Elevated Cardiovascular Risk Research Articles

Metabolism and Clinical Significance of Triglycerides

Triglycerides, the principal form of fat storage in animals and humans, are essential in view of their roles in energy metabolism and regulation. Indeed, they have been ascribed very vital functional significance in a plethora of physiological processes, which extends to energy storage, metabolic signaling, and disease pathology. Biochemistry and metabolism of triglycerides is a multivaried area of science that includes different mechanisms that control synthesis, storage, and utilization in organisms. For many years, the issue of triglycerides and their relationship to cardiovascular disease (CVD) has been one of the central themes of research. Elevated triglyceride levels frequently associate with an elevated cardiovascular risk, but the situation is complex and multifaceted at all. It has now been reported that triglycerides could act not only as a biomarker regarding cardiovascular risk but also play an actual part in the fostering of cardiovascular disorders. The present literature review juxtaposes key findings on triglyceride metabolism, thereby underlining implications for health and disease, with the end to identify works currently associating triglyceride implications in cardiovascular health, and further to explore determinants of triglyceride levels gap that warrant further investigation.

Prediabetes and cardiovascular diseases: a serious but overlooked issue

The elevated risk of cardiovascular diseases and prediabetes is a practical area of concern although there is dearth of data coming from across the globe despite epidemiological studies connecting the duo. Recent meta-analysis in BMJ reported relative risk of 1.15 for a composite of cardiovascular disease and 1.16 for ischaemic heart disease in the prediabetic population as opposed to that in the population with normal sugar levels. A recent research placed a 25% elevated risk of myocardial infarction in the prediabetic population along with greater chances of undergoing various forms of revascularization. Prediabetes although defined by numbers and classified as IFG (Impaired fasting glucose) and IGT (Impaired glucose tolerance), debates still exit on the cutoffs to be used and also on use of HbA1C to define prediabetes. Recent Chinese study looked at age specific cut offs for the interplay between prediabetes and elevated cardiovascular disease risk and found family history as an important pointer in the younger age group and life style factors to be of importance in older age group. More research and studies encompassing the global population at large needs to be done to eliminate the population bias involved in a nationwide studies, with insights into the Sirtuin proteins SRT1- 7 and its modulators, whose impact on cardiovascular disease is well established.

Relationship between renin, aldosterone, aldosterone-to-renin ratio and left ventricular mass index in young adults

Abstract Background Primary aldosteronism (PA), characterised by excessive aldosterone production and mineralocorticoid receptor activation, is associated with adverse cardiovascular outcomes including left ventricular hypertrophy and failure. Elevated cardiovascular risk is observed even in milder and subclinical forms of PA, especially in middle-aged and elderly populations. It is unclear if early changes in PA biomarkers can affect left ventricular mass index (LVMI), which is a strong predictor of cardiovascular diseases. Aim To evaluate the relationship between PA biomarkers, namely renin concentration, aldosterone concentration and aldosterone-to-renin ratio (ARR), and LVMI in young adults. Methods The Raine Study is a longitudinal, population-based cohort study in Western Australia that enrolled women during pregnancy. We analysed the data from the offspring of these women at age 27. Participants with PA biomarkers and LVMI measured by cardiac magnetic resonance imaging were included. Females who were on oral contraception were excluded due to its confounding effect on the ARR. We examined the relationship between LVMI and plasma renin, aldosterone, and ARR using multivariate-adjusted linear regression and used mediation analysis to test whether these relationships were dependent on systolic blood pressure (SBP). Results Of 758 participants, 252 (33.2%) were females and the mean (SD) age was 26.7 (0.4) years. Females had lower median plasma renin concentration (12.0 vs 15.4mU/L; p<0.001) and higher median ARR (21.0 vs 15.6; p<0.001) than males. There was no sex-difference in median plasma aldosterone concentration (257 vs 237pmol/L in males; p=0.143). Females had lower LVMI (52.2 vs 70.2 g/m²; p<0.001) than males. A significant association between LVMI and aldosterone was detected in males (β-coefficient 0.009; 95% CI 0.001 to 0.017; p=0.027), and between LVMI and ARR in females (β-coefficient 0.098; 95% CI 0.001 to 0.196; p=0.050) after adjusting for confounders. This relationship was not mediated by brachial SBP. Conclusion An elevated aldosterone concentration or ARR was associated with higher LVMI in young adults, independent of brachial SBP. Long-term follow-up is required to determine if the relationship persists over time and leads to reduced cardiac function. One may speculate that an intervention trial in young adults with subclinical PA is warranted to determine the role of aldosterone blockade in preventing future cardiovascular diseases.

Direct IL-6 inhibition prevents arterial thrombosis by reducing collagen-mediated platelets activation

Abstract Introduction Interleukin 6 (IL-6) has a pivotal role in atherothrombosis. Yet, targeting IL-6 to prevent atherothrombotic events still requires validation of efficacy and safety. The recent phase 2 RESCUE trial reported that direct inhibition of IL-6 ligand by the monoclonal antibody (mAb) Ziltivekimab is safe in patients with elevated cardiovascular risk. Purpose This project investigated the effects of direct IL-6 inhibition on arterial thrombosis, and assessed the underlying cellular mechanisms. Methods Three month old C56Bl/6 male mice received very-low dose LPS i.p. for 4 weeks. During the last week they were randomized to receive in addition either anti-mouse IL-6 mAb 200 μg i.p. every other day or IgG1 isotype control. Then thrombosis of left common carotid artery (LCCA) was induced by laser injury under anesthesia. Platelets of treated mice were isolated and stimulated with either adenosine di-phosphate (ADP), collagen-related peptide (CRP) or thrombin receptor activating peptide (TRAP). Platelets activation was measured by flow-cytometry, as expression of P-selectin and JON/A.The effect of direct IL-6 inhibition was confirmed in patients with stable coronary artery disease (sCAD) by ex-vivo incubation of isolated platelets with either anti-human IL-6 mAb 1.5 μg/mL or IgG1 isotype control. Platelet activation was measured by flow-cytometry, as expression of P-selectin. Results Mice treated with anti-IL6 antibody displayed a significantly longer time-to-occlusion after the LCCA (Figure 1), without any significant difference in coagulation parameters. After stimulation with CRP, platelets were significantly activated in control mice, but not in mice treated with anti-IL6 mAb. Similarly, activation of isolated platelets from patients with sCAD was significantly reduced (Figure 2) by the ex-vivo treatment with anti-IL6 mAb. Conclusion The direct inhibition of IL-6 reduces platelets reactivity to collagen, thereby blunting arterial thrombosis upon endothelial damage. These results provide a potential mechanism to explain the reduction of cardiovascular risk associated to direct IL-6 inhibition. Conclusion The direct inhibition of IL-6 reduces platelets reactivity to collagen, thereby blunting arterial thrombosis upon endothelial damage. These results provide a potential mechanism to explain the reduction of cardiovascular risk associated to direct IL-6 inhibition.Figure 1Figure 2

Cardiac risk confrontation in primary care as a teachable moment towards improved health outcomes

Abstract Background Urgent life events, such as acute coronary events, can evoke a teachable moment (TM) for lifestyle change. This study aims to investigate whether less urgent events, such as being confronted with an increased risk of cardiovascular disease, can evoke a TM, what psychosocial factors are associated with it, and whether experiencing such a TM predicts improved health outcomes. Methods The study included 114 patients who were informed about their elevated cardiovascular risk during a primary care visit. Participants completed a survey assessing whether they experienced a TM and several psychosocial factors linked to experiencing it: perceived risk, affective impact, changed self-concept. Participants monitored their weight and blood pressure for six months using an at-home self-monitoring device. Univariate and multivariate regression analyses were conducted to examine the associations between the psychosocial factors and the lifestyle change intentions with changes in blood pressure and weight. Results Of the participants, 55.3% experienced increased lifestyle change intentions. Lower risk perception ((B = -0.27; CI = -0.39-(-0.15)) and higher change in self-concept (B = 0.34; CI = 0.23-0.44) were associated with higher intention to change lifestyle. Higher risk perception (B = 0.23; CI = 0.06-0.42) and higher change in self-concept (B = 0.54; CI = 0.37-0.72) predicted a lower weight reduction at six months. A higher change in self-concept predicted a higher blood pressure reduction (B = -3.32; CI = -6.55-(0.09)). Lastly, a higher lifestyle change intention predicted bigger reductions blood pressure (B = -5.04; CI = -9.08-(-0.29)). Conclusions Results suggest that less urgent cardiac events, such as a confrontation with an increased cardiac risk, can be experienced as a TM that urges lifestyle change intentions and affects health outcomes. Risk confrontations in primary care therefore offer a unique opportunity to provide lifestyle counseling at the right moment. Key messages • A confrontation with an increased cardiac risk in primary care can be experienced as a teachable moment. • Experiencing a teachable moment after a cardiac risk confrontation in primary care affects health outcomes.

Free fatty acids and mortality among adults in the United States: a report from US National Health and Nutrition Examination Survey (NHANES)

Abstract Introduction Free fatty acids (FFAs) serve as vital energy sources in multiple body tissues and they have been associated with elevated cardiovascular disease risk and mortality. There is a scarcity of prospective studies examining the associations between specific FFAs and long-term health outcomes. Purpose To examine the correlation between different FFAs types and all-cause or cardiovascular mortality in a large, nationally representative sample of adults in the United States (US), and examine how different concentrations and types of FFAs may mediate this association. Methods This cohort study included 3719 and 3900 participants in the unsaturated fatty acids (USFAs) and saturated fatty acids (SFAs) populations, respectively, who participated in the US National Health and Nutrition Examination Survey (NHANES) from 2011-2014. Multiple model calibration was performed using univariate and multivariate cox regression analysis to explore the associations between circulating FFAs and all-cause or cardiovascular mortality. Results The UFAs (myristoleic acid (14:1 n-5), palmitoleic acid (16:1 n-7), cis-vaccenic acid (18:1 n-7), nervonic acid (24:1 n-9), eicosatrienoic acid (20:3 n-9), docosatetraenoic acid (22:4 n-6), and docosapentaenoic acid (22:5 n-6)) were associated with an elevated risk of all-cause mortality ((hazard ratio (HR) 1.02 [1.006-1.034]; P=0.004), (HR 1.001 [1.001–1.002]; P＜ 0.001), (HR 1.006 [1.003–1.009]; P＜ 0.001), (HR 1.007 [1.002–1.012]; P = 0.003), (HR 1.027 [1.009–1.046]; P= 0.003), (HR 1.024 [1.012–1.036]; P＜ 0.001) and (HR 1.019 [1.006–1.032]; P = 0.005), respectively), whereas docosahexaenoic acid (22:6 n-3) was linked to a lower risk (HR 0.998 [0.996–0.999]; P = 0.007). Among SFAs, palmitic acid 16:0 was associated with a higher all-cause risk (HR 1.00 [1.00–1.00]; P = 0.022), while tricosanoic acid (23:0) and lignoceric acid (24:0) were associated with lower risks (HR 0.975 [0.959–0.991]; P = 0.002) and (HR 0.992 [0.984–0.999]; P = 0.036). Kaplan–Meier survival curves according to FFAs quartiles shown the highest risk for all-cause mortality was observed in the group with the highest concentration, except serum 23:0. The association between FFAs concentration and cardiovascular mortality in the multivariate analysis indicated that only 22:6 n-3 (HR 0.997 [0.994-1.000]; P=0.035) had a lower risk of cardiovascular mortality in the USFAs group, while none of the SFAs was found to be associated with cardiovascular mortality. While, the relationship between 22:6 n-3, and cardiovascular mortality was characterized by neither a linear nor nonlinear association (P-linear = 0.215; P-nonlinear = 0.260). Conclusion In this cohort of US adults, the types and concentrations of FFAs exhibited significant associations with risk of all-cause mortality. Achieving optimal concentrations of specific FFAs effectively lowered this risk of all-cause mortality, but this benefit was not observed in regards to cardiovascular mortality.FFA and all-cause mortality

Unravelling cardiomyopathies: a comprehensive analysis of phenotypic diversity, endomyocardial biopsy patterns, and the impact of Gremlin-1 on clinical prognosis

Abstract Background Cardiomyopathies are the main cause of progressive heart failure (HF) and despite outstanding advances of diagnostics and therapies, mortality remains high.1,2 The current phenotype-based classification of non-ischemic cardiomyopathies (NICM) is based on a clinical workflow including endomyocardial biopsy (EMB).3-5 Inflammation and fibrosis are essentially involved in progression of HF and lead to development of adverse cardiovascular (CV) events.6,7 The diagnostic algorithm facilitates risk stratification of HF patients but nonetheless risk factors often remain inapparent prior to disease incidence. Objective In this study we investigate EMB patters in patients with NICM and elucidate alterations associated with phenotypic diversity and progression of HF. Methods We prospectively enrolled patients with HF due to NICM in a large-scale all-comers cohort (n=703). All patients underwent guideline-based phenotypic classification including EMB, and RNA data were acquired alongside histological analyses within the myocardium. We then performed a ten-year follow-up to screen for disease progression. Results A guideline-based classification of patients with NICM resulted in a phenotyping of aetiological risk groups (Figure 1A). We found that characteristic expression of fibroinflammatory mediators within the myocardium occurred in patients with symptomatic NICM (Figure 1B). We found that elevated expression of Gremlin-1 (Grem), a potent downstream profibrotic mediator of TGFß pathway, was associated with pro-fibrotic cardiac remodelling (Figure 1C). Further, Gremlin-1 was associated with a significant decrease of left ventricular functional capacity and inversely correlated with late gadolinium enhancement (LGE) (Figure 1D&E). Moreover, the expression of Gremlin-1 was enriched with pro-fibrotic and inflammatory RNA signalling pathways hinting at underlying pathophysiological cascades (Figure 2A&B). Most strikingly, the expression of Gremlin-1 was independently associated with an increased CV risk during the ten-year follow-up (Figure 2C). Thus, patients with Gremlin-1+ EMB were at elevated risk to suffer from all-cause mortality and number of patients eligible for ICD implantation was critically enhanced in patients with Gremlin-1+ EMB (Figure 2D-F). In addition, the estimation of an elevated CV risk by machine learning including Gremlin-1 improved the ten-year risk stratification among all patients with NICM (Figure 2G). Thus, Gremlin-1 was associated with cardiac remodelling and disease activity in HF patients (Figure 2H). Conclusion Our results unveiled that Gremlin-1 is associated with inflammation and cardiac remodelling in patients with symptomatic cardiomyopathy and patients with Gremlin-1+ EMB are at elevated risk to develop adverse CV events. Thus, the histological evaluation of Gremlin-1 may help to identify pathophysiological cascades and improve early risk discrimination and management of HF patients.Figure 1Figure 2

Sex related cardiovascular risk is non-dichotomous: artificial intelligence enhanced electrocardiography reveals continuum of risk in females

Abstract Background Females are typically underserved in cardiovascular medicine and often considered lower risk of cardiovascular disease. The use of sex as a dichotomous variable for risk stratification fails to capture the heterogeneity of risk within each sex. Purpose We aimed to develop an artificial intelligence-enhanced ECG (AI-ECG)-derived continuous sex score that can capture the continuum of risk and sex phenotypes within each sex, with the particular goal of addressing the female disadvantage. Methods We trained a convolution neural network to identify sex using the 12-lead ECG. The derivation cohort was 1,163,401 ECGs from 189,538 subjects from a USA secondary care hospital cohort and validated inthe UK Biobank (UKB). The model outputs a continuous value from 0 to 1 for sex prediction. The AI-ECG sex discordance score is the difference between predicted sex and biological sex. Results AI-ECG accurately identified sex in both the USA cohort (AUROC 0.943 (0.942-0.943)) and UKB datasets (n = 42,386, AUROC 0.971 (0.969-0.972)). In explainability analyses we found QRS duration, T wave morphology, QT interval, heart rate and QRS voltage as the most important factors in contributing to AI-ECG sex identification. In females only but not in males, sex discordance score was associated with a covariate-adjusted increased risk of cardiovascular death in outpatients with normal ECGs from the USA cohort, (Females hazard ratio (HR) 1.64 (1.18-2.29) p = 0.003, Males HR 1.04 (0.66-1.63), p = 0.86). This pattern persisted in the UKB: Females HR 1.39 (1.08-1.78) p = 0.01, Males HR 0.97 (0.77-1.22), p = 0.80, Fig 1). In phenome-wide association studies, we found females with a higher sex score discordance were more likely to have heart failure or myocardial infarction. Covariate-adjusted cox models confirmed the association of sex score discordance with increased future heart failure (HR 1.21 (1.07-1.37) p = 0.002 and future myocardial infarction (HR 1.32 (1.11-1.56) p = 0.001). In age- and body size-adjusted analyses, females with higher sex discordance score had increased left ventricular mass, and chamber volumes as well as increased muscle mass, reduced body fat percentage (Fig 2). In a genome-wide association study of sex discordance score we identified variants adjacent to IGF1R and NDRG4 in females, which have been previously associated with LV mass and sex hormone levels (Fig 2). Conclusion We describe sex discordance score as a novel AI-ECG biomarker capable of identifying females with disproportionately elevated cardiovascular risk. Sex discordance score may help uncover potential underlying mechanisms of cardiovascular disease among females, and future clinical studies are needed to determine its potential utility in identification of females at higher risk of cardiovascular events. Rather than exacerbating biases, AI-ECG has the potential to reduce female cardiovascular health inequalities.

Active surveillance for cardiac complications after major noncardiac surgery: implications on resource utilization and safety in high-risk patients

Abstract Background The 2022 ESC guidelines on cardiovascular assessment and management of patients undergoing noncardiac surgery recommend that high-risk patients should undergo active surveillance for cardiac complications, including perioperative myocardial infarction/injury (PMI), following major noncardiac surgery. Unfortunately, little is known about the resource use and safety of active surveillance compared to a control cohort (i.e. without active surveillance). Objective To quantify the impact of active surveillance for cardiac complications, by perioperative cardiac troponin (cTn) measurements and a systematic PMI work-up on working days, on resource usage and safety. Methods We did a retrospective comparison of non-randomised pre- vs post-implementation of an active surveillance program for cardiac complications in patients at elevated cardiovascular risk undergoing noncardiac surgery at two hospitals in Switzerland. The two cohorts' resource use and safety were compared. Resource use encompassed perioperative cTn measurements, ECGs, cardiac imaging, cardiology consultations as well as coronary angiography (CAG) and revascularisation procedures. Safety was assessed based on the number of "seemingly normal CAG" and complications arising from CAG and revascularisation procedures. Results A total of 13’147 patients, 10’346 in the active surveillance cohort and 2’805 in the standard-of-care (SOC) cohort, were eligible for this analysis. Patient characteristics between both cohorts were comparable (e.g. median age of 74 vs 73 and 44.8% vs 43% female, respectively). Patients in the active surveillance cohort underwent significantly more perioperative cTn measurements (86.4% vs 3.5%, respectively), postoperative ECGs (13.5% vs 5.7%), postoperative cardiac consultations (5.9% vs 2.4%), postoperative transthoracic echocardiogram (TTE) (7.5% vs 6.1%), postoperative myocardial perfusion imaging (MPI) (1.2% vs 0.6%), and postoperative CAG (0.8% vs 0.4%, all p <0.05). The increased resource use led to a substantial increase in detected cardiac complications within the first 48h after surgery: active surveillance 1’207 (12%) (95%CI 11%-12%) vs SOC 68 (2.4%) (95%CI 1.9%-3.1%). The active surveillance cohort generated an overall cardiac management cost of 236 Euros (95%CI 223–250) per patient vs 133 Euros (95%CI 110–160) per patient in the SOC cohort, resulting in an incremental cost for the active surveillance of 103 Euros (95%CI 110–160) per patient. Thereby the cost of detecting one additional cardiac complication within 48h was 989 Euros. Concerning safety, no significant differences in the number of "seemingly normal CAG" (6.4% vs 15%, p=0.1) and complications due to CAG and revascularisation (0.6% vs 5.1%, p=0.08) were observed. Conclusion The active surveillance for cardiac complications is safe when compared to a standard-of-care cohort while 989 Euros per additional detected cardiac complication seems reasonably priced.Resource-utilization tableOverview

Digital, Social Micro-Interventions to Promote Physical Activity Among Midlife Adults With Elevated Cardiovascular Risk: An Ambulatory Feasibility Study With Momentary Randomization.

Although regular physical activity (PA) mitigates the risk for cardiovascular disease (CVD) during midlife, existing PA interventions are minimally effective. Harnessing social influences in daily life shows promise: digital micro-interventions could effectively engage these influences on PA and require testing. This feasibility study employed ecological momentary assessment with embedded micro-randomization to activate two types of social influences (i.e., comparison, support; NCT04711512). Midlife adults (N = 30, MAge = 51, MBMI = 31.5kg/m2, 43% racial/ethnic minority) with ≥1 CVD risk conditions completed four mobile surveys per day for 7 days while wearing PA monitors. After 3 days of observation, participants were randomized at each survey to receive 1 of 3 comparison micro-interventions (days 4-5) or 1 of 3 support micro-interventions (days 6-7). Outcomes were indicators of feasibility (e.g., completion rate), acceptability (e.g., narrative feedback), and potential micro-intervention effects (on motivation and steps within-person). Feasibility and acceptability targets were met (e.g., 93% completion); ratings of micro-intervention helpfulness varied by intervention type and predicted PA motivation and behavior within-person (srs=0.16, 0.27). Participants liked the approach and were open to ongoing micro-intervention exposure. Within-person, PA motivation and behavior increased from baseline in response to specific micro-interventions (srs=0.23, 0.13), though responses were variable. Experimental manipulation of social influences in daily life is feasible and acceptable to midlife adults and shows potential effects on PA motivation and behavior. Findings support larger-scale testing of this approach to inform a digital, socially focused PA intervention for midlife adults.

Value of preparticipation cardiovascular evaluation of master athletes by self-reported symptoms and cardiovascular risk-score

Purpose The risk of sudden cardiac death (SCD) is increased during endurance competitive sports. Coronary artery disease (CAD) is the most common cause of SCD in master athletes ≥ 35 years old (MAs). To reduce the risk of SCD self-assessment of symptoms by questionnaire, and evaluation of cardiovascular risk-score, are recommended as pre-participation cardiovascular evaluation (PCVE). We aimed to examine whether PCVE predicts CVD in MAs with or without increased risk as measured by validated score instruments. Methods We performed a single-site observational cohort study of healthy MAs based on findings at PCVE. They were allocated in two different groups: those MAs with reported symptoms on the questionnaire and/or with elevated cardiovascular risk score were allocated to a symptom group (SG), while MAs with no symptoms, nor raised risk score were defined as control group (CG). Thereafter, all were examined with extended examinations: resting-ECG, cardiorespiratory exercise testing and echocardiography. Results Total, 81 (18 women) MAs participated in the study. There were no differences at baseline between SG (n = 39) and CG (n = 42); sex (p = 0.11), age (55.0 ± 9.8 vs. 51.9 ± 11.1 years; p = 0.18), maximal oxygen uptake (49.8 ± 7.6 vs. 51.6 ± 7.0 ml/kg/min; p = 0.26), resting heart rate (61.4 ± 12.8 vs. 60.2 ± 11.0/min; p = 0.66), training hours/week (7.0 ± 3.2 vs. 7.1 ± 3.1; p = 0.88). After further examination, sixteen (20%) MAs were found with CVD: 12 in SG, 4 in CG (p = 0.024). The negative predictive value and specificity of the PCVE were 90% and 58%, respectively. Conclusion Negative findings on PCVE by questionnaire and cardiovascular risk-score may be a strategy to exclude subjects from preparticipation screening, thus saving resources.

Unraveling the impact of abdominal arterial calcifications on kidney transplant waitlist mortality through ensemble machine learning

The scarcity of organ donors relative to the number of patients with End Stage Kidney Disease (ESKD) has led to prolonged waiting times for kidney transplants, contributing to elevated cardiovascular mortality risk. Transplant professionals are tasked with the complex allocation of limited organs to a vulnerable patient group facing heightened morbidity and mortality risk. The need for continuous re-evaluation of waitlisted patients is evident due to the significant number who perish while awaiting transplantation. Among individuals with ESKD, vascular calcification, particularly Abdominal Arterial Calcifications (AAC), holds predictive value for cardiovascular events and mortality. However, a standardized method to quantify AAC’s prognostic potential remains lacking, especially for kidney transplant evaluations. This study presents an ensemble machine learning (ML) approach to study the relationship between AAC score and mortality in patients on the waitlist and triage patients needing transplantation. Using the AAC score, the proposed ML model can predict kidney transplant waitlist morality with an accuracy of 78% while its accuracy is 68% without using this score. This study leverages explainable ML to explore the relationship between predictors and mortality in waitlisted patients, aiming to improve patient triage accuracy.

Elevated Plasma Atherogenic and Triglyceride-Glucose Indices: Markers of Cardiovascular Risk in Transfusion-Dependent Thalassemia

Background Transfusion-dependent thalassemia (TDT) is an autosomal recessive disorder characterized by defective hemoglobin synthesis, leading to severe complications such as iron overload and multi-organ dysfunction. This study aims to elucidate the distinctive clinical and biochemical profiles of TDT patients compared to healthy controls, with an emphasis on cardiovascular risk assessment using novel markers such as the Plasma Atherogenic Index (PAI) and Triglyceride-Glucose (TyG) index. Methods This cross-sectional study included 32 TDT patients and 36 healthy controls, matched for age and gender. Comprehensive demographic, laboratory, and imaging data were collected and analyzed. TDT patients were further stratified based on cardiac involvement and ferritin levels. Key assessments included hemoglobin levels, liver enzymes, lipid profiles, and cardiac imaging. The PAI and TyG index were calculated to evaluate cardiovascular risks. Statistical analyses were performed using SPSS 27.0, employing Student’s t-test, Mann–Whitney U test, and Pearson chi-square test as appropriate. Results No significant differences in basic demographic parameters were observed between groups; however, TDT patients exhibited significant clinical and laboratory differences. Notably, these patients had lower hemoglobin levels, higher platelet counts, elevated liver enzymes (ALT and AST), and markedly increased ferritin levels. Lipid profiles were significantly altered, with lower levels of total cholesterol, HDL, and LDL but elevated triglycerides. Importantly, the PAI was significantly higher in TDT patients, suggesting an increased atherosclerotic risk. Subgroup analysis revealed that patients with cardiac involvement had worse metabolic profiles, higher TyG indices, and prolonged QT intervals, indicating heightened cardiovascular risk. As the iron burden increases, the TyG index and PAI may lose their sensitivity in distinguishing between varying levels of iron overload, suggesting that their effectiveness plateaus beyond a certain threshold of iron accumulation. Conclusion TDT patients show significant hematological and metabolic deviations, including elevated cardiovascular risk markers like PAI and TyG index. As iron burden increases, these markers lose discriminative power, and cardiac involvement escalates rapidly once a critical iron threshold is surpassed, as supported by studies showing a non-linear relationship between iron load and cardiac complications. Comprehensive cardiovascular risk assessment and tailored management are essential for these patients. Future studies should focus on tracking cardiovascular risk progression and the effects of targeted interventions.

7431 Non-Insulin Treatment of Type 1 Diabetes Mellitus: The Power of GLP-1 and GLP-1/GIP RA

Abstract Disclosure: J. Ferri-Guerra: None. E. Kasper-Guerra: None. O. Abdulhussein: None. G. Madrigal Loria: None. J. Ambalavanan: None. K. Zhou: None. Background: Insulin is the mainstay of treatment of patients with type 1 diabetes mellitus (T1D). However, patients with T1D can also potentially benefit from adjunctive therapies such as GLP-1 receptor agonists or GLP-1/GIP receptor agonists, especially when obesity and elevated cardiovascular risk are present. Case 1: A 64-year-old male with severe coronary artery disease requiring revascularization and obesity with T1D has been wearing a pump for insulin delivery since the age of 43, started on closed loop system Control IQ with Tandem in April 2022. In December 2022, patient had myocardial infarction. At that time, Hba1c was elevated at 7.6% and BMI was elevated at 32.5 kg/m2, and patient was considered a good candidate for tirzepatide, which was prescribed. The tirzepatide dose was slowly increased, up to 10 mg weekly. The new therapy resulted in loss of 17 kg (20.1% decrease of body weight) with only some mild nausea. There was an improvement in HbA1c to 7.1% and a dramatic reduction in daily average insulin use from 90 units to 52 units. Case 2: A 59-year-old female with obesity and T1D diagnosed at the age of 8 had been wearing insulin pump, Medtronic 670G in manual mode, for insulin delivery for the past few years with poor glycemic control. In August 2021, patient was prescribed semaglutide for post prandial hyperglycemia and obesity management (BMI at 31.6kg/m2). Since being on the medication, she lost 12kg (16.8% decrease in body weight), despite being on the lowest dose of 0.25 mg (maximum tolerated). Her HbA1c has improved from 8.2% when therapy was initiated, to 7% with just the introduction of semaglutide to her insulin regimen. Conclusion: Although insulin is a required therapy for patients with T1D, adjunctive therapies may improve glycemic control, reduce insulin requirements and promote weight loss. GLP-1 and dual GLP-1/GIP receptor agonists should be considered for these patients. Presentation: 6/1/2024

The association between endothelial dysfunction and subclinical myocardial injury in male OSA patients

BackgroundEndothelial dysfunction was shown to contribute significantly to the elevated cardiovascular risk observed in the general population. However, the relationship between endothelial dysfunction and subclinical myocardial injury in obstructive sleep apnea (OSA) patients remains unclear.MethodsThis cross-sectional study recruited 165 consecutive male patients diagnosed with OSA. All participants underwent overnight polysomnography to confirm the diagnosis and assess the severity of OSA. Subclinical myocardial injury was evaluated using high-sensitivity cardiac troponin I (hs-cTnI) measurements, while endothelial dysfunction was assessed through the peripheral arterial tonometry.ResultsEndothelial dysfunction was present in 80 (48.5%) of the subjects. Hs-cTnI was detectable in 147 (89.1%) of the participants. When compared to OSA patients without endothelial dysfunction, those with endothelial dysfunction exhibited significantly lower percentages of hypertension (23.8%versus43.5%, p=0.007) and abdominal obesity (76.3%versus88.2%, p=0.043). Patients with endothelial dysfunction frequently manifest a lower apnea-hypopnea index and oxygen desaturation index. Despite comparable median hs-cTnI levels, a higher proportion of subjects with detectable hs-cTnI levels was observed among those with endothelial dysfunction (95%versus83.5%, p=0.018). Logistic regression analysis indicated that endothelial dysfunction was significantly associated with a detectable level of hs-cTnI after adjustment for multiple confounders.ConclusionsIn male OSA patients, endothelial dysfunction appears to be potentially correlated with an increased risk of subclinical myocardial injury, as evidenced by the higher prevalence of detectable hs-cTnI levels. Further investigations are warranted to elucidate the role of endothelial dysfunction in predicting future cardiovascular mortality in this population.

VascuFit: Aerobic exercise improves endothelial function independent of cardiovascular risk: A randomized-controlled trial.

Background and aimsEndothelial dysfunction predicts elevated cardiovascular (CV) risk in healthy individuals. Aerobic exercise reduces endothelial dysfunction in part by improving CV risk factors. Yet, this explains less than 50% of the effect and a direct influence of exercise training on the endothelium is discussed as possible contributor. The VascuFit study applied non-linear periodized aerobic exercise (NLPE) training to assess its multilevel effects on endothelial function including potential epigenetic endothelial modifications by circulating micro-ribonucleic acids (endomiRs). MethodsSedentary adults with elevated CV risk between 40-60 years were randomized 2:1 and engaged in an eight-week ergometer-based NLPE training (n=30) or received standard exercise recommendations (n=14). Macro-, microvascular, cellular and molecular adaptations were assessed via brachial-arterial flow-mediated dilation (baFMD), static retinal vessel analysis (SVA), flow cytometry, and endomiRs regulating key pathways of endothelial function. Statistics included ANCOVA, Principal Component Analysis (PCA), and regression analyses. ResultsbaFMD improved by 2.38% (CI:0.70-4.06, p=0.007) independent of CV risk, whereas SVA parameters and circulating endothelial (progenitor) cells did not significantly change in the NLPE group. The mean distance between baseline and follow-up PCA loadings of the endomiR dataset explaining 44.2% of dataset variability was higher in the NLPE-group compared to the control group (2.71±2.02 vs. 1.65±0.93). However, regression analyses showed no evidence of endomiRs explaining the improvement of baFMD. ConclusionsThe improvement of macrovascular endothelial function by aerobic exercise training was independent from CV risk factors. Increased heterogeneity among endomiRs did not explain this effect, but suggests an adaptive response to the exercise stimulus on the epigenetic level.

Relationship Between Renin, Aldosterone, Aldosterone-to-Renin Ratio and Arterial Stiffness and Left Ventricular Mass Index in Young Adults.

Primary aldosteronism, characterized by renin-independent aldosterone production, is associated with adverse cardiovascular remodeling and outcomes. Elevated cardiovascular risk is observed even in subclinical forms of primary aldosteronism according to studies conducted primarily in middle-aged and elderly populations. This study aimed to assess whether early changes in primary aldosteronism biomarkers during young adulthood are associated with arterial stiffness and left ventricular mass index (LVMI) before the onset of overt disease. The Raine Study is a longitudinal, population-based cohort study in Western Australia that enrolled women during pregnancy. We analyzed the data from the offspring of these women at 17 (2006-2009) and 27 (2016-2018) years of age. Participants with elevated high-sensitivity C-reactive protein (>10 mg/L) and female participants who were on oral contraception were excluded. Pulse wave velocity and aortic augmentation index were measured by SphygmoCor Pulse Wave System at both ages, and aortic distensibility and LVMI were measured by cardiac magnetic resonance imaging at 27 years. Multivariable linear regression was used to examine the relationship between plasma renin, aldosterone, or aldosterone-to-renin ratio and arterial stiffness and LVMI. Mediation analysis was used to test the role of systolic blood pressure. This study included 859 participants at 17 (38.0% female) and 758 participants at 27 (33.2% female) years of age. Females had lower renin concentration at both 17 (20.7 mU/L versus 25.7 mU/L; P<0.001) and 27 (12.0 mU/L versus 15.4 mU/L; P<0.001) years of age; hence, the aldosterone-to-renin ratio was significantly higher at both 17 (18.2 versus 13.5; P<0.001) and 27 (21.0 versus 15.6; P<0.001) years of age in females compared with males. At 27 years of age, a significant association was detected between aldosterone and LVMI in males (β=0.009 [95% CI, 0.001-0.017]; P=0.027) and between aldosterone-to-renin ratio and LVMI in females (β=0.098 [95% CI, 0.001-0.196]; P=0.050) independently of systolic blood pressure and other confounders. No association was found between primary aldosteronism biomarkers and measures of arterial stiffness (pulse wave velocity, aortic augmentation index, and aortic distensibility) at either age. Aldosterone concentration and aldosterone-to-renin ratio were positively associated with the LVMI in young males and females, respectively, independently of systolic blood pressure. Long-term follow-up is required to determine whether the relationship persists over time, and clinical trials are needed to assess the cardiovascular benefits of early interventions to block aldosterone.

Evaluation of wakefulness electroencephalogram in OSA patients.

Obstructive sleep apnea (OSA) has been associated with an elevated cardiovascular risk, increased daytime sleepiness, cognitive decline, and slower electroencephalographic activity (EEG). This study assesses EEG patterns during wakefulness in OSA patients compared to those without sleep-disordered breathing. This retrospective study analyzed 30 OSA patients with an Apnea/Hypopnea Index (AHI) of 15 or higher, as well as 29 individuals without sleep-disordered breathing (AHI of 5 or lower) who underwent hospital polysomnography and met all inclusion criteria. Sociodemographic and EEG data were obtained from the sleep laboratory database. Blinded EEG analysis was conducted by two observers, assessing activity in the frontal, central, and occipital regions. No significant differences were observed in EEG activity between OSA and non-OSA patients. However, a weak correlation was found between decreased C3 EEG frequency and higher AHI (p = 0.033), as well as increased total sleep time and higher O2 EEG frequency (p = 0.038). Lower amplitudes in C3 (p = 0.043) and O1 (p = 0.031) were correlated with reduced average oxygen saturation. Our findings suggest that OSA-related hypoxemia may impact neuronal activity, highlighting the need to address this sleep-disordered breathing in order to potentially prevent the cognitive decline observed in OSA patients.

Glycated Hemoglobin as a Predictor of Dyslipidemia and Cardiovascular Risk in Type 2 Diabetes Mellitus

Background: Type 2 Diabetes Mellitus (T2DM) is a globally prevalent metabolic disorder that significantly increases the risk of cardiovascular disease (CVD) through mechanisms such as dyslipidemia, characterized by elevated triglycerides, low high-density lipoprotein (HDL) levels, and small dense low-density lipoprotein (LDL) particles. Glycated hemoglobin (HbA1c) is a key biomarker of glucose control and has been associated with CVD risk. Methods: This cross-sectional study aimed to evaluate the relationship between glycated hemoglobin (HbA1c) levels and lipid profiles, specifically lipid ratios, in a Jordanian population with type 2 diabetes mellitus (T2DM). A total of 140 patients with T2DM and 20 healthy controls participated. Blood samples were analyzed for fasting blood sugar (FBS), HbA1c, total cholesterol, triglycerides, high-density lipoprotein (HDL-C), and low-density lipoprotein (LDL-C) levels. HbA1c levels were grouped: A (≤7%), B (7–9%), C (9–11%), and D (&gt;11%). Results: The T2DM group showed significantly elevated HbA1c levels compared to controls. Patients with higher HbA1c levels (Groups C and D) exhibited abnormal lipid profiles, including increased total cholesterol and triglycerides and reduced HDL-C. The LDL-C/HDL-C ratio was notably higher in patients with HbA1c &gt;9%, indicating a potential elevated cardiovascular risk. This correlation between HbA1c and lipid profile abnormalities supports the association between poor glycemic control and lipid metabolism dysregulation. Conclusion: HbA1c levels are significantly associated with dyslipidemia, and lipid ratios serve as sensitive indicators for cardiovascular risk in T2DM patients. These findings underscore the clinical importance of monitoring HbA1c and lipid ratios to improve risk assessment and guide intervention strategies in high-risk populations.

Glycogenic hepatopathy associated with hepatic steatosis in type 1 diabetes

AimsGlycogenic hepatopathy is associated with significant psychosocial consequences and health costs. Metabolic Dysfunction-Associated Steatotic Liver Disease and glycogenic hepatopathy are frequently confused as “fatty liver” when seen on ultrasonography. We wished to examine liver fat and glycogen content in groups defined based on metabolic and liver disease phenotypes. MethodsThis case-control study undertaken in a tertiary hospital used nuclear proton magnetic resonance spectroscopy (1H-MRS) to examine liver fat and glycogen content in five clinical groups, each containing five participants: 1. type 1 diabetes with glycogenic hepatopathy, 2. satisfactorily controlled type 1 diabetes with no liver disease, 3. poorly controlled type 1 diabetes without liver disease, 4. a control group of body mass index- and age-matched individuals without diabetes or liver disease, and 5. hepatic steatosis. ResultsFat content was highest in the hepatic steatosis (median 15.4 %, IQR 10.0–19.3) and glycogenic hepatopathy (median 6.5 %, IQR 4.5–9.1) groups and compared to both of these groups was lower in the control group (median 1.0 %, IQR 0.7–1.1, p 0.002 and 0.022), the T1DM group with satisfactory control (median 0.3 %, IQR 0.2–0.6, p < 0.001 and <0.001), and the T1DM group with poor control without liver disease (median 1.1 %, IQR 0.9–1.1, p 0.001 and 0.012).No participants from the type 1 diabetes poor control, type 1 diabetes satisfactory control or the no diabetes groups had 1H-MRS-diagnosed hepatic steatosis.1H-MRS glycogen content could not be interpreted in the majority of those with glycogenic hepatopathy because of interference from the fat signal. ConclusionsIn cases diagnosed with glycogenic hepatopathy there may be significant concomitant fat accumulation, compounding the already elevated cardiovascular risk in this cohort.The technique of 1H-MRS has not been demonstrated to be useful for diagnosing glycogenic hepatopathy.