Independent Predictor Of Cardiovascular Risk Research Articles

Endogenous Acetylcholine Contributes to Flow-Mediated Dilation in Humans

Background & Objective. Flow-mediated dilation (FMD) is a crucial function of the vascular endothelium wherein intraluminal shear stress stimulates endothelium-dependent vasodilation mediated primarily by nitric oxide. Brachial artery FMD (baFMD) is widely evaluated in clinical research as an index of endothelial function, and impaired baFMD is an independent predictor of cardiovascular risk. Despite the physiological and clinical relevance of FMD, the mechanisms by which shear stress is transduced to endothelium-dependent vasodilation (i.e., upstream of nitric oxide production) remain unclear. baFMD corresponds closely with sensitivity to the endothelium-dependent vasodilator acetylcholine (ACh), and preclinical models suggest ACh is released from endothelial cells in response to shear stress. Therefore, the present study tested the hypothesis that activation of muscarinic ACh receptors facilitates baFMD in humans. Methods. baFMD was evaluated using Doppler ultrasound in healthy participants (n=11; 5F/6M; 23±2 y; means ± SE) under control conditions and following local inhibition of muscarinic ACh receptors via intra-arterial atropine infused proximal to the measurement site. baFMD was assessed in response to transient and sustained shear stimuli in separate trials: 1) reactive hyperemia following 5 min of arterial cuff occlusion (RH-FMD) and 2) steady-state rhythmic handgrip exercise at graded intensities (10, 15, 20, & 25% maximal voluntary contraction, MVC) to produce step increases in shear rate (EX-FMD). Blockade effcacy was confirmed via a dose-response to intra-arterial ACh infusion pre and post atropine. Results. Baseline brachial artery diameter and forearm blood flow were similar in all trials (all P>0.05). Atropine reduced peak brachial artery dilation following cuff release (RH-FMD, Δ diameter, atropine: 4.6±0.8 vs. control: 6.5±0.8%, P=0.04) and increased the shear stimulus (shear rate area under the curve, SRAUC: atropine, 29±3 vs. control: 21±3 s−1×103, P=0.01) such that the percent change in brachial diameter was diminished by 35±16% when normalized to SRAUC (baFMD:SRAUC ratio, atropine: 1.7±0.3 vs. control: 3.9±1.0, P=0.02). Similarly, in the EX-FMD trial, atropine reduced brachial artery diameter at all exercise intensities (25% MVC, percent change in diameter: atropine, 10.8±1.4 vs. control, 15.5±1.7%, P=0.04) despite a greater shear stimulus (shear rate: atropine, 10.9±1.1 vs. control, 9.3±0.9 s−1×102, P=0.01). Thus, atropine reduced the slope describing the relationship between brachial artery vasodilation (percent change) and the change in shear rate by 38±8% across all exercise intensities (slope, atropine: 1.3±0.1 vs. control: 2.4±0.4% Δ×s×10−2, P=0.007). As expected, atropine reduced brachial artery vasodilation in response to upstream infusion of ACh (1.5 μg ACh/dl forearm volume/min, Δ diameter, atropine: 2±1 vs. control: 23±4%, P=0.001). Conclusions. The results suggest endogenous ACh facilitates baFMD in response to both transient and sustained shear stimuli, which highlights a novel physiological role of endogenous ACh in vascular regulation in humans and provides insight regarding the basic mechanisms of flow-mediated vasodilation. NIH R01 HL119337 and F31 HL142240. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Association Between Augmentation Index and Total Sleep Time in Night Shift Workers.

Augmentation index and pulse wave velocity are markers of vascular compromise and independent predictors of cardiovascular risk and mortality. While the link between shift work and heightened cardiovascular risk is established, the intricate genesis of early cardiovascular outcomes in shift workers remains incompletely understood. However, there is evidence that sleep duration plays a role in this regard. Here we evaluate the association of total sleep time with pulse wave velocity, augmentation index, and central blood pressure in night shift workers. This study cross-sectionally evaluated the association of total sleep time evaluated by 10-day monitoring actigraphy with augmentation index, pulse wave velocity, and brachial and central blood pressure evaluated by oscillometry in nursing professionals, 63 shift workers (89% women; age = 45.0 ± 10.5 years), and 17 (100% women; age = 41.8 ± 15.6) day workers. There were no differences in the studied variables between shift workers and day workers. Results of correlation analysis demonstrated that pulse wave velocity, central systolic blood pressure, central diastolic blood pressure, brachial systolic blood pressure, and brachial diastolic blood pressure tended to have significant correlation with each other, while these measures did not have a significant relationship with augmentation index in both groups. However, results of adjusted restricted cubic spline analysis showed a U-shaped-curve association between total sleep time and augmentation index (p < 0.001 for trend) with a nadir at 300-360 min of total sleep time in shift workers. The present study showed that total sleep time, assessed by actigraphy, had a U-shaped association with augmentation index in shift workers, which indicated better characteristics of vascular functionality when sleep time was 5-6 h in the workers studied.

P432 ARTERIAL STIFFNESS AND CARDIOVASCULAR RISK IN PATIENTS WITH NEPHROLITIASIS: A 10–YEAR PROSPECTIVE STUDY

Abstract Nephrolithiasis is frequently associated with several cardiovascular diseases, and the pathophysiological connection may rely on some common risk factors. In fact, systemic inflammation, promoting oxidative stress, may lead to arterial wall stiffening (which is considered an independent predictor of cardiovascular risk); however, the same mechanism may also play a role in Randall’s plaques deposition, which is a predisposing step to nephrolithiasis. This study aims to examine the correlation between arterial stiffness and nephrolithiasis, exploring its trend across aging. 82 patients (mean age 45±13 years, 36 males) referred to Geriatrics and Nephrology Outpatient Clinic were prospectively enrolled: at baseline and after 10 years they underwent a clinical evaluation (with particular focus on cardiovascular events and risk factors), and arterial stiffness measurement, obtaining carotid–femoral Pulse Wave Velocity (PWVcf) by arterial applanation tonometry. 66 patients were diagnosed with nephrolithiasis, whereas the remaining 16 formed the control group. At baseline, compared to the control group, patients with nephrolithiasis showed higher systolic blood pressure and PWVcf (128±18 vs 117±16 mmHg, p 0.02 and 7.78±1.53 vs 6.50±1.13 m/s, p 0.001 respectively). After 10 years, patients with nephrolithiasis (p 0.001), but not patients without (p 0.081), had a significant raise in PWVcf, as compared to the baseline evaluation (10.64±3 vs 7.78±1.55 m/s); this trend was confirmed even after adjustment for age and sex. In a backward regression model, considering PWVcf variation over the follow up years (ΔPWVcf) as dependent variable, and age, sex, follow up years, Δ mean arterial pressure, Body Mass Index, hypertension and nephrolithiasis as independent variables, nephrolithiasis was proved to be the only significant predictor of ΔPWVcf, accounting for 6.9% of the variance (p 0.027). In conclusion, the present study outlines an increased cardiovascular risk in patients affected by nephrolithiasis, which is represented by higher baseline PWVcf and wider increase in ΔPWVcf within 10 years. These findings endorse a comprehensive evaluation in subjects with nephrolithiasis, moving beyond the nephrological condition, and considering the patient’s cardiovascular risk profile, to identify, to prevent or to treat any possible organ damage.

The influence of body composition and fat distribution on circadian blood pressure rhythm and nocturnal mean arterial pressure dipping in patients with obesity.

Loss of physiological nocturnal blood pressure (BP) decline is an independent predictor of cardiovascular risk and mortality. The aim of the study was to investigate the influence of body composition and fat distribution on 24-hour BP pattern and nocturnal dipping of mean arterial pressure (MAP) in patients with obesity. The study comprised 436 patients, 18 to 65 years old (306 women), with BMI ≥30 kg/m2. Body composition was assessed with dual-energy X-ray absorptiometry (DXA) and blood pressure was assessed by 24-hour BP monitoring. The prevalence of hypertension was 64.5% in patients with BMI <40 kg/m2 and increased to 78.7% in individuals with BMI ≥50 kg/m2 (p = 0.034). The whole-body DXA scans showed that the hypertensive patients were characterized by a greater lean body mass (LBM) and a higher abdominal-fat-to-total-fat-mass ratio (AbdF/FM), while the normotensive participants had greater fat mass, higher body fat percentage and more peripheral fat. Loss of physiological nocturnal MAP decline was diagnosed in 50.2% of the patients. The percentage of non-dippers increased significantly: from 38.2% in patients with BMI <40 kg/m2 to 50.3% in those with BMI 40.0-44.9 kg/m2, 59.0% in patients with BMI 45.0-49.9 kg/m2, 71.4% in those with BMI 50.0-54.9 kg/m2 and 83.3% in patients with BMI ≥55 kg/m2 (p = 0.032, p = 0.003, p<0.001, and p = 0.002 vs. BMI <40 kg/m2, respectively). The multivariable regression analysis showed that patients at the highest quartiles of body weight, BMI, LBM and AbdF/FM had significantly reduced nocturnal MAP dipping compared with patients at the lowest quartiles, respectively.

NLR and PLR as Available and Inexpensive markers for Evaluation of Subclinical Inflammation in patients with Chronic Kidney Disease

Chronic kidney disease (CKD) is associated with high morbidity and increased cardiovascular mortality. Chronic inflammation was found to be correlated with cardiovascular disease (CVD) in CKD population. High-sensitivity C-reactive protein (hs-CRP), is one of biomarkers of subclinical inflammation, and widely used as an independent predictor of cardiovascular risk. Neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) were introduced as potential markers for evaluation of inflammation in several diseases. However, there are a few studies in CKD patients. We aimed to evaluate the relationship of NLR and PLR with hs-CRP levels in Syrian patients with CKD. The study included 100 CKD patients in stages 3 to 5 seen at Tishreen University Hospital, and 22 subjects served as control. CKD patients were divided into two groups, according to the presence or absence of inflammation, based on the high-sensitivity C-reactive protein (hs-CRP) cut off value of 3 mg/l. Blood samples were collected for blood count and hs-CRP levels determination. hs-CRP concentration was measured by immunoturbidimetry assay kit. NLR and PLR were calculated based on the absolute number of neutrophils, lymphocytes and platelets. We used the SPSS 25.0 program for the statistical analysis. Probability (P) value&lt;0.05 was considered statistically significant. NLR as well as PLR and hs-CRP levels were significantly higher in all CKD groups compared to control subjects (p&lt;0.05, for all). NLR and PLR values were significantly different between CKD groups with and without inflammation (for both, p&lt;0.001). Both NLR and PLR were positively correlated with hs-CRP (r=0.50, p&lt;0.001 for NLR; r=0.43, p&lt;0.001 for PLR) in CKD patients. The best cutoff point for NLR to detect inflammation was ≥3.06, with 70% sensitivity and 81.1% specificity. For PLR, the cut off was ≥144.78, with 59% sensitivity and 73% specificity. There was no significant difference between the area under the NLR and PLR curve (0.77 vs. 0.70, p=0.19) for this population. Our findings suggests that NLR and PLR are available, simple and less expensive methods that could be used as markers of inflammation in CKD patients instead of hs-CRP.

Predictors of left ventricular mass and coronary artery calcium phenotypes

Abstract Funding Acknowledgements Type of funding sources: Public Institution(s). Main funding source(s): National Medical Research Council, Ministry of Health, Singapore and the Lee Foundation Background Left ventricular (LV) mass and coronary artery calcium score (CACS) are both independent predictors of cardiovascular risk. There is paucity of data on the interplay of risk factors on LV mass in the presence or absence of subclinical coronary atherosclerosis. Purpose The objective of this present study was to explore the relationship of risk factors to indexed LV mass and CACS in a healthy Southeast-Asian population. Methods This study recruited volunteers with no known cardiovascular disease. LV mass, measured by cardiovascular magnetic resonance, was indexed to body surface area (LVMI), and CACS determined by non-contrast CT scanning. Blood pressure (BP) was measured via both office and ambulatory monitoring, and physical activity assessed through wearable devices. Analysis of LVMI was stratified into high, normal and low defined as more than one standard deviation away from the mean for each sex, with inter-group differences evaluated using chi-squared or ANOVA statistical tests. Subjects in each LVMI group were further subdivided by the presence and absence of coronary calcification (total 6 subgroups; LVMI/CACS phenotypes). Results A total of 880 subjects were included, including 428 males and 452 females. There was no significant difference in prevalence of coronary calcification across the LVMI groups for males, while females with high LVMI had significantly greater proportion of positive CACS (p = 0.036). Higher LVMI was observed in younger male subjects, but not in females. In both sexes, body mass index was positively associated with LVMI (p = 0.004 for males, p = 0.037 for females), but not CACS. Waist circumference was associated with higher LVMI in males only. Greater amounts of weekly self-reported exercise (p = 0.006) and daily calories burned (p = 0.022) were associated with increased LVMI for males only. However, wearable-derived measures of daily physical activity and step counts did not significantly affect LVMI or LVMI/CACS phenotypes in both sexes. BP was a strong predictor of LVMI in both sexes regardless of office or ambulatory readings, in both day and night-time. The association was also observed with LVMI/CACS phenotypes: higher systolic or diastolic BP was significantly associated with positive CACS across all risk groups. Notably, subjects with low LVMI and positive CACS were normotensive (office BP 129/82 for males, 123/77 for females). Higher HDL cholesterol levels correlated to absence of coronary calcification in males only (p = 0.010). In females, lower levels of total (p = 0.001) and LDL (p = 0.005) cholesterol were associated with absence of coronary calcification across all LVMI categories. Conclusion Only BP was strongly associated with LVMI and LVMI/CACS phenotypes in both sexes. There appears to be no correlation between physical activity and LVMI/CACS phenotypes. There is a need for causative studies to better evaluate the varying influence of risk factors on LVMI and CACS.

Abstract 14636: The Effects of Celecoxib on Endothelial Function in Healthy Volunteers; A Double Blind, Placebo Controlled Randomised Trial

Introduction: Non-steroidal anti-inflammatory drugs (NSAIDs), which work by blocking cyclooxygenase (COX)-2 can increase cardiovascular risk by up to 30% after 2 weeks of use and in animal models augments thrombosis. However, the effect of NSAIDs and loss of COX-2 on endothelial function and blood flow remains incompletely understood. A plausible explanation is inhibition of COX-2 affects endothelial function by inhibiting prostacyclin and/or reducing endothelial nitric oxide synthase (eNOS) activity/expression. We hypothesised that COX-2 inhibition with celecoxib will impact on endothelial function. Methods: Healthy male volunteers aged between 18 to 40 were randomised 1:1 to receive either celecoxib (200 mg twice daily) or matching placebo for 7 days. The primary outcome was change (Δ) in endothelial function assessed using the EndoPAT device. Participants were given a home blood pressure machine and diary as a secondary outcome measure. Participants and outcome assessors were blinded to the intervention. Results: Between June 2021 and January 2022, 44 participants were randomised of which 40 participants completed the study (20 allocated to each arm) and were included in the final analysis. Baseline characteristics were similar between the groups. Compared to placebo, there was a significant increase in augmentation index (AI) following celecoxib use: Δ 6.2; (95% CI 0.05 to 12.4) p:0.048. There was no difference in log reactive hyperaemia index (LnRHI): Δ -0.092; (95% CI -0.31 to 0.12) p:0.39, systolic blood pressure: Δ -3.5; (95% CI -9.9 to 3) p:0.28, or diastolic blood pressure: Δ 4.7; (95% CI -1.8 to 11.1) p:0.15 (Figure) . Conclusion: In healthy male volunteers, 7 days of treatment with celecoxib significantly increased augmentation index which is a surrogate for vascular stiffness and an independent predictor of cardiovascular risk. Further clinical and mechanistic studies are required to elucidate how COX-2 inhibition impacts on augmentation index.

Associations between Maternal Polychlorinated Dibenzo-p-dioxin and Dibenzofuran Serum Concentrations and Pulse Pressure in Early Pregnancy: A Cross-Sectional Study.

Pulse pressure (PP) is the difference between systolic blood pressure (SBP) and diastolic blood pressure (DBP), and an independent predictor of cardiovascular risk. Previous research suggests, with different conclusions, that exposure to polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) could affect blood pressure (BP). We conducted a cross-sectional study to determine the association of dioxin exposure with PP in early pregnancy. A total of 305 pregnant women in early pregnancy in Yingcheng, China, recruited from May 2018 to February 2021, were included in this study. We measured 17 congeners of PCDD/Fs in maternal serum via high-resolution gas chromatography tandem high-resolution mass spectrometry. A generalized linear regression model was used to analyze the influencing factors of dioxin exposure and their relationships with PP. The levels of total PCDD/Fs (∑PCDD/Fs) ranged from 163.52 pg/g lipid to 1,513,949.52 pg/g lipid, with a mean of 10,474.22 pg/g lipid. The mean toxicity equivalent (TEQ) of total PCDD/Fs (∑TEQ-PCDD/Fs) was 42.03 pg/g lipid. The ratio of tetrachlorinated to octa-chlorinated congeners in maternal serum was enriched with an increasing number of chlorines. Pregnant women with college and above education had higher concentrations of ∑PCDD/Fs than those with education levels of junior high school and below (β = 0.34, 95% CI: 0.01, 0.67). The adjusted model for ∑TEQ-PCDD/Fs was significantly and negatively associated with PP (β = -1.79, 95% CI: -2.91, -0.68). High levels of dioxins were found in this area, and exposure to dioxins may affect the PP of women in early pregnancy, with health risks.

24-hour arterial stiffness monitoring in hypertensive and normotensive patients with bronchial asthma

Background. Cardiovascular disease is one of the major causes of death throughout the world. Early detection of target organ damage is important for more successful cardiovascular prevention and improvement of patient outcomes. Vascular wall is one of the target organs, and its damage is associated with the loss of elastic properties and increase in stiffness. The increased vascular stiffness is an independent predictor of cardiovascular risk. Objective. To evaluate parameters of the 24-hour arterial stiffness monitoring in hypertensive and normotensive patients with bronchial asthma. Design and methods. The study enrolled 100 patients with asthma. The control group included 30 healthy volunteers matched by gender and age. Each patient underwent ambulatory blood pressure and arterial stiffness monitoring using BPLab MnSDP-2 device (Petr Telegin, Russia). Results. Normotensive patients with asthma show higher values of arterial stiffness index and pulse wave velocity in the aorta in comparison with the control group. Comorbid patients with bronchial asthma and hypertension show the highest arterial stiffness. Conclusion. Patients with asthma with and without hypertension demonstrated significantly increased arterial stiffness in comparison with control group.

AORTIC STIFFNESS ASSESSED BY HIGH-RESOLUTION PHOTOPLETHYSMOGRAPHY AND SINGLE-LEAD ECG

Objective: Aortic stiffness is an independent predictor of cardiovascular risk and plays an important role for the development of cardiovascular disease. However, it is rarely measured in clinical practice as it requires complicated methodology and expensive equipment. We assessed whether high-resolution photoplethysmography (PPG) and single-lead ECG, two methods available in current consumer devices, could be used to measure aortic stiffness. Design and method: Simultaneous recordings of infrared PPG (earlobe and index finger), single lead ECG (PowerLab, ADInstruments) and continuous blood pressure (BP) by the volume-clamp method (Ohmeda 2300, Finapres) at 1000 Hz were made in 33 subjects and repeated after 1–3 wks. Carotid-femoral pulse wave velocity (cfPWV, SphygmoCor, AtCor Medical) and aortic pulse wave velocity (aoPWV, Arteriograph, Tensiomed) were measured as reference. PPG fiducial point identification was refined using pulse wave shapes and the blood pressure signal. Pulse wave analysis extracted 23 features previously associated with arterial stiffness, which were ranked according to univariate strength of correlations with cfPWV and aoPWV. The feature with highest rank was used in a multiple linear regression model with heart rate, body height, mean arterial BP and PAT (ECG R-peak to PPG foot) as covariates. Results: Mean age was 44 (range 21–66) ys, 19 were men, and 5 had hypertension; office BP was 119 ± 12/72 ± 9 mm Hg. PWV was similar at visit 1 and 2 (cfPWV 6.74 ± 1.17 vs 6.80 ± 1.18; aoPWV 7.66 ± 1.80 vs 7.55 ± 1.52). Finger-PPG showed stronger relations with PWV than earlobe-PPG, and 17 of the 23 extracted features showed correlations (P &lt; 0.05) with cfPWV and aoPWV. The ratio of acceleration features (b-c-d-e)/a showed highest correlations with cfPWV and aoPWV (r2 = 0.58 and 0.64, respectively), that improved in multiple regression (r2 = 0.72 and 0.71, respectively; both P &lt; 0.001). Conclusions: High-resolution finger-PPG combined with advanced feature extraction can be used to assess aortic stiffness. Adding body height, BP and single-lead ECG improve the strength of the correlation. Easily available PPG based aortic stiffness may facilitate cardiovascular risk prevention, evaluation, and improve treatment.

The Importance of Arterial Stiffness Assessment in Patients with Familial Hypercholesterolemia.

Cardiovascular diseases are still the leading cause of mortality due to increased atherosclerosis worldwide. In the background of accelerated atherosclerosis, the most important risk factors include hypertension, age, male gender, hereditary predisposition, diabetes, obesity, smoking and lipid metabolism disorder. Arterial stiffness is a firmly established, independent predictor of cardiovascular risk. Patients with familial hypercholesterolemia are at very high cardiovascular risk. Non-invasive measurement of arterial stiffness is suitable for screening vascular dysfunction at subclinical stage in this severe inherited disorder. Some former studies found stiffer arteries in patients with familial hypercholesterolemia compared to healthy controls, while statin treatment has a beneficial effect on it. If conventional drug therapy fails in patients with severe familial hypercholesterolemia, PCSK9 inhibitor therapy should be administered; if these agents are not available, performing selective LDL apheresis could be considered. The impact of recent therapeutic approaches on vascular stiffness is not widely studied yet, even though the degree of accelerated athero and arteriosclerosis correlates with cardiovascular risk. The authors provide an overview of the diagnosis of familial hypercholesterolemia and the findings of studies on arterial dysfunction in patients with familial hypercholesterolemia, in addition to presenting the latest therapeutic options and their effects on arterial elasticity parameters.

Parâmetros Ecocardiográficos Simples são Fortes Preditores de Risco Cardiovascular em Indivíduos Assintomáticos: Coorte Elsa-Brasil

ResumoFundamento vários estudos avaliam alterações ecocardiográficas como preditores de risco cardiovascular; entretanto, nenhum associa risco cardiovascular global com alterações ecocardiográficas em brasileiros.Objetivo Este estudo avalia a associação entre risco cardiovascular global (ASCVD) e achados ecocardiográficos como hipertrofia ventricular esquerda (HVE), disfunção diastólica (DDVE) e aumento do volume do átrio esquerdo (AE).Métodos A população foi composta por participantes do ELSA-Brasil que realizaram ecocardiografia entre 2008 e 2010 (n = 2.973). Eram assintomáticos e não tinham história de doença cardiovascular (DCV). O escore ASCVD foi calculado em dois períodos: 2008-2010 e 2012-2014. Razões de prevalência (RP) foram estimadas com intervalos de confiança (IC) de 95%.Resultados Evidenciou-se associação entre alterações ecocardiográficas e alto risco cardiovascular global (escore ASCVD ≥ 7,5) nos dois períodos do estudo, separadamente. O risco global combinado (baixo risco no primeiro período e alto risco no segundo período) teve associação significativa apenas com DDVE (RP = 3,68; IC 95%: 2,63-5,15) e HVE (RP = 2,20; IC 95%: 1,62–3,00).Conclusão Alterações ecocardiográficas (DDVE, HVE e aumento do volume do AE) são preditores independentes de risco cardiovascular em adultos brasileiros sem DCV prévias.

Administration of Estradiol in Young Adulthood in the Male Sprague Dawley Rat to Mimic Female Physiological Levels is Associated with a Reduction in Body Weight, Lean Mass and Testicular Size

Transgender females are biological males at birth but identify as female by gender. The prevalence of the transgender population is increasing, yet the burden of increased cardiovascular (CV) risk is unclear. Sex is an independent predictor of CV risk but the role of sex hormones in mediating CV disease in the transgender population is unknown. Gender affirming therapy (GAT) in transfemales (male to female) involves administration of estradiol with a goal to achieve the female physiological range of estrogen. The aim of this study was to optimize estradiol levels in a rat model of GAT. Male Sprague Dawley (SD) rats were implanted with silastic capsules to deliver 17‐beta estradiol benzoate (E2) at doses of 2.5 (Low), 5 (Medium) and 7.5 (High) mg/day versus empty pellet (EP) starting at 13 weeks of age (n=4/group). At 16 weeks of age, E2 was determined by ELISA, lean and fat mass were measured via EchoMRI, and creatinine, BUN, lipids and liver enzymes were quantitated by Chemistry Analyzer. The different doses of E2 were compared to EP using unpaired t test (GraphPad) with p&lt;0.05 considered significant. All doses of E2 caused significant increases in circulating estradiol versus EP (Table, p&lt;0.001) that were equivalent to estradiol levels in age‐matched female SD rats as previously reported by our laboratory (PMID: 17724277). Food intake, body weight, and lean mass, were significantly reduced after 3 weeks of E2 compared to EP (Table, p&lt;0.001). Administration of E2 was also associated with a significant reduction in testicular weight versus EP (Table, p&lt;0.001). To conclude, optimization of E2 levels in the male rat is critical to the development of a rodent model that mimics GAT in male to female transgender. The use of a transfemale rodent model will allow study of the pathophysiology of increased CV risk associated with GAT across the lifespan.

Analysis of C reactive protein and other inflammatory markers in the cardiovascular risk prediction in women

Objective: To evaluate the role of C Reactive Protein and other inflammatory markers in cardiovascular risk prediction. Study Design: A prospective case-control study. Place and Duration: At Cardiology Department of Nishtar Medical University &amp; Hospital Multan from 5th Oct 2020 to 5th Oct 2021. Methodology: A total of 150 postmenopausal women were studied and divided into CVD patients (n=50) and control patients (n=100). The analyzed markers of inflammation included Interleukin-6, high-sensitivity C-reactive Protein, Soluble ICAM-1 (slCAM-1), and Amyloid-A. The Homocysteine, Lipid Profile, and Low and High-density lipoprotein levels were also evaluated. Cardiovascular events considered in our study were death after coronary artery disease, non-fatal heart attack or stroke, or requiring coronary-revascularization methods. Results: In univariate analysis, it was observed that high-sensitivity C-reactive protein levels were the strongest risk predictor of cardiovascular diseases. Amyloid-A, High-density lipoprotein, Cholesterol, Low-density lipoprotein cholesterol, Soluble lCAM-1, Interleukin-6, Apolipoprotein B-100, Homocysteine, total cholesterol, and the ratio of total cholesterol to high-density lipoprotein cholesterol also contributed to predicting cardiovascular diseases. High-sensitivity C-reactive protein (95% Cl: 1.4(1.0-2.0)) and Amyloid-A (95% Cl: 0.9(0.7-1.5)) were also strong risk predictors in women. On the other hand, in multivariate analyses, only High-sensitivity C-reactive protein and the ratio of total cholesterol to high-density lipoprotein cholesterol were independent risk predictors. Conclusion: As high-sensitivity CRP is an independent cardiovascular risk predictor, adding it to lipid screening may be a good procedure for identifying women at risk of cardiovascular diseases. Keywords: High sensitivity C-reactive protein, Cardiovascular events, Amyloid-A, Lipids, Inflammatory markers

Adiponectin and Stnfr2 peripheral levels are associated with cardiovascular risk in patients with schizophrenia

ObjectivesTo investigate the association between cytokine peripheral levels and the risk of cardiovascular disease in patients with schizophrenia and controls. MethodsA sample of 40 patients and 40 control subjects participated in the study. Psychiatric diagnosis was established following structured clinical assessment. The Framingham Score was used to assess cardiovascular risk (CVR). Serum levels of the cytokines IL-1β, IL-6, IL-8, IL-10, IL-12p70 and TNF-α were determined by cytometric bead array (CBA) technique, and the serum levels of IL-33, sST2, sTNFR1, sTNFR2, Leptin and Adiponectin by Enzyme-Linked Immunosorbent assay (ELISA). ResultsPatients with schizophrenia showed greater frequency of moderate CVR when compared with controls (p = 0.14). In addition, patients showed higher levels of sTNFR2 and Adiponectin compared to controls (p = 0.007 and p < 0.001, respectively). Adiponectin and sTNFR2 were associated with CVR only in patients (p = 0.0002 and p = 0.033, respectively). In multivariate analysis controlling for socio-demographic and clinical confounders, illness duration (r = 0.492; p < 0.002) and sTNFR2 (r = 0.665; p < 0.004) were independent predictors of CVR. ConclusionOur results reinforce the concept that patients with schizophrenia are at greater risk to develop cardiovascular diseases, and suggest that the associated chronic low-grade inflammation might play a role in this process.

TyG index as a cardiovascular risk factor, with reference to anthropometry in first year medical students - A cross sectional study

Triglyceride-Glucose (TyG) index is an independent predictor of cardiovascular risk in several pathological conditions such as T2DM, Metabolic syndrome (MetS), CVD, and CAD. Early studies which were done on TyG index focus on insulin resistance. High TGL level induces production of small density LDL particle. All these proposed theories, explains why TyG index used as an independent factor of cardiovascular risk.150 First year medical students were included and their anthropometric measures done using standard scale. Fasting blood glucose estimated by GOD POD method. Total cholesterol, triglyceride, High density lipoprotein and direct low density lipoprotein were estimated by IFCC approved methods. Statistical analysis was performed using IBM SPSS version 20.Results 26% were obese and 5.33% were overweight. Lipid profile found to be significant different among the group. Atherosclerotic indices were found to have mild to moderate correlation with anthropometric measures (p &amp;#60; 0.05).Present study showed a high prevalence of overweight to obesity ratio in first year medical students. With TyG index we observed an independent association of cardio-metabolic risk with BMI in young adult.

IMPACT OF MARATHON RUNNING ON ENDOTHELIAL FUNCTION AND SUBCLINICAL ATHEROSCLEROSIS

Objective: Aerobic exercise has beneficial effects on the cardiovascular system. Marathon running is both an aerobic but also an extremely vigorous exercise. Endothelial function and carotid subclinical atherosclerosis are independent predictors of cardiovascular risk. We sought to investigate the chronic alterations of these indices in marathon runners. Design and method: We studied 30 marathon runners and 20 age- and sex-matched recreationally active control subjects. Endothelial function was evaluated with brachial flow-mediated dilatation (FMD) and early atherosclerosis with carotid intima-media thickness (cIMT). Results: Marathon runners had significantly higher systolic and pulse pressure compared to controls. They also had reduced body-mass index, waist to hip ratio and heart rate compared to controls (p &lt; 0.05, for all). Common cIMT was significantly lower in athletes than controls (0.56 ± 0.11 vs. 0.63 ± 0.07, p = 0.029), while there was no difference in carotid bulb IMT between groups. FMD was higher in marathon runners compared to controls and nitrate-mediated dilatation (NMD) was similar in the two groups (9.0 ± 3.7 vs. 6.4 ± 1.7 and 12.6 ± 5.7 vs. 12.3 ± 3.4; p = 0.002 and p = 0.821, respectively). (Figure) We also observed a reverse U-shaped curve between endothelial function and amount of exercise. FMD was significantly inversely associated with the number of training days per week (r = -0.430, p = 0.018). Conclusions: Marathon runners have higher FMD compared to controls, indicating better vascular endothelial function, and also have lower cIMT compared to controls. Increased amount of exercise training seems to eradicate the beneficial effect of exercise on endothelial function. These findings provide further insights in the effects of marathon running on cardiovascular risk.

Improvement of Arterial Stiffness One Month after Bariatric Surgery and Potential Mechanisms.

Arterial stiffness (AS) is an independent predictor of cardiovascular risk. We aimed to analyze changes (Δ) in AS 1-month post-bariatric surgery (BS) and search for possible pathophysiological mechanisms. Patients with severe obesity (43% hypertensives) were prospectively evaluated before and 1-month post-BS, with AS assessed by pulse-wave velocity (PWV), augmentation index (AIx@75) and pulse pressure (PP). Ambulatory 24 h blood pressure (BP), anthropometric data, renin-angiotensin-aldosterone system (RAAS) components and several adipokines and inflammatory markers were also analyzed. Overall reduction in body weight was mean (interquartile range (IQR)) = 11.0% (9.6–13.1). A decrease in PWV, AIx@75 and PP was observed 1-month post-BS (all, p < 0.01). There were also significant Δ in BP, RAAS components, adipokines and inflammatory biomarkers. Multiple linear regression adjusted models showed that Δaldosterone was an independent variable (B coeff.95%CI) for final PWV (B = −0.003, −0.005 to 0.000; p = 0.022). Angiotensin-converting enzyme (ACE)/ACE2 and ACE were independent variables for final AIx@75 (B = 0.036, 0.005 to 0.066; p = 0.024) and PP (B = 0.010, 0.003 to 0.017; p = 0.01), respectively. There was no correlation between ΔAS and anthropometric changes nor with Δ of adipokines or inflammatory markers except high-sensitivity C-reactive protein (hs-CRP). Patients with PWV below median decreased PWV (mean, 95%CI = −0.18, −0.25 to −0.10; p < 0.001) and both AIx@75 and PP at 1-month, but not those with PWV above median. In conclusion, there is an improvement in AS 1-month post-BS that correlates with ΔBP and Δrenin-angiotensin-aldosterone components. The benefit is reduced in those with higher PWV.

Corrected QT interval prolongation: A new predictor of cardiovascular risk in patients with non-St-elevation acute coronary syndrome. Algerian cohort

Recently we reported that prolongation of the corrected QT (CTc) interval is an independent risk factor in patients with unstable angina and acute ischemic changes. The aim of this study was to determine the prognostic value of the corrected QT (CTc) interval in patients with non-ST-segment elevation acute coronary syndrome who do not exhibit acute ischemic changes on admission ECG. The study included 195 patients with this syndrome. On admission, a standard 12-lead ECG was recorded, the cardiac troponin-T was measured and aTIMI (Thrombolysis in Myocardial Infarction) risk score was calculated. The primary endpoint was the combination of nonfatal acute myocardial infarction, percutaneous or surgical revascularization, and cardiac death up to 30 days after discharge. Two independent investigators measured the QT interval manually and the corrected value was derived using Bazett's formula. In the statistical analysis, the following cut-off points were used: the median TIMI risk score, a cardiac troponin-T level of 0.04 ng/mL, and a QTc of 0.458 s. Of the 74 patients (38%) who reached the primary endpoint, 59 (80%) had QTc prolongation. Binary logistic regression analysis showed that QTc prolongation was an independent predictor of the combined endpoint. This study shows that QTc prolongation is an independent predictor of cardiovascular risk in patients with non-ST-segment elevation acute coronary syndrome but without acute ischemic changes on admission ECG.

Evaluation and Comparative Correlation of Abdominal Fat Related Parameters in Obese and Non-obese Groups Using Computed Tomography.

Obesity is a significant risk factor for cardiovascular (CV) disease. Abdominal fat is composed of abdominal subcutaneous fat and intra-abdominal (visceral) fat. Computed tomography (CT) is considered one of the most accurate and reliable methods for assessing abdominal fat. The present study was based on evaluating abdominal fat by computed tomography and the determination of association between CT obtained abdominal fat volumes, anthropometric indices, and lipid profile. The prospective study was carried out on 120 subjects referred to the Radiology department for a CT scan. Non - contrast CT scan was performed with 5 mm slice thickness. Abdominal fat volumes were recorded by using CT attenuation values (- 250 to -50 HU). The section was selected at the level of the umbilicus (L4-L5). Intra-abdominal fat and subcutaneous fat volumes were calculated. Body Mass Index (BMI) and lipid profile were recorded for each subject. A comparative study of the CT values, BMI, and lipid profile was undertaken. In the present study, by comparing the anthropometric parameters, CT findings, and lipid profile and blood parameters of the obese and non-obese groups by sex revealed significant sex differences in all the parameters under study. It was also found that the obese male and female groups showed a high prevalence of diabetes, Non-Alcoholic fatty liver disease (NAFLD), and hypertension than non-obese groups. This finding also adds to the chances of getting cardiovascular diseases, specifically in obese individuals. The results found that in obese males and females the abdominal fat-related parameters Visceral fatty acid (VFA) and subcutaneous fatty acid (SFA) showed highly significant relation to anthropometric parameters like BMI, waist circumference (WC) and waist/hip (W/H) ratio on the other hand blood parameters high-density lipoprotein (HDL), low-density lipoprotein (LDL), very-low-density lipoprotein (VLDL), total cholesterol and triglycerides to some extent have a significant relation to abdominal fat-related parameters. In non-obese groups, by studying the influence of anthropometric parameters on abdominal fat-related parameters, it was revealed that WC was strongly affected by the VFA in both sexes. In obese females, more fat was accumulated in the VFA and SFA and for obese males in SFA and for non-obese males in total fatty acid (TFA). Computed tomography assessed visceral fat area remains the most sensitive independent predictor of cardiovascular risk.