Search Results (72)

Inflammatory biomarkers, including high-sensitivity C-reactive protein (hsCRP), serum amyloid A (SAA), and interleukin-6 (IL-6), have been associated with an increased risk of future cardiovascular events. While they provide valuable prognostic information, these associations do not necessarily imply a direct causal role. The combined prognostic utility of these markers, however, remains insufficiently studied. We analysed 3300 well-characterised participants of the Ludwigshafen Risk and Cardiovascular Health (LURIC) study, all of whom underwent coronary angiography. Participants were stratified based on their serum concentrations of hsCRP, SAA, and IL-6. Associations between biomarker combinations and mortality were assessed using multivariate Cox regression and ROC analysis. Individuals with elevated hsCRP and SAA or IL-6 showed higher prevalence rates of coronary artery disease, heart failure, and adverse metabolic traits. These “both high” groups had lower estimated glomerular filtration rate, higher NT-proBNP, and increased HbA1c. Combined elevations of hsCRP and SAA were significantly associated with higher all-cause and cardiovascular mortality in partially adjusted models. However, these associations weakened after adjusting for IL-6. IL-6 alone demonstrated the highest predictive power (AUC: 0.638) and improved risk discrimination when included in multi-marker models. The co-elevation of hsCRP, SAA, and IL-6 identifies a high-risk phenotype characterised by greater cardiometabolic burden and increased mortality. IL-6 may reflect upstream inflammatory activity and could serve as a therapeutic target. Multi-marker inflammatory profiling holds promise for refining cardiovascular risk prediction and advancing personalised prevention strategies. Full article

Objective: The objective of this study was to analyze the prevalence and key sociodemographic and lifestyle determinants of metabolic syndrome (MetS) and the hypertriglyceridemic waist (HTGW) phenotype in a large occupational cohort. Background: Metabolic syndrome (MetS) and the hypertriglyceridemic waist (HTGW) phenotype, defined as the simultaneous presence of elevated waist circumference and high triglyceride levels, are major predictors of cardiometabolic morbidity and mortality. Despite their clinical relevance, data on their distribution and determinants in large occupational populations remain limited. Methods: A cross-sectional analysis was conducted on 139,634 employed adults (56,352 women and 83,282 men) across Spain, based on standardized clinical evaluations and validated questionnaires assessing physical activity, diet, smoking, alcohol consumption, education, and occupational class. Logistic regression models were used to estimate associations with MetS and HTGW. A longitudinal subsample of 40,431 individuals was followed over a 10-year period (2009–2019) to assess trends in metabolic risk phenotypes. Results: Male sex, older age, lower educational attainment, and unhealthy lifestyle behaviors were associated with a higher prevalence of both MetS and the HTGW phenotype. Physical inactivity, low adherence to the Mediterranean diet, and alcohol consumption were significantly associated with increased risk. The HTGW phenotype proved useful in identifying high-risk individuals, with a steadily increasing prevalence over time. Conclusions: Sociodemographic disparities and modifiable lifestyle factors significantly influence the prevalence and progression of MetS and HTGW in the Spanish workforce. Preventive strategies should emphasize early workplace screening, promotion of healthy behaviors, and reduction in educational and socioeconomic inequalities to mitigate cardiometabolic risk. Full article

Metabolic dysfunction-associated steatotic liver disease (MASLD) has emerged as the leading cause of chronic liver disease worldwide, driven by the global epidemics of obesity, type 2 diabetes, and metabolic syndrome. In this evolving nosological landscape, alcohol consumption—traditionally excluded from the diagnostic criteria of non-alcoholic fatty liver disease (NAFLD)—has regained central clinical importance. The recently defined MetALD phenotype acknowledges the co-existence of metabolic dysfunction and a significant alcohol intake, highlighting the synergistic nature of their pathogenic interactions. This narrative review provides a comprehensive analysis of the biochemical, mitochondrial, immunometabolic, and nutritional mechanisms through which alcohol exacerbates liver injury in MASLD. Central to this interaction is cytochrome P450 2E1 (CYP2E1), whose induction by both ethanol and insulin resistance enhances oxidative stress, lipid peroxidation, and fibrogenesis. Alcohol also promotes mitochondrial dysfunction, intestinal barrier disruption, and micronutrient depletion, thereby aggravating metabolic and inflammatory derangements. Furthermore, alcohol contributes to sarcopenia and insulin resistance, establishing a bidirectional link between hepatic and muscular impairment. While some observational studies have suggested a cardiometabolic benefit of a moderate alcohol intake, emerging evidence challenges the safety of any threshold in patients with MASLD. Accordingly, current international guidelines recommend alcohol restriction or abstinence in all individuals with steatotic liver disease and metabolic risk. The review concludes by proposing an integrative clinical model and a visual cascade framework for the assessment and management of alcohol consumption in MASLD, integrating counseling, non-invasive fibrosis screening, and personalized lifestyle interventions. Future research should aim to define safe thresholds, validate MetALD-specific biomarkers, and explore the efficacy of multidisciplinary interventions targeting both metabolic and alcohol-related liver injury. Full article

Metabolic syndrome (MetS) and its associated cardiometabolic phenotypes significantly contribute to the global burden of cardiovascular disease (CVD), especially in individuals with type 2 diabetes mellitus (T2DM) and prediabetes. This study aimed to explore the association between cardiometabolic phenotypes—specifically, metabolically unhealthy normal weight (MUHNW) and metabolically unhealthy obese (MUHO)—and various cardiovascular risk indices including the triglyceride-glucose (TyG) index and its derivatives, the atherogenic index of plasma (AIP), the cardiometabolic index (CMI), and the cardiac risk ratio (CRR). A total of 300 participants were evaluated (100 with prediabetes and 200 with T2DM). Anthropometric, biochemical, and lifestyle parameters were assessed and stratified across phenotypes. The results demonstrated that cardiovascular risk indices were significantly elevated in the MUHO compared to MUHNW phenotypes, with T2DM patients consistently exhibiting higher risk profiles than their prediabetic counterparts. TyG-derived indices showed strong correlations with BMI, waist–hip ratio (WHR), waist–height ratio (WHtR), and body fat percentage (%BF). The findings suggest that cardiometabolic phenotypes are more strongly associated with elevated cardiometabolic risk indices than body weight alone. These indices may enhance early risk stratification and intervention efforts. The study investigates the association of cardiometabolic phenotypes with surrogate cardiovascular risk indices, not direct CVD outcomes, However, the cross-sectional design and population homogeneity limit the generalizability of the results and preclude causal inference. Full article

The sarcopenic obesity-related phenotype (SOP) is defined by the coexistence of sarcopenia and obesity, leading to heightened disability, morbidity, and mortality. Its multifactorial pathogenesis involves chronic inflammation and metabolic alterations. In this cross-sectional study, 562 women were classified into four groups: control, sarcopenic, obese, and SOP. Body composition measurements, including fat mass, skeletal muscle mass, and extracellular water (ECW), were assessed using the bioimpedance method. Several inflammatory biomarkers were measured in plasma samples by ELISA. Discriminant function analysis identified age, ECW, chemerin, the systemic immune-inflammation index (SII), and the ratio of total cholesterol to high-density lipoprotein cholesterol (TC/HDL-C) as significant discriminators among groups, clearly distinguishing SOP from control. Multivariable logistic regression analysis revealed that these variables were independently associated with SOP status (SOP vs. control), regardless of age, with odds ratios (ORs) ranging from 1.87 (95% confidence interval [CI]: 1.23–2.85) for SII to 7.77 (95% CI: 3.67–16.44) for ECW. A generalized estimating equation (GEE) analysis further demonstrated that SOP significantly increased the odds (OR: 3.04; 95% CI: 1.39–6.67) of multimorbidity (hypertension (HTN) + hyperlipidemia (HLD) + type 2 diabetes (D2T)). These findings suggest SOP is a clinically relevant phenotype linked to cardiometabolic comorbidities and systemic inflammation. Identifying SOP using accessible body composition and biomarker assessments may support early risk stratification and guide personalized preventive strategies in clinical care. Full article

This study aimed to identify and analyse the copy number variations (CNVs) in the genes involved in the pathophysiology of obesity and correlate these findings with the phenotypic manifestations. Genetic screening of 59 apparently healthy individuals with elevated adipose tissue percentages was performed, assessing the duplications and deletions of obesity-related genes through the MLPA (Multiplex Ligation-dependent Probe Amplification) technique. Clinical and metabolic parameters, including insulin, HOMA-IR, leptin, and adiponectin levels, were measured to better describe the obesity profiles of the participants in this study. In our research, 11.86% of the subjects presented with genetic alterations in obesity-associated genes, with 16% of these modifications involving concurrent duplications in SEZ6L2-1 and SH2B1-2, linked to doubled insulin and tripled HOMA-IR levels. However, the same duplications were associated with a reduced trunk adipose tissue percentage (but not BMI), suggesting leptin signalling modulation. Duplications were more frequent in the metabolically unhealthy obese patients, resulting in a higher relative risk of an obese metabolically unhealthy diagnosis (1.85-fold increased risk in subjects with SEZ6L2-1/SH2B1-2 duplications, p = 0.52). No duplications or deletions were reported in the non-obese patient groups, defined according to the BMI criteria. A partial LEPR deletion was identified in one patient, associated with severe insulin resistance (second-highest HOMA-IR in the cohort). Another subject presented with 11 duplications (7 in LEPR) and reported the lowest adiponectin and second-highest leptin levels among the genetically altered subjects. The genetic profiles revealed complex associations between the CNVs and obesity phenotypes, highlighting the potential for early risk stratification. Despite the interpretative challenges, identifying the genetic predispositions could significantly predict cardiometabolic risk and be used to map personalised interventions to possibly modulate phenotypic expression. Full article

Objectives: To investigate the association between visceral fat accumulation and the risk of cardiometabolic multimorbidity (CMM) and the potential roles of accelerated biological aging in this relationship. Methods: Using data from the UK Biobank, a nationwide cohort study was conducted using the available baseline body roundness index (BRI) measurement. Biological aging was assessed using the Klemera–Doubal method for biological age and the phenotypic age algorithms. The association between the BRI and CMM was estimated using the Cox proportional hazards regression model, while the roles of biological aging were examined through interaction and mediation analyses. Results: During a median follow-up of 14.52 years, 6156 cases of CMM were identified. A significant association was observed between the BRI and CMM. The hazard ratio (HR) for CMM was 3.72 (95% confidence interval [CI]: 3.35–4.13) for individuals in the highest quartile compared with those in the lowest quartile of the BRI. More importantly, the BRI (AUC, 0.701; 95% CI, 0.694–0.707) demonstrated superior predictive performance relative to body mass index (AUC, 0.657; 95% CI, 0.650–0.664). Furthermore, the BRI exhibited additive interactions with accelerated biological aging on the risk of CMM, and accelerated biological aging partially mediated the association between the BRI and CMM. Conclusions: These findings provide evidence for the application of the BRI as a novel and readily accessible screening tool associated with CMM, suggesting that the effective management of visceral fat and biological aging deceleration may hold promise for reducing CMM risk. Full article

Metabolic dysfunction-associated steatotic liver disease (MASLD) corresponds to the condition of increased hepatic fat levels, which is the leading cause of hepatic failure and carcinoma. It is also an independent risk factor for cardiovascular disease (CVD) and mortality. MASLD can be due to obesity with insulin resistance and/or genetic predisposition, i.e., polymorphism in the patatin-like phospholipase domain-containing 3 (PNPLA3) gene. PNPLA3 polymorphism has been associated with increased hepatic fat levels, fibrosis, cirrhosis, and hepatocellular carcinoma, while its association with CVD remains to be fully understood. The aim of the current study was to examine whether the vascular phenotype of patients with MASLD differed between carriers and noncarriers of the PNPLA3 polymorphism. Adult patients with MASLD underwent clinical assessment, PNPLA3 genotyping, arterial tonometry for aortic stiffness measurement, and ultrasound examination of carotid arteries. In total, 117 patients with MASLD and no fibrosis (median hepatic stiffness was 4.71 kPa) were recruited. Carriers of the PNPLA3 polymorphism were younger and exhibited higher levels of ALT and APRI, as compared to wild-type subjects. On the other hand, carriers of the PNPLA3 polymorphism had not only a better metabolic profile (i.e., lower glucose and glycated hemoglobin) but also lower blood pressure, carotid intima-media thickness (IMT), and cardiovascular risk. In addition, PNPLA3 polymorphism was negatively correlated with aortic stiffness, which is a marker of arteriolosclerosis and vascular ageing. Our data are consistent with previous observations that in case of genetically-driven MASLD, there is an inverse association with common predictors of CVD. Our data support the view that the main contributors to CVD risk in patients with MASLD remain conventional cardiometabolic risk factors (i.e., age, glucose) that are more likely to be found in metabolic syndrome-related MASLD rather than genetically-driven MASLD, at least in the first stages of the disease. Full article

Up to 30% of individuals with obesity may exhibit normal insulin sensitivity, a favorable lipid profile, and no signs of hypertension. This prompts the exploration of factors distinguishing cardiometabolically healthy individuals from those developing complications. This cross-sectional study included 116 individuals categorized into four groups by combining abdominal obesity and cardiometabolic health statuses. We compared circulating adipokines and gut microbiota composition between these groups. Individuals with abdominal obesity had higher levels of hs-CRP, TNF-α, MCP-1, IL-18, chemerin, and leptin, and a less favorable gut microbiota composition, including higher levels of potentially harmful bacteria (CAG-Pathogen) and lower levels of beneficial bacteria (CAG-Ruminococcaceae and CAG-Akkermansia), compared to those with adequate waist circumference. Those with obesity but cardiometabolically healthy displayed similar adipokine levels and microbiota composition to those with adequate waist. In contrast, individuals with abdominal obesity cardiometabolically abnormal exhibited significantly higher levels of hs-CRP, IL-18, chemerin, and leptin, and lower levels of adiponectin and CAG-Ruminococcaceae compared to those with abdominal obesity cardiometabolically healthy and adequate waist. Additionally, they differed in hs-CRP and adiponectin/leptin ratio from individuals with obesity cardiometabolically healthy. These findings suggest that altered adipokine profiles and gut microbiota may contribute to the development or persistence of cardiometabolic complications in obesity. Full article

Normal weight obesity (NWO) is a body composition phenotype that is associated with increased cardiometabolic risk and is characterized by a normal weight body mass index but elevated body fat. The purpose of this study was to determine sex differences in aerobic capacity across body composition phenotypes, including normal weight lean (NWL), NWO, and traditional obesity (OB). We recruited 60 participants according to three body composition phenotypes: NWL (n = 10 females, n = 10 males), NWO (n = 10 females, n = 10 males), and OB (n = 10 females, n = 10 males). Measurements included fasting metabolic risk factors, body composition X-ray scan, and peak exercise test on a cycle ergometer to determine aerobic capacity (VO_2peak). Across groups, males (34.5 ± 11.7 mL/kg/min) exhibited greater VO_2peak than females (28.8 ± 8.8 mL/kg/min; p = 0.04). There were no differences in VO_2peak between sexes within the same body composition phenotype, but NWL (42.7 ± 9.0 mL/kg/min) exhibited greater VO_2peak than NWO (27.9 ± 4.4 mL/kg/min; p < 0.0001) and OB (24.4 ± 7.3 mL/kg/min; p < 0.0001). VO_2peak was inversely correlated with relative body fat in the full sample (r = −0.67; p < 0.0001), but was stronger in males (r = −0.78; p < 0.0001) than females (r = −0.53; p = 0.0028). Visceral adipose tissue was not significantly correlated with VO_2peak in the full sample (r = −0.25; p = 0.05) or in males (r = −0.23; p = 0.25), although they were inversely correlated in females (r = −0.36; p = 0.048). Our results suggest low aerobic capacity in both men and women with NWO, similar to men and women with OB. The relationship between body composition and aerobic capacity is strong across body composition phenotypes, but appears to be more consistent in females than males. For healthcare professionals aiming to lower cardiometabolic risk, attention should be given to improving aerobic fitness in both men and women with elevated body fat, including those with NWO. Full article

Background/Objectives: Non-dipper hypertension (HT), a condition in which blood pressure does not drop sufficiently at night compared to daytime, is considered a serious condition that increases the risk of cardiovascular disease, stroke, and organ damage. This study aimed to examine the relationship between dipper and non-dipper blood pressure patterns, hepatosteatosis, and biochemical markers in hypertensive and normotensive individuals. Methods: Demographic, biochemical, and hepatic ultrasonography data from 142 patients who underwent 24 h ambulatory blood pressure measurement (ABPM) were evaluated retrospectively and cross-sectionally in this study. Patients were categorized into four groups based on ABPM results: non-dipper normotensive (NDN), dipper normotensive (DN), non-dipper hypertensive (NDH), and dipper hypertensive (DH). Results: The study results indicate that NDH individuals had markedly elevated levels of hepatosteatosis and uric acid compared with DH and normotensive persons (p < 0.001). The grade of hepatosteatosis showed significant discriminatory capacity in differentiating between dipper and non-dipper hypertensive patients, with an AUC of 0.861, specificity of 94%, and sensitivity of 66%. Individuals with hypertension exhibiting a non-dipper pattern demonstrate a greater prevalence of hepatosteatosis and elevated uric acid levels. Conclusions: The study findings show non-dipper patterns have a higher risk for cardiometabolic diseases. This indicates that not only blood pressure, but also metabolic disorders should be closely monitored and treated in the management of non-dipper HT. Full article

Background/Objectives: There is a lack of empirical studies of out-of-pocket health expenditures associated with dyslipidemias, which are major cardiovascular risk factors, especially in underrepresented admixed populations. The study investigates associations of health costs with lipid traits, GWAS-derived genetic risk scores (GRSs), and other cardiometabolic risk factors. Methods: Data from the observational cross-sectional 2015 ISA-Nutrition comprised lifestyle, environmental factors, socioeconomic and demographic variables, and biochemical and genetic markers related to the occurrence of cardiometabolic diseases. GWAS-derived genetic risk scores were estimated from SNPs previously associated with lipid traits. There was phenotypic and genetic information available for 490 independent individuals, which was used as inputs for random forests and logistic regression to explain private quantitative and categorical health costs. Results: There were significant correlations between GRSs and their respective lipid phenotypes. The main relevant variables across techniques and outcome variables comprised income per capita, principal components of ancestry, diet quality, global physical activity, inflammatory and lipid markers, and LDL-c GRS and non-HDL-c GRS. The area under the ROC curve (AUC) of quartile-based categorical health expenditure without GRSs was 0.76. GRSs were not significant for this categorical outcome. Conclusions: We present an original contribution to the investigation of determinants of private health expenditures in a highly admixed population, providing insights on associations between genetic and socioeconomic dimensions of health in Brazil. Ancestry information was also among the main factors contributing to health expenses, providing a novel view of the role of genetic ancestry on cardiometabolic risk factors and its potential impact on health costs. Full article

Background/Objectives. A cardiovascular complication of type 2 diabetes mellitus like coronary artery disease is influenced by a complex interplay between environmental, phenotypic, and genetic factors. The genetic mechanisms in the development of this pathology are not established. This study aims to evaluate the association of polymorphisms rs1011970, rs62560775, and rs564398 from the 9p21.3 locus with coronary artery disease in diabetic patients of the Kazakh population. Methods. A total of 343 people participated in the case-control study: the control group consisted of 109 people with type 2 diabetes and coronary artery disease, while the control group included 234 people. Genotyping was performed using real-time PCR. Statistical analysis was carried out using Chi-square methods and calculating odds ratios (OR) with 95% confidence intervals (CI). Results. According to the results, only the rs564398 polymorphism of the ANRIL gene was associated with coronary artery disease (p = 0.04). The CC genotype increased the risk of developing coronary artery disease by more than 1.5 times (1.62 (1.02–2.56)), whereas the TT genotype reduced the risk of coronary artery disease (0.39 (0.17–0.91)). The remaining polymorphisms, rs1011970 and rs62560775, were not associated with coronary artery disease. Conclusions. Thus, this research further elicits the association of the ANRIL gene with cardiometabolic disease. Full article

High fructose consumption is associated with an increased risk of cardiometabolic disease, and fructose feeding dose-dependently induces markers reflective of poor metabolic health. However, unlike glucose, surprisingly little is known about person-to-person differences in postprandial plasma fructose patterns. Herein, we performed post hoc analyses of two published studies to address this question. In the first cohort, 16 participants’ all-day plasma fructose concentration patterns (08:00–23:30) were determined (8 women and 8 men) while consuming mixed meals (breakfast, lunch, and dinner) with a fructose-sweetened beverage at each meal (30% of calories). Individually plotted results demonstrate remarkably disparate fructose patterns with respect to peak concentration and timing. A secondary study confirmed substantial interindividual variability in plasma fructose patterns over 240 min in 16 adults consuming Ensure^®, a commercially available mixed macronutrient drink containing a low dose of fructose. The health ramifications of interindividual variations in postprandial fructose metabolism and the underlying physiological mechanisms driving differences in post-meal blood patterns remain to be explored. Future research is warranted to determine if interindividual variability in fructose digestion, metabolism, and postprandial blood concentration patterns is associated with cardiometabolic health phenotypes and disease risk. Full article

Background: Acute myocardial infarctions are deadly to patients and burdensome to healthcare systems. Most recorded infarctions are patients’ first, occur out of the hospital, and often are not accompanied by cardiac comorbidities. The clinical manifestations of the underlying pathophysiology leading to an infarction are not fully understood and little effort exists to use explainable machine learning to learn predictive clinical phenotypes before hospitalization is needed. Methods: We extracted outpatient electronic health record data for 2641 case and 5287 matched-control patients, all without pre-existing cardiac diagnoses, from the Michigan Medicine Health System. We compare six different interpretable, feature extraction approaches, including temporal computational phenotyping, and train seven interpretable machine learning models to predict the onset of first acute myocardial infarction within six months. Results: Using temporal computational phenotypes significantly improved the model performance compared to alternative approaches. The mean cross-validation test set performance exhibited area under the receiver operating characteristic curve values as high as 0.674. The most consistently predictive phenotypes of a future infarction include back pain, cardiometabolic syndrome, family history of cardiovascular diseases, and high blood pressure. Conclusions: Computational phenotyping of longitudinal health records can improve classifier performance and identify predictive clinical concepts. State-of-the-art interpretable machine learning approaches can augment acute myocardial infarction risk assessment and prioritize potential risk factors for further investigation and validation. Full article