Cardiovascular Markers Research Articles

Whole-Body Magnetic Resonance Imaging Assessment of the Contributions of Adipose and Nonadipose Tissues to Cardiovascular Remodeling in Adolescents.

Background Greater body mass index is associated with cardiovascular remodeling in adolescents. However, body mass index cannot differentiate between adipose and nonadipose tissues. We examined how visceral and subcutaneous adipose tissue are linked with markers of early cardiovascular remodeling, independently from nonadipose tissue. Methods and Results Whole-body magnetic resonance imaging was done in 82 adolescents (39 overweight/obese; 36 female; median age, 16.3 [interquartile range, 14.4-18.1] years) to measure body composition and cardiovascular remodeling markers. Left ventricular diastolic function was assessed by echocardiography. Waist, waist:height ratio, and body mass index z scores were calculated. Residualized nonadipose tissue, subcutaneous adipose tissue, and visceral adipose tissue variables, uncorrelated with each other, were constructed using partial regression modeling to allow comparison of their individual contributions in a 3-compartment body composition model. Cardiovascular variables mostly related to nonadipose rather than adipose tissue. Nonadipose tissue was correlated positively with left ventricular mass (r=0.81), end-diastolic volume (r=0.70), stroke volume (r=0.64), left ventricular mass:end-diastolic volume (r=0.37), and systolic blood pressure (r=0.35), and negatively with heart rate (r=-0.33) (all P<0.01). Subcutaneous adipose tissue was associated with worse left ventricular diastolic function (r=-0.42 to -0.48, P=0.0007-0.02) and higher heart rates (r=0.34, P=0.007) but linked with better systemic vascular resistance (r=-0.35, P=0.006). There were no significant relationships with visceral adipose tissue and no associations of any compartment with pulse wave velocity. Conclusions Simple anthropometry does not reflect independent effects of nonadipose tissue and subcutaneous adipose tissue on the adolescent cardiovascular system. This could result in normal cardiovascular adaptations to growth being misinterpreted as pathological sequelae of excess adiposity in studies reliant on such measures.

Association of Selected Cardiovascular Markers With Tuberculosis: Community-Based Exploratory Cross-Sectional Analytical Study in Puducherry.

Introduction India accounts for one-fourth of the global tuberculosis (TB) burden and also faces a rising burden of non-communicable diseases. Only a few have studied the association between the infective pathogenesis of TB and cardiovascular diseases (CVD). Methods A cross-sectional exploratory analytical design was used to compare CVD risk factors and immunological and radiological parameters. This was a pilot study conducted in two primary health centers in urban Puducherry between February 2020 and March 2021. Household contacts (HHC) were either spouses or siblings of the newly diagnosedpulmonary tuberculosis (PTB) patients selected for comparison as their exposure to infection would be similar to those who were diseased yet did not develop illness. Assuming a difference of 5% in CVD risk between the general population and TB patients, with a 95% confidence interval, the sample size calculated was 153 in each group by nMaster v2.0. Considering the feasibility and resource constrain, we recruited 50 newly diagnosed PTBpatients, their age- and gender-matched 50 HHCand 50 PTB patients who completed treatment a year before.CVD risk factors were compared using chi-square or Fisher exact test. Interleukins-6 (IL-6), interferon-gamma (INF-γ), highly specific - C reactive protein (hs-CRP), and carotid intima-media thickness (CIMT) were compared using ANOVA or Kruskal-Wallis test. Results Most participants from each group belonged to lower socio-economic strata and were males (40/50). Alcohol intake was higher among newly diagnosed and treatment-completed PTB patients (82.5% vs 72.5%). Excess salt intake (58%) was present more in newly diagnosed PTB patients. General and abdominal obesity were seen more among HHC (64% and 84%) and treatment-completed PTBpatients (50% and 74%). IL-6 was higher in newly diagnosed PTB patients, whereas INF-γ and hs-CRP were higher in treatment-completed PTB patients. The largest proportion of those having high CIMT values was also in the treatment-completed PTB patients. Conclusion Levels of immune markers hint at the role of inflammation due to TB disease being related to the high CIMT values among the newly diagnosed and treatment-completed PTB patients. CVD risk was higher among TB patients even if they had completed treatment and were declared cured.

Early echocardiographic signs of cardiovascular affection in pediatric familial hypercholesterolemia

Familial hypercholesterolemia (FH) is a rare autosomal dominant genetic disorder caused by defective low-density lipoprotein (LDL) receptors or abnormal apolipoprotein B. FH raises the risk of premature atherosclerotic disease and cardiovascular death in young adults. However, cardiovascular affection in children needs to be more adequately studied. Our study aimed to evaluate the effect of hypercholesterolemia on the cardiovascular system of pediatric patients with homozygous FH using conventional and advanced echocardiographic parameters such as tissue Doppler imaging (TDI) and 2-dimensional speckle-tracking echocardiography (2D-STE). This case-control study matched 25 healthy children with 21 patients with homozygous FH. Both groups had conventional echocardiography, TDI, and 2D-STE. Myocardial velocities of the left and right ventricles, left ventricular strain, and aortic stiffness parameters were measured. The FH group had greater systolic blood pressure, dilated coronary arteries, and hypertrophied left ventricle (LV) compared to the control (P = 0.0001, P = 0.001, P = 0.01, respectively). The mitral E/E′ ratio was higher in the patient group than in the control group (P = 0.007), indicating LV diastolic dysfunction in patients. At the same time, LV systolic function evaluated by 2D-STE was comparable to that in the control group. The abdominal aorta circumferential strain and ascending aorta M-mode-derived strain were significantly lower in patients compared to those in the control (P = 0.024, P = 0.0001, respectively), indicating increased aortic stiffness in the patients’ group; moreover, 85.7% of patients had mild aortic insufficiency. Conclusion: Mild aortic insufficiency, coronary artery dilatation, left ventricular (LV) diastolic dysfunction, and increased aortic stiffness are among early cardiovascular markers in pediatric patients with homozygous FH before impaired LV systolic function.What is Known:• Familial hypercholesterolemia (FH) in adults is associated with accelerated atherosclerosis, aortic valvopathy, dilated coronary arteries, ischemic heart disease, and premature cardiovascular death.• The cardiovascular effects of FH in children require additional research.What is New:• Pediatric patients with familial hypercholesterolemia tend to have an early affection for left ventricular diastolic function before the affection for the systolic function.• The diastolic dysfunction associated with pediatric FH is correlated to the aortic stiffness and low-density lipoprotein levels.

Explainable machine-learning algorithms to differentiate bipolar disorder from major depressive disorder using self-reported symptoms, vital signs, and blood-based markers

Background and objectiveCaused by shared genetic risk factors and similar neuropsychological symptoms, bipolar disorder (BD) and major depressive disorder (MDD) are at high risk of misdiagnosis, which is associated with ineffective treatment and worsening of outcomes. We aimed to develop a machine learning (ML)-based diagnostic system, based on electronic medical records (EMR) data, to mimic the clinical reasoning of human physicians to differentiate MDD and BD (especially BD depressive episodes) patients about to be admitted to a hospital and, hence, reduce the misdiagnosis of BD as MDD on admission. In addition, we examined to what extent our ML model could be made interpretable by quantifying and visualizing the features that drive the predictions. MethodsBy identifying 16,311 patients admitted to a hospital located in western China between 2009 and 2018 with a recorded main diagnosis of MDD or BD, we established three sub-cohorts with different combinations of features for both the MDD-BD cohort and the MDD-BD depressive episodes cohort, respectively. Four different ML algorithms (logistic regression, extreme gradient boosting (XGBoost), random forest, and support vector machine) and four train-test splits were used to train and validate diagnostic models, and explainable methods (SHAP and Break Down) were utilized to analyze the contribution of each of the features at both population-level and individual-level, including feature importance, feature interaction, and feature effect on prediction decision for a specific subject. ResultsThe XGBoost algorithm provided the best test performance (AUC: 0.838 (0.810–0.867), PPV: 0.810 and NPV: 0.834) for separating patients with BD from those with MDD. Core predictors included symptoms (mood-up, exciting, bad sleep, loss of interest, talking, mood-down, provoke), along with age, job, myocardial enzyme markers (creatine kinase, hydroxybutyrate dehydrogenase), diabetes-associated marker (glucose), bone function marker (alkaline phosphatase), non-enzymatic antioxidant (uric acid), markers of immune/inflammation (white blood cell count, lymphocyte count, basophil percentage, monocyte count), cardiovascular function marker (low density lipoprotein), renal marker (total protein), liver biochemistry marker (indirect bilirubin), and vital signs like pulse. For separating patients with BD depressive episodes from those with MDD, the test AUC was 0.777 (0.732–0.822), with PPV 0.576 and NPV 0.899. Additional validation in models built with self-reported symptoms removed from the feature set, showed test AUC of 0.701 (0.666–0.736) for differentiating BD and MDD, and AUC of 0.564 (0.515–0.614) for detecting patients in BD depressive episodes from MDD patients. Validation in the datasets without removing the patients with comorbidity showed an AUC of 0.826 (0.806–0.846). ConclusionThe diagnostic system accurately identified patients with BD in various clinical scenarios, and differences in patterns of peripheral markers between BD and MDD could enrich our understanding of potential underlying pathophysiological mechanisms of them.

The role of TLR2 in exercise-induced immunomodulation in normal weight individuals

Toll-like receptors (TLRs) have been targeted for therapeutic drug development for several disorders, including cardiovascular diseases (CVD), and diabetes mellitus. Daily levels physical activity (PA) has been purported to influence the systemic circulation of cytokines, affecting the overall activation of TLRs and influencing the inflammatory milieu. Objective and self-reported daily PA was tracked in 69 normal-weight adults. Freedson's cut-offs categorized daily PA intensity into the 25th lowest, medium, and top percentiles. Monocytic TLR2 expression was quantified by flow cytometry in fresh whole blood. Cross-sectional associations between flow cytometry measured TLR2+ subsets and clinical biomarkers were evaluated. PA increased circulation of TLR2+ monocytes. TLR2 expression was adversely corelated with reduced diastolic blood pressure (DBP), triglyceride (TG), and matrix metallopeptidase 9 (MMP9) levels. However, regression analysis indicated that only TG levels were independently linked with TLR2+ subsets in circulation in active participants. Higher daily levels of physical activity are associated with improved cardiovascular blood markers and elevated circulatory monocytic TLR2+ subsets. These findings suggest that TLR2 may play a role in modulating CVD risk factors in individuals leading physically active lifestyles.

Hypertensive Disorders of Pregnancy and Long-Term Maternal Cardiovascular and Metabolic Biomarkers.

This study aimed to measure the association between hypertensive disorders of pregnancy (HDP) and long-term maternal metabolic and cardiovascular biomarkers. Follow-up study of patients who completed glucose tolerance testing 5 to 10 years after enrollment in a mild gestational diabetes mellitus (GDM) treatment trial or concurrent non-GDM cohort. Maternal serum insulin concentrations and cardiovascular markers VCAM-1, VEGF, CD40L, GDF-15, and ST-2 were measured, and insulinogenic index (IGI, pancreatic β-cell function) and 1/ homeostatic model assessment (insulin resistance) were calculated. Biomarkers were compared by presence of HDP (gestational hypertension or preeclampsia) during pregnancy. Multivariable linear regression estimated the association of HDP with biomarkers, adjusting for GDM, baseline body mass index (BMI), and years since pregnancy. Of 642 patients, 66 (10%) had HDP: 42 with gestational hypertension and 24 with preeclampsia. Patients with HDP had higher baseline and follow-up BMI, higher baseline blood pressure, and more chronic hypertension at follow-up. HDP was not associated with metabolic or cardiovascular biomarkers at follow-up. However, when HDP type was evaluated, patients with preeclampsia had lower GDF-15 levels (oxidative stress/cardiac ischemia), compared with patients without HDP (adjusted mean difference: -0.24, 95% confidence interval: -0.44, -0.03). There were no differences between gestational hypertension and no HDP. In this cohort, metabolic and cardiovascular biomarkers 5 to 10 years after pregnancies did not differ by HDP. Patients with preeclampsia may have less oxidative stress/cardiac ischemia postpartum; however, this may have been observed due to chance alone given multiple comparisons. Longitudinal studies are needed to define the impact of HDP during pregnancy and interventions postpartum. · Hypertensive disorders of pregnancy were not associated with metabolic dysfunction.. · Cardiovascular dysfunction was not consistently seen after pregnancy hypertension.. · Longitudinal studies with postpartum interventions after preeclampsia are needed..

Chemerin as a cardiovascular biological marker: Present and future

Cardiovascular diseases are the leading cause of invalidity and mortality in the majority of developed countries and are recognized by the international community as a pandemic problem. An important task of modern cardiology is the search and study of new biological markers. This literature review aimed to consider chemerin as a new diagnostic and prognostic marker for cardiovascular pathologies. Thus far, studies on chemerin indicate the possibility of its use as a marker of cardiovascular pathology. Evidence points to the important role of chemerin in the development and progression of cardiovascular diseases. As an adipokine, chemerin modulates glucose, and lipid levels, thereby influencing lipid deposition in the endothelium and progression of atherosclerosis. As a chemoattractant, it facilitates the mobilization and interaction of macrophages with dendritic cells and natural killer cells in the vascular system and induces endothelial angiogenesis. The established role of chemerin in vascular inflammation, angiogenesis, and blood pressure modulation opens serious prospects for the development of therapeutics targeting this biomarker for the treatment of cardiovascular diseases. Several candidates targeting chemerin and the CMRK1 signaling pathway have shown promising potential in reducing vascular dysfunction in in vitro and in vivo studies. Further studies analyzing the efficacy and safety of new chemerin-targeting drugs are needed to assess their potential.

426-P: Semaglutide, Empagliflozin, and Cagrilintide Reduce Levels of Serum Endotrophin in Type 2 Diabetic Rats

Background: Glucagon-like peptide 1 receptor agonists (GLP-1 RAs) and sodium-glucose co-transporter-2 inhibitors (SGLT2i) demonstrated cardiovascular (CV) and kidney outcomes benefit in persons with type 2 diabetes (T2D). The long-acting amylin analogue, cagrilintide, is under investigation for the treatment of obesity and T2D. Endotrophin, a pro-fibrotic fragment derived from collagen type VI, is an independent risk marker of mortality, CV and kidney outcomes, and dulaglutide treatment decreased levels of this biomarker compared with insulin glargine in persons with T2D. We investigated for the first time the effect of semaglutide, empagliflozin, and cagrilintide on endotrophin in type 2 diabetic rats. Method: We measured endotrophin (by the rodent PRO-C6 ELISA) in serum collected at baseline and study end from diabetic ZDF rats treated with either vehicle (n = 10), semaglutide (n = 7), empagliflozin (n = 4), or cagrilintide (n = 10). The dose chosen for semaglutide (50 nmol/kg), empagliflozin (30 mg/kg), and cagrilintide (10 nmol/kg) was based on previous research. Results: Levels of endotrophin increased significantly during the study in vehicle-treated rats, reflecting the disease progression (median [95% CI] for increase: 182.5 [55.87-298.0], P &amp;lt; 0.01). Interestingly, treatment with semaglutide, empagliflozin, and cagrilintide each attenuated this increase, resulting in significantly lower levels of endotrophin compared to vehicle at study end (P &amp;lt; 0.01), (P &amp;lt; 0.05), and (P &amp;lt; 0.01), respectively. Conclusion: We developed a novel, robust assay to detect the clinically relevant endotrophin biomarker in rodents. Levels of serum endotrophin increased over time in vehicle-treated rats, which is in line with endotrophin predicting disease progression in persons with T2D. In addition to the beneficial effects on metabolic factors, semaglutide, empagliflozin, and cagrilintide each reduced levels of endotrophin, suggesting a potential effect to reduce fibrosis. Disclosure A.Møller: None. S.A.Melander: None. A.T.Larsen: Employee; Nordic Bioscience A/S. C.F.G.Laursen: None. F.Genovese: Employee; Nordic Bioscience A/S, Stock/Shareholder; Nordic Bioscience A/S. M.A.Karsdal: Speaker's Bureau; Pfizer Inc. D.Rasmussen: Employee; Nordic Bioscience A/S, Stock/Shareholder; Nordic Bioscience A/S. K.Henriksen: Employee; Nordic Bioscience A/S, Stock/Shareholder; Nordic Bioscience A/S.

Maternal haemodynamics in Hypertensive Disorders of Pregnancy under antihypertensive therapy (HyperDiP): study protocol for a prospective observational case–control study

IntroductionHypertensive disorders of pregnancy (HDP) are associated with a high incidence of maternal and perinatal morbidity and mortality. HDP, in particular pre-eclampsia, have been determined as risk factors for future...

Preliminary Study on the Association of Serum Branched-Chain Amino Acids With Lipid and Hepatic Markers.

Serum levels of branched-chain amino acids (BCAAs) are associated with various vital physiological functions and thus elevation in circulating levels results in several metabolic disturbances. Serum levels of BCAAs are strong predictors of various metabolic disorders. Their association with cardiovascular health is uncertain. The study aimed to investigate the association of BCAAs with circulating levels of vital cardiovascular and hepatic markers. The study population of 714 individuals was included from the population tested for the vital cardio and hepatic biomarkers at the Vibrant America Clinical Laboratories. The subjects were stratified into four quartiles based on the serum levels of BCAAs, and their association with vital markers was studied using the Kruskal-Wallis test. Pearson's correlation analyzed the univariant relationship of BCAAs with selected cardio and hepatic markers. BCAAs exhibited a strong negative correlation with serum HDL. Serum triglycerides were found to have a positive correlation with serum levels of leucine and valine. Univariant analysis exhibited a strong negative correlation between serum levels of BCAAs and HDL, and a positive correlation was observed between triglycerides and amino acids isoleucine and leucine. Among analyzed hepatic markers, alanine transaminase exhibited a considerable association with BCAAs. The elevated levels of serum BCAAs are strongly associated with serum HDL and triglycerides. Consumption of these supplements must be in coordination with healthcare providers to avoid metabolic and cardiovascular risk.

Social determinants of racial health inequities

Social determinants of racial health inequities

Trajectories in allostatic load as predictors of sleep quality among urban adults: Healthy aging in neighborhoods of diversity across the life span study

Objective/Background: The allostatic framework is a theoretical perspective that identifies allostatic load (AL) as a meaningful measure of dysregulation and desynchrony across biological processes due to cumulative stress exposure, thereby increasing disease risk. Research exploring the relationships of AL with sleep quality have yielded inconsistent findings. We examined AL at three visits (2004–2009 [Visit 1], 2009–2013 [Visit 2] and 2013–2017 [Visit 3]) in relation to sleep quality [Visit 3] among urban adults by sex, race and age group. Patients/methodsWe analyzed data on 1489 Healthy Aging in Neighborhoods of Diversity across the Life Span (HANDLS) participants [59.6% female, baseline age: 48.2 years, 58.5% African Americans] with available data on cardiovascular, metabolic and inflammatory AL markers and Pittsburgh Sleep Quality Index (PSQI) scores. Least squares regression models were constructed to evaluate AL score at Visit 1 (ALv1) and z-transformed probability of higher trajectory in AL score between Visit 1 and Visit 3 (ALtraj) as predictors of PSQI score at Visit 3, controlling for demographic, lifestyle and health characteristics at Visit 1. ALtraj was generated using group-based trajectory modeling. ResultsIn fully adjusted models, ALv1 and PSQI score were positively related among men only (β = 0.43, P = 0.001), whereas higher ALtraj was associated with PSQI score among women (β = 0.51, P = 0.001), White (β = 0.45, P = 0.011) and African American (β = 0.33, P = 0.014) populations. There were no statistically significant interactions according to age group (<50 vs. ≥ 50). ConclusionsDisparities exist whereby AL trajectory predicted sleep quality among women irrespective of race and baseline AL predicted sleep quality among men. Future studies should examine bi-directional AL-sleep relationships.

SFRP5 as a new cardiovascular biological marker: a literature review

Research into new biological markers may help early diagnosis and effective therapy for cardiology patients. The use of biomarkers to evaluate patients has made a major impact in oncology, but is still in its infancy in the cardiology field. Studies on secreted frizzled-related protein 5 (SFRP5) have revealed its potential use as a marker of cardiovascular pathology. Preclinical studies have highlighted the important role this protein plays in many biological processes. It reduces the proliferation and migration of cardiac fibroblasts and suppresses the Wnt5A/JNK signaling pathway thus reducing the severity of oxidative stress and inflammation. It normalizes nitric oxide production and has several other effects. However, recent clinical studies of SFRP5 have produced conflicting data. Nevertheless, this protein shows promise as a marker for several metabolic and cardiovascular diseases. Preliminary data also suggest SFRP5 may be a therapeutic target. Further study of SFRP5 and its role in cardiovascular pathology is necessary, and will create new diagnostic and prognostic possibilities for this biological marker.

Amniotic Fluid Mesenchymal Stromal Cells Derived from Fetuses with Isolated Cardiac Defects Exhibit Decreased Proliferation and Cardiomyogenic Potential.

Amniotic fluid mesenchymal stromal cells (AF-MSCs) represent an autologous cell source to ameliorate congenital heart defects (CHDs) in children. The AF-MSCs, having cardiomyogenic potential and being of fetal origin, may reflect the physiological and pathological changes in the fetal heart during embryogenesis. Hence, the study of defects in the functional properties of these stem cells during fetal heart development will help obtain a better understanding of the cause of neonatal CHDs. Therefore, in the present study, we compared the proliferative and cardiomyogenic potential of AF-MSCs derived from ICHD fetuses (ICHD AF-MSCs) with AF-MSCs from structurally normal fetuses (normal AF-MSCs). Compared to normal AF-MSCs, the ICHD AF-MSCs showed comparable immunophenotypic MSC marker expression and adipogenic and chondrogenic differentiation potential, with decreased proliferation, higher senescence, increased expression of DNA-damaged genes, and osteogenic differentiation potential. Furthermore, the expression of cardiac progenitor markers (PDGFR-α, VEGFR-2, and SSEA-1), cardiac transcription factors (GATA-4, NKx 2-5, ISL-1, TBX-5, TBX-18, and MeF-2C), and cardiovascular markers (cTNT, CD31, and α-SMA) were significantly reduced in ICHD AF-MSCs. Overall, these results suggest that the AF-MSCs of ICHD fetuses have proliferation defects with significantly decreased cardiomyogenic differentiation potential. Thus, these defects in ICHD AF-MSCs highlight that the impaired heart development in ICHD fetuses may be due to defects in the stem cells associated with heart development during embryogenesis.

Are preoperative monocytes and HDL values ​​an early predictor of recurrence in the surgical ablation treatment of atrial fibrillation?

Objective: Monocyte HDL (high-density lipoprotein) cholesterol ratio has been accepted as a newly emerging cardiovascular prognostic marker. The aim of this study is to investigate the determinants of monocyte and HDL cholesterol values ​​in the early recurrence of atrial fibrillation (AF) treated with cryoablation and radiofrequency ablation.&#x0D; &#x0D; Materials and Methods: This retrospective study was conducted between September 2006 and July 2014 in the Department of Cardiovascular Surgery, Adana City Hospital, Health Sciences University, including 100 patients who underwent surgical AF ablation with open heart surgery. Logistic regression analysis was used to determine monocytes and HDL cholesterol values, which are among the factors affecting recurrence in the first 3 months postoperatively.&#x0D; &#x0D; Results: 100 patients who underwent surgical ablation together with open heart surgery were evaluated for early postoperative recurrence. According to the logistic regression analysis, the most effective features and measurements for early recurrence were diabetes mellitus (DM), AF duration, left atrial diameter, and low HDL cholesterol and high monocyte values ​​before the procedure.&#x0D; &#x0D; Conclusion: Preoperative low HDL and high monocyte values ​​can be considered as a determining factor for early recurrence in surgical ablation treatment of AF.

Fast and Sensitive Detection of Protein Markers Using an All-Printing Photonic Crystal Microarray via Fingertip Blood.

With the demand for point-of-care testing (POCT) in cardiovascular diseases, the detection of biomarkers in trace blood samples is of great significance in emergency medicine settings. Here, we demonstrated an all-printed photonic crystal microarray for POCT of protein markers (named "P4 microarray"). The paired nanobodies were printed as probes to target the soluble suppression of tumorigenicity 2 (sST2) as a certified cardiovascular protein marker. Benefiting from photonic crystal-enhanced fluorescence and integrated microarrays, quantitative detection of sST2 is 2 orders of magnitude lower than that of a traditional fluorescent immunoassay. The limit of detection is down to 10 pg/mL with the coefficient of variation being less than 8%. Detection of sST2 via fingertip blood is achieved in 10 min. Moreover, the P4 microarray after 180 days of storage at room temperature showed excellent stability for detection. This P4 microarray, as a convenient and reliable immunoassay for rapid and quantitative detection of protein markers in trace blood samples, has high sensitivity and strong storage stability, which hold great potential to advance cardiovascular precision medicine.

Deep phenotyping as a contribution to personalized depression therapy: the GEParD and DaCFail protocols

Depressive patients suffer from a complex of symptoms of varying intensity compromising their mood, emotions, self-concept, neurocognition, and somatic function. Due to a mosaic of aetiologies involved in developing depression, such as somatic, neurobiological, (epi-)genetic factors, or adverse life events, patients often experience recurrent depressive episodes. About 20–30% of these patients develop difficult-to-treat depression. Here, we describe the design of the GEParD (Genetics and Epigenetics of Pharmaco- and Psychotherapy in acute and recurrent Depression) cohort and the DaCFail (Depression-associated Cardiac Failure) case–control protocol. Both protocols intended to investigate the incremental utility of multimodal biomarkers including cardiovascular and (epi-)genetic markers, functional brain and heart imaging when evaluating the response to antidepressive therapy using comprehensive psychometry. From 2012 to 2020, 346 depressed patients (mean age 45 years) were recruited to the prospective, observational GEParD cohort protocol. Between 2016 and 2020, the DaCFail case–control protocol was initiated integrating four study subgroups to focus on heart-brain interactions and stress systems in patients > 50 years with depression and heart failure, respectively. For DaCFail, 120 depressed patients (mean age 60 years, group 1 + 2), of which 115 also completed GEParD, and 95 non-depressed controls (mean age 66 years) were recruited. The latter comprised 47 patients with heart failure (group 3) and 48 healthy subjects (group 4) of a population-based control group derived from the Characteristics and Course of Heart Failure Stages A–B and Determinants of Progression (STAAB) cohort study. Our hypothesis-driven, exploratory study design may serve as an exemplary roadmap for a standardized, reproducible investigation of personalized antidepressant therapy in an inpatient setting with focus on heart comorbidities in future multicentre studies.

Multicomponent recreational team handball training improves global health status in postmenopausal women at the long term – A randomised controlled trial

ABSTRACT We studied the long-term effects of a multicomponent exercise training protocol (recreational team handball training, RTH) on global health status in inactive postmenopausal women. Participants (n = 45; age 65 ± 6 years, stature 157 ± 6 cm, body mass 66.2 ± 9.4 kg, fat mass 41.4 ± 5.5%, VO2peak 25.7 ± 3.6 mL/min/kg) were randomised into a control group (CG; n = 14) and a multicomponent exercise training group (EXG; n = 31, performing two to three weekly 60-min RTH sessions). Attendance was 2.0 ± 0.4 sessions/week (first 16 weeks) and 1.4 ± 0.5 (following 20 weeks) and mean heart rate (HR) loading was 77 and 79% of maximal HR (p = .002) for the first 16 and the following 20 weeks, respectively. Cardiovascular, bone, metabolic health, body composition and physical fitness markers were evaluated at baseline, and after 16 and 36 weeks. An interaction (p ≤ .046) was shown for the 2-h oral glucose tolerance test, HDL, Yo-Yo intermittent endurance level 1 test (YYIE1) and knee strength, in favour of EXG. At 36 weeks, YYIE1 and knee strength were higher (p ≤ .038) for EXG vs CG. Also, within-group improvements (p ≤ .043) were observed after 36 weeks for EXG in VO2peak, lumbar spine bone mineral density, lumbar spine bone mineral content, P1NP, osteocalcin, total cholesterol, HDL, LDL, body mass, android fat mass, YYIE1, knee strength, handgrip strength and postural balance. At 36 comparatively to 16 weeks, EXG showed an increase (p ≤ .036) in fasting blood glucose, HDL, knee strength and handgrip strength, and a decrease (p ≤ .025) in LDL. Collectively, this multicomponent exercise training (RTH) induces beneficial changes in global health status in postmenopausal women. Highlights We evaluated the long-term effects of a recreational team handball-based multicomponent training on broad-spectrum health and physical fitness markers of inactive postmenopausal women. Improvements in VO2peak and aerobic performance achieved after 16 weeks of training were maintained at 36 weeks. The 20-week extension of the training intervention resulted in further improvements in lipid profile markers and physical fitness variables. Recreational team handball could be suggested as an effective and safe strategy to counteract postmenopausal health-related constrains.

Effect of diet on cardiovascular health-related circulating parameters in men and women athletes participating in a marathon race: A cross-sectional study.

The main objective of this study is to understand how diet affects performance and cardiovascular health in a group of women participating in a demanding aerobic race such as marathon, compared to men. Fifteen women participating in the Barcelona Marathon-2016 were recruited to participate in the study. A group of men (n=15) that performed the same marathon race was selected. Anthropometric parameters and diet records were collected before the race. Circulating parameters were analyzed 24 h-pre-race, immediately after the race and 48 h-post-race. These included certain minerals, lipid profile, muscle damage, inflammatory and cardiovascular health markers. Diets were very similar in the men and women, with inadequate amounts of carbohydrates and proteins for endurance events. Creatine kinase (CK; a muscle damage marker) and C-reactive protein (CRP; a marker of inflammation) remained elevated 48 h post-race in all participants, but was significant in women (641 vs. 143 U/L for CK and 5.8 vs. 0.7mg/dL for CRP). Cardiac markers (high sensitivity troponin T (Hs-TnT), suppression of tumorigenicity and N-terminal pro B-type natriuretic peptide) increased post-race and returned to pre-race values after 48 h in men and women. In particular, Hs-TnT (marker of myocyte stress) increased from 2.2 to 62.5ng/L post-race in women and from 3.1 to 52.9ng/L in men. Finally, circulating lipid parameters were at borderline unhealthy levels in both sexes. Structural and functional cardiac advantages that women display compared to men in aerobic efforts are not manifested when diet is not adequately designed.

The role of systemic inflammation and oxidative stress in the association of particulate air pollution metal content and early cardiovascular damage: A panel study in healthy college students

Exposure to fine particulate matter (PM2.5) has been associated with adverse cardiovascular outcomes. However, the effects of toxic metals in PM2.5 on cardiovascular health remain unknown. To investigate the early cardiovascular effects of specific PM2.5 metal constituents at the personal level, we conducted a panel study on 45 healthy college students in Caofeidian, China. Personal exposure concentrations and cardiovascular effect markers were monitored simultaneously within one year in four study periods. Four linear mixed-effects models were used to analyze the relationship between personal exposure to PM2.5 and 15 metal fractions (Al, V, Cr, Mn, Fe, Co, Ni, Cu, Zn, As, Se, Mo, Cd, Sb, and Pb) with soluble CD36 (sCD36), C-reactive protein (CRP), and oxidized low-density lipoprotein (OX-LDL) levels, heart rate, and blood pressure. The concentrations of most individual metals (Mn, Cu, Zn, As, Se, Mo, Cd, Sb and Pb) were the highest in winter. Meanwhile, there were significant differences in inflammatory (sCD36 and CRP) and oxidative stress (OX-LDL) markers in the serum of participants over the four seasons. In particular, the estimated effects of personal metal exposure (such as V, As, Se, Cd, and Pb) on sCD36 and pulse pressure (PP) levels were consistently significant across the four LME models. A significant mediating role of sCD36 was also found in the relationship between personal exposure to Zn and Cr and changes in PP levels. Our findings provide clues and potential mechanisms regarding the cardiovascular effects of specific toxic constituents of PM2.5 in healthy young adults.