Traditional Cardiometabolic Risk Factors Research Articles

Cardiovascular Risk in Patients with Ankylosing Spondylitis.

Objectives: Ankylosing spondylitis (AS) is an autoinflammatory, chronic disease. Patients with AS are at increased risk of cardiovascular disease (CVD). The link between AS and subclinical atherosclerosis is multifactorial and still not completely understood. The aim of this study was to examine the potential associations between carotid intima-media thickness (cIMT) and different cardiometabolic biomarkers in individuals with AS. Methods: A total of 96 patients with AS were prospectively included. cIMT was measured via ultrasonography. Multiple linear regression analysis was used to find the best predictors of cIMT values. Principal component analysis (PCA) was implemented to extract factors that were further tested via binary logistic regression analysis in relation to cIMT. Results: Waist circumference (WC), low-density lipoprotein cholesterol (LDL-c), and the BASDAI score were independently correlated with cIMT in AS patients (p = 0.037, p = 0.060, and p = 0.048, respectively; adjusted R2 = 0.113). PCA extracted four panels of biomarkers, i.e., "haematology-lipid-related factor" (i.e., ferritin, haemoglobin, HDL-c, and triglycerides), "proinflammatory-prothrombotic-related factor" (i.e., platelets, neutrophils, and C-reactive protein), "LDL-c-vitamin-related factor" (i.e., vitamins D and B12, and LDL-c), and "age-glucometabolic-related factor" (i.e., age and HbA1c), in relation to higher cIMT in patients with AS. Among these four clusters, "age-glucometabolic-related factor" was an independent predictor of increased cIMT (p < 0.001). Conclusions: In addition to traditional cardiometabolic risk factors, WC and LDL-c, the disease activity score (BASDAI) is independently related to subclinical atherosclerosis in AS patients. The joint involvement of heterogeneous cardiometabolic risk factors may reflect different pathophysiological processes of subclinical atherosclerosis in patients with AS.

Prevalence of Cardiometabolic Risk Factors in Women: Insights From the Houston HeartReach Study.

Cardiovascular disease is the leading cause of death among women in the United States. Past research has highlighted the importance of the relationship between female-specific demographics and traditional risk factors. The present analysis aimed to identify the prevalence of modifiable risk factors in women attending a community cardiovascular health screening. Data collected between 2011 and 2019 were obtained from the Houston HeartReach Registry. Participants were classified as having or not having each of 4 traditional cardiometabolic risk factors: hypertension, diabetes, body mass index indicating overweight or obesity, and dyslipidemia. Differences in prevalence were compared using the Pearson χ2 test. Most participants had hypertension, overweight or obesity, and dyslipidemia. Older women (≥65 years) had the highest prevalence of all cardiometabolic risk factors. Black participants had a higher prevalence of hypertension (P = .006) and a lower prevalence of dyslipidemia (P = .009) than non-Black participants. Hispanic participants had a lower prevalence of hypertension (P < .001) and a higher prevalence of overweight or obesity (P = .03) than non-Hispanic participants. Participants in the lowest household income bracket (<$25,000) were more likely to have diabetes (P = .001) and overweight or obesity (P = .004) than participants in the highest income bracket (≥$50,000). Unemployed participants had a higher prevalence of diabetes (P < .001), overweight or obesity (P = .004), and dyslipidemia (P < .001) than employed participants. Comorbidity analysis revealed clustering of multiple cardiometabolic risk factors. Moreover, risk factor hot spots were identified by zip code, which could help select future sites for targeted screening. The analysis found that cardiometabolic risk factor prevalence varies with demographic and socioeconomic status. Geographic areas where cardiometabolic risk factor prevalence was highest were also identified. Further participant recruitment and analysis are required to create predictive models of cardiovascular disease risk in women.

Early Onset Atherosclerotic Cardiovascular Disease.

Recent trends indicate a concerning increase in early-onset atherosclerotic cardiovascular disease (ASCVD) among younger individuals (age < 55 in men and <65 in women). These findings highlight the pathobiology of ASCVD as a disease process that begins early in life and underscores the need for more tailored screening methods and preventive strategies. Increasing attention has been placed on the growing burden of traditional cardiometabolic risk factors in young individuals while also recognizing unique factors that mediate risk of premature atherosclerosis in this demographic such as substance use, socioeconomic disparities, adverse pregnancy outcomes, and chronic inflammatory states that contribute to the increasing incidence of early ASCVD. Additionally, mounting evidence has pointed out significant disparities in the diagnosis and management of early ASCVD and cardiovascular outcomes based on sex and race. Moving toward a more personalized approach, emerging data and technological developments using diverse tools such as polygenic risk scores and coronary artery calcium scans have shown potential in earlier detection of ASCVD risk. Thus, we review current evidence on causal risk factors that drive the increase in early ASCVD and highlight emerging tools to improve ASCVD risk assessment in young individuals.

NAFLD and MAFLD independently increase the risk of major adverse cardiovascular events (MACE): a 20-year longitudinal follow-up study from regional Australia

Background and aimsThe association between fatty liver disease (FLD) and cardiovascular disease (CVD) in an Australian context has yet to be defined. The primary aim of this study was to investigate the association between FLD and 3-point major adverse cardiovascular events (MACE).MethodsThis was a longitudinal follow-up study of a randomly sampled adult cohort from regional Australia between 2001 and 2003. Baseline covariates included demographic details, anthropometry, health and lifestyle data, and laboratory tests. Non-alcoholic fatty liver disease (NAFLD) and metabolic-(dysfunction) associated fatty liver disease (MAFLD) were diagnosed in participants with fatty liver index (FLI) ≥ 60 and meeting other standard criteria. ICD-10 codes were used to define clinical outcomes linked to hospitalisations. Three-point MACE defined as non-fatal myocardial infarction (MI) and cerebrovascular accident (CVA) and CVD death.ResultsIn total, 1324 and 1444 participants met inclusion criteria for NAFLD and MAFLD analysis, respectively. Over 23,577 and 25,469 person-years follow-up, NAFLD and MAFLD were independent predictors for 3-point MACE, adjusting for demographic covariates and known cardiometabolic risk factors, whilst considering non-CVD death as a competing event (NAFLD: sub-hazard ratio [sHR] 1.56, 95% confidence interval [CI 1.12–2.19]; MAFLD: sHR 1.51, 95% CI 1.11–2.06). The results held true on several sensitivity analyses.ConclusionsBoth forms of FLD increase the risk for CVD independent of traditional cardiometabolic risk factors.

Accumulation of advanced glycation end products in skin and increased vascular ageing in the general population: the Malmö Offspring Study.

Advanced glycation end product (AGE) is an established risk marker for diabetic vascular disease, and associated with the degree of diabetes complications, renal failure, and atherosclerosis in middle-aged and older individuals. The relationship between AGEs and aortic stiffness has not been thoroughly examined in the younger general population. We aimed to evaluate the association between AGEs and aortic stiffness in the general population of young and middle-aged adults. We analysed cross-sectionally 2518 participants from a Swedish population-based cohort, the Malmö Offspring Study (mean age 41.8 ± 14.5 years, 52.2%). Advanced glycation end-products (AGEs) were measured by a well validated, noninvasive method using skin autofluorescence with AGE-Reader. Aortic stiffness was assessed by carotid-femoral pulse wave velocity (PWV) and augmentation index (Aix) was calibrated to a standard heart rate of 75 bpm at the arteria radialis using SphygmoCor. Multivariable linear regression was performed stratified by age to analyse the association between skin AGE and aortic stiffness. Increased levels of AGEs were significantly associated with higher direct measurements of aortic stiffness (vascular ageing) in younger individuals (PWV β 0.55 m/s, P < 0.001) after adjustment for traditional cardiometabolic risk factors, however, not in older individuals (PWV β 0.23 m/s, P = 0.10). Indirect vascular ageing was also significantly associated with higher levels of AGEs in both younger (Aix β 7.78, P < 0.001) and older individuals (Aix β 3.69, P < 0.001). Higher levels of skin autofluorescence-AGEs are positively associated with increased vascular ageing in younger adults from the general population, independent of cardiometabolic risk factors.

Higher Plasma Levels of Endocannabinoids and Analogues Correlate With a Worse Cardiometabolic Profile in Young Adults.

The endocannabinoid system (ECS) is a signaling system composed of endocannabinoids (eCBs), their receptors, and the enzymes involved in their synthesis and metabolism. Alterations in the ECS are linked to the development of cardiometabolic diseases. Here, we investigated the relationship between plasma levels of eCBs and their analogues with body composition and cardiometabolic risk factors. The study included 133 young adults (age 22.1 ± 2.2 years, 67% women). Fasting plasma levels of eCBs and their analogues were measured using liquid chromatography-tandem mass spectrometry. Body composition, brown adipose tissue (BAT) volume, glucose uptake, and traditional cardiometabolic risk factors were measured. Plasma levels of eCBs and several eCB analogues were positively correlated with adiposity and traditional cardiometabolic risk factors (eg, serum insulin and triacylglyceride levels, all r ≥ 0.17 and P ≤ .045). Plasma levels of 2-arachidonoyl glycerol and N-pentadecenoylethanolamine were negatively correlated with BAT volume and glucose uptake (all r ≤ -0.17 and P ≤ .047). We observed that the plasma levels of eCBs and their analogues were higher in metabolically unhealthy overweight-obese participants than in metabolically healthy overweight-obese participants. Our findings show that the plasma levels of eCBs and their analogues are related to higher levels of adiposity and worse cardiometabolic profile.

Abstract 14305: Experiences of Racism and Risk of Preeclampsia: Results From the Black Women’s Health Study

Introduction: In the United States (US) Black women have higher rates of preeclampsia than White women, which contributes to cardiovascular disease disparities. Differences in traditional cardiometabolic risk factors do not fully explain this disparity, and there is growing consensus that experiences of racism may be a root cause. Few studies have evaluated associations between racism and preeclampsia, and none have done so among a cohort of exclusively Black women. Research Question: Are daily and institutional racism associated with preeclampsia among Black women? Methods: We analyzed data from the Black Women’s Health Study, a follow-up study of approximately 59,000 US Black women beginning in 1995. We included 5,315 women who were nulliparous at baseline and had their first pregnancy between 1995 and 2009. Racism was measured as a total daily racism score (reported as daily exposure to interpersonal racism) and an institutional racism score (reported as ever treated unfairly due to race with respect to police, housing, or job). We used unadjusted and adjusted (age at first birth, total gravidity, baseline education attainment, health insurance, smoking, alcohol use, and Body Mass Index) logistic regression models to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for preeclampsia in quartiles of daily racism and domains of institutional racism. A sensitivity analysis examined associations for women with only one birth. Results: Among 5,315 participants, 9.2% had preeclampsia. [BK1] Compared to women in the lowest quartile of exposure to daily racism, those in the highest quartile had 53% increased odds of preeclampsia (adjusted OR 1.53; 95% CI 1.14, 2.05). Compared to women with no history of institutional racism, the ORs for preeclampsia in women who experienced institutional racism in two or three domains were 1.37 (95% CI 1.04, 1.80) and 1.27 (95% CI 0.085,1.86), respectively. Results were similar among women with only one birth: compared to the lowest quartile, women in the highest quartile of daily racism had an 89% higher risk (adjusted OR 1.89; 95% CI 1.31, 2.75). Conclusion: Racism is associated with an increased risk of preeclampsia in US Black women and may contribute to their disproportionately high prevalence of preeclampsia.

Next Generation, Modifiable Cardiometabolic Biomarkers: Mitochondrial Adaptation and Metabolic Resilience: A Scientific Statement From the American Heart Association.

Cardiometabolic risk is increasing in prevalence across the life span with disproportionate ramifications for youth at socioeconomic disadvantage. Established risk factors and associated disease progression are harder to reverse as they become entrenched over time; if current trends are unchecked, the consequences for individual and societal wellness will become untenable. Interrelated root causes of ectopic adiposity and insulin resistance are understood but identified late in the trajectory of systemic metabolic dysregulation when traditional cardiometabolic risk factors cross current diagnostic thresholds of disease. Thus, children at cardiometabolic risk are often exposed to suboptimal metabolism over years before they present with clinical symptoms, at which point life-long reliance on pharmacotherapy may only mitigate but not reverse the risk. Leading-edge indicators are needed to detect the earliest departure from healthy metabolism, so that targeted, primordial, and primary prevention of cardiometabolic risk is possible. Better understanding of biomarkers that reflect the earliest transitions to dysmetabolism, beginning in utero, ideally biomarkers that are also mechanistic/causal and modifiable, is critically needed. This scientific statement explores emerging biomarkers of cardiometabolic risk across rapidly evolving and interrelated "omic" fields of research (the epigenome, microbiome, metabolome, lipidome, and inflammasome). Connections in each domain to mitochondrial function are identified that may mediate the favorable responses of each of the omic biomarkers featured to a heart-healthy lifestyle, notably to nutritional interventions. Fuller implementation of evidence-based nutrition must address environmental and socioeconomic disparities that can either facilitate or impede response to therapy.

Platelets as Potential Non-Traditional Cardiovascular Risk Factor-Analysis Performed in Healthy Donors.

Abnormal lipid profile, increased glucose level, and elevated body weight are traditional cardiometabolic risk factors; however, the role of platelets in the development of cardiovascular disease (CVD) is increasingly being highlighted. The aim of this study was to select platelet-related parameters (non-genetic molecular and routine laboratory measurements) that may be associated with increased cardiovascular risk among healthy populations. We evaluated the level of platelet indices, platelet-based inflammatory markers, platelet reactivity parameters, and platelet reactive oxygen species (ROS) generation in relation to selected cardiometabolic risk factors. We noted the association between total cholesterol and LDL cholesterol with platelet aggregation and platelet ROS generation. We found the relationship between triglycerides, glucose, and body mass index with the relatively new multi-inflammatory indices (MII-1 and MII-3). Moreover, we noticed that the mean platelet volume-to-lymphocyte ratio in healthy subjects is not a good source of information about platelets and inflammation. We also highlighted that platelet-to-HDL-cholesterol ratio may be a promising prognostic cardiometabolic indicator. The association between platelet-related (especially molecular) and cardiometabolic parameters requires further research. However, the goal of this study was to shed light on the consideration of platelets as a non-traditional cardiovascular risk factor and a crucial element in identifying individuals at high-risk of developing CVD in the future.

Impact of upper-body ergometer rowing exercise on aerobic fitness and cardiometabolic disease risk in individuals with spinal cord injury: A 6-month follow-up study

Objective We recently demonstrated that upper-body rowing exercise (UBROW) improved aerobic fitness in individuals with spinal cord injury (SCI), with no effect on traditional cardiometabolic risk factors. Here, we tested the hypothesis that the exercise-induced increase in aerobic fitness was maintained at 6-month (6M) follow-up. Design Six-month follow-up. Setting University/hospital. Participants Seventeen wheelchair-dependent participants with SCI. Interventions 12-week of exercise training (UBROW) or control (CON). Outcome Measures Aerobic fitness (POpeak and V̇O2peak), body composition, blood pressure, and blood biomarkers of cardiometabolic risk were assessed at 6M follow-up and compared to baseline (BL) and immediately post-intervention (12-week). Minutes of mild, moderate, and heavy intensity leisure time physical activity (LTPA) were assessed by self-report. Results Fourteen participants returned at 6M follow-up (CON, n = 6; UBROW, n = 8). In UBROW, POpeak (median (Q1-Q3)) increased from BL (70 W (37–84)) to 12-week (77 W (58–109), P = 0.01) and 6M follow-up (81 W (51–96), P = 0.01), with no difference between 12-week and 6M follow-up (P = 0.21). Similarly, V̇O2peak increased from BL (15.4 ml/kg/min (10.5–19.4)) to 12-week (16.6 ml/kg/min (12.8–21.3), P = 0.01) with no difference between 12-week and 6M follow-up (16.3 ml/kg/min (12.9–19.7), P = 0.74). No differences were found in CON for either POpeak (P = 0.22) or V̇O2peak (P = 0.27). There were no changes over time in traditional cardiometabolic risk factors or for minutes of different LTPA intensities. Conclusion We demonstrate that improvements in aerobic fitness are maintained for at least six months after completion of a 12-week exercise intervention, supporting the use of periodic exercise interventions to boost aerobic fitness level in individuals with SCI. Trial registration: ClinicalTrials.gov identifier: NCT04390087..

Association between remnant lipoprotein cholesterol levels and risk of non-alcoholic fatty liver disease in non-obese populations: a Chinese longitudinal prospective cohort study

ObjectivesThe association between remnant lipoprotein cholesterol (RLP-C) levels and the incidence of non-alcoholic fatty liver disease (NAFLD) is unclear, especially in non-obese populations.SettingWe used data from a health assessment database....

Prevalence of Subclinical Cardiovascular Disease in Patients with Nonalcoholic Fatty Liver Disease: Analysis of the Paracelsus 10,000 Cohort Study

Background: In patients with nonalcoholic fatty liver disease (NAFLD), cardiovascular diseases are more often the cause of death than the liver disease itself. However, the prevalence of atherosclerotic manifestations in individuals with NAFLD is still uncertain. This study aimed to explore the association between NAFLD and coronary artery calcification (CAC) in a Central European population. Methods: A total of 1,743 participants from the Paracelsus 10,000 study were included. The participants underwent CAC scoring and were assessed for fatty liver index (FLI), fibrosing nonalcoholic steatohepatitis (NASH) index (FNI), and fibrosis-4 index (FIB-4 score), which are indicators for steatosis and fibrosis. Multivariable logistic regression models were calculated. Results: Results revealed an association between liver steatosis/fibrosis and CAC. An FLI >60 was associated with higher odds of NAFLD (odds ratio [OR] 3.38, 95% CI: 2.61–4.39, p < 0.01) and increased prevalence of CAC score >300 compared to FLI <30 (9% vs. 3%, p < 0.01), even after adjusting for traditional cardiometabolic risk factors. While the crude ORs of the FIB-4 scores ≥ 1.3 and FNI score were significantly associated with increased odds of CAC, they became nonsignificant after adjusting for age, sex, and MetS. Conclusion: This study reveals a significant association between NAFLD and CAC. The findings suggest that assessing liver fat and fibrosis could enhance the assessment of cardiovascular risk, but further research is needed to determine whether hepatic fat plays an independent role in the development of atherosclerosis and whether targeting liver steatosis can mitigate vascular risk.

Associations of adipokines and metabolic hormones with low-density lipoprotein hypercholesterolemia in men and women under 45 years of age.

Aim To study the adipokine profile in young people with hypercholesterolemia and low-density lipoproteins (LDL) and to evaluate the relationship between concentrations of LDL cholesterol (LDL-C) and metabolic hormones in men and women younger than 45 years.Material and methods This study included 304 subjects (group 1, 56 men with LDL-C concentration &lt;2.1 mmol/l; group 2, 87 men with LDL-C concentration ≥4.2 mmol/l; group 3, 90 women with LDL-C concentration &lt;2.1 mmol/l; and group 4, 71 women with LDL-C concentration ≥4.2 mmol/l). Serum concentrations of total cholesterol (C), triglycerides (TG), high-density lipoprotein C, and glucose were measured by an enzymatic assay with ThermoFisher Scientific kits and a KonelabPrime 30i biochemical analyzer. LDL-C was calculated using the Friedewald's formula. Concentrations of amylin, C-peptide, ghrelin, glucose-dependent insulinotropic polypeptide, glucagon-like peptide 1 (GLP-1), glucagon, interleukin 6, insulin, leptin, monocyte chemotactic protein 1 (MCP-1), pancreatic polypeptide (PP), peptide YY (PYY), tumor necrosis factor alpha (TNF-α), adiponectin, adipsin, lipocalin-2, plasminogen activator inhibitor 1 (PAI-1), and resistin were measured by multiplex analysis (Human Metabolic Hormone V3 and Human Adipokine Panel 1 panels).Results The groups differed in traditional cardiometabolic risk factors. In the male and female patient groups with LDL-C ≥4.2 mmol/l, the prevalence of impaired fasting glucose, incidence of insulin resistance, TG, and TC were higher than in subjects with LDL-C &lt;2.1 mmol/l. The odds for the presence of LDL hypercholesterolemia (LDL-C ≥4.2 mmol/l) were significantly associated with increased concentrations of C-peptide and lipocalin-2 in men and with increased concentrations of lipocalin-2 and decreased concentrations of GLP-1 in women (р&lt;0.05).Conclusion Increased concentrations of LDL-C in young people were associated with changes in the adipokine profile and with the presence of metabolic syndrome components. These results were confirmed by changes in blood concentrations of metabolic markers that characterize disorders of metabolic processes.

Prevalence and risk factors for chronic kidney disease in Indonesia: An analysis of the National Basic Health Survey 2018.

BackgroundThe prevalence of chronic kidney disease (CKD) in Indonesia is rising, but the exact extent of the burden of CKD in Indonesia is unknown. To design a screening program for individuals at high-risk, more knowledge is required regarding the prevalence and risk factors of CKD in Indonesia. The latter could have a big impact on the prevention and management of patients with CKD in Indonesia.MethodsFor this purpose, we analysed data from The National Basic Health Survey 2018 (Riset Kesehatan Dasar, Riskesdas 2018), a descriptive cross-sectional study in 34 provinces, 416 districts and 98 cities in Indonesia. We included subjects aged ≥18 years and analysed the prevalence of CKD. Using multiple logistic regression, we investigated the association between CKD and potential risk factors such as demographic factors (age, gender, occupational status, level of education), lifestyle and behaviours (consumption of salty food, consumption of fruit and vegetables, smoking, alcohol consumption, carbonated drink consumption, physical activity), comorbid conditions (hypertension, heart disease, diabetes mellitus, hepatitis, stroke, nutritional status) and others (clean water supply, pregnancy complication, access to health care).ResultsWe included 389 093 subjects in this study out of 713 783 subjects that participated in Riskesdas 2018 survey. The prevalence of CKD was 0.5%. The survey included mostly younger adults age 18-59 years (83.1%) with a mean (SD) age of 44.3 (15.1) years. The majority of subjects were female (60.3%), unemployed (58.4%), and the proportion of obese subject was 25.4%. Hypertension was the major comorbid condition (40.8%), while the proportion of diabetes mellitus (DM), heart disease, stroke and hepatitis were quite low (3.3%, 2.6%, 1.7% and 0.5%; respectively). Despite the high proportion of hypertension, only 36.2% of subjects did receive a prescription for anti-hypertensive medication of which only 21.7% used this medication regularly. The multiple logistic regression analysis demonstrated that hepatitis was the strongest risk factor of CKD (odds ratio (OR) = 3.406; 95% confidence interval (CI) = 2.496-4.648), exceeding the risk of CKD in patients with physical inactivity (OR = 1.236; 95% CI = 1.128-1.354), low education status (OR = 1.307; 95% CI = 1.191-1.434), male (OR = 1.527; 95% CI = 1.398-1.668), stroke (OR = 1.916; 95% CI = 1.570-2.338), heart disease (OR = 2.941; 95% CI = 2.356-3.671), and DM (OR = 2.462; 95% CI = 1.979-3.063). We also observed that DM (OR = 4.280; 95% CI = 3.756-4.876) and male subjects (OR = 1.474; 95% CI = 1.352-1.606) were identified as independent risk factors for CKD in hepatitis-positive subjects.ConclusionsThis population-based survey confirmed the increasing burden of CKD in Indonesia and suggested that besides traditional metabolic risk factors, viral hepatitis has proven to be an independent risk factor for CKD in Indonesia. Furthermore, the risk of CKD is greater in male hepatitis patients with DM. The result of this study demonstrates the need for an aggressive screening program for patients with a high risk for the development of CKD. Apart from patients with traditional cardiometabolic risk factors, such a program should include patients with viral hepatitis.

Frailty and risk of cardiovascular disease and mortality.

Prospective cohort studies suggest that frailty is associated with an increased risk of incident cardiovascular disease (CVD) morbidity and mortality, but their mechanistic and developmental relations are not fully understood. We investigated whether frailty predicted an increased risk of incident nonfatal and fatal CVD among community-dwelling older adults. A population cohort of 5015 participants aged 55 years and above free of CVD at baseline was followed for up to 10 years. Pre-frailty and frailty were defined as the presence of 1-2 and 3-5 modified Fried criteria (unintentional weight loss, weakness, slow gait speed, exhaustion, and low physical activity), incident CVD events as newly diagnosed registered cases of myocardial infarction (MI), stroke, and CVD-related mortality (ICD 9: 390 to 459 or ICD-10: I00 to I99). Covariate measures included traditional cardio-metabolic and vascular risk factors, medication therapies, Geriatric Depression Scale (GDS), Mini-Mental State Exam (MMSE), and blood biomarkers (haemoglobin, albumin, white blood cell counts and creatinine). Pre-frailty and frailty were significantly associated with elevated HR = 1.26 (95%CI: 1.02-1.56) and HR = 1.54 (95%CI:1.00-2.35) of overall CVD, adjusted for cardio-metabolic and vascular risk factors and medication therapies, but not after adjustment for GDS depression and MMSE cognitive impairment. The HR of association between frailty status and both CVD mortality and overall mortality, however, remained significantly elevated after full adjustment for depression, cognitive and blood biomarkers. Frailty was associated with increased risk of CVD morbidity and especially mortality, mediated in parts by traditional cardio-metabolic and vascular risk factors, and co-morbid depression and associated cognitive impairment and chronic inflammation. Given that pre-frailty and frailty are reversible by multi-domain lifestyle and health interventions, there is potential benefits in reducing cardiovascular diseases burden and mortality from interventions targeting pre-frailty and early frailty population.

Metabolically healthy obesity in a paediatric obesity clinic.

Metabolically healthy obese (MHO) children is a described subgroup of obese children who do not exhibit traditional cardiometabolic risk factors. The aim of this study was to determine the prevalence and characterize patients with this phenotype. Cross-sectional study, performed in a paediatric obesity clinic (tertiary university hospital) in 2019. Children were classified with "MHO" or "metabolically unhealthy obesity" according to the criteria proposed by Damanhoury based on HDL, triglycerides, systolic and diastolic blood pressure (DBP) and fasting glucose values. 241 participants were included, with ages between two and 17years. The prevalence of the MHO phenotype was 61.8%. The body mass index (Z-score) in children aged five years or older was significantly lower in those with MHO (p=0.040). In the MHO group, mean total cholesterol levels were higher (p<0.001), due to the high value of HDL (p<0.001); triglyceride levels (p<0.001), systolic blood pressure (SBP) (p=0.036), DBP (p=0.029) and the homeostasis model assessment- insulin resistance (HOMA-IR) index (p=0.001) were significantly lower. HDL (OR=1.421; 95% CI 1.279-1.579; p<0.001) and SBP (OR=0.943; 95% CI 0.903-0.985; p=0.008) were the only independent predictors for the development of MHO. Almost two-thirds of the participants had an MHO phenotype. The high and low values of HDL and SBP, respectively, were the only variables that proved to be predictors of MHO.

Prevalence and clinical characteristics of metabolically healthy obese versus metabolically unhealthy obese school children.

IntroductionChildren with obesity in the absence of traditional cardiometabolic risk factors (CRF) have been described as metabolically healthy obese (MHO). Children with MHO phenotype has a favorable metabolic profile with normal glucose metabolism, lipids, and blood pressure compared to children with metabolically unhealthy obese (MUO) phenotype. This study aimed to compare several parameters related to obesity between these two groups and to examine the predictors associated with the MHO phenotype.MethodsThis study included a cross-sectional baseline data of 193 children with obesity (BMI z-score > +2 SD) aged 8-16 years enrolled in MyBFF@school program, a school-based intervention study conducted between January and December 2014. Metabolic status was defined based on the 2018 consensus-based criteria with MHO children had no CRF (HDL-cholesterol > 1.03 mmol/L, triglycerides ≤ 1.7 mmol/L, systolic and diastolic blood pressure ≤ 90th percentile, and fasting plasma glucose ≤ 5.6 mmol/L). Those that did not meet one or more of the above criteria were classified as children with MUO phenotype.ResultsThe prevalence of MHO was 30.1% (95% CI 23.7 – 37.1) among schoolchildren with obesity and more common in younger and prepubertal children. Compared to MUO, children with MHO phenotype had significantly lower BMI, lower waist circumference, lower uric acid, higher adiponectin, and higher apolipoprotein A-1 levels (p < 0.01). Multivariate logistic regression showed that adiponectin (OR: 1.33, 95% CI 1.05 – 1.68) and apolipoprotein A-1 (OR: 1.02, 95% CI 1.01 – 1.03) were independent predictors for MHO phenotype in this population.ConclusionsMHO phenotype was more common in younger and prepubertal children with obesity. Higher serum levels of adiponectin and apolipoprotein A-1 increased the possibility of schoolchildren with obesity to be classified into MHO phenotype.

Association of left ventricular diastolic function with coronary artery calcium score: A Project Baseline Health Study

BackgroundCoronary artery calcium (CAC) and left ventricular diastolic dysfunction (LVDD) are strong predictors of cardiovascular events and share common risk factors. However, their independent association remains unclear. MethodsIn the Project Baseline Health Study (PBHS), 2082 participants underwent cardiac-gated, non-contrast chest computed tomography (CT) and echocardiography. The association between left ventricular (LV) diastolic function and CAC was assessed using multidimensional network and multivariable-adjusted regression analyses. Multivariable analysis was conducted on continuous LV diastolic parameters and categorical classification of LVDD and adjusted for traditional cardiometabolic risk factors. LVDD was defined using reference limits from a low-risk reference group without established cardiovascular disease, cardiovascular risk factors or evidence of CAC, (n ​= ​560). We also classified LVDD using the American Society of Echocardiography recommendations. ResultsThe mean age of the participants was 51 ​± ​17 years with 56.6% female and 62.6% non-Hispanic White. Overall, 38.1% had hypertension; 13.7% had diabetes; and 39.9% had CAC >0. An intertwined network was observed between diastolic parameters, CAC score, age, LV mass index, and pulse pressure. In the multivariable-adjusted analysis, e’, E/e’, and LV mass index were independently associated with CAC after adjustment for traditional risk factors. For both e’ and E/e’, the effect size and statistical significance were higher across increasing CAC tertiles. Other independent correlates of e’ and E/e’ included age, female sex, Black race, height, weight, pulse pressure, hemoglobin A1C, and HDL cholesterol. The independent association with CAC was confirmed using categorical analysis of LVDD, which occurred in 554 participants (26.6%) using population-derived thresholds. ConclusionIn the PBHS study, the subclinical coronary atherosclerotic disease burden detected using CAC scoring was independently associated with diastolic function. Clinicaltrials.gov identifierNCT03154346.

Sex Differences in Vascular Endothelial Function After Liver Transplant

INTRODUCTIONLiver transplant (LT) recipients have an increased risk of developing cardiovascular disease (CVD) after transplant. Sex differences may be a significant determinant in the pathophysiology of CVD. However, sex‐differences in vascular dysfunction, an established precursor to CVD, have not been explored in LT recipients. The purpose of this study was to investigate the sex differences in vascular function and cardiometabolic risk‐factors to CVD among LT patients.METHODSConduit artery endothelial function was measured via flow‐mediated dilation of the brachial artery (FMDBA) with duplex ultrasound in 23 age‐matched LT patients (11 Male, 12 Female; Mean ± SEM: Age 55 ± 2 years). Aortic pressure waves were synthesized from radial artery waveforms acquired by applanation tonometry and the use of a generalized transfer function. Novel plasma based cardiometabolic risk factors were assessed with nuclear magnetic resonance spectroscopy. Lipoprotein insulin resistance index (LPIR) was calculated as a weighted combination of concentrations and particle sizes of very low‐density, low‐density, and high‐density lipoproteins. Diabetes risk index (DRI) factors LPIR and branched‐chain amino acid levels to predict the risk of type 2 diabetes. Metabolic inflammation index (INFX) combines concentrations of the inflammation biomarker GlycA and high‐density lipoprotein particle subspecies.RESULTSMales had lower FMDBA than females (3.98 ± 0.63 vs 6.27 ± 0.43%, p &lt; 0.01). There were no sex differences in aortic systolic pressure (Male vs Female; 129 ± 3 vs 118 ± 5 mmHg, p = 0.09), body mass index (38 ± 2 vs 36 ± 2 kg/m2, p = 0.61), LPIR (57 ± 7 vs 55 ± 7, p = 0.89), DRI (53 ± 7 vs 44 ± 6, p = 0.38), or INFX (47 ± 2 vs 54 ± 3, p = 0.13).CONCLUSIONSMales had poorer vascular endothelial function compared to females following LT, suggesting that males may be more susceptible to the development of CVD after LT. However, this increased risk cannot be explained by differences in traditional cardiometabolic risk factors. Future research should identify non‐traditional CVD risk factors that contribute to sex differences in vascular function towards implementing precision medicine for the prevention and management of CVD in LT patients.

IDF21-0507 Serum nitrotyrosine – A [LDQUO]molecular mirror[RDQUO] from metabolic syndrome to overt type 2 diabetes mellitus

Background: Metabolic syndrome (MetS) represents a cluster of metabolic abnormalities, including central obesity, hypertension, hypertriglyceridemia, low HDL-cholesterol and hyperglycemia. Insulin resistance and chronic low-grade inflammation are considered also as key players in the pathogenesis of the syndrome. MetS increases the risk of development of type 2 diabetes mellitus (T2DM) more than 5 times, but this could not be totally explained by the traditional cardiometabolic risk factors. Hence, investigation of new possible markers which can reflect both the development of MetS itself and its progression to T2DM is perspective.