Search Results (498)

Background: BMI is widely used for obesity classification, yet it does not adequately reflect adiposity distribution and related metabolic risk. Normal-weight obesity (NWO), defined as excess adiposity despite normal BMI, has emerged as a clinically relevant phenotype associated with increased cardiometabolic risk. However, its prevalence and implications in young populations remain insufficiently characterized. Objective: To evaluate the prevalence of normal-weight obesity and its association with cardiometabolic risk markers in a cohort of young adults undergoing occupational health assessments. Methods: A cross-sectional study was conducted in 12,874 adults aged 22–30 years undergoing routine occupational health assessments. NWO was defined using a strict criterion (normal BMI with a waist-to-height ratio ≥ 0.5) and an expanded definition including additional adiposity markers derived from body fat percentage and visceral fat estimates. Anthropometric, adiposity-related, biochemical, and lifestyle data were collected using standardized protocols. Multivariable logistic regression models adjusted for age and sex were used to assess associations between NWO and cardiometabolic risk markers. Results: Among individuals with normal BMI (n = 9290), the prevalence of NWO was 1.79% (n = 166) using the strict definition and 2.30% (n = 214) with the expanded definition. Compared with metabolically healthy normal-weight individuals, those with NWO exhibited higher triglycerides, fasting glucose, and atherogenic lipid indices, along with lower HDL cholesterol (all p < 0.05). In multivariable analyses, NWO was independently associated with elevated triglycerides (OR 4.99; 95% CI 2.90–8.58), an unfavorable triglyceride-to-HDL ratio (OR 7.44; 95% CI 5.19–10.65), and impaired fasting glucose (OR 3.87; 95% CI 2.19–6.82). Associations were consistent across sensitivity and sex-stratified analyses. Conclusions: Normal-weight obesity is present in a measurable proportion of young adults and is associated with an unfavorable cardiometabolic profile despite normal BMI. The triglyceride-to-HDL ratio was consistently associated with normal-weight obesity and showed marked differences across adiposity-defined phenotypes. These findings highlight the limitations of BMI-based classification alone and suggest that additional anthropometric and metabolic markers may help identify individuals with less favorable cardiometabolic characteristics. Full article

Background: Cardiometabolic diseases are shaped by complex interactions between biological and social determinants. While socioeconomic inequalities in cardiometabolic risk are well established, less is known about how these inequalities are distributed across multidimensional cardiometabolic phenotypes and whether they differ by sex. Objective: We aimed to examine sex differences in the socioeconomic gradient of cardiometabolic phenotypes using latent class analysis in a working-age population. Methods: A cross-sectional study was conducted in 3108 adults aged 18–65 years undergoing occupational health assessments in the Balearic Islands (Spain). Educational level was used as an indicator of socioeconomic position. Cardiometabolic risk was assessed using obesity, insulin resistance (METS-IR), metabolic dysfunction-associated steatotic liver disease (FLI), atherogenic index of plasma, and metabolic syndrome. Latent class analysis was applied to identify cardiometabolic phenotypes. Multinomial logistic regression models stratified by sex and interaction analyses were used to assess associations between educational level and class membership. Tests for linear trend and predicted probabilities were also estimated. Results: Four cardiometabolic phenotypes were identified: low-risk (40.8%), obesity-dominant (24.1%), dysmetabolic (19.3%), and high-risk multimorbid (15.8%). A clear socioeconomic gradient was observed, with lower educational attainment associated with a higher likelihood of belonging to adverse cardiometabolic profiles. This gradient was stronger among women. For the high-risk multimorbid class, the relative risk ratio comparing low vs. high educational level was 1.82 (95% CI 1.34–2.46) in men and 2.47 (95% CI 1.68–3.64) in women (p for interaction = 0.012). A significant linear trend across educational levels was observed in both sexes (p for trend < 0.001). Predicted probabilities further confirmed a steeper increase in high-risk profiles among women with lower educational attainment. Conclusions: Cardiometabolic risk is structured into distinct phenotypic profiles that are socially patterned. Socioeconomic inequalities are strongly associated with adverse cardiometabolic phenotypes, with a more pronounced gradient among women. These findings highlight the need for gender-sensitive strategies addressing social determinants to reduce cardiometabolic health inequalities. Full article

Background/Objectives: The aim of the study was to assess the metabolic response of women to a six-week consumption of full-fat sheep milk yogurt, with a focus on cardiovascular risk markers, lipid profile, and subfractions of low-density (LDL) and high-density (HDL) lipoproteins of both atherogenic and non-atherogenic nature. Methods: A total of 55 women were enrolled in the nutritional intervention after the application of inclusion criteria. Blood samples were collected at baseline and after the six-week intervention period. Lipoprotein subfractions were determined in serum using the Lipoprint System LDL/HDL Subfractions Kit in combination with the Lipoprint^® analyzer. Results: In the group of women over 40 years of age with overweight or obesity, without adjustment for total cholesterol, a significant increase was observed in selected HDL subfractions (intermediate HDL-6, HDL-7 and small HDL-8, HDL-9; p < 0.05), while the small/large HDL ratio, LDL subfractions, and mean LDL particle size remained unchanged (p > 0.05). A decrease in triglycerides, LDL/HDL ratio, TG/HDL ratio, and cardiovascular risk index was recorded, alongside a slight increase in LDL-C and HDL-C levels. After adjustment for total cholesterol (T-C), no significant deterioration in the lipid profile was observed in either the group with normal or elevated T-C levels; in the group with elevated T-C, only the intermediate HDL-7 subfraction increased significantly (p < 0.05). Despite the presence of risk-level values in some parameters already at baseline (VLDL, IDL-A, IDL-B, small HDL), no worsening was observed. Conclusions: Six-week consumption of full-fat sheep milk yogurt did not lead to deterioration of the lipid profile or lipoprotein subfractions. The results suggest a neutral to mildly beneficial effect on selected cardiovascular risk markers. Full article

The interaction between Pneumocystis jirovecii and systemic inflammation has emerged as a potential modulator of cardiovascular risk. This review describes the potential of β-glucans to contribute to atherogenic inflammation. A narrative review was developed on the PubMed/MEDLINE, Scopus, Web of Science and Google Scholar databases. The inflammatory pathways induced by β-glucans from P. jirovecii contrast with the immunometabolic effects of dietary β-glucans. The relevance of serum (1→3)-β-D-glucans as a marker of systemic exposure was also described, although it is not specific to P. jirovecii. P. jirovecii β-glucans activate Syk–CARD9–NFκB, MAPK and STAT3 signalling pathways. This signalling promotes proinflammatory monocyte/macrophage polarization and a systemic microenvironment of low-grade inflammation with proatherogenic potential. The serum persistence of (1→3)-β-D-glucan indicates prolonged exposure, even in the absence of overt clinical manifestations of colonization. Conversely, dietary β-glucans have been observed to elicit regulatory effects facilitated by microbiota and metabolism. In experimental setting, a causal link has been established between fungal β-glucans and atherosclerosis. P. jirovecii β-glucans act as immunological mediators capable of amplifying pulmonary and systemic inflammation, constituting a possible modulator of cardiovascular risk. Distinguishing between fungal and dietary β-glucans is imperative for comprehending emerging mechanisms of vascular inflammation. Full article

Acute cardiovascular events driven by atherosclerosis primarily originate from thrombosis triggered by vulnerable plaque rupture or endothelial erosion. Endothelial barrier destabilization—characterized by glycocalyx impairment, intercellular junction disassembly, and abnormal cytoskeletal tension—is a core upstream pathological stage that promotes atherogenic lipoprotein leakage, inflammatory cell infiltration, and matrix degradation. Hemodynamics, primarily through wall shear stress (WSS), shape the spatial distribution and plaque phenotypes of atherosclerosis; notably, low or oscillatory shear stress is associated with, and in experimental systems can promote, pro-inflammatory, pro-oxidant and pro-permeability endothelial phenotypes that contribute to plaque initiation and vulnerability. Conversely, regular exercise training, as an intervention that modulates hemodynamics, is widely suggested to promote anti-inflammatory, antioxidant, and antithrombotic endothelial phenotypes by significantly increasing antegrade shear stress and reducing detrimental retrograde/oscillatory shear stress. With a central focus on the axis of “exercise-shear stress-glycocalyx-cytoskeleton/junction-permeability-plaque stability,” this review integrates evidence from in vitro flow chambers, animal models and human studies to critically discuss: (1) the spatiotemporal heterogeneity of WSS and its relationship with plaque vulnerability; (2) the composition, barrier function, and plasticity of the glycocalyx as the primary interface for shear stress; (3) the mechanosensory complexes at the glycocalyx and junctions that transduce shear stimuli to protective pathways such as Phosphoinositide 3-kinase (PI3K)-Akt-endothelial nitric oxide synthase (eNOS) and Krüppel-like factor 2 (KLF2), thereby stabilizing adherens/tight junctions; (4) how improved barrier homeostasis promotes the maintenance of the fibrous cap collagen scaffold by reducing lipoprotein leakage and dampening the inflammation–matrix metalloproteinase (MMP) axis. Finally, this review highlights the boundary conditions of the biological effects of shear stress: low/oscillatory shear stress is primarily associated with plaque initiation and susceptible sites, whereas focal, extremely high WSS in established stenotic lesions may contribute to late-stage high-risk remodeling. Therefore, the protective hemodynamic adaptations induced by exercise should not be simply equated with the pathologically high WSS found at stenotic sites. Full article

Background: Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial lung disease characterized by poor prognosis and accumulating evidence of systemic vascular involvement. Although cardiovascular comorbidities are recognized in IPF, the presence and extent of subclinical atherosclerosis are yet to be fully characterized. This study determined whether patients with IPF exhibit increased carotid intima–media thickness (CIMT) and altered atherogenic indices compared with healthy controls. Methods: This retrospective case–control study enrolled 117 patients with IPF diagnosed based on international guidelines and 104 age- and sex-matched healthy controls. All participants underwent comprehensive pulmonary function testing, the 6-min walk test (6MWT), laboratory evaluation (including lipid profiles), and bilateral carotid Doppler ultrasonography for CIMT measurement. Atherogenic indices, including the atherogenic coefficient, cholesterol ratio risk (CRR), and atherogenic index, were calculated. Dyspnea severity was evaluated using the visual analog scale (VAS). Results: Patients with IPF exhibited significantly higher CIMT (0.78 ± 0.12 mm vs. 0.68 ± 0.10 mm, p < 0.001) and CRR (4.12 ± 1.23 vs. 3.45 ± 0.98, p < 0.001) compared with controls. After adjustment for age, sex, cumulative smoking exposure expressed as pack-years, BMI, and controlled hypertension, IPF status remained independently associated with higher CIMT (adjusted β = 0.086 mm, 95% CI: 0.057–0.115; p < 0.001) and CRR (adjusted β = 0.482, 95% CI: 0.191–0.773; p = 0.001). Furthermore, patients with IPF had significantly lower HDL cholesterol levels and higher VLDL cholesterol levels. CIMT correlated negatively with 6MWT distance (r = −0.312, p = 0.001) and positively with VAS dyspnea scores (r = 0.287, p = 0.002). Conclusions: Patients with IPF showed higher CIMT and more unfavorable atherogenic profiles than healthy controls, and these associations persisted after adjustment for major vascular risk factors. The observed relationships between CIMT, functional capacity, and dyspnea severity suggest a potential association between IPF and subclinical cardiovascular involvement. Prospective studies are warranted to clarify the clinical relevance and prognostic implications of these findings. Full article

Despite increasing efforts to improve cardiovascular disease (CVD) risk evaluation and management, it remains a leading cause of mortality and morbidity worldwide. This has driven interest in high-density lipoprotein (HDL)-related biomarkers as indicators of oxidative stress and atherogenic processes not fully captured by traditional lipid measurements. In this study, we examined specific paraoxonase 1 (PON1) activity and its relationship with anthropometric, blood pressure, and lipid metabolism measures in 100 middle-aged Lithuanian individuals at high cardiovascular risk. HDL fractions were isolated using iodixanol-based density gradient centrifugation. PON1 concentration and arylesterase activity were measured, and specific activity was defined as arylesterase activity normalized to PON1 concentration. No significant associations were observed between specific PON1 activity and age, body mass index, waist circumference, blood pressure, smoking status, or statin use. Specific PON1 activity was independently associated with lower risk-weighted apolipoprotein B and lower low-density lipoprotein cholesterol levels. These exploratory findings suggest that higher specific PON1 activity may reflect a less atherogenic lipid profile in individuals at high cardiovascular risk, as indicated by its association with LDL-C and with risk-weighted apolipoprotein B. Because direct oxidative stress and inflammatory markers were not measured, interpretations regarding oxidative burden should be considered indirect and hypothesis-generating. Given the cross-sectional nature of the study and the relatively small sample size, these results should be interpreted as exploratory and hypothesis-generating. Further longitudinal studies in larger populations are needed to confirm these observations. Full article

Despite advances in lifestyle-based therapy, achieving clinically meaningful reductions in blood lipid levels remains a major challenge in obese men with secondary hypercholesterolemia. Hypoxic exposure encompassing both training sessions and nocturnal rest may offer a novel adjunct to conventional interventions; however, no study has evaluated such a protocol in this population. Twenty sedentary men with obesity-related hypercholesterolemia were randomly allocated to a hypoxic group (H) or normoxic control group (C). Both groups completed an identical two-week high-intensity training program under an individualized calorie-restricted diet, residing at the same lowland location (~100 m above sea level). The H group trained and rested under normobaric hypoxia (FiO₂ = 14.4%, simulated altitude ~3000 m, 8 h nightly); C remained under normoxic conditions. The H group demonstrated significantly greater reductions in body mass (−4.1%) and fat mass (−11.0%). Significant reductions in total cholesterol (−20.1%), low-density lipoprotein cholesterol (−21.3%), non-high-density lipoprotein cholesterol (−23.1%), atherogenic index of plasma (−42.4%), and Castelli Risk Index I (−19.4%) occurred exclusively in the H group, accompanied by a strong downward trend in Castelli Risk Index II (p = 0.072). High-density lipoprotein cholesterol did not change; for triglycerides, a clear downward trend was observed in the H group, approaching statistical significance within-group (p = 0.052). The magnitude of cholesterol reduction was significantly associated with body mass and fat loss (r = 0.61–0.67). A two-week intervention combining hypoxic training with nocturnal normobaric hypoxic exposure and caloric restriction produces clinically relevant improvements in lipid profile and body composition in men with obesity-related hypercholesterolemia. Full article

Metabolic dysfunction–associated steatotic liver disease (MASLD) is a highly prevalent multisystem disorder and is strongly associated with increased cardiovascular risk. Cardiovascular diseases represent the leading cause of mortality in this population. As the hepatic manifestation of systemic metabolic dysfunction, MASLD is initiated by excess lipid accumulation driven by increased dietary fatty acid intake and accelerated de novo lipogenesis. This triglyceride overload induces lipotoxicity, triggering hepatocellular injury, immune activation, and mitochondrial dysfunction. Excessive mitochondrial reactive oxygen species (ROS) generation acts as a critical second hit, promoting inflammatory cytokine production and disease progression. Beyond lipid dysregulation, impaired hepatic insulin signaling leads to hyperglycemia and compensatory hyperinsulinemia, further stimulating lipogenesis and reinforcing a self-perpetuating metabolic cycle. Persistent ROS production overwhelms antioxidant defenses and depletes hepatic glutathione (GSH), resulting in systemic redox imbalance. These disturbances extend beyond the liver, contributing to atherogenic dyslipidemia and chronic inflammation. In parallel, gut dysbiosis and increased intestinal permeability amplify immune activation. Reduced circulating GSH further weakens systemic antioxidant capacity; oxidative stress may represent a central mechanistic link between MASLD and CVD. In concert with metabolic and inflammatory mediators, ROS disrupt pathways governing vascular and myocardial homeostasis, leading to coronary atherosclerosis, microvascular dysfunction, left ventricular remodeling, hypertrophy, and impaired relaxation. Clinically, this translates into an increased burden of coronary artery disease and heart failure, particularly heart failure with preserved ejection fraction. Given this integrated pathophysiology, early identification of subclinical cardiovascular involvement is essential. We highlight emerging biomarkers, advocate for multidisciplinary screening strategies, and discuss integrated pharmacological approaches targeting shared metabolic pathways. Recognizing MASLD as a cardiovascular risk amplifier is critical for improving risk stratification and enabling the development of effective, co-targeted therapeutic strategies. Full article

Background: While existing research has examined the association between the atherogenic index of plasma (AIP) and the incidence of new-onset diabetes, there is a paucity of evidence concerning the influence of physical activity (PA) on this relationship. This study aims to elucidate the intricate relationships among AIP, PA, and new-onset diabetes in middle-aged and older adults. Methods: Data from the 2011–2020 CHARLS cohort were analyzed. Multivariable logistic regression and restricted cubic splines (RCS) assessed the association between AIP and diabetes risk. Effect modification by physical activity was examined via interaction terms and subgroup analyses, with sensitivity analyses excluding participants with dyslipidemia. Results: During follow-up, 717 participants developed diabetes. Each one-standard-deviation increase in AIP was associated with a significantly increased risk of diabetes (odds ratio (OR) = 2.266, 95% confidence interval (CI): 1.807–2.843), with a linear dose–response relationship. A significant interaction was observed between AIP and physical activity. The association between AIP and diabetes was robust among non-exercisers (OR = 2.735, 95% CI: 2.087–3.582), but was markedly attenuated and non-significant among regular exercisers (OR = 1.471, 95% CI: 0.962–2.247). Sensitivity analysis yielded consistent results (OR = 2.259, 95% CI: 1.776–2.873). Conclusions: AIP is independently associated with an increased risk of new-onset diabetes in Chinese adults aged ≥45 years. Subgroup analyses indicated that physical activity significantly modified this association. The association was robust among non-exercisers but was markedly attenuated and became non-significant among regular exercisers. Full article

Background/Objectives: Cardiovascular diseases remain a leading cause of global mortality. The C-X-C motif chemokine ligand 12 (CXCL12) gene has been implicated in atherosclerosis; however, its relationship with lipoprotein subfraction profiles remains unclear. The primary objective of this study was to investigate the association between the CXCL12 rs1801157 C>T single nucleotide polymorphism (SNP) and coronary artery disease (CAD) risk in a Turkish population. The secondary objective was to evaluate the relationship between this polymorphism and LDL and HDL lipoprotein subfraction profiles. Methods: This case–control study included 139 patients with angiographically confirmed CAD and 125 healthy controls. Genotyping was performed using TaqMan real-time polymerase chain reaction (PCR). Low-density lipoprotein (LDL) and high-density lipoprotein (HDL) subfractions were analyzed using the Lipoprint^® polyacrylamide gel electrophoresis system. Multivariable logistic and linear regression analyses were performed, adjusting for age, sex, body mass index (BMI), and major cardiovascular risk factors. Results: No significant differences in rs1801157 genotype or allele distributions were observed between groups (overall χ² = 0.459, p = 0.796). Logistic regression confirmed that the polymorphism was not an independent predictor of CAD risk (CT: OR = 1.396, p = 0.409; TT: OR = 1.458, p = 0.694). HDL-C was an independent protective factor (OR = 0.952, 95% CI: 0.910–0.996; p = 0.029). Notably, TT homozygous carriers exhibited significantly higher large HDL (p = 0.018) and intermediate HDL (p < 0.001) subfraction levels and markedly lower small LDL concentrations (p < 0.001). Multivariable linear regression confirmed these associations were independent of age, sex, and BMI. Conclusions: The CXCL12 rs1801157 variant does not directly influence CAD susceptibility but modulates lipoprotein quality by promoting larger HDL subfractions and reducing atherogenic small LDL particles, suggesting an indirect cardioprotective role through lipid metabolism. Full article

Rheumatoid arthritis (RA) is a chronic inflammatory disorder associated with a substantially increased risk of cardiovascular (CV) disease, driven by both persistent systemic inflammation and a high burden of traditional cardiometabolic risk factors. In recent years, glucagon-like peptide-1 receptor agonists (GLP-1RAs), licensed for type 2 diabetes mellitus and obesity, have attracted attention for their broader metabolic and cardiovascular benefits, raising the question of their potential role in RA. This scoping review summarizes current evidence on the impact of GLP-1RAs on RA disease activity, CV comorbidities, and the underlying immuno-metabolic mechanisms. Experimental studies suggest that GLP-1RAs could modulate key inflammatory pathways in synovial cells, reducing pro-inflammatory cytokine production, oxidative stress, and tissue-degrading enzymes, while improving mitochondrial function. Although clinical data remains limited, observational studies report improvements in disease activity, inflammatory markers, and pain in patients with RA treated with GLP-1RAs in addition to immunosuppressive treatment. Extensive evidence from randomized trials in metabolic populations demonstrates that GLP-1RAs improve glycemic control, induce significant weight loss, and reduce modestly but consistently blood pressure and atherogenic lipids, ultimately lowering major CV events and mortality. Although this evidence cannot be directly translated to RA populations, early real-world data specific to the disease suggest similar favorable trends, including reductions in cardiometabolic risk factors and thromboembolic events. Taken together, these findings suggest that GLP-1RAs may offer dual benefits in RA by addressing both metabolic dysfunction and inflammation. However, the current evidence base is heterogeneous and largely non-randomized, underscoring the need for dedicated trials. Full article

Atherosclerosis is a chronic inflammatory arterial disease and the primary underlying cause of cardiovascular morbidity and mortality worldwide. Its development and progression are driven by a mechanistically interconnected triad of endothelial dysfunction, oxidative stress, and vascular inflammation. Current pharmacotherapy, primarily focused on low-density lipoprotein cholesterol (LDL-C) reduction through statin-based and adjunctive therapies, does not fully address the residual inflammatory and calcific components of atherosclerotic risk. Menaquinone-7 (MK-7), a long-chain isoform of vitamin K2 with superior bioavailability and extrahepatic tissue distribution, has emerged as a multi-target modulator of atherogenic processes. Its classical function is to serve as a cofactor for the gamma-carboxylation of vitamin K-dependent proteins (VKDPs), principally matrix Gla protein (MGP), the primary endogenous inhibitor of vascular calcification. Beyond this established pathway, a growing body of experimental evidence indicates that MK-7 may modulate endothelial nitric oxide (NO) production through carboxylation-dependent activation of Growth Arrest-Specific Protein 6 (Gas6) and suppress lipid peroxidation and ferroptosis via Ferroptosis Suppressor Protein 1 (FSP1)-mediated reduction of vitamin K hydroquinone (VKH₂). In addition, it may attenuate nuclear factor kappa-B (NF-κB)-driven inflammatory gene transcription in vascular cells. Previous reviews mainly focused on how vitamin K2 influences vascular calcification and cardiovascular outcomes. However, emerging mechanistic evidence linking MK-7 to endothelial dysfunction, oxidative stress, ferroptosis, and vascular inflammation has not been comprehensively integrated. This review summarizes the current knowledge of in vitro, animal, observational, and randomized controlled trial evidence for MK-7 in the context of atherosclerosis. It particularly emphasises mechanistic pathways, the strength of evidence, and translational limitations, highlighting the lack of direct human vascular evidence in several areas. Full article

Micro- and nanoplastics (MNPs) are ubiquitous environmental pollutants recognized as emerging and relevant risk factors for numerous human diseases, including cardiovascular diseases. MNPs enter the human body through ingestion, inhalation, and dermal penetration, and their toxicity varies according to size, shape, and chemical composition, most notably between microplastics (>1 µm) and nanoplastics (<1 µm), which differ in cellular uptake mechanisms and biodistribution. Recent evidence has confirmed their presence in cardiac and vascular tissues, raising significant concerns about their potential impact on human health. This review summarizes current knowledge on MNP exposure sources, physicochemical properties, and systemic bioavailability, with a particular emphasis on the mechanisms of transport that facilitate their deposition within the myocardium and vasculature. It further addresses a broad spectrum of cardiotoxic effects, including oxidative stress, mitochondrial injury, immune activation, ion channel disruption, cell death, and fibrosis. Endothelial dysfunction, vascular injury, and pro-atherogenic activity are also discussed. In addition to outlining existing detection techniques and emerging in vitro models, the review highlights initial steps toward the development of preventive strategies. Concluding with key knowledge gaps and future research directions, this article underscores the urgent need for standardized measurement tools, deeper insights into damage mechanisms, and clinical interventions to prevent MNP-induced cardiovascular diseases. Full article

Background: Frailty is a common finding in elderly subjects with severe aortic stenosis (AoS) and a strong predictor of mortality and disability after aortic valve surgery. The atherogenic index of plasma (AIP) is related to different cardiovascular (CV) risk factors, which in turn are correlated to the progression of frailty as well as of AoS. Aim: to analyze the association of AIP with different CV risk factors and frailty scores and its value as a determinant of mortality in older adults with severe AoS. Methods: The association of AIP with a multidimensional assessment of frailty by using Fried criteria and the following indices; timed up-and-go test (TUG) for gait function; Charlson Index (CI), basic activities of daily living (BADL) and instrumental activities of daily living (IADL) for disability; mini–mental state examination for cognitive function evaluation (MMSE); Geriatric Depression Score for mood disorder (GDS); Mini Nutritional Assessment (MNA) for nutritional status was assessed in 102 elderly AoS patients (33 males; mean age 83 ± 6 yrs). Moreover, the relationship between AIP and demographic, lifestyle, traditional CV risk factors and CV mortality was also evaluated. Results: Significant relationships between AIP and glycemia and inflammatory parameters (CRP, ESR and fibrinogen) as well as with troponin I were found. Moreover, AIP significantly correlates with CI, BADL, IADL and MNA. However, the Kaplan–Meier analysis did not show any significant difference for survival rates according to AIP intervals of risk, whereas ejection fraction remained the only significant determinant after multivariate adjustment for mortality at the Cox proportional hazard models analysis in this patient population. Conclusions: Higher AIP is significantly associated with cardiometabolic risk and increased physical dysfunction risk and frailty in AoS pts, evidencing its potential use as a simple biomarker in this clinical setting, although it did not represent a significant determinant for mortality in this population. Full article