Cardiometabolic Disease Biomarkers Research Articles

Change in cardiometabolic risk factors in a pilot safety-net plant-based lifestyle medicine program.

Interventions emphasizing healthful lifestyle behaviors are proliferating in traditional health care settings, yet there is a paucity of published clinical outcomes, outside of pay-out-of-pocket or employee health programs. We assessed weight, hemoglobin A1c (HbA1c), blood pressure, and cholesterol for 173 patients of the Plant-Based Lifestyle Medicine Program piloted in a New York City safety-net hospital. We used Wilcoxon signed-rank tests to assess changes in means, from baseline to six-months, for the full sample and within baseline diagnoses (i.e., overweight or obesity, type 2 diabetes, prediabetes, hypertension, hyperlipidemia). We calculated the percentage of patients with clinically meaningful changes in outcomes for the full sample and within diagnoses. The full sample had statistically significant improvements in weight, HbA1c, and diastolic blood pressure. Patients with prediabetes or overweight or obesity experienced significant improvements in weight and those with type 2 diabetes had significant improvements in weight and HbA1c. Patients with hypertension had significant reductions in diastolic blood pressure and weight. Data did not show differences in non-high-density lipoprotein cholesterol (non-HDL-C), but differences in low-density lipoprotein cholesterol (LDL-C) were approaching significance for the full sample and those with hyperlipidemia. The majority of patients achieved clinically meaningful improvements on all outcomes besides systolic blood pressure. Our study demonstrates that a lifestyle medicine intervention within a traditional, safety-net clinical setting improved biomarkers of cardiometabolic disease. Our findings are limited by small sample sizes. Additional large-scale, rigorous studies are needed to further establish the effectiveness of lifestyle medicine interventions in similar settings.

Dynamic changes in clinical biomarkers of cardiometabolic diseases by changes in exercise behavior, and network comparisons: a community-based prospective cohort study in Korea.

Lifestyles, including exercise behaviors, change continually over time. This study examined whether the clinical biomarkers (CBs) related to cardiometabolic diseases (CMDs) and their relationships differed with changes in exercise behavior. The Ansan-Ansung cohort study (third to fifth phases; n=2,668) was used in the current study. Regular exercise behavior was investigated using a yes/no questionnaire. Changes in exercise behavior were classified into 4 groups: Y-N, N-Y, Y-Y, and N-N, with "Y" indicating that a participant regularly engaged in exercise at a given time point and "N" indicating that he or she did not. Fourteen CBs related to CMDs were used, and the associations between changes in exercise behavior and relative changes in CBs were examined. CB networks were constructed and topological comparisons were conducted. Y-N was associated with increases in fasting blood sugar and insulin levels in men, and increased total cholesterol and low-density lipoprotein cholesterol levels in women. Meanwhile, N-Y was inversely associated with body fat percentage, visceral fat percentage, fasting insulin, and triglyceride level. Waist circumference played a central role in most networks. In men, more edges were found in the N-Y and Y-Y groups than in the N-N and Y-N groups, whereas women in the N-Y and Y-Y groups had more edges than those in the N-N and Y-N groups. Consistent exercise or starting to engage in regular exercise had favorable effects on CBs related to CMDs, although their network patterns differed between the sexes.

Objective sleep and cardiometabolic biomarkers: results from the community of mine study.

Examining multiple dimensions of sleep health may better capture associations between sleep and health risks, including cardiometabolic disease (CMD). Hispanics have elevated risk for inadequate sleep and CMD biomarkers. Few studies have explored whether associations between sleep and CMD differ by Hispanic ethnicity. Leveraging data from the Community of Mine (CoM) study, a cross-sectional investigation of 602 ethnically diverse participants, we derived accelerometer-measured sleep duration and efficiency, and self-reported sleep quality. Accelerometer-measured sleep exposures were analyzed both as continuous and categorical variables. Multivariate and quantile regression models were used to assess associations between sleep and CMD biomarkers (insulin resistance, systolic blood pressure, and low-density-lipoprotein cholesterol), controlling for age, sex, ethnicity, education, smoking status, and body mass index. We examined the potential effect modification of Hispanic ethnicity. We observed mixed results based on CMD biomarkers and sleep exposure. Increased sleep duration was significantly related to low-density lipoprotein cholesterol in adjusted models (estimate = 0.06; 95% CI: 0.02, 0.11). Poor sleep efficiency was associated with greater insulin resistance in the adjusted quantile (estimate = 0.20; 95% CI: 0.04, 0.36) model at the 90th percentile. Self-reported sleep quality was not associated with CMD outcomes. There was no evidence of effect modification by Hispanic ethnicity. In this cohort, sleep health measures were found to have mixed and at times opposing effects on CMD outcomes. These effects did not demonstrate an interaction with Hispanic ethnicity.

Abstract 14044: Leveraging Multi-Omics to Identify Biologically-Informed Clusters of Individuals With Differing Underlying Disease Risk Mechanisms Using an Innovative Network Modelling Approach

Background: The rates of known cardiometabolic risk elevation are highly variable among patients suggesting that there are other risk mediators underlying diseases. We hypothesized that using cutting-edge and innovative multi-omics integrative network analysis in conjunction with the consensus clustering approach would identify clusters of individuals which may represent novel functional and/or pathophysiological risk mechanisms of cardiometabolic disorders. Methods: The genetically predicted levels of metabolites and proteins constructed from the GWAS data of Framingham/Malmö and KORA-TWINS were imputed in 13,562 BioVU participants. These 2 layers of omics data were integrated using similarity network fusion in conjunction with consensus clustering approaches. The identified clusters of individuals were tested for associations with 14 cardiometabolic diseases using logistic regression adjusting for known risk factors to identify endotypic determinants of diseases. Pathway analysis comparing each cluster to the rest of participants was performed using Reactome and MetaboAnalyst. Results: We identified 5 clusters across which LDL-C was significantly (p=0.001) different. The significant associations were found for cluster 1 with coronary artery disease (p=0.04), cluster 2 with cardiomyopathy(p=0.004) and atrial fibrillation (p=0.03) and cluster 4 with congenital heart disease (p=0.03) [ Fig 1 ]. Thus, clusters 1, 2 and 4 are endotypic determinants of the above diseases. Each of these clusters was associated with distinct pathways indicating candidate mechanisms of diseases related to the clusters. Conclusions: This novel discovery-oriented multi-omics clustering method identified biologically-related subgroups of individuals and revealed novel risk mechanism and biomarkers of cardiometabolic diseases. The innovative network-based models advance precision medicine by enabling future prognostic risk prediction tools.

Plasma Ceramides Pathophysiology, Measurements, Challenges, and Opportunities.

Ceramides are a family of lipid molecules, composed of sphingosine and a fatty acid, and transported by lipoproteins (primarily by low-density lipoproteins) in the bloodstream. They are not only structural lipids, but multifunctional and bioactive molecules with key roles in many important cellular pathways, such as inflammatory processes and apoptosis, representing potential biomarkers of cardiometabolic diseases as well as pharmacological targets. Recent data reported ceramide modulation by diet and aerobic exercise, suggesting nutrients and exercise-targeting sphingolipid pathways as a countermeasure, also in combination with other therapies, for risk and progression of chronic disease prevention and health maintenance. In this review, we focus on the available data regarding remarks on ceramide structure and metabolism, their pathophysiologic roles, and the effect of dietary habit and aerobic exercise on ceramide levels. Moreover, advancements and limitations of lipidomic techniques and simplification attempts to overcome difficulties of interpretation and to facilitate practical applications, such as the proposal of scores, are also discussed.

Effects of White Wine and Tyrosol on Circulating Ceramides in Individuals at Cardiovascular Risk

Abstract Objectives Ceramides (Cer) are a class of bioactive lipids that are receiving increasing attention as biomarkers of cardiometabolic diseases. Tyrosol (Tyr) is a phenolic compound present in olive oil and wine. Once ingested, it is partially biotransformed into hydroxytyrosol (HOTyr). Tyr and its partial biotransformation into HOTyr promote cardiovascular health-related benefits in humans. The aim of this study was to evaluate the effects of white wine and Tyr on circulating Cer. Methods Thirty-three participants (12 women and 21 men) at cardiovascular risk (age 65 ± 6 years; BMI, 32.6 ± 4.2 kg/m2, LDL cholesterol 118 ± 34 mg/dL) received either white wine (females 1, males 2 standard drinks/days), white wine plus tyrosol capsules (one 25 mg capsule per drink) and water (control, ad libitum) according to a randomized-controlled cross-over design. Each intervention lasted 4 weeks and was preceded by a 3-week washout period. Arterial stiffness biomarkers were measured before and after each intervention. Fasting blood samples were collected before and after each intervention period. The plasma levels of seven Cer (C14:0, C16:0, C18:0, C20:0, C22:0, C24:0, and C24:1) were measured by LC/MS/MS. Results Amongst the three interventions, only white wine plus Tyr significantly altered the levels of circulating ceramides (P < 0.05). White wine plus Tyr decreased the Cer C16:0/C24:0 ratio (P = 0.0018), Cer C18:0/C24:0 ratio (P = 0.040), and Cer C24:1/C24:0 ratio (P = 0.005), compared to white wine alone or water interventions. The final values of Cer ratios after the white wine plus Tyr intervention correlated with arterial stiffness biomarkers (endothelin 1 and augmentation index), which in turn were decreased by this intervention (P < 0.05). Conclusions The Cer ratios C16:0/C24:0, C18:0/C24:0, and C24:1/C24:0 (which had been previously reported to be cardiovascular and mortality risk factors) were decreased by the administration of dietary doses of white wine plus Tyr. Reductions in these ceramides correlated with improvements in arterial stiffness biomarkers. These results, which were not observed after white wine alone, provide new insights on the cardiovascular protective activity of Tyr and its partial conversion into HOTyr. Funding Sources Funded by the Instituto de Salud Carlos III. JRM acknowledges a Sara Borrell contract.

Protocol for a randomized controlled trial of pre-pregnancy lifestyle intervention to reduce recurrence of gestational diabetes: Gestational Diabetes Prevention/Prevenci\xf3n de la Diabetes Gestacional

BackgroundGestational diabetes mellitus (GDM) is associated with several maternal complications in pregnancy, including preeclampsia, preterm labor, need for induction of labor, and cesarean delivery as well as increased long-term risks of type 2 diabetes, metabolic syndrome, and cardiovascular disease. Intrauterine exposure to GDM raises the risk for complications in offspring as well, including stillbirth, macrosomia, and birth trauma, and long-term risk of metabolic disease. One of the strongest risk factors for GDM is the occurrence of GDM in a prior pregnancy. Preliminary data from epidemiologic and bariatric surgery studies suggest that reducing body weight before pregnancy can prevent the development of GDM, but no adequately powered trial has tested the effects of a maternal lifestyle intervention before pregnancy to reduce body weight and prevent GDM recurrence.MethodsThe principal aim of the Gestational Diabetes Prevention/Prevención de la Diabetes Gestacional is to determine whether a lifestyle intervention to reduce body weight before pregnancy can reduce GDM recurrence. This two-site trial targets recruitment of 252 women with overweight and obesity who have previous histories of GDM and who plan to have another pregnancy in the next 1–3 years. Women are randomized within site to a comprehensive pre-pregnancy lifestyle intervention to promote weight loss with ongoing treatment until conception or an educational control group. Participants are assessed preconceptionally (at study entry, after 4 months, and at brief quarterly visits until conception), during pregnancy (at 26 weeks’ gestation), and at 6 weeks postpartum. The primary outcome is GDM recurrence, and secondary outcomes include fasting glucose, biomarkers of cardiometabolic disease, prenatal and perinatal complications, and changes over time in weight, diet, physical activity, and psychosocial measures.DiscussionThe Gestational Diabetes Prevention /Prevención de la Diabetes Gestacional is the first randomized controlled trial to evaluate the effects of a lifestyle intervention delivered before pregnancy to prevent GDM recurrence. If found effective, the proposed lifestyle intervention could lay the groundwork for shifting current treatment practices towards the interconception period and provide evidence-based preconception counseling to optimize reproductive outcomes and prevent GDM and associated health risks.Trial registrationClinicalTrials.gov NCT02763150. Registered on May 5, 2016

Durability of Changes in Biomarkers of Cardiometabolic Disease: 1-Year Family-Based Intervention in Children with Obesity

Background: The sustainability of health benefits in response to lifestyle-based interventions remains unclear in children with overweight and obesity, and cardiometabolic disease (CMD). We determined the changes in novel biomarkers of CMD in a 1-year family-based intervention (FBI) program, during 6-month active monitoring phase and at 12-month follow-up. Methods: Children with an age-adjusted body mass index (BMI) percentile ≥85 (N = 130; age 8-11 years) were recruited for a 1-year (6-month monitored and 6-month unmonitored) randomized controlled FBI program. Anthropometry and selected biomarkers of CMD were measured in 87 participants, randomly allocated to intervention (INT) and education-only (EDU) groups, at baseline, immediately after a 6-month active intervention or control period, and at 12-month unmonitored follow-up. Results: Samples from 87 participants (age 10.00 ± 0.11 years and Tanner stage ≤3) with obesity (BMI%ile = 97.45 ± 0.15) were available. Overall intervention effect (between groups), was observed for total (T) and high molecular weight (HMW) adiponectin, ratio of total to HMW adiponectin, fibrinogen, and interleukin (IL)-6 (P < 0.05 for all). However, between-group beneficial changes after adjusting for baseline levels were limited to BMI percentile, T and HMW adiponectin and their ratio, IL-6, and fibrinogen (P < 0.05 for all) mainly during the 6-month period of monitored intervention. Changes in traditional risk factors such as lipids and triglycerides were inconsistent. During the 6-month follow-up period, the changes in biomarkers leveled-off, except for T and HMW adiponectin, IL-6, and fibrinogen that continued to show benefits (P < 0.05) from the 6- to 12-month follow-up. Conclusions: The FBI program beneficially altered novel biomarkers of CMD during the monitored intervention phase in school-age children with obesity, but they mostly moved back toward baseline during the unmonitored follow-up phase. The changes in novel biomarkers of CMD appear to be more sensitive compared to the traditional risk factors. The study implies the need for refinements in lifestyle-based approaches in the preservation of cardiovascular health and calls for robust biomarkers to monitor the changes. The study was registered at ClinicalTrials.gov (NCT01146314).

Metabolic syndrome, fatty liver, and artificial intelligence-based epicardial adipose tissue measures predict long-term risk of cardiac events: a prospective study

BackgroundWe sought to evaluate the association of metabolic syndrome (MetS) and computed tomography (CT)-derived cardiometabolic biomarkers (non-alcoholic fatty liver disease [NAFLD] and epicardial adipose tissue [EAT] measures) with long-term risk of major adverse cardiovascular events (MACE) in asymptomatic individuals.MethodsThis was a post-hoc analysis of the prospective EISNER (Early-Identification of Subclinical Atherosclerosis by Noninvasive Imaging Research) study of participants who underwent baseline coronary artery calcium (CAC) scoring CT and 14-year follow-up for MACE (myocardial infarction, late revascularization, or cardiac death). EAT volume (cm3) and attenuation (Hounsfield units [HU]) were quantified from CT using fully automated deep learning software (< 30 s per case). NAFLD was defined as liver-to-spleen attenuation ratio < 1.0 and/or average liver attenuation < 40 HU.ResultsIn the final population of 2068 participants (59% males, 56 ± 9 years), those with MetS (n = 280;13.5%) had a greater prevalence of NAFLD (26.0% vs. 9.9%), higher EAT volume (114.1 cm3 vs. 73.7 cm3), and lower EAT attenuation (−76.9 HU vs. −73.4 HU; all p < 0.001) compared to those without MetS. At 14 ± 3 years, MACE occurred in 223 (10.8%) participants. In multivariable Cox regression, MetS was associated with increased risk of MACE (HR 1.58 [95% CI 1.10–2.27], p = 0.01) independently of CAC score; however, not after adjustment for EAT measures (p = 0.27). In a separate Cox analysis, NAFLD predicted MACE (HR 1.78 [95% CI 1.21–2.61], p = 0.003) independently of MetS, CAC score, and EAT measures. Addition of EAT volume to current risk assessment tools resulted in significant net reclassification improvement for MACE (22% over ASCVD risk score; 17% over ASCVD risk score plus CAC score).ConclusionsMetS, NAFLD, and artificial intelligence-based EAT measures predict long-term MACE risk in asymptomatic individuals. Imaging biomarkers of cardiometabolic disease have the potential for integration into routine reporting of CAC scoring CT to enhance cardiovascular risk stratification.Trial registration NCT00927693.

A longitudinal study of rural Bangladeshi children with long-term arsenic and cadmium exposures and biomarkers of cardiometabolic diseases.

There is growing interest in understanding the contribution of environmental toxicant exposure in early life to development of cardiometabolic diseases (CMD) in adulthood. We aimed to assess associations of early life exposure to arsenic and cadmium with biomarkers of CMD in children in rural Bangladesh. From a longitudinal mother-child cohort in Matlab, Bangladesh, we followed up 540 pairs. Exposure to arsenic (U-As) and cadmium (U-Cd) was assessed by concentrations in urine from mothers at gestational week 8 (GW8) and children at ages 4.5 and 9 years. Blood pressure and anthropometric indices were measured at 4.5 and 9 years. Metabolic markers (lipids, glucose, hemoglobin A1c, adipokines, estimated glomerular filtration rate (eGFR) were determined in plasma/blood of 9 years old children. In linear regression models, adjusted for child sex, age, height-for-age z score (HAZ), BMI-for-age z score (BAZ), socioeconomic status (SES) and maternal education, each doubling of maternal and early childhood U-Cd was associated with 0.73 and 0.82mmHg increase in systolic blood pressure (SBP) respectively. Both early and concurrent childhood U-Cd was associated with diastolic (D)BP (β=0.80at 4.5 years; β=0.75at 9 years). Each doubling of U-Cd at 9 years was associated with decrements of 4.98mg/dL of total cholesterol (TC), 1.75mg/dL high-density lipoprotein (HDL), 3.85mg/dL low-density lipoprotein (LDL), 0.43mg/dL glucose and 4.29 units eGFR. Each doubling of maternal U-Cd was associated with a decrement of 1.23mg/dL HDL. Both maternal and childhood U-As were associated with decrement in TC and HDL. Multiple comparisons were checked with family-wise error rate Bonferroni-type-approach. The negative associations of arsenic and cadmium with biomarkers of CMD in preadolescent children indicated influence of both metal(loid)s on fat and carbohydrate metabolism, while cadmium additionally influenced kidney function and BP. Thus, fewer outcomes were associated with U-As compared to U-Cd at preadolescence.

Metabolic Syndrome, Fatty Liver, And Artificial Intelligence-based Epicardial Adipose Tissue Measures Predict Long-term Risk Of Cardiac Events

Introduction: We sought to evaluate the association of metabolic syndrome (MetS) and computed tomography (CT) biomarkers of cardiometabolic disease (fatty liver and artificial intelligence (AI)-based EAT measures) with long-term risk of major adverse cardiovascular events (MACE) in asymptomatic subjects.

Association Between a Physical Activity Vital Sign and Cardiometabolic Disease in High-Risk Patients.

To determine the association between the physical activity vital sign (PAVS) and markers of cardiometabolic disease. Patients were assessed through the PAVS, a validated tool self-reporting the frequency and duration of physical activity. Patients were categorized into 3 groups: inactive (0 minutes per week), underactive (1-149 minutes per week), and active (>150 minutes per week). Associations were tested between the PAVS and the cardiometabolic disease biomarkers of body mass index, hemoglobin A1c (A1c), blood pressure, and low-density lipoprotein (LDL) using one-way analyses of variance. High-risk family medicine residency clinic. Two thousand three hundred twenty-one adult patients (age ≥ 18 years). Participants reported a mean of 97.87 (SD = 149.35) minutes per week of exercise. Overall, 50.1% reported physical inactivity, 25.7% were underactive, and 24.3% were active. Younger individuals (P < 0.001) and men (P < 0.05) reported more physical activity than older individuals and women. Patients who reported being active were significantly less likely to be overweight (P < 0.05), obese (P < 0.05), or hypertensive (P < 0.05), but there was no association with A1c or LDL levels. This is the first investigation to examine the PAVS in a high-risk population. In these patients, reported levels of physical inactivity are 150% higher than other clinical settings, and the PAVS is only associated with improvements in 2 of 4 major cardiometabolic risk factors. For this group, self-reported levels of physical activity may need to be higher for cardiovascular benefits to be realized in all 4 cardiometabolic domains. The PAVS offers health professionals an opportunity to encourage lifestyle-based interventions to reduce cardiovascular risk, but refinements may be necessary to address this population.

A Randomized Placebo-Controlled Trial of Secukinumab on Aortic Vascular Inflammation in Moderate-to-Severe Plaque Psoriasis (VIP-S)

Psoriasis, a chronic immune-mediated disease, is associated with an increased risk of cardiovascular events and mortality. Secukinumab selectively neutralizes IL-17A and has reported high efficacy with a favorable safety profile in various psoriatic disease manifestations. Subsequent to the 12-week randomized, placebo-controlled, double-blind treatment period, patients with moderate-to-severe psoriasis received secukinumab for 40 weeks. Vascular inflammation using 18F-2-fluorodeoxyglucose-positron emission tomography/computed tomography imaging and blood-based cardiometabolic was assessed at week 0, 12, and 52. The difference in change in aortic inflammation from baseline to week 12 for secukinumab (n = 46) versus placebo (n = 45) was -0.053 (95% confidence interval= -0.169 to 0.064; P= 0.37). Small increases in total cholesterol, low-density lipoprotein, and low-density lipoprotein particles, but no changes in markers of inflammation, adiposity, insulin resistance, or predictors of diabetes, were observed with secukinumab treatment compared with placebo. At week 52, reductions in TNF-α (P= 0.0063) and ferritin (P= 0.0354), and an increase in fetuin-A (P= 0.0024), were observed with secukinumab treatment compared with baseline. No significant changes in aortic inflammation or markers of advanced lipoprotein characterization, adiposity, or insulin resistance were observed with secukinumab treatment compared with baseline. Secukinumab exhibited a neutral impact on aortic vascular inflammation and biomarkers of cardiometabolic disease after 52 weeks of treatment.

Activity Tracker-Based Metrics as Digital Markers of Cardiometabolic Health in Working Adults: Cross-Sectional Study.

BackgroundGreater adoption of wearable devices with multiple sensors may enhance personalized health monitoring, facilitate early detection of some diseases, and further scale up population health screening. However, few studies have explored the utility of data from wearable fitness trackers in cardiovascular and metabolic disease risk prediction.ObjectiveThis study aimed to investigate the associations between a range of activity metrics derived from a wearable consumer-grade fitness tracker and major modifiable biomarkers of cardiometabolic disease in a working-age population.MethodsThis was a cross-sectional study of 83 working adults. Participants wore Fitbit Charge 2 for 21 consecutive days and went through a health assessment, including fasting blood tests. The following clinical biomarkers were collected: BMI, waist circumference, waist-to-hip ratio, blood pressure, triglycerides (TGs), high-density lipoprotein (HDL) and low-density lipoprotein cholesterol, and blood glucose. We used a range of wearable-derived metrics based on steps, heart rate (HR), and energy expenditure, including measures of stability of circadian activity rhythms, sedentary time, and time spent at various intensities of physical activity. Spearman rank correlation was used for preliminary analysis. Multiple linear regression adjusted for potential confounders was used to determine the extent to which each metric of activity was associated with continuous clinical biomarkers. In addition, pairwise multiple regression was used to investigate the significance and mutual dependence of activity metrics when two or more of them had significant association with the same outcome from the previous step of the analysis.ResultsThe participants were predominantly middle aged (mean age 44.3 years, SD 12), Chinese (62/83, 75%), and male (64/83, 77%). Blood biomarkers of cardiometabolic disease (HDL cholesterol and TGs) were significantly associated with steps-based activity metrics independent of age, gender, ethnicity, education, and shift work, whereas body composition biomarkers (BMI, waist circumference, and waist-to-hip ratio) were significantly associated with energy expenditure–based and HR-based metrics when adjusted for the same confounders. Steps-based interdaily stability of circadian activity rhythm was strongly associated with HDL (beta=5.4 per 10% change; 95% CI 1.8 to 9.0; P=.005) and TG (beta=−27.7 per 10% change; 95% CI −48.4 to −7.0; P=.01). Average daily steps were negatively associated with TG (beta=−6.8 per 1000 steps; 95% CI −13.0 to −0.6; P=.04). The difference between average HR and resting HR was significantly associated with BMI (beta=−.5; 95% CI −1.0 to −0.1; P=.01) and waist circumference (beta=−1.3; 95% CI −2.4 to −0.2; P=.03).ConclusionsWearable consumer-grade fitness trackers can provide acceptably accurate and meaningful information, which might be used in the risk prediction of cardiometabolic disease. Our results showed the beneficial effects of stable daily patterns of locomotor activity for cardiometabolic health. Study findings should be further replicated with larger population studies.

Per- and polyfluoroalkyl substance concentrations during pregnancy and post-pregnancy biomarkers of cardiometabolic health in Project Viva

OPS 20: Chemicals, biomarkers, omics, Room 110, Floor 1, August 27, 2019, 4:30 PM - 5:30 PM Background/Aim: Per- and polyfluoroalkyl substances (PFAS) are persistent chemicals linked to weight gain and type 2 diabetes. We tested whether PFAS concentrations during pregnancy are associated with postpartum biomarkers of cardiometabolic disease. Methods: We studied 1,631 women recruited 1999-2002 in the Project Viva cohort with pregnancy (median 9.7 weeks, range 4.8-21.4) plasma measurements of 6 PFAS, including perfluorooctanesulfonic acid (PFOS), perfluorooctanoic acid (PFOA), and 2-(N-ethyl-perfluorooctane sulfonamide) acetic acid (Et-PFOSA-AcOH). PFAS were log2-transformed. At 3 years post-pregnancy we measured anthropometry and, in a subset, serum biomarkers including sex hormone binding globulin (SHBG), interleukin-6 (IL-6), and hemoglobin A1c (HbA1c). We excluded women who were pregnant within the last 6 months (n=193); the analysis sample was n=831 after loss to follow-up. We used multivariable regression, adjusting for age, pre-pregnancy body mass index, marital status, race/ethnicity, education, income, smoking, and parity. We multiply imputed missing covariates and adjusted for loss to follow-up using inverse probability of censoring weights. Results: PFAS exposure was associated with greater triceps skinfold thickness (0.69 [95%CI: 0.10, 1.28] mm per doubling in PFOS and 0.72 [95%CI: 0.06, 1.38] mm per doubling of PFOA) and greater subscapular skinfold thickness (0.53 [95%CI: -0.03, 1.09] mm per doubling in PFOS and 0.42 [95%CI: 0.02, 0.82] mm per doubling of Et-PFOSA-AcOH). PFAS were also associated with greater mid-upper arm circumference (0.27 [95%CI: -0.01, 0.54] cm per doubling of PFOA and 0.18 [95%CI: -0.01, 0.36] cm per doubling of Et-PFOSA-AcOH) and greater waist circumference (0.55 [95%CI: 0.06, 1.05] cm per doubling in Et-PFOSA-AcOH). Finally, each doubling of Et-PFOSA-AcOH was associated with lower log-SHBG (-0.06 mg/L [95%CI: -0.11, -0.00]), higher log-IL-6 (0.11 pg/mL [95%CI: 0.04, 0.18]) and higher HbA1c (0.030% [95%CI: 0.01, 0.05]). Conclusions: Though effect sizes are small, the direction of associations taken together suggests PFAS exposure is associated with an unfavorable cardiometabolic profile.

Branched chain amino acids: Passive biomarkers or the key to the pathogenesis of cardiometabolic diseases?

The metabolomic approach to research on lifestyle diseases has led to the discovery of new potential biomarkers of pathological conditions as well as key metabolic pathways that may become targets of therapeutic intervention. Current evidence supports plasma branched chain amino acids (BCAAs) as potential diagnostic and prognostic biomarkers of cardiometabolic diseases. However, the biological mechanisms of the associations that have been identified are still not completely understood and should be clarified before implementing BCAA-based biomarkers in the clinical setting. The most crucial issue that needs to be solved first is determining whether BCAA plasma profile disturbances are only passive biomarkers or whether they facilitate dysmetabolic processes. In this context, further research is also warranted to investigate the role of dietary BCAAs. Gaining this knowledge would be significant progress in molecular nutrition research, providing perspective for target therapeutic and prophylactic interventions. This paper provides a comprehensive review of the main hypotheses and mechanistic models that consider circulating BCAAs both as passive biomarkers and as contributors to cardiometabolic diseases.

Dietary Quality Assessed by the HEI-2010 and Biomarkers of Cardiometabolic Disease: An Exploratory Analysis

Objectives: This study explores relationships between cardiometabolic measures of antioxidant capacity or inflammation and diet quality assessed by the Healthy Eating Index (HEI)-2010 which measures conformity to Dietary Guidelines for Americans. This cross-sectional study was an ancillary analysis of baseline data for a randomized controlled trial with older adults at risk for cardiometabolic disease (ClinicalTrials.gov #NCT00955903).Methods: Community-dwelling older adults (n = 133, 49% male, 70.4 ± 4.8 years) with a body mass index of 30–40 kg/m2 provided a fasted blood sample for measurement of antioxidant capacity, high-sensitivity C-reactive protein, tumor necrosis factor-alpha, and interleukin-6. Dietary data were generated from the mean of three 24-hour recalls.Results: After adjustment for potential confounders, HEI-2010 composite scores were not significantly associated with decreased inflammation or greater antioxidant capacity. In analysis of the 12 components composing the HEI-2010, significant positive association was observed between total dairy and total serum antioxidant capacity (0.043; 95% CI, 0.008–0.069). Significant associations observed in inflammatory markers were between total vegetable and tumor necrosis factor-alpha (−0.078; 95% CI, −0.151 to −0.005), sodium and interleukin-6 (0.091; 95% CI, 0.023–0.158), and scores for combined calories from solid fats, alcoholic beverages, and added sugars and interleukin-6 (0.139; 95% CI, 0.027–0.252). In models adjusting for HEI-2010 composite score when significant associations were observed between component scores and biomarkers, two of six associations were strengthened by adding the composite score as a potential confounder.Conclusions: Largely null findings along with those inconsistent with scientific expectations suggest caution in extrapolating adherence to the HEI-2010 with an individual’s inflammatory or antioxidant status. Results merit additional investigation with other biomarkers of chronic disease and emphasis on dietary patterns given potential synergy within food combinations.

Association Between Oxidation-Modified Lipoproteins and Coronary Plaque in Psoriasis.

Psoriasis is a systemic inflammatory skin disease associated with cardiovascular disease and lipid dysfunction. However, traditional lipid parameters have limited prognostic value, whereas assessing oxidation-modified lipids in this inflammatory driven condition may capture additional risk. Recently, a study showed that psoriasis was associated with increased lipid-rich coronary plaques; therefore, investigating potential relationships with oxidation-modified lipids may speed understanding of increased cardiovascular disease in psoriasis. To understand whether oxidation-modified lipids associate with traditional lipid phenotypes, cardiometabolic disease biomarkers, and total coronary plaque, with focus on noncalcified burden (NCB) by coronary computed tomographic angiography in psoriasis. Psoriasis subjects and controls (n=252) had profiling for oxidation-modified LDL (low-density lipoprotein), HDL (high-density lipoprotein), Lp(a) (lipoprotein[a]), cholesterol efflux capacity, lipoprotein particle size and number by NMR spectroscopy, and PON-1 (paraoxonase-1) activity. Blinded coronary computed tomographic angiography coronary artery disease characterization included total burden, NCB, and dense-calcified burden. Compared with healthy volunteers, psoriasis subjects were older (mean age, 50.1), had increased body mass index, and homeostatic model assessment of insulin resistance. Psoriasis subjects had increase in oxidized Lp(a), Lp(a), and oxidized HDL (oxHDL; P <0.05 for all) with significant association of oxidized LDL (β=0.10; P=0.020) and oxHDL (β=-0.11; P=0.007) with NCB. Moreover, psoriasis subjects expressed significantly higher PON-1 (kU/µL) activity compared with healthy volunteers (8.55±3.21 versus 6.24±3.82; P=0.01). Finally, psoriasis treatment was associated with a reduction in oxHDL (U/mL; 203.79±88.40 versus 116.36±85.03; P<0.001) and with a concomitant decrease in NCB at 1 year (1.04±0.44 versus 0.95±0.32; P=0.03). Traditional lipids did not capture risk of lipid-rich plaque as assessed by NCB, whereas assaying oxidation-modification of lipids revealed significant association with oxidized LDL and oxHDL. The PON-1 activity was increased in psoriasis suggesting possible compensatory antioxidative effect. Psoriasis treatment was associated with a reduction in oxHDL. These findings support performance of larger studies to understand oxidation-modified lipids in inflammatory states.

Mineralocorticoid Receptor and Aldosterone-Related Biomarkers of End-Organ Damage in Cardiometabolic Disease.

The mineralocorticoid receptor (MR) was first identified as a blood pressure regulator, modulating renal sodium handling in response to its principal ligand aldosterone. The mineralocorticoid receptor is also expressed in many tissues other than the kidney, such as adipose tissue, heart and vasculature. Recent studies have shown that MR plays a relevant role in the control of cardiovascular and metabolic function, as well as in adipogenesis. Dysregulation of aldosterone/MR signaling represents an important cause of disease as high plasma levels of aldosterone are associated with hypertension, obesity and increased cardiovascular risk. Aldosterone displays powerful vascular effects and acts as a potent pro-fibrotic agent in cardiovascular remodeling. Mineralocorticoid receptor activation regulates genes involved in vascular and cardiac fibrosis, calcification and inflammation. This review focuses on the role of novel potential biomarkers related to aldosterone/MR system that could help identify cardiovascular and metabolic detrimental conditions, as a result of altered MR activation. Specifically, we discuss: (1) how MR signaling regulates the number and function of different subpopulations of circulating and intra-tissue immune cells; (2) the role of aldosterone/MR system in mediating cardiometabolic diseases induced by obesity; and (3) the role of several MR downstream molecules as novel potential biomarkers of cardiometabolic diseases, end-organ damage and rehabilitation outcome.

Socioeconomic inequalities in the prevalence of biomarkers of cardio-metabolic disease in South Korea: Comparison of the Health Examinees Study to a nationally representative survey.

Background/ObjectivesThis study aimed to examine socioeconomic inequalities in the prevalence of biomarkers of cardiovascular disease and diabetes in the newly developed large-scale genomic cohort study of Korean adults, the Health Examinees-Gem (HEXA-G), with a comparison of the nationally representative cross-sectional study, the Korea National Health and Nutrition Examination Survey (K-NHANES).Subjects/MethodsUsing the HEXA-G and the K-NHANES from 2007–2012, we analyzed the age-adjusted relative risk (RR) and prevalence of enlarged waist circumference (EWC), elevated triglycerides (ET), low HDL cholesterol (LHC), elevated blood pressure (EBP) and elevated blood glucose (EBG) by income and educational groups for adults at age 40–69.ResultsFor men, the prevalence of risk factors was similar across different income and educational groups (p>0.1), and between the K-NHANES and the HEXA-G. Among five risk factors, EBG showed the greatest discrepancy by 7 to 11 percentage points (i.e., the prevalence of 0.43 and 0.36 for college graduates, respectively, in K-NHANES and HEXA-G). For women, socioeconomic inequalities appeared for the five risk factors. Prevalence of risk factors was mostly lower in the HEXA-G than the K-NHANES, by approximately 11.0 percentage points. Especially, the discrepancy between K-NHANES and HEXA-G was largest in EBG (i.e., the prevalence of 0.31 and 0.20 for the lowest income groups, respectively).ConclusionThe HEXA-G shows broadly similar socioeconomic inequality in prevalence of cardio-metabolic risk factors to the nationally representative sample with more modest socioeconomic inequality among women in the HEXA-G than the K-NHANES.