Cardiometabolic Health Research Articles

Exercise as an anti-inflammatory Therapy in Axial Spondyloarthritis Therapeutic Intervention (EXTASI study): a randomised control trial

Abstract Objectives Axial Spondyloarthritis (AxSpA) is a chronic inflammatory disease, yet despite known anti-inflammatory effects of exercise, the effect of exercise on inflammatory immune cell populations and associated inflammatory profiles in AxSpA is unknown. This randomised-control trial investigated the effect of 12-weeks of walking on symptom severity, cardiometabolic health, inflammatory biomarkers, and immune cell populations. Methods Twenty people (60% male) living with AxSpA who were on stable dose non-steroidal anti-inflammatory (NSAIDs) medication participated. Participants were randomly assigned to control or exercise (30 min of walking five x per week). Participants were invited back every four-weeks for assessment. Results There was a 0% drop out and no adverse events in the exercise group showing walking exercise was well tolerated. Home-based walking for 12-weeks lowered the proportion of pro-inflammatory monocytes, whereas they increased in the control group. Changes were associated with lower interleukin-6 (IL-6) and C-reactive protein (CRP) concentrations, lower spinal pain, and lower systolic blood pressure in the exercise group, whereas these markers increased in the control group. Reductions in IL-6 and pro-inflammatory monocytes with exercise were independent of lower body fat percentage. Conclusion Supplementing NSAID therapy with walking exercise can improve inflammatory immune profiles in people with AxSpA coinciding with reductions in spinal pain. Importantly, the exercise was well tolerated, suggesting walking exercise can be used as an adjuvant anti-inflammatory therapy for NSAID treatments. This should now be explored in people living with AxSpA who have had high enough disease activity to necessitate the prescription of biologic or synthetic DMARD treatments. Clinical trials registration ClinicalTrials.Gov, NCT04368494

The pan-PPAR agonist lanifibranor improves cardiometabolic health in patients with metabolic dysfunction-associated steatohepatitis

Lanifibranor, a pan-PPAR agonist, improves liver histology in patients with metabolic dysfunction-associated steatohepatitis (MASH), who have poor cardiometabolic health (CMH) and cardiovascular events as major mortality cause. NATIVE trial secondary and exploratory outcomes (ClinicalTrials.gov NCT03008070) were analyzed for the effect of lanifibranor on IR, lipid and glucose metabolism, systemic inflammation, blood pressure (BP), hepatic steatosis (imaging and histological grading) for all patients of the original analysis. With lanifibranor, triglycerides, HDL-C, apolipoproteins, insulin, HOMA-IR, HbA1c, fasting glucose (FG), hs-CRP, ferritin, diastolic BP and steatosis improved significantly, independent of diabetes status: most patients with prediabetes returned to normal FG levels. Significant adiponectin increases correlated with hepatic and CMH marker improvement; patients had an average weight gain of 2.5 kg, with 49% gaining ≥2.5% weight. Therapeutic benefits were similar regardless of weight change. Here, we show that effects of lanifibranor on liver histology in MASH are accompanied with CMH improvement, indicative of potential cardiovascular clinical benefits.

Understanding the impact of maternal and infant nutrition on infant/child health: Multiethnic considerations, knowledge translation, and future directions for equitable health research.

A mother's intrauterine environment influences her health and that of her offspring, at birth and in the future. Herein, we present an overview of our Canadian Institutes of Health Research (CIHR)-funded grant "Understanding the impact of maternal and infant nutrition on infant/child health" - set within The NutriGen Birth Cohort Alliance. NutriGen is a consortium of four Canadian prospective birth cohorts representing > 5000 mother-child pairs of diverse ethnic groups including South Asians, White Europeans, and Indigenous peoples. We summarize our objectives and main findings on outcomes of maternal diet, gestational diabetes, birth weight, cardiometabolic health, the microbiome, and epigenetic modifications. We append this work with 10 key messages when conducting multiethnic research and review our knowledge translation products. We describe the clinical impact of our research on maternal and child health and conclude with future directions on biomarker discovery, expansion to other ethnic groups, and interventions for high-risk populations.

Effects of a personalized nutrition program on cardiometabolic health: a randomized controlled trial.

Large variability exists in people's responses to foods. However, the efficacy of personalized dietary advice for health remains understudied. We compared a personalized dietary program (PDP) versus general advice (control) on cardiometabolic health using a randomized clinical trial. The PDP used food characteristics, individual postprandial glucose and triglyceride (TG) responses to foods, microbiomes and health history, to produce personalized food scores in an 18-week app-based program. The control group received standard care dietary advice (US Department of Agriculture Guidelines for Americans, 2020-2025) using online resources, check-ins, video lessons and a leaflet. Primary outcomes were serum low-density lipoprotein cholesterol and TG concentrations at baseline and at 18 weeks. Participants (n = 347), aged 41-70 years and generally representative of the average US population, were randomized to the PDP (n = 177) or control (n = 170). Intention-to-treat analysis (n = 347) between groups showed significant reduction in TGs (mean difference = -0.13 mmol l-1; log-transformed 95% confidence interval = -0.07 to -0.01, P = 0.016). Changes in low-density lipoprotein cholesterol were not significant. There were improvements in secondary outcomes, including body weight, waist circumference, HbA1c, diet quality and microbiome (beta-diversity) (P < 0.05), particularly in highly adherent PDP participants. However, blood pressure, insulin, glucose, C-peptide, apolipoprotein A1 and B, and postprandial TGs did not differ between groups. No serious intervention-related adverse events were reported. Following a personalized diet led to some improvements in cardiometabolic health compared to standard dietary advice. ClinicalTrials.gov registration: NCT05273268 .

A Mediterranean diet improves glycation markers in healthy people and in those with chronic diseases: a systematic review of clinical trials.

Consumption of the Mediterranean diet (MedDiet) has beneficial effects on cardiometabolic health and aging. This systematic review aimed to critically investigate the effect of the MedDiet on glycation markers in healthy or overweight individuals with type 2 diabetes or cardiovascular disease. MEDLINE, EMBASE, Web of Science, and the Cochrane Library were searched, using the terms "Mediterranean diet" AND "glycation end products, advanced". Three randomized and 3 nonrandomized clinical trials, containing data on 2935 adult and elderly individuals with normal weight or overweight, were included. All extracted data were compiled, compared, and critically analyzed. The authors of most of the studies demonstrated a reduction in serum concentrations of advanced glycation end products (AGEs), such as εN-carboxymethyllysine and methylglyoxal, and in skin autofluorescence levels after at least 4 weeks of adherence to the MedDiet. The MedDiet also led to positive effects on gene expression of receptors for AGEs, as RAGE and AGER1, and an enzyme involved in detoxification (glyoxalase I). There is no evidence that short-term adherence affects glycation markers. Glycation markers improved in response to the MedDiet. The possible mechanisms involved may be related to the low AGE and refined sugars content of the diet, as well as its high monounsaturated fatty acid, phenolic compound, and dietary fiber contents. PROSPERO registration no. CRD42021284006.

Association between meeting 24-h movement guidelines and health in children and adolescents aged 5–17 years: a systematic review and meta-analysis

Twenty-four-hour movement behaviors have significant implications for physical and mental health throughout one’s lifespan. Consistent with movement behaviors, several countries have formulated and published 24-h movement guidelines. This review summarized the studies related to 24-h movement guidelines among children and adolescents from six databases (MEDLINE, EMBASE, PubMed, Web of Science, CINAHL, and SPORTDiscus). In a total of 61 studies that discussed compliance with 24-h movement guidelines, the overall adherence rate was very low (7.1%), with boys exceeding girls, children surpassing adolescents, and regional differences. A total of 39 studies examined the associations between 24-h movement guidelines and health indicators. Findings indicated that meeting all three guidelines was favorably associated with adiposity, cardiometabolic health, mental and social health, physical fitness, health-related quality of life, academic achievement, cognitive development, perceived health, dietary patterns, and myopia. Future research should utilize longitudinal and experimental designs to enhance our understanding of the associations between 24-h movement guidelines and health indicators, thereby aiding the formulation and refinement of such guidelines.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, CRD42023481230.

Food security status and cardiometabolic health by sex/gender and race/ethnicity among adults in the United States

BackgroundMinoritized racial/ethnic groups and women in the United States (US) are disproportionately burdened by food insecurity, which likely contributes to disparities in cardiovascular health (CVH). Disparities are projected to widen due to the worsening climate crisis that is straining the agricultural system including food supplies. Nonetheless, studies have not investigated the relationship between food security status and ‘ideal’ CVH in a large, nationally-representative and racially/ethnically diverse US sample.Methods and resultsWe investigated household food security status in relation to ‘ideal’ CVH among US adults (N = 157,001) using 2014–2018/2020 National Health Interview Survey data. Food security status was defined as very low, low, marginal, or high. A summed score of 4 health behaviors and 3 clinical factors totaling 7 different measures was dichotomized (yes/no) to assess modified ‘ideal’ CVH (mICVH). Using Poisson regression with robust variance, we estimated prevalence ratios (PRs) and 95% CIs of mICVH by household food security status. We stratified models by sex/gender and race/ethnicity. Very low food security prevalence was higher among non-Hispanic (NH)-Black (8.0%) compared to Hispanic/Latinx (5.1%), NH-White (3.1%) and NH-Asian (1.7%) adults. The association between very low versus high food security and mICVH was stronger among women (PR = 0.23 [95% CI: 0.17–0.31]) than men (PR = 0.48 [95% CI: 0.35–0.66]). Compared to NH-White adults with high food security, racially/ethnically minoritized groups with very low to high food security were generally less likely (range: [PRvery low = 0.25[95% CI: 0.14–0.44] – [PRhigh = 0.88 [95% CI: 0.79–0.97]) to meet mICVH criteria.ConclusionsFood insecurity was associated with lower mICVH prevalence and racially/ethnically minoritized groups were disproportionately burdened.

The Association between Cardiometabolic Risk and Cognitive Function among Older Americans and Chinese.

Cardiometabolic risk (CMR) is associated with cognitive health, but the association can be affected by broader social, economic, and medical contexts. The US and China have very different developmental and epidemiological histories, and thus CMR among older people could be linked to cognitive function differently in the two countries. Cross-sectional and longitudinal OLS regression models were estimated for each country using nationally representative samples of populations over age 50: 7,430/4,474 Americans and 6,108/3,655 Chinese in the cross-sectional/longitudinal samples. In the US, higher CMR is associated with worse cognitive function (b=-0.08, p<0.016). Longitudinally, CMR increase is associated with worse cognitive function at a marginally significant level (b=-0.10, p=0.055). No relationship between CMR level or change and cognitive function is observed in China. Higher education levels are linked to better cognitive function and slower cognitive decline in both countries. Unlike older Americans, relative to those with very low education levels, among older Chinese with the highest education level, a higher CMR links to better cognitive function (b=0.63, p=0.013) and slower cognitive decline (b=0.35, p=0.062); Nevertheless, a rapid increase in CMR is additionally harmful (b=-0.54, p=0.050) for cognitive function and may lead to faster cognitive decline (b=-0.35, p=0.079). The significant relationship between CMR and cognitive function in the US suggests the importance of monitoring and controlling CMR factors at older ages. The insignificant relationship in China may be explained by the high CMR among those with high education levels, highlighting the need for improving cardiometabolic health through education and promoting healthy lifestyles.

Integrated neuromuscular training intervention applied in schools induces a higher increase in salivary high molecular weight adiponectin and a more favorable body mass index, cardiorespiratory fitness and muscle strength in children as compared to the traditional physical education classes

BackgroundHigh-molecular-weight adiponectin (HMW-adiponectin) is a cardio-metabolic health protector. Objectives: (1) to compare body mass index (BMI), cardiorespiratory fitness (CRF) and muscle strength (MS) in healthy school-children depending on their baseline salivary-HMW-adiponectin concentration; and (2) to apply a 3-month integrated neuromuscular training (INT) and evaluate its effects on salivary-HMW-adiponectin concentration, BMI, CRF and MS in the same children. Additional goal: to identify if any potential changes during the 3-month period may be related to a potential change in salivary-HMW-adiponectin concentration.MethodsNinety children (7.4 ± 0.3 years) were recruited in primary schools and randomly allocated into control or intervention group. The intervention consisted of a 3-month INT applied during physical education (PE) classes, twice-weekly, while the control group had traditional PE classes. Body mass and height were measured, BMI was calculated and HMW-adiponectin was quantified in saliva. To assess CRF and MS, 800 m-run and hand-dynamometry were applied, respectively. All measurements were performed twice, at baseline and after 3 months.ResultsChildren with higher baseline salivary-HMW-adiponectin have more favorable BMI (p = 0.006) and slightly higher CRF (p = 0.017) in comparison to the children with lower baseline salivary-HMW-adiponectin. There were no big changes after the 3-month-period neither in the control, nor the INT group. However, it is worthy to note that the INT induced slightly higher increase in salivary-HMW-adiponectin (p = 0.007), and a slightly higher improvement in BMI (p = 0.028), CRF (p = 0.043) and MS (p = 0.003), as compared to the traditional PE classes. Finally, the INT-induced improvement in CRF was associated with the increased post-salivary-HMW-adiponectin concentration (p = 0.022).ConclusionMain findings may suggest the potential utility of an INT as a cost-effective strategy that can be applied in schools to induce cardio-protective effects in school-children.

Neighborhood physical environments and change in cardiometabolic risk factors over 14 years in the study of Women's health across the nation

BackgroundNeighborhood physical environments may influence cardiometabolic health, but prior studies have been inconsistent, and few included long follow-up periods. MethodsChanges in cardiometabolic risk factors were measured for up to 14 years in 2830 midlife women in the Study of Women's Health Across the Nation, a multi-ethnic/racial cohort of women from seven U.S. sites. Data on neighborhood food retail environments (modified Retail Food Environment Index) and walkability (National Walkability Index) were obtained for each woman's residence at each follow-up. Data on neighborhood access to green space, parks, and supermarkets were available for subsets (32–42%) of women. Models tested whether rates of change in cardiometabolic outcomes differed based on neighborhood characteristics, independent of sociodemographic and health-related covariates. ResultsLiving in more (vs. less) walkable neighborhoods was associated with favorable changes in blood pressure outcomes (SBP: −0.27 mmHg/year, p = 0.002; DBP: −0.22 mmHg/year, p < 0.0001; hypertension status: ratio of ORs = 0.79, p < 0.0001), and small declines in waist circumference (−0.09 cm/year, p = 0.03). Small-magnitude associations were also observed between low park access and greater increases in blood pressure outcomes (SBP: 0.37 mmHg/year, p = 0.003; DBP: 0.15 mmHg/year, p = 0.04; hypertension status: ratio of ORs = 1.16, p = .04), though associations involving DBP and hypertension were only present after adjustment for sociodemographic variables. Other associations were statistically unreliable or contrary to hypotheses. ConclusionNeighborhood walkability may have a meaningful influence on trajectories of blood pressure outcomes in women from midlife to early older adulthood, suggesting the need to better understand how individuals interact with their neighborhood environments in pursuit of cardiometabolic health.

MASLD/MASH and type 2 diabetes: two sides of the same coin? From single PPAR to pan-PPAR agonists

Type 2 diabetes (T2D) and metabolic dysfunction-associated steatotic liver disease (MASLD), mainly related to nutrition and lack of physical activity, are both very common conditions, share several disease pathways and clinical manifestations, and increasingly co-occur with disease progression. Insulin resistance is an upstream node in the biology of both conditions and triggers liver parenchymal injury, inflammation and fibrosis. Peroxisome proliferator-activated receptor (PPAR) nuclear transcription factors are master regulators of energy homeostasis - insulin signaling in liver, adipose and skeletal muscle tissue - and affect immune and fibrogenesis pathways. Among distinct yet overlapping effects, PPARα regulates lipid metabolism and energy expenditure, PPAR β/δ has anti-inflammatory effects and increases glucose uptake by skeletal muscle, while PPARγ improves insulin sensitivity and exerts direct antifibrotic effects on hepatic stellate cells. Together PPARs thus represent pharmacological targets across the entire biology of MASH. Single PPAR agonists are approved for hypertriglyceridemia (PPARα) and T2D (PPARγ), but these, as well as dual PPAR agonists, have shown mixed results as anti-MASH treatments in clinical trials. Agonists of all three PPAR isoforms have the potential to improve the full disease spectrum from insulin resistance to fibrosis, and correspondingly to improve cardiometabolic and hepatic health, as has been shown (phase II data) with the pan-PPAR agonist lanifibranor.

Cohort profile: the Environmental Reproductive and Glucose Outcomes (ERGO) Study (Boston, Massachusetts, USA) — a prospective pregnancy cohort study of the impacts of environmental exposures on parental cardiometabolic health

PurposePregnancy and the postpartum period are increasingly recognised as sensitive windows for cardiometabolic disease risk. Growing evidence suggests environmental exposures, including endocrine-disrupting chemicals (EDCs), are associated with an increased risk...

Risk prediction model of metabolic syndrome in perimenopausal women based on machine learning

IntroductionMetabolic syndrome (MetS) is considered to be an important parameter of cardio-metabolic health and contributing to the development of atherosclerosis, type 2 diabetes. The incidence of MetS significantly increases in postmenopausal women, therefore, the perimenopausal period is considered a critical phase for prevention. We aimed to use four machine learning methods to predict whether perimenopausal women will develop MetS within 2 years. MethodsWomen aged 45–55 years who underwent 2 consecutive years of physical examinations in Ninth Clinical College of Peking University between January 2021 and December 2022 were included. We extracted 26 features from physical examinations, and used backward selection method to select top 10 features with the largest area under the receiver operating characteristic curve (AUC). Extreme gradient boosting (XGBoost), Random forest (RF), Multilayer perceptron (MLP) and Logistic regression (LR) were used to establish the model. Those performance were measured by AUC, accuracy, precision, recall and F1 score. SHapley Additive exPlanation (SHAP) value was used to identify risk factors affecting perimenopausal MetS. ResultsA total of 8700 women had physical examination records, and 2,254 women finally met the inclusion criteria. For predicting MetS events, RF and XGBoost had the highest AUC (0.96, 0.95, respectively). XGBoost has the highest F1 value (F1 = 0.77), followed by RF, LR and MLP. SHAP value suggested that the top 5 variables affecting MetS in this study were Waist circumference, Fasting blood glucose, High-density lipoprotein cholesterol, Triglycerides and Diastolic blood pressure, respectively. ConclusionWe’ve developed a targeted MetS risk prediction model for perimenopausal women, using health examination data. This model enables early identification of high MetS risk in this group, offering significant benefits for individual health management and wider socio-economic health initiatives.

FEASIBILITY, ACCEPTABILITY, AND EFFICACY OF A PILOT EXERCISE PHYSIOLOGY GROUP SERVICE FOR OLDER ADULTS WITH TYPE 2 DIABETES

INTRODUCTION &amp; AIMS Type 2 diabetes prevalence increases with ageing, affecting over half a million older Australians. Medicare type 2 diabetes group interventions can support older adults’ diabetes management. However, Accredited Exercise Physiologist (AEP) delivered service feasibility and acceptability is yet to be assessed. This study aimed to assess feasibility, acceptability and preliminary efficacy of a Medicare type 2 diabetes group exercise and education intervention for older adults. METHODS This study was a single arm feasibility, acceptability, and preliminary efficacy trial of an AEP delivered type 2 diabetes group service for older adults. Participants attended the Diabetes Clinic once per week for 8 weeks, for a group exercise and education session. Attendance, participation, enjoyment, suitability, usefulness, and pre-post clinical health outcomes were assessed. RESULTS The intervention was feasible and acceptable, with 40 participants (71.8±4.5 years old, range 65-81 years, 45% female) attending 87% of sessions, with high treatment compliance within sessions (aerobic training: 86%; resistance training: 86%; education: 87%). Almost all participants (97%) strongly agreed that the program was enjoyable. Significant post intervention improvements (mean difference [95% CI]) were observed for right arm systolic blood pressure (SBP) (-7mmHg [-12, -2], p=0.007), left arm diastolic blood pressure (DBP) (-3mmHg [-5, -0], p=0.021), body weight (-0.7kg [-1.3, -0.0], p=0.039), waist circumference (-1.3cm [-2.2, -0.4], p=0.006), 6-minute walk test (22.8m, [9.1. 36.5], p=0.002), 5 times sit to stand (-0.8sec [-1.2, -0.5], p&amp;lt;0.001), short physical performance battery ordinal scale (0.3 [0.1, 0.5], p=0.009), and whole-body muscle strength (32.2kg [22.3, 42.1], p&amp;lt;0.001). CONCLUSION Older adults attended and enjoyed the AEP led Diabetes Clinic program, while also improving fitness and cardiometabolic health outcomes. Ways to enhance referrals and engage older adults in the programs warrant further investigation. The potential for additional sessions to achieve greater physical activity engagement and diabetes self-management should be further investigated.

Association of natriuretic peptides and receptor activity with cardio-metabolic health at middle age

Natriuretic peptides (NP) have multiple actions benefitting cardiovascular and metabolic health. Although many of these are mediated by Guanylyl Cyclase (GC) receptors NPR1 and NPR2, their role and relative importance in vivo is unclear. The intracellular mediator of NPR1 and NPR2, cGMP, circulates in plasma and can be used to examine relationships between receptor activity and tissue responses targeted by NPs. Plasma cGMP was measured in 348 participants previously recruited in a multidisciplinary community study (CHALICE) at age 50 years at a single centre. Associations between bio-active NPs and bio-inactive aminoterminal products with cGMP, and of cGMP with tissue response, were analysed using linear regression. Mediation of associations by NPs was assessed by Causal Mediation Analysis (CMA). ANP’s contribution to cGMP far exceed those of other NPs. Modelling across three components (demographics, NPs and cardiovascular function) shows that ANP and CNP are independent and positive predictors of cGMP. Counter intuitively, findings from CMA imply that in specific tissues, NPR1 responds more to BNP stimulation than ANP. Collectively these findings align with longer tissue half-life of BNP, and direct further therapeutic interventions towards extending tissue activity of ANP and CNP.

Reproductive factors and cardiometabolic disease among middle-aged and older women: a nationwide study from CHARLS

BackgroundCardiometabolic disease is skyrocketing to epidemic proportions due to the high prevalence of its components and the aging of the worldwide population. More efforts are needed to improve cardiometabolic health. The aim of this nationally representative study based on the China Health and Retirement Longitudinal Study (CHARLS, 2014–2018) was to examine the association between reproductive factors and cardiometabolic disease among Chinese women aged ≥45 years.MethodsThe CHARLS is an ongoing longitudinal study initiated in 2011, and the latest follow-up was completed in 2018. In total, 6,407 participants were analyzed. Effect-sizes are expressed as odds ratios (OR) and 95% confidence intervals (CI). Confounding was considered from statistical adjustment, subsidiary exploration, and unmeasured confounding assessment aspects.ResultsOf 6,407 accessible participants, 60.9% were recorded as having one or more of five predefined cardiovascular or metabolic disorders. Compared to those with two children, participants who had 0–1 child were found to have a lower risk of cardiometabolic disease (OR = 0.844, 95% CI: 0.714–0.998), and those who had ≥3 children had a greater risk (OR = 1.181, 95% CI: 1.027–1.357). Age at menarche of 16–18 years was a protective factor compared with ≤16 years of age (OR = 0.858, 95% CI: 0.749–0.982). In contrast, participants with a history of abortion were 1.212 times more likely to have cardiometabolic disorders (OR = 1.212, 95% CI: 1.006–1.465). The likelihood for the presence of unmeasured confounding was low, as reflected by E-values.ConclusionsOur findings demonstrate that number of children, age at menarche, and history of abortion were associated with a significant risk of cardiometabolic disease among Chinese women aged ≥45 years.

Sleep patterns are associated with cardiometabolic risk factors in nine-year-old Swedish children.

Sleep duration and bedtime may play a role in children's cardiometabolic health, but research is lacking. This study examined associations between sleep patterns and cardiometabolic risk factors in Swedish nine-year-olds. This cross-sectional study used data from three studies, where identical outcome measures were conducted in 411 nine-year-olds, 51% boys, between 2016 and 2020. Sleep was assessed with wrist-worn accelerometers and sleep journals. Children were grouped based on meeting the sleep guidelines of 9-11 h and going to bed early or late based on the median bedtime. Analysis of covariance was used to examine associations between sleep patterns and cardiometabolic risk factors. Meeting sleep guidelines and going to bed early were associated with lower metabolic syndrome score (-0.15 vs. 0.42, p = 0.029), insulin resistance (0.30 vs. 0.60, p = 0.025) and insulin levels (6.80 vs. 8.87 mIU/L, p = 0.034), compared with their peers who did not meet the guidelines and went to bed later. When adjusting for total sleep time, analyses still showed associations with the metabolic syndrome score (-0.19 vs. 0.50, p = 0.011). The findings indicate that good sleep patterns could help mediate positive overall cardiometabolic health in children.

Understanding the Cardiovascular and Metabolic Health Effects of Air Pollution in the Context of Cumulative Exposomic Impacts.

Poor air quality accounts for more than 9 million deaths a year globally according to recent estimates. A large portion of these deaths are attributable to cardiovascular causes, with evidence indicating that air pollution may also play an important role in the genesis of key cardiometabolic risk factors. Air pollution is not experienced in isolation but is part of a complex system, influenced by a host of other external environmental exposures, and interacting with intrinsic biologic factors and susceptibility to ultimately determine cardiovascular and metabolic outcomes. Given that the same fossil fuel emission sources that cause climate change also result in air pollution, there is a need for robust approaches that can not only limit climate change but also eliminate air pollution health effects, with an emphasis of protecting the most susceptible but also targeting interventions at the most vulnerable populations. In this review, we summarize the current state of epidemiologic and mechanistic evidence underpinning the association of air pollution with cardiometabolic disease and how complex interactions with other exposures and individual characteristics may modify these associations. We identify gaps in the current literature and suggest emerging approaches for policy makers to holistically approach cardiometabolic health risk and impact assessment.

Proteomics, Human Environmental Exposure, and Cardiometabolic Risk.

Rationale: The biological mechanisms linking environmental exposures with cardiovascular disease (CVD) pathobiology are incompletely understood. We sought to identify circulating proteomic signatures of environmental exposures, and examine their associations with cardiometabolic and respiratory disease (CMD) in observational cohort studies. Methods: We tested the relations of >6500 circulating proteins with 29 environmental exposures across the built environment, green space, air pollution, temperature, and social vulnerability indicators in nearly 3000 participants of the Coronary Artery Risk Development in Young Adults (CARDIA) study across 4 centers using penalized and ordinary linear regression. In >3500 participants from the Framingham Heart Study (FHS) and Jackson Heart Study (JHS), we evaluated the prospective relations of proteomic signatures of the envirome with CVD and mortality using Cox models.Results: Proteomic signatures of the envirome identified novel/established CVD-relevant pathways including DNA damage, fibrosis, inflammation, and mitochondrial function. The proteomic signatures of the envirome were broadly related to CMD and respiratory phenotypes (e.g., body mass index, lipids, and left ventricular mass) in CARDIA, with replication in FHS/JHS. A proteomic signature of social vulnerability was associated with a composite of CVD/mortality (1428 events; FHS: HR=1.16, 95% CI 1.08-1.24, P=1.77e-05; JHS: HR=1.25 95% CI 1.13-1.38, P=6.38e-06; HR expressed as per 1 standard deviation increase in proteomic signature), robust to adjustment for known clinical risk factors. Conclusions: Environmental exposures are related to an inflammatory-metabolic proteome, which identifies individuals with CMD and respiratory phenotypes and outcomes. Future work examining the dynamic impact of the environment on human cardiometabolic health is warranted.

Construct validity and test-retest reliability of a chrononutrition questionnaire for shift work and non-shift work populations

ABSTRACT The irregular eating patterns of both shift workers and evening chronotypes adversely affect cardiometabolic health. A tool that conveniently captures temporal patterns of eating alongside an indicator of circadian rhythm such as chronotype will enable researchers to explore relationships with diverse health outcome measures. We aimed to investigate the test-retest reliability and convergent validity of a Chrononutrition Questionnaire (CNQ) that captures temporal patterns of eating and chronotype in the general population (non-shift workers, university students, retirees, unemployed individuals) and shift work population. Participants attended two face-to-face/virtual sessions and completed the CNQ and food/sleep/work diaries. Outcomes included subjective chronotype, wake/sleep/mid-sleep time, sleep duration, meal/snack regularity, meal/snack/total frequency, times of first/last/largest eating occasions (EO), main meal (MM) 1/2/3, and duration of eating window (DEW). 116 participants enrolled (44.5 ± 16.5 years, BMI: 27.3 ± 5.8 kg/m2, 73% female, 52% general population); 105 completed the study. Reliability was acceptable for chronotype, sleep, and all temporal eating patterns except on night shifts. Convergent validity was good for chronotype and sleep except for certain shift/shift-free days. Generally, meal/snack regularity and frequency, and times of first/last EO showed good validity for the general population but not shift workers. Validity was good for DEW (except work-free days and afternoon shifts) and times of MM 1/2/3 (except afternoon and night shifts), while time of largest EO had poor validity. The CNQ has good test-retest reliability and acceptable convergent validity for the general and shift work population, although it will benefit from further validation, especially regarding regularity, frequency, and times of first and last eating occasions across more days amongst a larger sample size of shift workers. Use of the CNQ by researchers will expand our current understanding of chrononutrition as relationships between timing of food intake and the multitude of health outcomes are examined.