9 research outputs found
A machine-learning based bio-psycho-social model for the prediction of non-obstructive and obstructive coronary artery disease
Background: Mechanisms of myocardial ischemia in obstructive and non-obstructive coronary artery disease (CAD), and the interplay between clinical, functional, biological and psycho-social features, are still far to be fully elucidated. Objectives: To develop a machine-learning (ML) model for the supervised prediction of obstructive versus non-obstructive CAD. Methods: From the EVA study, we analysed adults hospitalized for IHD undergoing conventional coronary angiography (CCA). Non-obstructive CAD was defined by a stenosis < 50% in one or more vessels. Baseline clinical and psycho-socio-cultural characteristics were used for computing a Rockwood and Mitnitski frailty index, and a gender score according to GENESIS-PRAXY methodology. Serum concentration of inflammatory cytokines was measured with a multiplex flow cytometry assay. Through an XGBoost classifier combined with an explainable artificial intelligence tool (SHAP), we identified the most influential features in discriminating obstructive versus non-obstructive CAD. Results: Among the overall EVA cohort (n = 509), 311 individuals (mean age 67 ± 11 years, 38% females; 67% obstructive CAD) with complete data were analysed. The ML-based model (83% accuracy and 87% precision) showed that while obstructive CAD was associated with higher frailty index, older age and a cytokine signature characterized by IL-1β, IL-12p70 and IL-33, non-obstructive CAD was associated with a higher gender score (i.e., social characteristics traditionally ascribed to women) and with a cytokine signature characterized by IL-18, IL-8, IL-23. Conclusions: Integrating clinical, biological, and psycho-social features, we have optimized a sex- and gender-unbiased model that discriminates obstructive and non-obstructive CAD. Further mechanistic studies will shed light on the biological plausibility of these associations. Clinical trial registration: NCT02737982
The Sex-Specific Detrimental Effect of Diabetes and Gender-Related Factors on Pre-admission Medication Adherence Among Patients Hospitalized for Ischemic Heart Disease: Insights From EVA Study
Background: Sex and gender-related factors have been under-investigated as relevant determinants of health outcomes across non-communicable chronic diseases. Poor medication adherence results in adverse clinical outcomes and sex differences have been reported among patients at high cardiovascular risk, such as diabetics. The effect of diabetes and gender-related factors on medication adherence among women and men at high risk for ischemic heart disease (IHD) has not yet been fully investigated.Aim: To explore the role of sex, gender-related factors, and diabetes in pre-admission medication adherence among patients hospitalized for IHD.Materials and Methods: Data were obtained from the Endocrine Vascular disease Approach (EVA) (ClinicalTrials.gov Identifier: NCT02737982), a prospective cohort of patients admitted for IHD. We selected patients with baseline information regarding the presence of diabetes, cardiovascular risk factors, and gender-related variables (i.e., gender identity, gender role, gender relations, institutionalized gender). Our primary outcome was the proportion of pre-admission medication adherence defined through a self-reported questionnaire. We performed a sex-stratified analysis of clinical and gender-related factors associated with pre-admission medication adherence.Results: Two-hundred eighty patients admitted for IHD (35% women, mean age 70), were included. Around one-fourth of the patients were low-adherent to therapy before hospitalization, regardless of sex. Low-adherent patients were more likely diabetic (40%) and employed (40%). Sex-stratified analysis showed that low-adherent men were more likely to be employed (58 vs. 33%) and not primary earners (73 vs. 54%), with more masculine traits of personality, as compared with medium-high adherent men. Interestingly, women reporting medication low-adherence were similar for clinical and gender-related factors to those with medium-high adherence, except for diabetes (42 vs. 20%, p = 0.004). In a multivariate adjusted model only employed status was associated with poor medication adherence (OR 0.55, 95%CI 0.31–0.97). However, in the sex-stratified analysis, diabetes was independently associated with medication adherence only in women (OR 0.36; 95%CI 0.13–0.96), whereas a higher masculine BSRI was the only factor associated with medication adherence in men (OR 0.59, 95%CI 0.35–0.99).Conclusion: Pre-admission medication adherence is common in patients hospitalized for IHD, regardless of sex. However, patient-related factors such as diabetes, employment, and personality traits are associated with adherence in a sex-specific manner
Epicardial fat inflammation response to COVID‐19 therapies
OBJECTIVE: Adipose tissue plays a role in the novel coronavirus disease 2019 (COVID‐19). Epicardial adipose tissue (EAT), a unique visceral fat, presents with high degree of inflammation in severe COVID‐19 disease. Whether and how adipose tissue may respond to the COVID‐19 therapies is unknown. METHODS: We retrospectively analyzed the difference in computed tomography (CT) measured EAT and subcutaneous (SAT) attenuation, defined as mean attenuation expressed in Hounsfield units (HU), in 72 patients [mean±SD age was 59.6±12.4 years, 50 (69%) were men] at the hospital admission for COVID‐19 and 99 days [IQR (71‐129)] after discharge. RESULTS: At the admission, EAT HU was significantly correlated with blood glucose levels, interleukin 6 , troponin T levels and waist circumference. EAT HU decreased from ‐87.21±16.18 to ‐100.0±11 (p<0.001) whereas SAT HU did not change (‐110.21±12.1 to ‐111.11±27.82, p=0.78) after therapy. Changes in EAT HU (expressed as ∆) significantly correlated with dexamethasone therapy (r= ‐ 0.46, p= 0.006), and when dexamethasone was combined with tocilizumab (r= ‐0.24, p=0.04). CONCLUSIONS: Dexamethasone therapy was associated with significant reduction of EAT inflammation in COVID‐19 patients, whereas SAT showed no changes. Anti‐inflammatory therapies targeting visceral fat may be helpful in COVID‐19 diseases
Recommended from our members
Abdominal obesity phenotype is associated with COVID-19 chest X-ray severity score better than BMI-based obesity
Chest X-ray (CXR) severity score and BMI-based obesity are predictive risk factors for COVID-19 hospital admission. However, the relationship between abdominal obesity and CXR severity score has not yet been fully explored.
This retrospective cohort study analyzed the association of different adiposity indexes, including waist circumference and body mass index (BMI), with CXR severity score in 215 hospitalized patients with COVID-19.
Patients with abdominal obesity showed significantly higher CXR severity scores and had higher rates of CXR severity scores ≥ 8 compared to those without abdominal obesity (P < 0.001; P = 0.001, respectively). By contrast, patients with normal weight, with overweight and those with BMI-based obesity showed no significant differences in either CXR severity scores or in the rates of CXR severity scores ≥ 8 (P = 0.104; P = 0.271, respectively). Waist circumference and waist-to-height ratio (WHtR) correlated more closely with CXR severity scores than BMI (r = 0.43, P < 0.001; r = 0.41, P < 0.001; r = 0.17, P = 0.012, respectively). The area under the curves (AUCs) for waist circumference and WHtR were significantly higher than that for BMI in identifying a high CXR severity score (≥ 8) (0.68 [0.60-0.75] and 0.67 [0.60-0.74] vs 0.58 [0.51-0.66], P = 0.001). A multivariate analysis indicated abdominal obesity (risk ratio: 1.75, 95% CI: 1.25-2.45, P < 0.001), bronchial asthma (risk ratio: 1.73, 95% CI: 1.07-2.81, P = 0.026) and oxygen saturation at admission (risk ratio: 0.96, 95% CI: 0.94-0.97, P < 0.001) as the only independent factors associated with high CXR severity scores.
Abdominal obesity phenotype is associated with a high CXR severity score better than BMI-based obesity in hospitalized patients with COVID-19. Therefore, when visiting the patient in a hospital setting, waist circumference should be measured, and patients with abdominal obesity should be monitored closely. Level of evidence Cross-sectional descriptive study, Level V
Recommended from our members
Corrigendum to “Tri-Ponderal Mass Index vs body Mass Index in discriminating central obesity and hypertension in adolescents with overweight” [Nutrition, metabolism and cardiovascular diseases 31 (2021) 1613–1621]
Recommended from our members
Human Epicardial Adipose Tissue Expresses Glucose-dependent Insulinotropic Polypeptide, Glucagon and Glucagon-Like Peptide 1 Receptors as Potential Targets of Pleiotropic Therapies
Human Epicardial Adipose Tissue (EAT) plays a crucial role in the development and progression of coronary artery disease, atrial fibrillation and heart failure. Microscopically, EAT is composed of adipocytes, nerve tissues, inflammatory, stromovascular and immune cells. EAT is a white adipose tissue, albeit it also has brown-fat like or beige fat features. No muscle fascia divides EAT and myocardium; this allows a direct interaction and cross talk between the epicardial fat and the myocardium. Thus, it might be a therapeutic target for pharmaceutical compounds acting on G-Protein-Coupled Receptors, such as those for Glucose-dependent Insulinotropic Polypeptide (GIP), Glucagon (GCG) and Glucagon-Like Peptide-1 (GLP-1), whose selective stimulation with innovative drugs has demonstrated beneficial cardiovascular effects. The precise mechanism of these novel drugs and their tissue and cellular target(s) need to be better understood.
We evaluate whether human EAT expresses GIP, GCG and GLP-1 receptors and whether their presence is related to EAT transcriptome. We also investigated protein expression and cell type localization specifically for GIPR and GCGR.
EAT samples were collected from 33 patients affected by cardiovascular diseases undergoing open heart surgery (90.9% males, age 67.2±10.5 years mean ± SD). Microarray and immunohistochemistry analysis were performed.
Microarray analysis showed that GIPR and GCGR messenger Ribonucleic Acids (mRNAs) are expressed in EAT, beyond confirming the previously found GLP-1(3776±1377 arbitrary unit (A.U.), 17.77±14.91 A.U., and 3.41±2.27 A.U., respectively). The immunohistochemical analysis consistently indicates that GIPR and GCGR are expressed in EAT, mainly in macrophages, isolated and in crown-like structures. In contrast, only some mature adipocytes of different sizes showed cytoplasmic immunostaining, similar to endothelial cells and pericytes in the capillaries and pre-capillary vascular structures. Notably, EAT GIPR is statistically associated with the low expression of genes involved in Free Fatty Acid (FFA) oxidation and transport and those promoting FFA biosynthesis and adipogenesis (p<0.01). EAT GCGR, in turn, is related to genes involved in FFA transport, mitochondrial fatty acid oxidation, and white-to-brown adipocyte differentiation, in addition to genes involved in the reduction of fatty acid biosynthesis and adipogenesis (p<0.01).
Having reported the expression of the GLP-1 receptor previously, here, we showed that GIPR and GCGR similarly present at mRNA and protein levels in human EAT, particularly in macrophages and partially adipocytes, suggesting these G-protein-coupled receptors as pharmacological targets on the ongoing innovative drugs, which seem cardiometabolically healthy well beyond their effects on glucose and body weight.
Recommended from our members
Antibody responses to BNT162b2 mRNA vaccine: Infection-naive individuals with abdominal obesity warrant attention
Objective The excess of visceral adipose tissue might hinder and delay immune response. How people with abdominal obesity (AO) will respond to mRNA vaccines against SARS-CoV-2 is yet to be established. SARS-CoV-2-specific antibody responses were evaluated after the first and second dose of the BNT162b2 mRNA vaccine, comparing the response of individuals with AO with the response of those without, and discerning between individuals with or without prior infection. Methods Immunoglobulin G (IgG)-neutralizing antibodies against the Trimeric complex (IgG-TrimericS) were measured at four time points: at baseline, at day 21 after vaccine dose 1, and at 1 and 3 months after dose 2. Nucleocapsid antibodies were assessed to detect prior SARS-CoV-2 infection. Waist circumference was measured to determine AO. Results Between the first and third month after vaccine dose 2, the drop in IgG-TrimericS levels was more remarkable in individuals with AO compared with those without AO (2.44-fold [95% CI: 2.22-2.63] vs. 1.82-fold [95% CI: 1.69-1.92], respectively, p < 0.001). Multivariable linear regression confirmed this result after inclusion of assessed confounders (p < 0.001). Conclusions The waning antibody levels in individuals with AO may further support recent recommendations to offer booster vaccines to adults with high-risk medical conditions, including obesity, and particularly to those with a more prevalent AO phenotype