Search Results (3,407)

Endothelial dysfunction (ED) arises in multiple pathologies, and its severity correlates with disease progression. Common ED biomarkers could provide prognostic value for associated complications. This study aims to identify shared ED biomarkers and assess their prognostic significance. Endothelial cells in culture (human microvascular endothelial cells, HMEC-1) were exposed to sera from patients in five disease groups (n = 20 patients/group)—liver cirrhosis with portal hypertension, idiopathic pulmonary arterial hypertension, placental disorders such as intrauterine growth restriction, coronary artery disease with acute myocardial infarction, and chronic kidney disease—or matched controls, in the absence/presence of anti-inflammatory (apixaban) and antioxidant (EUK134) compounds. We explored changes in: VCAM-1, ICAM-1, eNOS, VWF, extracellular matrix thrombogenicity, and reactive oxygen species (ROS). In serum samples, proteomics and metabolomics analyses (including lipids, amino acids, and polar metabolites) were performed through an extraction protocol to identify common ED biomarkers. Expression of VCAM-1, ICAM-1, VWF, platelet adhesion, and ROS increased in most groups versus controls (p < 0.05). Both drugs decreased all biomarker levels except eNOS (n = 6 for in vitro experiments). For serum ED biomarkers, 18 metabolites and 24 proteins showed AUC-ROC and hit rates >77.5%, and six metabolites were associated with event-free survival. These diseases share ED driven by systemic inflammatory, oxidative, and metabolic stress, are partially reversible in vitro, and are linked to biomarkers associated with clinical outcomes. Overall, ED emerges as a modifiable pathological axis with potential prognostic value. Full article

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most prevalent chronic liver disease worldwide and a major contributor to the global cardiometabolic burden. Early identification of patients at risk of metabolic dysfunction-associated steatohepatitis (MASH) and advanced fibrosis is essential to prevent liver-related and cardiovascular complications. In Spain, the burden of MASLD is increasing, yet information on routine clinical management by gastroenterologists remains limited. Methods: A nationwide cross-sectional online survey was conducted among members of the Spanish Society of Digestive Diseases (SEPD). The questionnaire explored five domains: MASLD knowledge, use of non-invasive biomarkers and imaging, awareness and implementation of clinical guidelines, cardiometabolic and alcohol-related risk assessment, and coordination with primary care. Results: A total of 429 specialists responded, 33.1% reported more than 20 years of practice and most worked in public hospitals, including 29.2% in large tertiary centers. Awareness of the MASLD definition was high, and 91.2% identified fibrosis as the main prognostic determinant. Non-invasive fibrosis biomarkers were widely used, whereas steatosis biomarkers were less frequently applied. Elastography was available to 96.1%. Guideline knowledge was reported by 80.4%, although implementation was lower. Cardiovascular risk evaluation varied: 75.1% reported systematic screening. Alcohol consumption was usually assessed. Coordination with primary care was limited: 91.1% expressed concerns regarding physicians’ familiarity with MASLD classification, and only 31.1% reported shared protocols. Conclusions: Spanish gastroenterologists show high awareness of MASLD and broad access to non-invasive diagnostic tools. However, important gaps remain in cardiovascular and alcohol risk assessment, guideline implementation, and coordination with primary care. Full article

Background/Objectives: This study analyzes the relationship between obesity phenotypes and sleep apnea risk in the Korean population. Methods: This study utilized data from the Korean National Health and Nutrition Examination Survey (KNHANES) collected between 2019 and 2021 (n = 10,970 adults; age ≥ 40 years). Obesity phenotypes were classified into four groups based on body mass index (BMI) and the presence of metabolic syndrome: metabolically healthy normal weight (MHNW), metabolically abnormal normal weight (MANW), metabolically healthy obese (MHO), and metabolically abnormal obese (MAO). Sleep apnea risk was assessed using the STOP-Bang questionnaire, and multivariate logistic regression analyses were performed to evaluate the association between obesity phenotypes and sleep apnea. Results: Among the 10,970 participants, the phenotypes were as follows: MHNW, 51.1%; MANW, 10.3%; MHO, 15.8%; and MAO, 21.8%. Baseline characteristics differed significantly across phenotypes, with the metabolically unhealthy groups (MANW and MAO) being older and exhibiting more cardiometabolic risk factors than the metabolically healthy groups. The prevalence of STOP-Bang questionnaire components differed significantly across phenotypes (all p < 0.001), and the mean STOP-Bang score increased from MHNW to MAO. In multivariate logistic regression analyses, the odds (adjusted odds ratio [95% CI]) of high sleep apnea risk were significantly elevated in all non-MHNW phenotypes: MAO (10.27 [7.71–13.68]), MHO (6.17 [4.35–8.75]), and MANW (1.91 [1.22–2.98]). Notably, MAO conferred a significantly higher risk than MHO (OR 1.69 [1.34–2.13]), highlighting the synergy of obesity and metabolic dysfunction. Obesity phenotypes, defined by BMI and metabolic health status, were differentially associated with sleep apnea risk in Korean adults. The highest risk was observed in individuals with both obesity and metabolic syndrome, while metabolically abnormal normal-weight adults also showed a significantly increased risk. Conclusions: Metabolic dysfunction may contribute to sleep apnea risk beyond body size alone and may be considered in risk stratification strategies. Full article

The global rise in obesity and cardiometabolic disease represents a major public health concern and contributes significantly to cardiovascular morbidity and mortality. Contemporary Western dietary patterns and excess adiposity are strongly associated with atherosclerotic cardiovascular disease. Although pharmacologic therapies have expanded, lifestyle interventions remain the cornerstone of prevention and management. However, identifying sustainable and effective dietary approaches continues to be challenging given the wide range of available nutrition regimens. Intermittent fasting (IF) has emerged as a promising strategy for weight reduction and metabolic improvement. In this article, we review the physiological effects of IF, including metabolic switching, ketosis, and improvements in insulin sensitivity and inflammatory regulation. We also evaluate clinical evidence regarding the impact on cardiovascular risk, as well as its safety and tolerability. We examine the hormonal responses to IF based on sex. While early studies raised concerns regarding potential reproductive and endocrine disturbances, recent data suggest beneficial effects in both males and females. IF may modestly reduce testosterone in men without impairing muscle mass or strength and may improve metabolic and reproductive outcomes in women, particularly those with hyperandrogenic conditions such as polycystic ovarian syndrome, with favorable effects also observed in postmenopausal women, especially when combined with physical activity. Full article

Objectives: Atrial fibrillation (AF), the most common sustained cardiac arrhythmia, and cardiometabolic comorbidity, have been increasingly associated with cognitive impairment and dementia. These associations, however, remain underexplored and underappreciated in middle-aged individuals with AF. This study aimed to explore the associations of early cognitive impairment with the presence of cardiometabolic comorbidities and potential associations with echocardiographic markers in middle-aged patients with and without AF. Methods: Between 2023–2024, fifty-six consecutive outpatients with a diagnosis of AF aged 45–65 years underwent clinical evaluation, transthoracic echocardiography, and comprehensive neuropsychological assessment using the Montreal Cognitive Assessment (MoCA) and the Consortium to Establish a Registry for Alzheimer’s Disease battery (CERAD). A control group of 58 age group-matched individuals without known cardiometabolic disease was included in comparative cognitive analyses. Results: Patients with AF and cardiometabolic comorbidities demonstrated early cognitive deficits, particularly in episodic memory and visuospatial functions, detectable even in individuals with normal MoCA scores, compared with the control group. However, no associations were observed between cognitive performance and conventional echocardiographic parameters in the group with AF. Conclusions: This study corroborated prior evidence of an association between cardiometabolic impairment and subtle cognitive impairment, but did not identify a specific contribution of echocardiography markers. More extensive and sensitive biomarkers of left atrial structure and function may be required to detect harmful associations with subtle cognitive impairment in middle-aged individuals. Further prospective studies, with a more balanced control for comorbidities, are warranted to clarify the clinical relevance of atrial structural remodeling in this context. Full article

Coffee is a very popular psychoactive beverage with a complex composition. Besides its stimulant effect due to caffeine, it contains several bioactive compounds with antioxidant properties and potent metabolic activity. Its clinical efficacy is fundamentally determined by the bioavailability and metabolic fate of its constituents. The bioactive components of coffee, such as polyphenols, melanoidins, phytosterols, biogenic amines, and carotenoids, have notable antioxidant, anti-inflammatory, and immunomodulatory effects. This review aims to present the main bioactive components of coffee, their biological effects, mechanisms of action, and the influence of preparation methods and individual variability on metabolic outcomes in common chronic diseases. The data are synthesized from clinical, prospective, and interventional studies to examine how processing variables and biological metabolism influence the health-promoting potential of coffee antioxidants. Brewing methods like hot filtration optimize the extraction of these antioxidants. Individual clinical outcomes are further modulated by genetic polymorphisms and gut microbiota variability, which influence the activation of the cellular Nrf2 antioxidant defense pathway. Full article

Background: Trace elements function as essential micronutrients involved in oxidative balance, mitochondrial activity, and cardiovascular metabolism. Cigarette smoking represents a significant source of toxic metals and may disrupt systemic trace element homeostasis. Alterations in micronutrient and metal balance may contribute to oxidative stress, endothelial dysfunction, and myocardial remodeling, which are central mechanisms in the pathogenesis of heart failure with preserved ejection fraction (HFpEF). This study aimed to investigate whether smokers with HFpEF exhibit distinct hair trace element profiles compared with smokers without HFpEF. Methods: In this prospective pilot study, scalp hair samples were collected from adults undergoing clinical evaluation for suspected cardiovascular disease. Trace element concentrations were determined using inductively coupled plasma mass spectrometry (ICP-MS). Participants were first stratified according to smoking status and subsequently, within the smoker subgroup, according to HFpEF diagnosis based on the Heart Failure Association Pre-test assessment, Echocardiography and natriuretic peptide score (HFA-PEFF) algorithm. Differences in trace element concentrations were analyzed using appropriate statistical tests, with multiple-comparison correction using the Benjamini–Hochberg false discovery rate (FDR). Active smoking was defined as ≥10 cigarettes per day for at least 1 year, and cumulative exposure was quantified in pack-years. Results: Fifty-eight participants were included, including 27 active smokers. In unadjusted analyses, several trace elements differed between smokers with HFpEF and those without HFpEF, including vanadium, lithium, aluminum, and copper. However, after FDR correction, only copper remained significantly elevated in smokers with HFpEF (q = 0.004). Hair copper concentrations were markedly higher in the HFpEF group compared with smokers without HFpEF. These differences were observed alongside echocardiographic features consistent with diastolic dysfunction and structural cardiac remodeling. Conclusions: In this hypothesis-generating pilot study, smokers with HFpEF demonstrated elevated hair copper concentrations, suggesting disturbances in trace element and micronutrient homeostasis. Altered copper metabolism may reflect oxidative stress-related cardiometabolic remodeling associated with HFpEF. These findings raise the hypothesis that cardiometabolic phenotype, rather than smoking exposure alone, may modulate trace element homeostasis in HFpEF; however, causal relationships cannot be established. Full article

Background: The purpose of this study was to compare the effects of two months of exergaming, conventional resistance exercise training, and no exercise on body composition and cardiometabolic risk factors in physically inactive older adults. Methods: For the preliminary study, twenty-four physically inactive adults aged 60–74 yrs. were allocated to an active video game training group (AVG n = 8), a conventional exercise group (CEG n = 7), or a non-exercising control group (CON n = 9). The AVG and CEG completed 24 supervised exercise training sessions over two months (three sessions per week) at self-selected, predominantly moderate-to-vigorous intensity, while the CON maintained usual daily activities. Body weight, skeletal muscle mass, body fat percentage, phase angle, and fasting blood biomarkers (glucose, total cholesterol, LDL, HDL, VLDL, and triglycerides) were assessed before and after the intervention. Results: No significant interactions were observed for body composition variables. Body weight decreased significantly following exercise training in both the AVG and CEG (p < 0.05). Significant interactions were found for total cholesterol (p = 0.001) and LDL cholesterol (p = 0.009). The AVG demonstrated significant reductions in fasting glucose, total cholesterol, and LDL cholesterol (p < 0.05), whereas the CEG showed a significant reduction only in total cholesterol. In contrast, the CON exhibited a significant increase in total cholesterol over the same period (p < 0.05). Conclusions: Two months of exergaming-based exercise training may lead to greater improvements in lipid-related cardiometabolic risk factors compared with conventional resistance exercise training in physically inactive older adults. These findings suggest that exergaming could be a promising exercise modality for supporting cardiometabolic health in aging populations. Full article

Bilirubin, historically recognized solely as a waste product of heme catabolism, has recently gained attention for its potential protective role in the cardiovascular system. Experimental and clinical studies suggest that bilirubin exhibits potent antioxidant, anti-inflammatory, anti-apoptotic, and cytoprotective properties that may protect the heart against oxidative stress, ischemia–reperfusion injury, and the progression of cardiovascular diseases, such as heart failure. As an endogenous hormone, bilirubin activates peroxisome proliferator-activated receptor-α (PPARα), a nuclear receptor that controls energy balance and lipid metabolism. Moderately elevated circulating bilirubin levels have been associated with a reduced risk of coronary artery disease, heart failure, and myocardial infarction; however, the mechanisms underlying bilirubin’s protective effects remain incompletely understood. Conversely, the gut microbiota’s metabolism of bilirubin to urobilin is detrimental, given urobilin’s association with cardiometabolic dysfunction. The therapeutic potential of bilirubin in the management of cardiovascular disease is becoming increasingly apparent, supported by preclinical research and emerging technologies that enhance bilirubin delivery via nanoparticles and methods to elevate plasma bilirubin levels. Collectively, these scientific advancements position bilirubin as a promising, biologically plausible endogenous therapeutic for the prevention and treatment of heart disease. Full article

Background: Migration from low- and middle-income to high-income settings is often accompanied by dietary and lifestyle changes that may increase long-term risk of non-communicable diseases. African migrants represent a growing but under-studied population in Australia, with limited evidence on post-migration nutrition transitions and associated chronic disease risk. This study examined changes in diet and lifestyle among Nigerian-born adults before and after migration to Australia and explored any association with chronic diseases. Methods: A pilot cross-sectional study was conducted among adults who migrated from Nigeria to New South Wales, Australia, between 1992 and 2019. Data were collected via a culturally adapted, self-administered online questionnaire assessing socio-demographic characteristics, dietary intake, lifestyle behaviours, and self-reported chronic conditions in the 12 months immediately before and after migration. Descriptive statistics (frequencies and proportions) and inferential analyses (Chi-square tests, McNemar test, and the Bowker test) were used to compare pre- and post-migration behaviours and examine associations with chronic disease outcomes. Results: Ninety-three participants completed the survey (mean age 37.0 ± 7.2 years; 50.5% male). Post-migration, regular breakfast consumption declined (−24.3%), while irregular eating (low and moderate) patterns increased (+7.6% and +16.7%). Regular vegetable intake improved (+5.4%), whereas fruit intake remained low (13.0%). Regular consumption of Nigerian local foods decreased markedly (−53.7%), while regular intake of meat (+18.5%), dairy foods, fats (+14.3%), and non-alcoholic beverages increased (+22.8%). Salt use shifted away from the highest-risk category (−22.2%), and smoking and alcohol consumption remained low and stable. Self-reported chronic conditions were uncommon; hypertension (6.5%) and obesity (5.4%) were the most frequently reported. Conclusions: Nigerian migrants in Australia experience substantial post-migration dietary and lifestyle transitions that may elevate long-term chronic disease risk despite a currently low reported disease burden. Early, culturally responsive nutrition and lifestyle interventions are needed to support healthy adaptation and prevent the progression of cardiometabolic conditions in this growing migrant population. 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

Background: Obesity represents a major public health challenge worldwide and contributes substantially to the burden of type 2 diabetes and hypertension. While body mass index (BMI) is widely used in clinical practice, indices reflecting central adiposity may provide additional prognostic value. This study aimed to assess the prevalence of general and central obesity in an adult population across different age groups from Stara Zagora, Bulgaria, and to examine their associations with cardiometabolic outcomes and lifestyle factors. Methods: A quasi-representative cross-sectional study was conducted among 3512 adults (mean age 53.7 ± 14.9 years). Anthropometric indices, including BMI, waist circumference, waist-to-hip ratio, and waist-to-height ratio were measured. Cardiometabolic outcomes included diabetes, hypertension, and their combined presence. Multicollinearity was assessed using the Variance Inflation Factor (VIF), and the discriminatory ability of indices was evaluated using Receiver Operating Characteristic (ROC) analysis and DeLong’s test. Results: The prevalence of overweight/obesity (BMI ≥25) was 68.4%, while central obesity (WHtR ≥0.5) affected 66.9% of participants. BMI demonstrated the highest discriminatory ability in this dataset for hypertension (AUC = 0.852) and diabetes (AUC = 0.796), significantly outperforming WC and WHR (p < 0.05). However, 24.4% of individuals with normal BMI exhibited high-risk central adiposity. Significant sex-specific differences were observed: short sleep duration (<6 h) was a strong predictor of obesity in women (aOR = 2.98), whereas smoking showed stronger associations in men. Age-stratified analyses revealed that while BMI stabilizes in the oldest age group (75–89 years), WHtR continues to increase, reflecting age-related redistribution of visceral fat. A strong protective effect of physical activity was observed, supported by quasi-complete separation in active subgroups. Conclusions: General and central obesity represent a substantial health burden in this urban population. While BMI remains a robust screening tool, the integration of WHtR enhances the identification of “hidden” cardiometabolic risk particularly in older adults and individuals with normal BMI. Given the quasi-representative nature of the sample, these findings are primarily generalizable to similar urban populations and may inform targeted regional public health strategies. Full article

Background/Objectives: This secondary and exploratory meta-analysis re-evaluated 30 randomized controlled trials on free and added sugars (FS) detailed in the European Food Safety Authority’s (EFSA) report on the tolerable upper intake level for dietary sugars, focusing on the influence of food source (beverages, foods, or mixed) on cardiometabolic and anthropometric health. Methods: The EFSA’s method of analyzing the relative FS intake (difference between treatment and comparator arms, Δ%E^fs) was used, with further adjustment for the reported intake of all sources of FS and energy. The EFSA’s “high vs. low” random-effects meta-analysis comparing groups with the highest and lowest FS intake was replicated, and additional exploratory dose–response meta-regressions (linear and non-linear) were performed, stratified by food source. Given the secondary and observational nature of the analysis, all source-stratified findings should be interpreted as hypothesis-generating, rather than causal. Results: There were no interactions between Δ%E^fs and food source for any outcome, and within a source there were linearly positive and statistically significant regressions for body weight (mixed), low-density lipoprotein cholesterol (LDL-C, foods), and uric acid (beverages). Across 13 outcomes, Δ%E^fs was positively and linearly related to greater fasting glucose, high-density lipoprotein cholesterol (HDL-C), and LDL-C, and non-linearly to body weight. However, the data were limited in their representation of FS intake at typical population levels, and there were insufficient data to investigate the effect of FS from foods on most anthropometric outcomes. Conclusions: Meta-regressive dose–responses revealed little relationship between Δ%E^fs from specific food sources and health outcomes, but such effects might be masked by confounding factors. Future trials that test realistic intakes of FS across diverse food matrices and account for dietary compensation would help to overcome limitations in the body of evidence. Full article

Background: Testosterone is the most abundant biologically active sex steroid in women, yet the therapeutic implications of its age-related decline remain undercharacterized. Published trials have focused predominantly on sexual function, leaving gaps in understanding how testosterone replacement therapy (TRT) affects broader symptom domains and metabolic biomarkers in women. Objective: To investigate whether individualized, biomarker-guided TRT in women is associated with improvements across multiple symptom domains and favorable hormonal, hematologic, and cardiometabolic biomarker changes, and to examine whether symptomatic benefit varies with treatment duration. Methods: In this retrospective observational study, women (n = 332; ages 27 to 78; mean 45.7 ± 7.1 years) receiving TRT as part of routine clinical care through a telehealth-based platform completed a structured survey at a single post-treatment time point assessing eight symptom domains: energy/fatigue, memory, concentration, irritability, depression, anhedonia, sexual interest, and relationship satisfaction. Respondents were stratified by TRT duration (1 month to >12 months) and a subset (n = 120) underwent paired biomarker assessment at baseline and 12 weeks for total testosterone, free testosterone, SHBG, hemoglobin, and triglycerides. Results: Improvement was reported across all eight domains, with energy/fatigue showing the strongest response (84.3% improved). Depression, irritability, anhedonia, and sexual interest each exceeded 65% improvement. Cognitive domains showed a delayed trajectory, with meaningful gains emerging at 4 to 6 months. Quality of life improvement was reported by 89.7%, with significant improvement rising from 5.4% at 1 month to 51.5% at greater than 12 months. Energy/fatigue (64.2%) and mood (49.7%) ranked above sexual desire (41.3%) as self-identified areas of greatest benefit. All five biomarkers changed favorably: total testosterone +151.8% (d = 3.60), free testosterone +216.7% (d = 3.01), hemoglobin +5.5% (d = 2.03), SHBG −13.3% (d = 1.57), and triglycerides −12.6% (d = 1.28). Conclusions: Individualized TRT in women was associated with broad symptomatic improvement spanning energy/fatigue, depression, irritability, anhedonia, cognitive function, and sexual interest, with duration-dependent gains and favorable biomarker changes across all five markers assessed. These findings suggest that the value of testosterone in women extends beyond sexual function and supports the need for larger controlled trials with extended follow-up. Full article

Background/Objectives: Candidates with cardiometabolic risk are considered for living kidney donation more frequently because of the global organ shortage. The 2017 Kidney Disease: Improving Global Outcomes (KDIGO) guidelines introduced individualized risk assessment based on composite donor profiles rather than categorical exclusion, but the long-term implications of accepting donors with potential risk factors require careful evaluation. This review synthesizes current evidence on outcomes of living kidney donors with obesity, prediabetes, hypertension, and smoking. Methods: A literature search was conducted in PubMed/MEDLINE for studies published between 1 January 2000 and 28 February 2026, including cohort studies, registry analyses, meta-analyses, and clinical guidelines evaluating living kidney donors with obesity, smoking, prediabetes, or hypertension. Priority was given to large cohorts with long-term follow-up. Over 70 publications were included in the final synthesis. Findings were synthesized narratively by risk factors and outcomes. Results: Obesity was associated with an 86% increased end-stage kidney disease (ESKD) risk and 32% increased 20-year mortality. Central adiposity measures outperformed body mass index (BMI) for predicting estimated glomerular filtration rate (eGFR) decline. Post-donation weight gain increased the risk for developing hypertension and diabetes. Smoking conferred a 7.5-fold chronic kidney disease (CKD) risk, with impaired compensatory renal adaptation after donation. Prediabetic donors showed comparable outcomes to normoglycemic donors, with 57.8% reverting to normoglycemia at 10 years. Pre-donation hypertension increased 15-year ESKD risk 3-fold, but absolute risk remained low. At 15 years post-donation, over 50% of the donors developed hypertension. Glucagon-like peptide-1 (GLP-1) receptor agonists reduce diabetes progression by 73–94% in at-risk populations, but prospective studies in donors are lacking. Conclusions: Each risk factor carries quantifiable risks for individualized stratification. These risk factors usually coexist and interact. Refinement of risk prediction models, strategies for metabolic optimization and prospective evaluation of emerging pharmacologic therapies are key priorities. Full article