Search

Background Short-term exposure to air pollution has been associated with cardiovascular events, potentially by promoting endothelial cell activation and inflammation. A few large-scale studies have examined the associations and have had mixed results. Methods We included 3820 non-current smoking participants (mean age 56 years, 54% women) from the Framingham Offspring cohort examinations 7 (1998–2001) and 8 (2005–2008), and Third Generation cohort examination 1 (2002–2005), who lived within 50 km of a central monitoring station. We calculated the 1- to 7-day moving averages of fine particulate matter (PM2.5), black carbon (BC), sulfate (SO42-), nitrogen oxides (NOx), and ozone before examination visits. We used linear mixed effect models for P-selectin, monocyte chemoattractant protein 1 (MCP-1), intercellular adhesion molecule 1, lipoprotein-associated phospholipase A2 activity and mass, and osteoprotegerin that were measured up to twice, and linear regression models for CD40 ligand and interleukin-18 that were measured once, adjusting for demographics, life style and clinical factors, socioeconomic position, time, and meteorology. Results We found negative associations of PM2.5 and BC with P-selectin, of ozone with MCP-1, and of SO42- and NOx with osteoprotegerin. At the 5-day moving average, a 5 µg/m3 higher PM2.5 was associated with 1.6% (95% CI: − 2.8, − 0.3) lower levels of P-selectin; a 10 ppb higher ozone was associated with 1.7% (95% CI: − 3.2, − 0.1) lower levels of MCP-1; and a 20 ppb higher NOx was associated with 2.0% (95% CI: − 3.6, − 0.4) lower levels of osteoprotegerin. Conclusions We did not find evidence of positive associations between short-term air pollution exposure and endothelial cell activation. On the contrary, short-term exposure to higher levels of ambient pollutants were associated with lower levels of P-selectin, MCP-1, and osteoprotegerin in the Framingham Heart Study.

Background: In the US Diabetes Prevention Program (DPP) trial, a lifestyle intervention program focused on changes in diet and physical activity led to a 58% reduction in risk of developing type 2 diabetes. A variety of modifications to the DPP have been tested in clinical trials. We sought to compare the effects of different strategies for implementation of the US DPP on weight and other cardiometabolic outcomes. Methods: We conducted systematic searches of MEDLINE and Embase from January 2002 to August 2020. We included randomized controlled trials of adults that tested the effect of an intervention based on the US DPP on change in weight. Studies of at least 6 months duration were included. Two investigators independently extracted data. DPP implementation strategies were classified into eight different categories. Results: A total of 30 comparisons from 28 articles with 8,284 participants were included. Different strategies for implementing the DPP led to significant decreases in change in weight in the DPP compared with control arms during follow-up (Table). These strategies included intervention delivery through group sessions or combination of group and individual sessions. Additionally, interventions delivered by telehealth or by a combination of in-person and telehealth were effective. Conclusion: A number of different strategies for implementing the DPP lead to clinically meaningful decreases in weight. Disclosure K. S. Dorans: None. K. T. Mills: None. Y. Feng: None. A. A. Sethi: None. X. Li: None. J. He: None. Funding National Institute of General Medical Sciences (1P20GM109036-01A1)

Introduction: A significant proportion of persons with metabolic syndrome, prediabetes, or type 2 diabetes do not develop atherosclerotic cardiovascular disease (ASCVD). Discordantly normal apolipoprotein B (ApoB) relative to elevated LDL-cholesterol (LDL-C) may help to explain underlying heterogeneity in ASCVD risk among these individuals. Hypothesis: We hypothesized that discordantly normal ApoB (> 100 mg/dL) would be associated with a lower atherosclerosis burden among individuals with metabolic disorders. Methods: There were 331 Bogalusa Heart Study participants with metabolic syndrome (n=107), prediabetes (n=291), or type 2 diabetes (n=34) and LDL-C > 100 who were free of carotid plaque at baseline (2001-02) and underwent carotid ultrasound at follow-up (2013-16). Carotid plaque was defined as a focal wall thickening >1.5 mm. Modified Poisson regression with robust error variance estimated the long-term absence of plaque for normal ApoB after adjusting for established risk factors. Results: Participants were on average 36.3 years old at baseline, 202 (61.0%) were women, and 93 (29.9%) were African American. Overall, LDL-C explained 42.3% of the variability in ApoB as the lipoprotein markers were only modestly correlated (r=0.65). Participants with ApoB > 90 (74.6% versus 57.4%, p=0.001, Figure ). In multivariable modeling, persons with ApoB Conclusions: More than half of persons with metabolic disorders and elevated LDL-C had normal ApoB with a lower burden of carotid atherosclerosis over 13 years follow-up. ApoB better represents the atherogenic lipid burden among persons with metabolic disorders compared to LDL-C and may be especially helpful for persons with the pattern of high triglycerides and low HDL-cholesterol.

Background Type 2 diabetes mellitus (T2DM) is a major cause of morbidity and mortality globally. Strong evidence supports the importance of diet and other lifestyle factors in preventing T2DM. Among individuals with T2DM, low-carbohydrate diets lead to decreases in hemoglobin A1c (HbA1c). However, research on the effects of low-carbohydrate diets on glycemic outcomes among individuals not currently on glucose-lowering medications who have elevated HbA1c is limited. Methods The objective of this randomized controlled trial is to study the effect of a healthy low-carbohydrate diet achieved through behavioral intervention and key food supplementation compared with usual diet on HbA1c and other metabolic risk factors among individuals with HbA1c from 6.0 to 6.9% who are not on glucose-lowering medications. In this parallel trial, 150 participants will be randomized to the intervention or control group for 6 months. The healthy low-carbohydrate diet target is Discussion We expect that the results from this study will lead to new approaches for developing and implementing dietary approaches (other than the most commonly used reduced fat diet) that will substantially reduce risk of cardiometabolic disease among adults with or at high risk of T2DM. The study intervention involves behavioral counseling and promotes consumption of dietary components thought to reduce risk of cardiometabolic disease and has expected applicability in clinical practice. Trial registration ClinicalTrials.gov NCT03675360. Registered on September 18, 2018 (prior to enrolment of the first participant).

Background Patients with chronic kidney disease (CKD) have an increased risk of peripheral arterial disease (PAD). The ankle–brachial index (ABI), a noninvasive measure of PAD, is a predictor of adverse events among individuals with CKD. In general populations, changes in ABI have been associated with mortality, but this association is not well understood among patients with CKD. Methods We conducted a prospective study of 2920 participants in the Chronic Renal Insufficiency Cohort Study without lower extremity revascularization or amputation at baseline and with at least one follow-up ABI measurement (taken at annual visits) during the first 4 years of follow-up. The ABI was obtained by the standard protocol. Results In Cox proportional hazard regression analyses, we found a U-shaped association of average annual change in ABI with all-cause mortality. After adjusting for baseline ABI and other covariates, compared with participants with an average annual change in ABI of 0– Conclusions This study indicates both larger decreases and increases in average annual changes in ABI (>0.04/year) were associated with higher mortality risk. Monitoring changes in ABI over time may facilitate risk stratification for mortality among individuals with CKD.

Background: Women with prior gestational diabetes (GDM) are at elevated risk of type 2 diabetes and cardiovascular disease. We sought to compare cardiometabolic risk factors among parous U.S. women ages 20 to 44 by history of GDM. Methods: We used data from the National Health and Nutrition Examination Survey (NHANES) from 2007-2016. We included 3562 parous women. We compared anthropometric measures, glycemic markers, blood pressure and lipids by self-reported history of GDM, both with and without adjusting for demographic and behavioral factors and waist circumference. Analyses took NHANES multi-stage survey design into account. Results: Women without history of GDM were younger and, in crude analyses, had more favorable cardiometabolic risk factor profile than women with history of GDM (Table). Similar patterns were observed after adjusting for age, race/ethnicity, education and smoking. After also adjusting for waist circumference, only hemoglobin A1c, fasting glucose, high-density lipoprotein cholesterol and low-density lipoprotein cholesterol were significantly higher among women with history of GDM compared to women without GDM. Conclusions: Among parous U.S. women ages 20 to 44, those with a history of GDM had less favorable cardiometabolic risk factor profiles than did women without GDM, though results were attenuated after adjusting for markers of demographics, behavior, and central obesity. Disclosure K.S. Dorans: None. L.A. Bazzano: None. J. He: None. Funding Tulane Center of Biomedical Research (P20GM109036)

Background: The increasing prevalence of diabetes mellitus, a major cause of morbidity and mortality worldwide, is a critical public health concern. Though a number of studies have evaluated the associations of metabolites with prediabetes and diabetes, further exploration in this relatively new field may identify novel biomarkers for predicting, detecting, and managing hyperglycemia and diabetes. Objective: We conducted a metabolome-wide association study among 805 white and 426 African-American participants of the Bogalusa Heart Study (BHS) to identify metabolites associated with markers of glycemia and diabetes. Methods: After rigorous quality control, 1,202 metabolites quantified by untargeted, ultra-high performance liquid chromatography tandem-mass spectroscopy were tested for association with fasting glucose, hemoglobin A1c and diabetes. Multiple regression analyses were run in race-stratified and combined samples, adjusting for age, sex, education, blood pressure, body mass index, HDL-cholesterol, smoking, eGFR, fasting glucose (for HbA1c and diabetes), and race (in combined analyses). For fasting glucose and HbA1c, those taking diabetes medications were excluded. Metabolites were considered significant if they were significant (P-5 ; Bonferroni corrected for 1,202 metabolites) in one race group and the entire cohort, with a similar trend observed in the other race group. Results: After Bonferroni corrections, among 72 metabolites significantly associated with at least one glycemic outcome, 27 were novel and in known pathways: 5 from amino acid, 1 from carbohydrate, 18 from lipid, 1 from xenobiotics, and 2 from nucleotide pathways. Metabolites consistently associated with diabetes are shown in the Table . Conclusions: These results identified novel metabolites associated with glycemic outcomes, providing additional evidence on the importance of serum metabolites in hyperglycemia and diabetes.

Background and aims To examine the associations between history of gestational diabetes mellitus (GDM) and breastfeeding with branched-chain amino acids (BCAA) and their metabolites in later life. Methods and results 638 women (mean age 48.0 y) who had participated in the Bogalusa Heart Study and substudies of pregnancy history had untargeted, ultrahigh performance liquid chromatography-tandem mass spectroscopy conducted by Metabolon© on serum samples. Metabolites were identified that were BCAA or associated with BCAA metabolic pathways. History of GDM at any pregnancy (self-reported, confirmed with medical records when possible) as well as breastfeeding were examined as predictors of BCAA using linear models, controlling for age, race, BMI, waist circumference, and menopausal status. None of the BCAA differed statistically by history of either GDM or breastfeeding, although absolute levels of each of the BCAA were higher with GDM and lower with breastfeeding. Of the 27 metabolites on the leucine, isoleucine and valine metabolism subpathway, 1-carboxyethylleucine, 1-carboxyethyvaline, and 3-hydroxy-2-ethylpropionate were higher in women with a history of GDM, but lower in women in women with a history of breastfeeding. Similar results were found for alpha-hydroxyisocaproate, 1-carboxyethylisoleucine, and N-acetylleucine. Conclusions GDM and breastfeeding are associated in opposite directions with several metabolites on the BCAA metabolic pathway.

Highlights • Not all individuals with prediabetes, T2D and/or MetS develop significant ASCVD. • Discordantly normal ApoB relative to high LDL-C may help explain such heterogeneity. • 51% of persons with metabolic disorders and high LDL-C had discordantly normal ApoB. • Lower ApoB associated with long-term absence of carotid plaque, while LDL-C did not. • Measurement of ApoB may be useful in young persons with metabolic disease., Objective A significant proportion of persons with metabolic syndrome (MetS), prediabetes, or type 2 diabetes (T2D) do not develop atherosclerotic cardiovascular disease (ASCVD). We sought to determine whether discordantly normal apolipoprotein B (ApoB) relative to elevated LDL-C may help to explain heterogeneity in ASCVD risk among persons with metabolic disorders. Methods There were 278 Bogalusa Heart Study participants with MetS (n=95), prediabetes (n=233), or T2D (n=31) and LDL-C ≥100 mg/dL who were free of carotid plaque at baseline (2001-02) and underwent carotid ultrasound at follow-up (2013-16). Multivariable modified Poisson regression estimated the long-term absence of carotid plaque for lower ApoB, continuously and categorically. Results Participants were on average 36.1 years old at baseline, 61.5% were women, and 31.7% were black. A total of 50.7% had discordantly normal ApoB (, Graphical abstract Image, graphical abstract

We examined associations between ambient air pollution and hepatic steatosis among 2,513 participants from the Framingham (Massachusetts) Offspring Study and Third Generation Cohort who underwent a computed tomography scan (2002-2005), after excluding men who reported >21 drinks/week and women who reported >14 drinks/week. We calculated each participant's residential-based distance to a major roadway and used a spatiotemporal model to estimate the annual mean concentrations of fine particulate matter. Liver attenuation was measured by computed tomography, and liver-to-phantom ratio (LPR) was calculated. Lower values of LPR represent more liver fat. We estimated differences in continuous LPR using linear regression models and prevalence ratios for presence of hepatic steatosis (LPR ≤ 0.33) using generalized linear models, adjusting for demographics, individual and area-level measures of socioeconomic position, and clinical and lifestyle factors. Participants who lived 58 m (25th percentile) from major roadways had lower LPR (β = -0.003, 95% confidence interval: -0.006, -0.001) and higher prevalence of hepatic steatosis (prevalence ratio = 1.16, 95% confidence interval: 1.05, 1.28) than those who lived 416 m (75th percentile) away. The 2003 annual average fine particulate matter concentration was not associated with liver-fat measurements. Our findings suggest that living closer to major roadways was associated with more liver fat.

Aims The objective of this study was to evaluate the association of chocolate consumption and heart failure (HF) in a large population of Swedish men. Methods We conducted a prospective cohort study of 31,917 men 45-79 years old with no history of myocardial infarction, diabetes, or HF at baseline who were participants in the population-based Cohort of Swedish Men study. Chocolate consumption was assessed through a self-administrated food frequency questionnaire. Participants were followed for HF hospitalization or mortality from January 1, 1998, to December 31, 2011, using record linkage to the Swedish inpatient and cause-of-death registries. Results During 14 years of follow-up, 2,157 men were hospitalized (n=1,901) or died from incident HF (n=256). Compared with subjects who reported no chocolate intake, the multivariable-adjusted rate ratio of HF was 0.88 (95% CI 0.78-0.99) for those consuming 1-3 servings per month, 0.83 (95% CI 0.72-0.94) for those consuming 1-2 servings per week, 0.82 (95% CI 0.68-0.99) for those consuming 3-6 servings per week, and 1.10 (95% CI 0.84-1.45) for those consuming ≥1 serving per day ( P for quadratic trend=.001). Conclusions In this large prospective cohort study, there was a J -shaped relationship between chocolate consumption and HF incidence. Moderate chocolate consumption was associated with a lower rate of HF hospitalization or death, but the protective association was not observed among individuals consuming ≥1 serving per day. Journal Subject Codes: Etiology: Epidemiology, Heart failure: Congestive

Objective Higher traffic-related air pollution has been associated with higher body mass index (BMI) among children. However, few studies have assessed the associations among adults. Methods Participants (N = 2,372) from the Framingham Offspring and Third Generation cohorts who underwent multidetector-computed tomography scans (2002–2005) were included. Residential-based proximity to the nearest major roadway and 1-year average levels of fine particulate matter (PM2.5) air pollution were estimated. BMI was measured at Offspring examination 7 (1998–2001) and Third Generation examination 1 (2002–2005); subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) were measured using multidetector-computed tomography. Linear regression models were used for continuous BMI, SAT, and VAT and logistic models for the binary indicator of obesity (BMI ≥30 kg/m2), adjusting for demographic variables, individual- and area-level measures of socioeconomic position, and clinical and lifestyle factors. Results Participants who lived 60 m from a major roadway had 0.37 kg/m2 higher BMI (95% CI: 0.10 to 0.65 kg/m2), 78.4 cm3 higher SAT (95% CI: 4.5 to 152.3 cm3), and 41.8 cm3 higher VAT (95% CI: −4.7 to 88.2 cm3) than those who lived 440 m away. Conclusions Living closer to a major roadway was associated with higher overall and abdominal adiposity.

Objective: To examine associations of proximity to major roadways, sustained exposure to fine particulate matter (PM2.5), and acute exposure to ambient air pollutants with adipokines and measures of glucose homeostasis among participants living in the northeastern United States. Methods: We included 5958 participants from the Framingham Offspring cohort examination cycle 7 (1998–2001) and 8 (2005–2008) and Third Generation cohort examination cycle 1 (2002–2005) and 2 (2008–2011), who did not have type 2 diabetes at the time of examination visit. We calculated 2003 annual average PM2.5 at participants' home address, residential distance to the nearest major roadway, and daily PM2.5, black carbon (BC), sulfate, nitrogen oxides (NOx), and ozone concentrations. We used linear mixed effects models for fasting glucose, insulin, and homeostasis model assessment of insulin resistance (HOMA-IR) which were measured up to twice, and used linear regression models for adiponectin, resistin, leptin, and hemoglobin A1c (HbA1c) which were measured only once, adjusting for demographics, socioeconomic position, lifestyle, time, and seasonality. Results: The mean age was 51years and 55% were women. Participants who lived 64m (25th percentile) from a major roadway had 0.28% (95% CI: 0.05%, 0.51%) higher fasting plasma glucose than participants who lived 413m (75th percentile) away, and the association appeared to be driven by participants who lived within 50m from a major roadway. Higher exposures to 3- to 7-day moving averages of BC and NOx were associated with higher glucose whereas the associations for ozone were negative. The associations otherwise were generally null and did not differ by median age, sex, educational attainment, obesity status, or prediabetes status. Conclusions: Living closer to a major roadway or acute exposure to traffic-related air pollutants were associated with dysregulated glucose homeostasis but not with adipokines among participants from the Framingham Offspring and Third Generation cohorts. Keywords: Air pollution, Adipokines, Glucose homeostasis, Epidemiology, Particulate matter

Background Short‐term exposure to elevated air pollution has been associated with higher risk of acute cardiovascular diseases, with systemic oxidative stress induced by air pollution hypothesized as an important underlying mechanism. However, few community‐based studies have assessed this association. Methods and Results Two thousand thirty‐five Framingham Offspring Cohort participants living within 50 km of the Harvard Boston Supersite who were not current smokers were included. We assessed circulating biomarkers of oxidative stress including blood myeloperoxidase at the seventh examination (1998–2001) and urinary creatinine‐indexed 8‐epi‐prostaglandin F 2α (8‐epi‐ PGF 2α ) at the seventh and eighth (2005–2008) examinations. We measured fine particulate matter ( PM 2.5 ), black carbon, sulfate, nitrogen oxides, and ozone at the Supersite and calculated 1‐, 2‐, 3‐, 5‐, and 7‐day moving averages of each pollutant. Measured myeloperoxidase and 8‐epi‐ PGF 2α were log e transformed. We used linear regression models and linear mixed‐effects models with random intercepts for myeloperoxidase and indexed 8‐epi‐ PGF 2α , respectively. Models were adjusted for demographic variables, individual‐ and area‐level measures of socioeconomic position, clinical and lifestyle factors, weather, and temporal trend. We found positive associations of PM 2.5 and black carbon with myeloperoxidase across multiple moving averages. Additionally, 2‐ to 7‐day moving averages of PM 2.5 and sulfate were consistently positively associated with 8‐epi‐ PGF 2α . Stronger positive associations of black carbon and sulfate with myeloperoxidase were observed among participants with diabetes than in those without. Conclusions Our community‐based investigation supports an association of select markers of ambient air pollution with circulating biomarkers of oxidative stress.

Objective— Long-term exposure to traffic and particulate matter air pollution is associated with a higher risk of cardiovascular disease, potentially via atherosclerosis promotion. Prior research on associations of traffic and particulate matter with coronary artery calcium Agatston score (CAC), an atherosclerosis correlate, has yielded inconsistent findings. Given this background, we assessed whether residential proximity to major roadway or fine particulate matter were associated with CAC in a Northeastern US study. Approach and Results— We measured CAC ≤2 times from 2002 to 2005 and 2008 to 2011 among Framingham Offspring or Third-Generation Cohort participants. We assessed associations of residential distance to major roadway and residential fine particulate matter (2003 average; spatiotemporal model) with detectable CAC, using generalized estimating equation regression. We used linear mixed effects models to assess associations with log e (CAC). We also assessed associations with CAC progression. Models were adjusted for demographic variables, socioeconomic position markers, and time. Among 3399 participants, 51% had CAC measured twice. CAC was detectable in 47% of observations. At first scan, mean age was 52.2 years (standard deviation 11.7); 51% male. There were no consistent associations with detectable CAC, continuous CAC, or CAC progression. We observed heterogeneous associations of distance to major roadway with odds of detectable CAC by hypertensive status; interpretation of these findings is questionable. Conclusions— Our findings add to prior work and support evidence against strong associations of traffic or fine particulate matter with the presence, extent, or progression of CAC in a region with relatively low levels of and little variation in fine particulate matter.

Background— Compared with no alcohol consumption, heavy alcohol intake is associated with a higher rate of heart failure (HF) whereas light-to-moderate intake may be associated with a lower rate. However, several prior studies did not exclude former drinkers, who may have changed alcohol consumption in response to diagnosis. This study aimed to investigate the association between alcohol intake and incident HF. Methods and Results— We conducted a prospective cohort study of 33 760 men aged 45 to 79 years with no HF, diabetes mellitus, or myocardial infarction at baseline participating in the Cohort of Swedish Men Study. We excluded former drinkers. At baseline, participants completed a food frequency questionnaire and reported other characteristics. HF was defined as hospitalization for or death from HF, ascertained by Swedish inpatient and cause-of-death records from January 1, 1998, through December 31, 2011. We constructed Cox proportional hazards models to estimate multivariable-adjusted incidence rate ratios. During follow-up, 2916 men were hospitalized for (n=2139) or died (n=777) of incident HF. There was a U-shaped relationship between total alcohol intake and incident HF ( P =0.0004). There was a nadir at light-to-moderate alcohol intake: consuming 7 to Conclusions— In this cohort of Swedish men, there was a U-shaped relationship between alcohol consumption and HF incidence, with a nadir at light-to-moderate intake. Heavy intake did not seem protective.

Background: The relationship between alcohol intake and incident heart failure (HF) is complex. Compared with no alcohol consumption, heavy alcohol intake is associated with higher HF risk whereas light or moderate consumption may be associated with lower risk. Methods: We analyzed 34,581 men 45-79 years old with no history of HF, diabetes mellitus or myocardial infarction (MI) who were participants in the population-based Cohort of Swedish Men study. We excluded former drinkers. At baseline, participants reported how frequently they consumed specific alcoholic beverages in the past year and other characteristics. HF was defined as hospitalization for or death from HF (primary diagnosis), ascertained by Swedish inpatient and cause-of-death records from January 1, 1998 to December 31, 2011. Due to missing values for two covariates, we used Markov chain Monte Carlo multiple imputation to simulate 5 complete datasets. We used Cox proportional hazards models to estimate rate ratios and 95% confidence intervals, adjusting for age, total energy intake, education, body mass index, physical activity, a dietary component score, cigarette smoking, marital status, family history of MI before age 60, history of hypertension and history of high cholesterol. Results: At baseline, mean age was 58.6 years. There were 1592 incident cases of HF over the follow-up period. Compared with never drinkers, the multivariable-adjusted rate of HF was 19% lower among men who drank Conclusions: Light-to-moderate drinking is associated with lower rate of HF compared with never drinking, but the association was not statistically significant.