadjusted genotype comparisons were not statistically significant after correction for multiple testing, multivariable analysis provides evidence supporting an independent association between the MIA3 rs17465637 variant and CAD susceptibility in this Saudi cohort. The observed associations with adverse lipid profiles further provide evidence linking this specific locus to the molecular mechanisms underlying cardiovascular disease. Replication in larger, multi-center studies incorporating genome-wide ancestry-informative markers and functional investigations is warranted to further minimize the possibility of residual population stratification, confirming these findings and clarifying the biological mechanisms underlying this association. Full article

Background: Non-group 1 pulmonary hypertension, also known as secondary pulmonary hypertension (SPH), is predominantly observed among females. However, there is a significant lack of data concerning factors associated with hospitalization among patients diagnosed with SPH. This study aims to provide clinicians with vital insights for the identification of high-risk groups and for the more effective management of contributory risk factors within the female population affected by SPH. Methods: Using the 2019 National Inpatient Sample, we identified female admissions with SPH (n = 648,190), accounting for 3.8% of the total 17,236,228 female admissions. An Artificial Neural Network (ANN) analysis was conducted to evaluate predictive factors. We randomly allocated 3,319,543 patients into training and testing datasets at a ratio of 70:30, comprising 2,323,696 (70%) for training and 995,847 (30%) for testing, to calibrate and validate the performance of the ANN algorithm. Model performance was assessed by comparing misclassification rates between training and testing sets and by the area under the receiver operating characteristic curve (AUC); only internal validation was performed. Results: Females hospitalized with SPH were generally of older age, with a median of 75 years compared to 58 years, and more frequently identified as White (67.7% versus 65.5%) or Black (20.5% versus 15.5%) relative to those without SPH. They also demonstrated a higher prevalence of most atherosclerotic cardiovascular disease (ASCVD) risk factors or their equivalents, including complicated hypertension (50.6% versus 17.8%), diabetes with chronic complications (30.6% versus 13.7%), and hyperlipidemia (50.8% versus 29.2%), as well as other comorbidities such as COPD (43.4% versus 20.2%) and CKD (43.3% versus 14.0%), and exhibited increased all-cause mortality (4.5% versus 1.8%) (p < 0.001). Our ANN model achieved an AUC of 0.823, indicating good predictive capability. The rates of incorrect predictions were comparable in both the testing and training cohorts, at 3.8% each. The factors most strongly associated with a coded SPH diagnosis included age at admission, complicated hypertension, chronic kidney disease, chronic obstructive pulmonary disease, uncomplicated hypertension, prior VTE, race, arthropathies, and AIDS. Conclusions: Our ANN model identified demographic and comorbidity factors associated with a coded SPH diagnosis among hospitalized females, with good discrimination (AUC = 0.823). Because the model classifies the presence of an existing diagnosis rather than predicting future hospitalization, and was validated only internally, external and prospective validation is required before clinical application. Once validated, these factors could support individualized, sex-specific risk stratification for high-risk female populations, consistent with the goals of personalized medicine. Full article

Obstructive sleep apnea syndrome (OSAS) is heavily implicated in subclinical cardiovascular disease; however, traditional polysomnographic metrics fail to capture the localized mechanical trauma exerted on the carotid artery. To address this methodological gap, this study evaluated exploratory associations between frequency-domain snoring characteristics and right carotid artery alterations in 50 patients with OSAS. Snoring was quantified using a dual-modality bioelectronic approach: an ambient microphone captured airborne snoring sound energy (SSE), while a portable neck-surface piezoelectric sensor recorded tissue-conducted snoring vibratory energy (SVE). Subclinical vascular changes, including carotid intima-media thickness (CIMT) and atherosclerosis, were assessed via ultrasonography. Hierarchical multivariable regression demonstrated that acoustic SSE%-404–500 Hz and mechanical SVE%-112–144 Hz independently correlated with preliminary CIMT increases (adjusted β = 0.033 and 0.021, respectively; both p < 0.05), alongside neck circumference. Conversely, SSE%-404–500 Hz emerged as an exploratory marker for focal carotid atherosclerosis (adjusted odds ratio = 1.828; p = 0.009). Integrating this metric with baseline parameters yielded exploratory diagnostic capacity (area under the curve = 0.833; p < 0.001), achieving 89% sensitivity and 69% specificity. These findings suggest that dual-modality spectral analysis provides a non-invasive exploratory framework for cardiovascular risk stratification, isolating localized mechanotransduction phenotypes independently of systemic hypoxia. Full article

Cardio-oncology has emerged as a critical discipline in modern medicine due to the growing population of cancer survivors and the increasing recognition of cardiovascular disease as a major cause of morbidity and mortality in this population. While there have been significant advances in chemotherapy such as advances in chemotherapy, targeted therapies, immunotherapies, and radiation therapy, these treatments are linked to a wide range of cardiovascular toxicities such as myocarditis, arrhythmias, and progressive fibrotic remodeling. These toxicities tend to be caused by interrelated and multifactorial cellular processes including endothelial damage, immunological dysregulation and mitochondrial dysfunction. Therefore, early diagnosis of subclinical harm using multimodal surveillance strategies integrating clinical risk assessment, specialized clinical imaging, and circulating biomarkers has replaced reactive care of overt cardiotoxicity in modern cardio-oncology. Echocardiographic techniques such as longitudinal strain, with the help of biomarker-guided surveillance of natriuretic peptides and cardiac troponins, have made the early detection of cardiac dysfunction more effective. However, the current prediction risk models are still constrained and limited by their dependence on static clinical variables and their partial integration of biological mechanisms. This review examines the current methods for risk stratification and surveillance throughout the cancer care continuum, including baseline assessment, monitoring during active therapy, and long-term survivorship surveillance. Future approaches for tailored cardiovascular care are also highlighted, including new advances in precision cardio-oncology such as multi-omics profiling, molecular biomarkers, artificial intelligence, and mechanism-guided preventative strategies. Therefore, advancing biologically informed and risk-adapted monitoring frameworks may enhance early diagnosis, maximize cardioprotective measures, and lower long-term cardiovascular consequences. Full article

Background/Objectives: Albuminuria is an important marker of kidney and cardiovascular risk in adults with type 2 diabetes mellitus (T2DM). Regional data from Mexico remain limited among patients with preserved estimated glomerular filtration rate (eGFR) and no previous diagnosis of diabetic kidney disease. This study aimed to describe albuminuria categories observed at a single screening assessment and to explore clinical factors associated with higher urinary albumin-to-creatinine ratio (uACR) categories in adults with T2DM receiving care at a regional hospital in western Mexico. Methods: This exploratory single-center cross-sectional study included 119 adults with T2DM (mean age, 53.3 ± 11.7 years), preserved eGFR (≥60 mL/min/1.73 m²), and no previous diagnosis of diabetic kidney disease. Albuminuria was classified from a single first-morning uACR measurement as A1 (<30 mg/g), A2 (30–300 mg/g), or A3 (>300 mg/g). Exploratory multivariable ordinal logistic regression evaluated factors associated with higher uACR categories. A secondary exploratory binary model evaluated screen-detected uACR ≥ 30 mg/g (A2/A3 versus A1). Results: A1 was observed in 67 patients (56.3%), A2 in 40 (33.6%), and A3 in 12 (10.1%); 52 patients (43.7%) had uACR ≥ 30 mg/g at screening. The median uACR was 25.6 mg/g, the median HbA1c was 11.2%, and the median fasting glucose was 280 mg/dL. In the exploratory ordinal model, longer T2DM duration (OR 1.51 per 5 years; 95% CI 1.09–2.10; p = 0.012), higher HbA1c (OR 1.18 per 1% increase; 95% CI 1.01–1.38; p = 0.036), and lower eGFR (OR 0.69 per 10 mL/min/1.73 m² increase; 95% CI 0.55–0.88; p = 0.003) were associated with higher uACR categories after adjustment for the measured covariates. In the secondary binary model, longer T2DM duration and lower eGFR were associated with screen-detected uACR ≥ 30 mg/g. Conclusions: A single screening assessment identified uACR ≥ 30 mg/g in 43.7% of this selected regional cohort. These findings represent screen-detected albuminuria and do not establish persistent albuminuria, diabetic kidney disease, temporality, or causality. Confirmation with repeated uACR measurements and validation in larger longitudinal multicenter studies with detailed medication data are required. Full article

Background and Objectives: Cardiovascular disease remains the leading cause of premature mortality worldwide. Subclinical glucose dysregulation, a contributor to accelerated vascular aging, is undetectable by conventional screening in apparently healthy individuals; even within the normal glycemic range, postprandial glucose excursions promote endothelial injury and inflammatory pathways independently of mean glucose levels. Hypothesis: Continuous glucose monitoring (CGM)-guided metabolic phenotyping, combined with personalized dietary optimization, structured fasting protocols, and selective longevity-oriented pharmacotherapy, constitutes a mechanistically coherent, hypothesis-generating preventive strategy that may attenuate cardiovascular risk and biological aging in apparently healthy non-diabetic adults, pending confirmation in prospective outcome trials. Materials and Methods: This narrative review synthesizes evidence from prospective cohort studies, randomized controlled trials, and mechanistic investigations connecting CGM-guided metabolic assessment with preventive cardiology and the emerging field of longevity medicine, focusing on glycemic variability biology, nutrient-sensing pathways, and the cardiovascular and longevity profiles of low-dose metformin and acarbose. Results: CGM-derived metrics capture inter-individual glycemic variability invisible to standard assessments and provide behavioral feedback for dietary personalization. Structured fasting and low-dose metformin converge on shared nutrient-sensing pathways implicated in both vascular aging and longevity, with CGM enabling objective confirmation of metabolic adaptation. Acarbose has shown cardiovascular and lifespan benefit signals in secondary trial analyses and preclinical longevity models, though these findings require replication and are not yet established in non-diabetic populations. Conclusions: We propose a four-phase research framework integrating CGM metabolic phenotyping, dietary optimization, fasting titration, and selective pharmacological augmentation for apparently healthy adults at cardiovascular risk. Prospective hard-endpoint trials are lacking, and this framework should be regarded as hypothesis-generating rather than an established clinical strategy, warranting rigorous outcome-based evaluation before clinical adoption. Full article

Heart rate variability (HRV) is a non-invasive marker of cardiac autonomic regulation that reflects the dynamic interaction between sympathetic and parasympathetic influences on the sinoatrial node. Reduced HRV is a hallmark of autonomic dysfunction and has been consistently associated with adverse outcomes across a wide range of cardiovascular conditions, particularly heart failure (HF). HRV is markedly reduced in HF, reflecting profound autonomic imbalance characterized by vagal withdrawal, impaired baroreflex sensitivity, and altered cardiorespiratory coupling. In heart failure with reduced ejection fraction (HFrEF), lower global HRV, particularly reduced SDNN, is consistently associated with mortality, sudden cardiac death, and disease progression. In heart failure with preserved ejection fraction (HFpEF), emerging observational evidence suggests that HRV alterations may accompany early autonomic dysregulation and may be associated with sex-specific patterns, although their mechanistic and prognostic significance remains incompletely defined. In acute HF, HRV assessed during hospitalization may provide additional prognostic information, although current evidence remains limited and heterogeneous. Pharmacological therapies, cardiac resynchronization therapy, exercise training, and lifestyle interventions have variably modulated HRV across studies, but the evidence is heterogeneous and changes in HRV should not be assumed to translate directly into improved clinical outcomes. Despite persistent challenges related to methodological standardization and clinical implementation, emerging technologies and multimodal approaches may refine the feasibility of integrating HRV into risk assessment frameworks. This narrative review aims to summarize the physiological basis of HRV, critically evaluate its alterations across different HF phenotypes, and discuss its prognostic associations, therapeutic modulation, and current practical limitations in clinical application. Full article