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Background: Food insecurity is associated with high morbidity and mortality and is typically measured with the 10-item US Adult Food Security Survey Module. Shorter instruments may capture similar information, but this has not been validated against mortality in general populations., Methods: A nationally representative sample of individuals aged 20 to 74 years from the US National Health Interview Survey 2011 to 2018 was included, with deaths linked to the National Death Index through 2019. Cardiovascular disease deaths were ascertained by International Classification of Diseases-Tenth Revision codes for heart disease or stroke. Standard 10-, 6-, and 2-item food security instruments were compared for associations with premature all-cause and cardiovascular disease deaths occurring before age 75 years using Cox regression adjusted for demographics and social determinants of health and C statistics. Findings were replicated in the National Health and Nutrition Examination Survey 2004 to 2018, and differences were explored using mediation analysis., Results: We included 218 136 National Health Interview Survey participants (mean age, 45.3 years; 50.8% women). Over a mean 5.0-year follow-up, 7025 premature deaths were observed (1711 from cardiovascular disease). In multivariable-adjusted models, hazard ratios (95% CIs) for all-cause death were similar among food security instruments (10-item, 1.22 [1.13, 1.32]; 6-item, 1.23 [1.13, 1.34]; and 2-item, 1.23 [1.14, 1.32]), and C statistics were identical (0.823). Hazard ratios (95% CIs) for cardiovascular disease deaths were also similar among food security instruments (10-item, 1.38 [1.17, 1.62]; 6-item, 1.27 [1.07, 1.51]; and 2-item, 1.41 [1.20, 1.66]), and C statistics ranged from 0.852 to 0.853. In the National Health and Nutrition Examination Survey replication (n=37 027, mean 7.8-year follow-up), associations were attenuated and became not statistically significant after adjustment for several cardiometabolic intermediates, particularly enrollment in food assistance programs, diabetes, low diet quality, inadequate or excessive sleep, and depression., Conclusions: A 2-item food security instrument captures similar mortality risk information compared with 10- and 6-item instruments. Furthermore, potential intermediate cardiometabolic factors may explain associations between food insecurity and mortality.

Objective: MicroRNA-19 (miR-19) plays a critical role in cardiac development and cardiovascular disease (CVD). We examined whether change in circulating miR-19 was associated with change in CVD risk during weight loss., Methods: This study included 509 participants with overweight or obesity from the 24-month weight-loss diet intervention study (the POUNDS Lost trial) and with available data on circulating miR-19a-3p and miR-19b-3p at baseline and 6 months. The primary outcome for this analysis was the change in atherosclerotic CVD (ASCVD) risk at 6 and 24 months, which estimates the 10-year probability of hard ASCVD events. Secondary outcomes were the changes in ASCVD risk score components., Results: Circulating miR-19a-3p and miR-19b-3p levels significantly decreased during the initial 6-month dietary intervention period (P = 0.008, 0.0004, respectively). We found that a greater decrease in miR-19a-3p or miR-19b-3p was related to a greater reduction in ASCVD risk (β[SE] = 0.33 [0.13], P = 0.01 for miR-19a-3p; β[SE] = 0.3 [0.12], P = 0.017 for miR-19b-3p) over 6 months, independent of concurrent weight loss. Moreover, we found significant interactions between change in miR-19 and sleep disturbance on change in ASCVD risk over 24 months of intervention (P interaction = 0.01 and 0.008 for miR-19a-3p and miR-19b-3p, respectively). Participants with a greater decrease in miR-19 without sleep disturbance had a greater reduction of ASCVD risk than those with slight/moderate/great amounts of sleep disturbance. In addition, change in physical activity significantly modified the associations between change in miR-19 and change in ASCVD risk over 24 months (P interaction = 0.006 and 0.004 for miR-19a-3p and miR-19b-3p, respectively). A greater decrease in miR-19 was significantly associated with a greater reduction in ASCVD risk among participants with an increase in physical activity, while non-significant inverse associations were observed among those without an increase in physical activity., Conclusions: In conclusion, decreased circulating miR-19 levels during dietary weight-loss interventions were related to a significant reduction in ASCVD risk, and these associations were more evident in people with no sleep disturbance or increase in physical activity., Trial Registration: ClinicalTrials.gov NCT00072995., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Cardiovascular disease (CVD) mortality is persistently higher in the Black population than in other racial and ethnic groups in the United States., Objective: To examine the degree to which social, behavioral, and metabolic risk factors are associated with CVD mortality and the extent to which racial differences in CVD mortality persist after these factors are accounted for., Design: Prospective cohort study., Setting: NHANES (National Health and Nutrition Examination Survey) 1999 to 2018., Participants: A nationally representative sample of 50 808 persons aged 20 years or older., Measurements: Data on social, behavioral, and metabolic factors were collected in each NHANES survey using standard methods. Deaths from CVD were ascertained from linkage to the National Death Index with follow-up through 2019., Results: Over an average of 9.4 years of follow-up, 2589 CVD deaths were confirmed. The age- and sex-standardized rates of CVD mortality were 484.7 deaths per 100 000 person-years in Black participants, 384.5 deaths per 100 000 person-years in White participants, 292.4 deaths per 100 000 person-years in Hispanic participants, and 255.1 deaths per 100 000 person-years in other race groups. In a multiple Cox regression analysis adjusted for all measured risk factors simultaneously, several social (unemployment, low family income, food insecurity, lack of home ownership, and unpartnered status), behavioral (current smoking, lack of leisure-time physical activity, and sleep <6 or >8 h/d), and metabolic (obesity, hypertension, and diabetes) risk factors were associated with a significantly higher risk for CVD death. After adjustment for these metabolic, behavioral, and social risk factors separately, hazard ratios of CVD mortality for Black compared with White participants were attenuated from 1.54 (95% CI, 1.34 to 1.77) to 1.34 (CI, 1.16 to 1.55), 1.31 (CI, 1.15 to 1.50), and 1.04 (CI, 0.90 to 1.21), respectively., Limitation: Causal contributions of social, behavioral, and metabolic risk factors to racial and ethnic disparities in CVD mortality could not be established., Conclusion: The Black-White difference in CVD mortality diminished after adjustment for behavioral and metabolic risk factors and completely dissipated with adjustment for social determinants of health in the U.S. population., Primary Funding Source: National Institutes of Health., Competing Interests: Disclosures: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M23-0507.

Importance: Low-carbohydrate diets decrease hemoglobin A1c (HbA1c) among patients with type 2 diabetes at least as much as low-fat diets. However, evidence on the effects of low-carbohydrate diets on HbA1c among individuals with HbA1c in the range of prediabetes to diabetes not treated by diabetes medications is limited., Objective: To study the effect of a behavioral intervention promoting a low-carbohydrate diet compared with usual diet on 6-month changes in HbA1c among individuals with elevated untreated HbA1c., Design, Setting, and Participants: This 6-month randomized clinical trial with 2 parallel groups was conducted from September 2018 to June 2021 at an academic medical center in New Orleans, Louisiana. Laboratory analysts were blinded to assignment. Participants were aged 40 to 70 years with untreated HbA1c of 6.0% to 6.9% (42-52 mmol/mol). Data analysis was performed from November 2021 to September 2022., Interventions: Participants were randomized to a low-carbohydrate diet intervention (target <40 net grams of carbohydrates during the first 3 months; <60 net grams for months 3 to 6) or usual diet. The low-carbohydrate diet group received dietary counseling., Main Outcomes and Measures: Six-month change in HbA1c was the primary outcome. Outcomes were measured at 0, 3, and 6 months., Results: Of 2722 prescreened participants, 962 underwent screening, and 150 were enrolled (mean [SD] age, 58.9 [7.9] years; 108 women [72%]; 88 Black participants [59%]) and randomized to either the low-carbohydrate diet intervention (75 participants) or usual diet (75 participants) group. Six-month data were collected on 142 participants (95%). Mean (SD) HbA1c was 6.16% (0.30%) at baseline. Compared with the usual diet group, the low-carbohydrate diet intervention group had significantly greater 6-month reductions in HbA1c (net difference, -0.23%; 95% CI, -0.32% to -0.14%; P < .001), fasting plasma glucose (-10.3 mg/dL; 95% CI, -15.6 to -4.9 mg/dL; P < .001), and body weight (-5.9 kg; 95% CI, -7.4 to -4.4 kg; P < .001)., Conclusions and Relevance: In this randomized clinical trial, a low-carbohydrate dietary intervention led to improvements in glycemia in individuals with elevated HbA1c not taking glucose-lowering medication, but the study was unable to evaluate its effects independently of weight loss. This diet, if sustained, might be a useful dietary approach for preventing and treating type 2 diabetes, but more research is needed., Trial Registration: ClinicalTrials.gov Identifier: NCT03675360.

Background: Chronic kidney disease (CKD) is associated with anxiety and depression. Although the coronavirus disease 2019 (COVID-19) pandemic has increased stressors on patients with CKD, assessments of anxiety and its predictors and consequences on behaviors, specifically virus mitigation behaviors, are lacking., Methods: From June to October 2020, we administered a survey to 1873 patients in the Chronic Renal Insufficiency Cohort (CRIC) Study, asking participants about anxiety related to the COVID-19 pandemic. We examined associations between anxiety and participant demographics, clinical indexes, and health literacy and whether anxiety was associated with health-related behaviors and COVID-19 mitigation behaviors., Results: The mean age of the study population was 70 years (SD=9.6 years), 47% were women, 39% were Black non-Hispanic, 14% were Hispanic, and 38% had a history of cardiovascular disease. In adjusted analyses, younger age, being a woman, Hispanic ethnicity, cardiovascular disease, household income <$20,000, and marginal or inadequate health literacy predicted higher anxiety. Higher global COVID-19-related anxiety scores were associated with higher odds of reporting always wearing a mask in public (OR=1.3 [95% CI, 1.14 to 1.48], P <0.001) and of eating less healthy foods (OR=1.29 [95% CI, 1.13 to 1.46], P <0.001), reduced physical activity (OR=1.32 [95% CI, 1.2 to 1.45], P <0.001), and weight gain (OR=1.23 [95% CI, 1.11 to 1.38], P =0.001)., Conclusions: Higher anxiety levels related to the COVID-19 pandemic were associated not only with higher self-reported adherence to mask wearing but also with higher weight gain and less adherence to healthy lifestyle behaviors. Interventions are needed to support continuation of healthy lifestyle behaviors in patients with CKD experiencing increased anxiety related to the pandemic., Competing Interests: L.J. Appel reports honoraria from Wolters Kluwer and other interests or relationships with Bloomberg Philanthropies. D.L. Cohen reports consultancy for Medtronic, Metavention, Novartis, and Recor; ownership interest in Incyte and Kura (spouse); research funding from the Chronic Renal Insufficiency Cohort (CRIC) Study and Medtronic; honoraria from Medtronic, Metavention, Novartis, and Recor; patents or royalties from Incyte (spouse); and an advisory or leadership role for Kura (spouse). H.I. Feldman reports being an employee of Perleman School of Medicine, University of Pennsylvania; consultancy for InMed, Inc., Kyowa Hakko Kirin Co., Ltd. (ongoing), and the National Kidney Foundation (ongoing); and an advisory or leadership role for the American Journal of Kidney Disease (editor in chief), the CRIC Study (steering committee chair), and the National Kidney Foundation (member of the Advisory Board). J.P. Lash reports an advisory or leadership role for Kidney360. R.G. Nelson reports being an employee of the National Institutes of Health. M. Rahman reports consultancy for Barologics; research funding from Bayer Pharmaceuticals and Duke Clinical Research Institute; honoraria from Bayer, Reata, and Relypsa; and an advisory or leadership role for CJASN (associate editor) and the American Journal of Nephrology (editorial board member). P.S. Rao reports honoraria from AstraZeneca, and an advisory or leadership role for the AstraZeneca nephrology fellowship advisory board, GSK scientific advisory board, and the Renal Research Institute. S.J. Schrauben reports honoraria from Cowen and Company, LLC. J.A. Wright Nunes reports research funding as Co-I in a state-wide collaborative research with UM team and Blue Cross Blue Shield to improve kidney care across Michigan; a patent pending with others on a kidney model for display and kidney learning (no royalties and was derived from a project at UM); an advisory or leadership role with the American Kidney Fund (board), Medical Advisory Committee (chair), the CSN Program (chair), and Kidney Patient Education and Outreach (vice chair); and is funded by NIH R01 DK115844-01. All remaining authors have nothing to disclose., (Copyright © 2022 by the American Society of Nephrology.)

Background and Aims: Women with prior gestational diabetes mellitus (GDM) are at elevated risk of type 2 diabetes mellitus and cardiovascular disease. We compared cardiometabolic risk factors among parous U.S. women ages 20-44 by history of GDM., Methods and Results: Using data from the National Health and Nutrition Examination Survey (NHANES) from 2007 to 2018, 3537 parous women were classified by self-reported GDM history. We compared anthropometric measures, glycemia, blood pressure, lipids, lifestyle factors, cardiovascular health, and cardiometabolic disease prevalence by GDM status. NHANES survey design was taken into account. Women without history of GDM were younger and, after adjusting for age, race/ethnicity, and education, had more favorable cardiometabolic risk factor profiles for measures of anthropometry, glycemia, diabetes, many lipids, physical activity, diet, and overall cardiovascular health than women with history of GDM. Many patterns persisted after further adjustment for lifestyle factors. In analyses stratified by race/ethnicity, many patterns persisted, though there were key differences. Hypertension prevalence differed by GDM history only among Hispanic women. In women of other race/ethnicity, there was no difference in healthy eating or body mass index by GDM history. In non-Hispanic Black women, there was no difference in healthy eating by GDM history., Conclusion: Among parous U.S. women ages 20-44, those with history of GDM had less favorable cardiometabolic risk factor profiles than those without history of GDM. This highlights the importance of continued efforts to develop and test multilevel interventions to improve cardiometabolic risk factors among reproductive-age women with a history of GDM., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2022 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

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-<0.02, individuals with an average annual change in ABI <-0.04 or ≥0.04 had multivariable-adjusted hazard ratios (HRs) of 1.81 [95% confidence interval (CI) 1.34-2.44) and 1.42 (95% CI 1.12-1.82) for all-cause mortality, respectively. Compared with the cumulative average ABI of 1.0-<1.4, multivariable-adjusted HRs for those with a cumulative average ABI of <0.9, 0.9-<1.0 and ≥1.4 were 1.93 (95% CI 1.42-2.61), 1.20 (0.90-1.62) and 1.31 (0.94-1.82), respectively., 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., (© The Author(s) 2020. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.)

Importance: After decades of decline, the US cardiovascular disease mortality rate flattened after 2010, and racial and ethnic differences in cardiovascular disease mortality persisted., Objective: To examine 20-year trends in cardiovascular risk factors in the US population by race and ethnicity and by socioeconomic status., Design, Setting, and Participants: A total of 50 571 participants aged 20 years or older from the 1999-2018 National Health and Nutrition Examination Surveys, a series of cross-sectional surveys in nationally representative samples of the US population, were included., Exposures: Calendar year, race and ethnicity, education, and family income., Main Outcomes and Measures: Age- and sex-adjusted means or proportions of cardiovascular risk factors and estimated 10-year risk of atherosclerotic cardiovascular disease were calculated for each of 10 two-year cycles., Results: The mean age of participants ranged from 49.0 to 51.8 years and the proportion of women from 48.2% to 51.3% in the surveys. From 1999-2000 to 2017-2018, age- and sex-adjusted mean body mass index increased from 28.0 (95% CI, 27.5-28.5) to 29.8 (95% CI, 29.2-30.4); mean hemoglobin A1c increased from 5.4% (95% CI, 5.3%-5.5%) to 5.7% (95% CI, 5.6%-5.7%) (both P < .001 for linear trends). Mean serum total cholesterol decreased from 203.3 mg/dL (95% CI, 200.9-205.8 mg/dL) to 188.5 mg/dL (95% CI, 185.2-191.9 mg/dL); prevalence of smoking decreased from 24.8% (95% CI, 21.8%-27.7%) to 18.1% (95% CI, 15.4%-20.8%) (both P < .001 for linear trends). Mean systolic blood pressure decreased from 123.5 mm Hg (95% CI, 122.2-124.8 mm Hg) in 1999-2000 to 120.5 mm Hg (95% CI, 119.6-121.3 mm Hg) in 2009-2010, then increased to 122.8 mm Hg (95% CI, 121.7-123.8 mm Hg) in 2017-2018 (P < .001 for nonlinear trend). Age- and sex-adjusted 10-year atherosclerotic cardiovascular disease risk decreased from 7.6% (95% CI, 6.9%-8.2%) in 1999-2000 to 6.5% (95% CI, 6.1%-6.8%) in 2011-2012, then did not significantly change. Age- and sex-adjusted body mass index, systolic blood pressure, and hemoglobin A1c were consistently higher, while total cholesterol was lower in non-Hispanic Black participants compared with non-Hispanic White participants (all P < .001 for group differences). Individuals with college or higher education or high family income had consistently lower levels of cardiovascular risk factors. The mean age- and sex-adjusted 10-year risk of atherosclerotic cardiovascular disease was significantly higher in non-Hispanic Black participants compared with non-Hispanic White participants (difference, 1.4% [95% CI, 1.0%-1.7%] in 1999-2008 and 2.0% [95% CI, 1.7%-2.4%] in 2009-2018]). This difference was attenuated (-0.3% [95% CI, -0.6% to 0.1%] in 1999-2008 and 0.7% [95% CI, 0.3%-1.0%] in 2009-2018) after further adjusting for education, income, home ownership, employment, health insurance, and access to health care., Conclusions and Relevance: In this serial cross-sectional survey study that estimated US trends in cardiovascular risk factors from 1999 through 2018, differences in cardiovascular risk factors persisted between Black and White participants; the difference may have been moderated by social determinants of health.

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 (<90 mg/dL) and the mean ApoB and LDL-C concentrations were 91.6 mg/dL and 137.7 mg/dL, respectively. In addition to having higher HDL-C and lower triglyceride values, individuals with ApoB <90 were more likely to maintain persistent absence of plaque compared to those with ApoB ≥90 (73.1% versus 58.4%, p=0.01). Contrastingly, there was no significant difference in the proportion of individuals who remained free of plaque with increasing LDL-C (p=0.45). Independent of traditional risk factors including LDL-C, each 10 mg/dL lower ApoB (RR=1.11, 95% CI: 1.03-1.19) and ApoB <90 (RR=1.22, 95% CI: 1.00-1.43) were significantly associated with the persistent absence of carotid plaque., Conclusions: One-half of young persons with metabolic disorders and elevated LDL-C had discordantly normal ApoB and a low burden of carotid atherosclerosis over 13 years, suggesting that ApoB better represents the atherogenic lipid burden compared to LDL-C in this patient population. These results suggest a utility for assessing whether routine ApoB measurement can improve ASCVD risk stratification in young persons with metabolic disorders who have high triglycerides and low HDL-cholesterol., Competing Interests: None., (© 2021 Published by Elsevier B.V.)

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 < 40 g of net carbohydrates during the first 3 months and < 40 to 60 net grams for months 3 to 6. This diet is characterized by abundant unsaturated fat and protein, high-fiber foods such as non-starchy vegetables and nuts, and minimal refined carbohydrates. The primary outcome is the difference in HbA1c change from baseline to 6 months in the intervention compared with usual diet group. Secondary outcomes include differences between groups in 6-month changes in fasting glucose, systolic blood pressure, total-to-high-density lipoprotein (HDL) cholesterol ratio, and body weight. Exploratory outcomes include differences in 6-month changes in fasting insulin, homeostasis model assessment of insulin resistance, diastolic blood pressure, waist circumference, and 10-year cardiovascular disease risk. An intention-to-treat analysis will be used., 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: 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 (PM 2.5 ), black carbon (BC), sulfate (SO 4 2- ), nitrogen oxides (NO x ), 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 PM 2.5 and BC with P-selectin, of ozone with MCP-1, and of SO 4 2- and NO x with osteoprotegerin. At the 5-day moving average, a 5 µg/m 3 higher PM 2.5 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 NO x 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., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Hypertension is a major risk factor for cardiovascular disease and all-cause mortality. Compared with prior guidelines, the 2017 American College of Cardiology/American Heart Association (ACC/AHA) hypertension guideline recommends lower blood pressure thresholds for defining hypertension, for initiating antihypertensive medication, and for antihypertensive medication treatment goals., Methods and Results: To better understand potential impacts of the 2017 guideline, we studied trends in mean systolic blood pressure and diastolic blood pressure, prevalence and burden of hypertension, and proportion of controlled hypertension in the US adult population aged ≥20 from 1999 through 2016. We used data from 38 276 adults from the National Health and Nutrition Examination Survey. Age-standardized prevalence of hypertension decreased from 48.4% in 1999-2000 to 45.4% in 2015-2016. However, absolute burden of hypertension consistently increased, from 87.0 million in 1999-2000 to 108.2 million in 2015-2016. The age-standardized proportion of controlled hypertension among adults receiving antihypertensive pharmacologic treatment increased from 1999-2000 (25.6%) to 2015-2016 (43.5%). There was not consistent improvement in control throughout the full period among non-Hispanic blacks, individuals aged ≥60, or those with diabetes mellitus, chronic kidney disease, or high cardiovascular disease risk., Conclusions: Based on the 2017 guideline, from 1999 to 2016, the age-standardized prevalence of hypertension decreased and the proportion of control among those treated for hypertension improved. However, the absolute hypertension burden increased. Among those treated, the control rate did not consistently improve in all subgroups. These data emphasize the need for continuous efforts in the prevention and control of hypertension in the US general population., (© 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.)

Background: Exposure to ambient air pollution has been associated with lower lung function in adults, but few studies have investigated associations with radiographic lung and airway measures., Methods: We ascertained lung volume, mass, density, visual emphysema, airway size, and airway wall area by computed tomography (CT) among 2,545 nonsmoking Framingham CT substudy participants. We examined associations of home distance to major road and PM2.5 (2008 average from a spatiotemporal model using satellite data) with these outcomes using linear and logistic regression models adjusted for age, sex, height, weight, census tract median household value and population density, education, pack-years of smoking, household tobacco exposure, cohort, and date. We tested for differential susceptibility by sex, smoking status (former vs. never), and cohort., Results: The mean participant age was 60.1 years (standard deviation 11.9 years). Median PM2.5 level was 9.7 µg/m (interquartile range, 1.6). Living <100 m from a major road was associated with a 108 ml (95% CI = 8, 207) higher lung volume compared with ≥400 m away. There was also a log-linear association between proximity to road and higher lung volume. There were no convincing associations of proximity to major road or PM2.5 with the other pulmonary CT measures. In subgroup analyses, road proximity was associated with lower lung density among men and higher odds of emphysema among former smokers., Conclusions: Living near a major road was associated with higher average lung volume, but otherwise, we found no association between ambient pollution and radiographic measures of emphysema or airway disease.

Objective: To examine associations of proximity to major roadways, sustained exposure to fine particulate matter (PM 2.5 ), 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 PM 2.5 at participants' home address, residential distance to the nearest major roadway, and daily PM 2.5 , black carbon (BC), sulfate, nitrogen oxides (NO x ), 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 NO x 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., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

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., (© The Author(s) 2017. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: The objective of this study is to examine associations between short-term exposure to ambient air pollution and circulating biomarkers of systemic inflammation in participants from the Framingham Offspring and Third Generation cohorts in the greater Boston area., Approach and Results: We included 3996 noncurrent smoking participants (mean age, 53.6 years; 54% women) who lived within 50 km from a central air pollution monitoring site in Boston, MA, and calculated the 1- to 7-day moving averages of fine particulate matter (diameter<2.5 µm), black carbon, sulfate, nitrogen oxides, and ozone before the examination visits. We used linear mixed effects models for C-reactive protein and tumor necrosis factor receptor 2, which were measured up to twice for each participant; we used linear regression models for interleukin-6, fibrinogen, and tumor necrosis factor α, which were measured once. We adjusted for demographics, socioeconomic position, lifestyle, time, and weather. The 3- to 7-day moving averages of fine particulate matter (diameter<2.5 µm) and sulfate were positively associated with C-reactive protein concentrations. A 5 µg/m 3 higher 5-day moving average fine particulate matter (diameter<2.5 µm) was associated with 4.2% (95% confidence interval: 0.8, 7.6) higher circulating C-reactive protein. Positive associations were also observed for nitrogen oxides with interleukin-6 and for black carbon, sulfate, and ozone with tumor necrosis factor receptor 2. However, black carbon, sulfate, and nitrogen oxides were negatively associated with fibrinogen, and sulfate was negatively associated with tumor necrosis factor α., Conclusions: Higher short-term exposure to relatively low levels of ambient air pollution was associated with higher levels of C-reactive protein, interleukin-6, and tumor necrosis factor receptor 2 but not fibrinogen or tumor necrosis factor α in individuals residing in the greater Boston area., (© 2017 American Heart Association, Inc.)

Objectives: Traffic and ambient air pollution exposure are positively associated with cardiovascular disease, potentially through atherosclerosis promotion. Few studies have assessed associations of these exposures with thoracic aortic calcium Agatston score (TAC) or abdominal aortic calcium Agatston score (AAC), systemic atherosclerosis correlates. We assessed whether living close to a major road and residential fine particulate matter (PM 2.5 ) exposure were associated with TAC and AAC in a Northeastern US cohort., Design: Cohort study., Setting: Framingham Offspring and Third Generation participants residing in the Northeastern USA., Participants and Outcome Measures: Among 3506 participants, mean age was 55.8 years; 50% female. TAC was measured from 2002 to 2005 and AAC up to two times (2002-2005; 2008-2011) among participants from the Framingham Offspring or Third Generation cohorts. We first assessed associations with detectable TAC (logistic regression) and AAC (generalised estimating equation regression, logit link). As aortic calcium scores were right skewed, we used linear regression models and mixed-effects models to assess associations with natural log-transformed TAC and AAC, respectively, among participants with detectable aortic calcium. We also assessed associations with AAC progression. Models were adjusted for demographic variables, socioeconomic position indicators and time., Results: There were no consistent associations of major roadway proximity or PM 2.5 with the presence or extent of TAC or AAC, or with AAC progression. Some estimates were in the opposite direction than expected., Conclusions: In this cohort from a region with relatively low levels of and variation in PM 2.5 , there were no strong associations of proximity to a major road or PM 2.5 with the presence or extent of aortic calcification, or with AAC progression., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

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., (Copyright © 2016 Elsevier Inc. All rights reserved.)

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 (PM 2.5 ) 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/m 2 ), 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/m 2 higher BMI (95% CI: 0.10 to 0.65 kg/m 2 ), 78.4 cm 3 higher SAT (95% CI: 4.5 to 152.3 cm 3 ), and 41.8 cm 3 higher VAT (95% CI: -4.7 to 88.2 cm 3 ) than those who lived 440 m away., Conclusions: Living closer to a major roadway was associated with higher overall and abdominal adiposity., (© 2016 The Obesity Society.)

Objective: To study whether physical activity during adulthood or early life is associated with multiple sclerosis (MS) incidence in 2 prospective cohorts of women., Methods: Women in the Nurses' Health Study (NHS) (n = 81,723; 1986-2004) and NHS II (n = 111,804; 1989-2009) reported recent physical activity at baseline and in selected follow-up questionnaires. Using this information, we calculated total metabolic equivalent hours of physical activity per week, a measure of energy expenditure. There were 341 confirmed MS cases with first symptoms after baseline. Participants also reported early-life activity. To estimate relative rates (RRs) and 95% confidence intervals (CIs), we used Cox proportional hazards models, adjusting for age, latitude of residence at age 15, ethnicity, smoking, supplemental vitamin D, and body mass index at age 18., Results: Compared with women in the lowest baseline physical activity quartile, women in the highest quartile had a 27% reduced rate of MS (RR pooled = 0.73, 95% CI 0.55-0.98; p-trend 0.08); this trend was not present in 6-year lagged analyses. Change in physical activity analyses suggested that women reduced activity before onset of MS symptoms. In NHS and NHS II, higher strenuous activity at ages 18-22 years was weakly associated with a decreased MS rate. However, in NHS II, total early-life activity at ages 12-22 was not associated with MS., Conclusions: Though higher physical activity at baseline was weakly associated with lower MS risk, this may have been due to women reducing physical activity in response to subclinical MS., (© 2016 American Academy of Neurology.)

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 loge(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., (© 2016 American Heart Association, Inc.)

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 F2α (8-epi-PGF2α) at the seventh and eighth (2005-2008) examinations. We measured fine particulate matter (PM2.5), 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-PGF2α were loge transformed. We used linear regression models and linear mixed-effects models with random intercepts for myeloperoxidase and indexed 8-epi-PGF2α, 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 PM2.5 and black carbon with myeloperoxidase across multiple moving averages. Additionally, 2- to 7-day moving averages of PM2.5 and sulfate were consistently positively associated with 8-epi-PGF2α. 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., (© 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.)

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 <14 standard drinks per week was associated with a 19% lower multivariable-adjusted rate of HF compared with never drinking (incidence rate ratio, 0.81; 95% confidence interval, 0.69-0.96)., 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., (© 2015 American Heart Association, Inc.)

Rationale: Few studies have examined associations between long-term exposure to fine particulate matter (PM2.5) and lung function decline in adults., Objectives: To determine if exposure to traffic and PM2.5 is associated with longitudinal changes in lung function in a population-based cohort in the Northeastern United States, where pollution levels are relatively low., Methods: FEV1 and FVC were measured up to two times between 1995 and 2011 among 6,339 participants of the Framingham Offspring or Third Generation studies. We tested associations between residential proximity to a major roadway and PM2.5 exposure in 2001 (estimated by a land-use model using satellite measurements of aerosol optical thickness) and lung function. We examined differences in average lung function using mixed-effects models and differences in lung function decline using linear regression models. Current smokers were excluded. Models were adjusted for age, sex, height, weight, pack-years, socioeconomic status indicators, cohort, time, season, and weather., Measurements and Main Results: Living less than 100 m from a major roadway was associated with a 23.2 ml (95% confidence interval [CI], -44.4 to -1.9) lower FEV1 and a 5.0 ml/yr (95% CI, -9.0 to -0.9) faster decline in FEV1 compared with more than 400 m. Each 2 μg/m(3) increase in average of PM2.5 was associated with a 13.5 ml (95% CI, -26.6 to -0.3) lower FEV1 and a 2.1 ml/yr (95% CI, -4.1 to -0.2) faster decline in FEV1. There were similar associations with FVC. Associations with FEV1/FVC ratio were weak or absent., Conclusions: Long-term exposure to traffic and PM2.5, at relatively low levels, was associated with lower FEV1 and FVC and an accelerated rate of lung function decline.