Association between secondhand smoke exposure and incident heart failure: The Multi-Ethnic Study of Atherosclerosis (MESA).

AIMS: There are no studies on the association between secondhand smoke (SHS) exposure and incident heart failure (HF). This cohort study aimed to examine the associations of self-reported and urinary cotinine-assessed SHS exposure with incident HF. METHODS AND RESULTS: This study included 5548 non-active smoking participants aged 45-84 years and free of known cardiovascular diseases and HF at baseline who self-reported SHS exposure time in the Multi-Ethnic Study of Atherosclerosis (MESA) at baseline (2000-2002). A cohort subset of 3376 non-active smoking participants underwent urinary cotinine measurements. HF events were verified by medical records or death certificates and ascertained from baseline through 2019. Multivariable Cox proportional hazards regression analysis was used with adjustment for demographic variables, traditional cardiovascular risk factors, physical activity, tobacco pack-years and medications. During a median follow-up of 17.7 years, 353 and 196 HF events were identified in the self-report cohort and cohort subset, respectively. In the self-report cohort, compared with the SHS unexposed group (0 h/week), the highest tertile of the SHS exposed group (7-168 h/week) was not associated with incident HF (hazard ratio [HR] 0.70, 95% confidence interval [CI] 0.49-1.00; p = 0.052). In contrast, in the cohort subset, participants with detectable urinary cotinine >7.07 ng/ml had a higher risk of incident HF than those with undetectable urinary cotinine ≤7.07 ng/ml (HR 1.45, 95% CI 1.03-2.06; p = 0.034). There were no significant heterogeneities in HF risk by age, sex, race/ethnicity, or past smoking status. CONCLUSION: Secondhand smoke exposure reflected by modestly increased urinary cotinine (>7.07 ng/ml) rather than self-report in non-active smokers was associated with a 40-50% higher risk of any HF event.

Prevalence of Subclinical Atrial Fibrillation in Heart Failure With Preserved Ejection Fraction.

BACKGROUND: Atrial fibrillation (AF) is common in patients with heart failure with preserved ejection fraction (HFpEF) and is associated with poorer clinical outcomes. The prevalence of subclinical AF in patients with HFpEF remains unknown. OBJECTIVES: The aim of this study was to determine whether subclinical AF was more prevalent in individuals with HFpEF than in individuals without histories of heart failure (HF). METHODS: Patients with HFpEF with no prior diagnoses of AF were screened for subclinical AF, and the prevalence of subclinical AF was compared with that among control subjects without HF drawn from MESA (Multi-Ethnic Study of Atherosclerosis) who underwent the same electrocardiographic monitoring. Multivariable logistic regression was used to adjust for demographic and clinical comorbidities. RESULTS: Ninety patients with HFpEF and 1,230 MESA participants were included. Patients with HFpEF were younger (median age 69 years [Q1-Q3: 63-76 years] vs 72 years [Q1-Q3: 66-80 years]; P = 0.02), more obese (median body mass index 36 kg/m2 [Q1-Q3: 30-45 kg/m2] vs 27 kg/m2 [Q1-Q3: 24-30 kg/m2]; P < 0.001), and more likely to have diabetes (34% vs 21%; P = 0.01). The prevalence of subclinical AF was 8.9% in patients with HFpEF and 4.1% in non-HF participants. After multivariable adjustment for age, sex, race, body mass index, diabetes, smoking, and total analyzable time on electrocardiographic monitor, there was a significantly higher odds of subclinical AF in patients with HFpEF compared with MESA (OR: 3.01; 95% CI: 1.13-7.99; P = 0.03). CONCLUSIONS: Patients with HFpEF had a higher prevalence of subclinical AF than participants without HF from a community-based study. Screening for atrial arrhythmias may be appropriate among patients with HFpEF for timely initiation of thromboembolic prophylaxis and may identify individuals at greater risk for clinical decompensation.

Prevalence and Outcomes of Patients With Acute Ischemic Stroke and Concomitant Non-ST-Elevation Myocardial Infarction (Results from the National Inpatient Sample 2016 to 2019).

Acute myocardial infarction (MI) may concomitantly occur with acute ischemic stroke. The incidence and outcomes of acute non-ST-elevation MI (NSTEMI) in acute ischemic stroke are not well studied. We examined hospitalized patients with acute ischemic stroke and a concomitant NSTEMI diagnosis who were included in the National Inpatient Sample 2016 to 2019. Acute ischemic stroke and NSTEMI were defined by using the International Classification of Diseases, Tenth Revision codes. Patients with ST-elevation MI were excluded. The outcomes were expressed as percentages. A multivariable logistic regression analysis was used to examine the association of concomitant acute ischemic stroke and NSTEMI with the primary outcome of mortality and the secondary outcomes. A subgroup analysis of patients with NSTEMI with acute ischemic stroke that underwent percutaneous coronary intervention (PCI) (angiography and angioplasty) was also performed. Of the total hospitalized patients with acute ischemic stroke (n = 1,726,265), 1.60% (n = 27,630) patients (mean age 73.5 years, 52.2% women, 67% White race) had NSTEMI diagnosed during the hospitalization. Of these, 14.1% (n = 3,890) died in the NSTEMI group and 3.4% (n = 57,670) died in the non-NSTEMI group. The most common outcomes in the NSTEMI group were Acute kidney injury 31.8%, Intracranial hemorrhage 6.6%, and sepsis 6.13%. NSTEMI in acute ischemic stroke was associated with mortality (odds ratio [OR] 3.60, 95% confidence interval [CI] 3.29 to 3.93, p ≤0.001), ICH (OR 1.46, 95% CI 1.30 to 1.63, p <0.001), and having any of the secondary outcomes (OR 2.73, 95% CI 2.57 to 2.90, p <0.001). PCI was performed in 9.14% of patients with acute ischemic stroke with NSTEMI. PCI was associated with having any of the secondary outcomes (OR 0.83, 95% CI 0.7 to 1.02, p = 0.8), mortality (OR 0.35, 95% CI 0.23 to 0.54, p <0.001), and ICH (OR 0.42, 95% CI 0.25 to 0.7, p = 0.01). In conclusion, NSTEMI in acute ischemic stroke is associated with increased mortality and other adverse events. PCI in the subgroup of patients with NSTEMI was not associated with increased mortality or intracranial bleeding.

Association between polyunsaturated fatty acids intake and insulin resistance in Brazilian adolescents (ERICA Study).

OBJECTIVE: Some studies have proposed a beneficial effect of polyunsaturated fatty acid (PUFA) intake with regard to insulin sensitivity. The aim of this study was to estimate the energy percentage and the daily PUFA intake to investigate the association between PUFAs and insulin resistance in a large sample of Brazilian adolescents. METHODS: We evaluated 37 023 adolescents ages 12 to 17 y, who were participants in ERICA (Study of Cardiovascular Risk in Adolescents). Energy percentage and PUFA daily intake were extracted from a 24-h dietary recall. The mean daily intake of total fat, median, and the respective 95% confidence intervals (95% CI) of daily intake of linoleic acid (LA), α-linolenic acid (ALA) and the ratio of LA to ALA were estimated according to sociodemographic variables. Associations of PUFA and markers of glucose homeostasis were analyzed by Poisson regression model. RESULTS: Mean total fat intake was 30.1% of energy (95% CI, 29.9-30.4). Most participants met the current recommended values of PUFA and LA/ALA ratio ranging from 5:1 to 10:1 (80.9%, 95% CI, 79.8-81.8). ALA intake was inversely associated with higher waist circumference (prevalence ratio [PR], 0.996; 95% CI, 0.994-0.998). LA/ALA ratio ≥9:1 was significantly associated with higher levels of homeostasis model assessment of insulin resistance (HOMA-IR; PR, 1.01; 95% CI, 1.006-1.02), and ratio >10:1 also showed significant association with higher levels of HOMA-IR (PR, 1.02; 95% CI, 1.01-1.03) and glycated hemoglobin (PR, 1.14; 95% CI, 1.04-1.26). These associations remained significant after adjustment. CONCLUSION: Promotion of ALA intake and balanced LA/ALA ratio should be considered as a possible health strategy aimed at contributing to better control of glucose homeostasis and insulin resistance in adolescents.

The association of circulating fibroblast growth factor 21 levels with incident heart failure: The Multi-Ethnic Study of Atherosclerosis.

BACKGROUND: Fibroblast growth factor 21 (FGF21) levels are often elevated in heart failure (HF), although this has not been assessed using a longitudinal study design. Therefore, we investigated the association between baseline plasma FGF21 levels and incident HF in the Multi-Ethnic Study of Atherosclerosis (MESA). METHODS: A total of 5408 participants, free of clinically apparent cardiovascular disease, were included in the analysis, of which 342 developed HF over a median follow-up period of 16.7 years. Multivariable Cox regression analysis was performed and the additive value of FGF21 in the performance of risk prediction over other well-established cardiovascular biomarkers was assessed. RESULTS: The mean age of the participants was 62.6 years with 47.6 % male. Regression spline analysis demonstrated a significant association of FGF21 levels with incident HF among participants with FGF21 levels ≥239.0 pg/mL (hazard ratio = 1.84 [95 % confidence interval 1.21, 2.80] per SD increase in ln-transformed levels) after adjustment for traditional cardiovascular risk factors and biomarkers, but not in participants with FGF21 levels <239.0 pg/mL (p for heterogeneity = 0.004). Among participants with FGF21 levels ≥239.0 pg/mL, FGF21 levels were associated with HF with preserved ejection fraction (HR [95 % CI] = 2.57 [1.51, 4.37]), but not HF with reduced ejection fraction. CONCLUSIONS: The present study suggests baseline FGF21 levels could predict the development of incident HF with preserved ejection fraction, among participants with elevated FGF21 levels at baseline. This study may suggest a pathophysiological role of FGF21 resistance in HF with preserved ejection fraction.

Joint effect of highly-sensitive cardiac troponin T and ankle-brachial index on incident cardiovascular events: The MESA and CHS.

Background: Elevated highly-sensitive cardiac troponin-T (hs-cTnT≥14 ng/L) and low ankle-brachial index (ABI<0.9) are risk factors for atherosclerotic cardiovascular diseases (ASCVD) but their joint effect on the risk of ASCVD events is unknown. Methods: We used data from the two population-based cohort studies, the Multi-Ethnic study of Atherosclerosis (MESA) and Cardiovascular Heart Study (CHS) among 10,897 participants free of CVD events at baseline (mean age 66.3 years, 44.7% males). Incident ASCVD was defined as CHD (fatal/non-fatal MI or revascularization), transient ischemic attack, or stroke,. Hazard ratio (HR) and 95% CI was calculated from a Cox regression model. Interaction on the additive scale was assessed using relative excess risk due to interaction (RERI) and interaction on the multiplicative scale was assessed by Likelihood ratio (LR) test. Results: At baseline (2000-2002 for MESA and 1989-1990 for CHS), 10.2% of participants had elevated hs-cTnT and 7.5% had low ABI. During a median follow-up of 13.6 years (interquartile range, 7.5-14.7 years), there were 2590 incident ASCVD and 1542 incident CHD events. The hazard of CHD and ASCVD was higher in participants with both elevated hs-cTnT and low ABI [HR(95% CI): CHD: 2.04 (1.45, 2.88), ASCVD: 2.05 (1.58, 2.66)] than those with only elevated hs-cTnT [CHD: 1.65 (1.37, 1.99), ASCVD: 1.67 (1.44, 1.99)] or only low ABI [CHD: 1.87 (1.52, 2.31), ASCVD: 1.67 (1.42, 1.97)]. Antagonistic multiplicative interaction was observed for CHD (LR test p-value=0.042) but not for ASCVD (LR test p-value =0.08). No significant additive interaction was detected for CHD and ASCVD (RERI p-value ≥0.23). Conclusion: The observed joint effect of elevated cTnT and low ABI on ASCVD risk was smaller (i.e., antagonistic interaction) than that expected by the combined independent effects of each risk factor.

Snippets of the History of the American Journal of Epidemiology.

In this article, I present a brief summary of landmark events in the American Journal of Epidemiology, including its founding, the first few decades, the change in name, the increasing focus on nontransmissible disease, and selected key manuscripts. A list of developments that will likely result in new papers submitted to epidemiology journals are also described, and they include themes such as consequential epidemiology and the use of artificial intelligence methods in epidemiologic data analyses.

Positive Additive and Multiplicative Interactions among Clustered Components of Metabolic Syndrome with Type 2 Diabetes Mellitus among Brazilian Adolescent Students.

Background: It is still controversial whether the joint effect of Metabolic syndrome (MetS) components is greater than that expected based on their independent effects, regarding type 2 diabetes mellitus in adolescents. We evaluated additive and multiplicative interactions between pair-wise combinations of metabolic syndrome components regarding type 2 diabetes mellitus. Methods: We studied 37,815 Brazilian adolescents from a national school-based survey, The Study of Cardiovascular Risk Factors in Adolescents (Portuguese acronym, ERICA). A Poisson regression model was used to calculate sex-, age-, obesity-, smoking status-, sedentary behavior-, physical inactivity-, alcoholic consumption- and socioeconomic status-adjusted prevalence ratios to evaluate both additive and multiplicative interactions. Results: In the comparison of observed and expected joint effects, relative excess risk due to additive interaction (RERI) for high triglycerides and low high-density lipoprotein-cholesterol, high triglycerides and elevated waist circumference, elevated waist circumference and low high-density lipoprotein-cholesterol and elevated waist circumference and high blood pressure were 2.53 (−0.41, 5.46), 2.86 (−2.89, 8.61), 1.71 (−1.05, 4.46) and 0.97 (0.15, 1.79), respectively, thus suggesting additive interactions. Multiplicative interactions for those pairs of components were also observed, as expressed by interaction ratios > 1.0. Conclusions: The joint presence of some of the components of MetS showed a greater association with the prevalence of type 2 diabetes mellitus in adolescents than expected from the sum of their isolated effects. From a public health perspective, preventing one of the components of the pairs that interact may result in a greater reduction in the prevalence of T2DM than focusing on an individual component that does not interact with another component.

Persistent Asthma Is Associated With Carotid Plaque in MESA.

Background Asthma and atherosclerotic cardiovascular disease share an underlying inflammatory pathophysiology. We hypothesized that persistent asthma is associated with carotid plaque burden, a strong predictor of atherosclerotic cardiovascular disease events. Methods and Results The MESA (Multi-Ethnic Study of Atherosclerosis) enrolled adults free of known atherosclerotic cardiovascular disease at baseline. Subtype of asthma was determined at examination 1. Persistent asthma was defined as asthma requiring use of controller medications, and intermittent asthma was defined as asthma without controller medications. B-mode carotid ultrasound was performed to detect carotid plaques (total plaque score [TPS], range 0-12). Multivariable regression modeling with robust variances evaluated the association of asthma subtype and carotid plaque burden. The 5029 participants were a mean (SD) age of 61.6 (10.0) years (53% were women, 26% were Black individuals, 23% were Hispanic individuals, and 12% were Chinese individuals). Carotid plaque was present in 50.5% of participants without asthma (TPS, 1.29 [1.80]), 49.5% of participants with intermittent asthma (TPS, 1.25 [1.76]), and 67% of participants with persistent asthma (TPS, 2.08 [2.35]) (P≤0.003). Participants with persistent asthma had higher interleukin-6 (1.89 [1.61] pg/mL) than participants without asthma (1.52 [1.21] pg/mL; P=0.02). In fully adjusted models, persistent asthma was associated with carotid plaque presence (odds ratio, 1.83 [95% confidence interval, 1.21-2.76]; P<0.001) and TPS (ß=0.66; P<0.01), without attenuation after adjustment for baseline interleukin-6 (P=0.02) or CRP (C-reactive protein) (P=0.01). Conclusions Participants with persistent asthma had higher carotid plaque burden and higher levels of inflammatory biomarkers, compared with participants without asthma. Adjustment for baseline inflammatory biomarkers did not attenuate the association between carotid plaque and asthma subtype, highlighting the increased atherosclerotic cardiovascular disease risk among those with persistent asthma may be multifactorial.

Secondhand tobacco smoke exposure, urine cotinine, and risk of incident atrial fibrillation: The multi-ethnic study of atherosclerosis.

BACKGROUND: Secondhand tobacco smoke (SHS) exposure may reduce heart rate variability and lead to atrial fibrillation (AF); however prior study findings have not been confirmed using objective measures for both SHS and AF events. METHODS: We prospectively examined the association between SHS exposure and incident AF in 5731 participants, ages of 45-84 years and free of known AF and other cardiovascular diseases (CVD) at baseline (2000-2002), who were followed through 2015 in the Multi-Ethnic Study of Atherosclerosis (MESA). SHS weekly exposure time was identified by self-report. Urine cotinine was collected in a cohort subset of 3237 current non-smoking cohort participants. AF events were identified using Medicare claims, hospital records, and 12­lead electrocardiographic findings. A multivariable Cox proportional hazards regression analysis was used with simultaneous adjustment for demographic factors, educational level, health insurance status, active smoking status, tobacco pack-years, traditional CVD risk factors, depressive symptoms and medications. RESULTS: During a median follow-up of 14.0 years, 856 and 452 AF events were identified in the overall and the cohort subset, respectively. No association of SHS exposure time or urine cotinine with incident AF was observed. However, a higher AF risk with greater urine cotinine (8.53-442.0 ng/mL) compared with lower urine cotinine (≤7.07 ng/mL) was observed in never smokers [hazard ratios (HR) and 95% confidence intervals: 1.60 (1.16, 2.19)], but not in former smokers [HR: 0.88 (0.63, 1.23)] (p-value for multiplicative interaction: 0.009 and for additive interaction: 0.017, respectively). CONCLUSION: Objectively measured greater SHS exposure expressed by urine cotinine might be associated with 1.6-fold higher risk of incident AF in never smokers.

Statin Use and Risk of Diabetes by Subclinical Atherosclerosis Burden (from a Multi-Ethnic Study of Atherosclerosis Report).

Although there is a significant reduction in atherosclerotic cardiovascular disease risk with statins, a higher risk of diabetes mellitus has been demonstrated in randomized clinical trials. The risk of incident diabetes with statins may be heterogeneous by presence of coronary artery calcium (CAC). We evaluated participants without prevalent diabetes at baseline from the MESA (Multi-Ethnic Study of Atherosclerosis), a prospective cohort study of subjects free of clinical cardiovascular disease at baseline. We used multivariable-adjusted Cox proportional hazards models to study the association between statin use and incident diabetes, adjusting for sociodemographic and cardiovascular risk factors, including time-varying statin use and stratifying by baseline CAC (0, 1 to 100, ≥100). The study population included 5,943 participants with a mean (SD) age of 62 (10) years, 54% women, 41% White, 26% Black, 12% Chinese-American, and 21% Hispanic. In the unadjusted analyses, statin use was associated with a higher risk of incident diabetes (hazard ratio [HR] 1.62, 95% confidence interval [CI] 1.27 to 2.06). After adjustment, this risk was no longer significant (HR 1.13, 95% CI 0.83 to 1.54). Although imprecise, the HR expressing the association of statins with diabetes was lower for those with CAC = 0 (HR 0.80, 95% CI 0.45 to 1.40) than for those with a higher CAC burden (HR 1.30, 95% CI 0.71 to 2.39 for CAC 1 to 100 and HR 1.39, 95% CI 0.85 to 2.28 for CAC ≥100), but this heterogeneity was not statistically significant. In conclusion, statin therapy was not significantly associated with incident diabetes mellitus in this observational study. The risk of incident diabetes did not significantly differ by baseline CAC.

Association between Obesity, Overweight, Elevated Waist Circumference, and Insulin Resistance Markers among Brazilian Adolescent Students.

(1) Background: There is still controversy concerning the most effective and efficient strategy to identify insulin resistance in adolescents. We estimated the level of fasting insulin (fasting insulin equivalent, FIeq) that would replicate the strength of the associations of obesity, overweight, and waist circumference with two insulin resistance markers: triglyceride/high-density lipoprotein (TG/HDL) and triglyceride/glucose (TyG); (2) Methods: We studied approximately 38,000 adolescents aged 12 to 17 years, sampled from a multicenter Brazilian school-based survey, The Study of Cardiovascular Risk Factors in Adolescents (Portuguese acronym, ERICA), conducted in 2013-2014. Fasting insulin equivalents for adiposity variables were calculated by dividing the beta coefficient of each adiposity measure by the fasting insulin beta coefficient from linear regression analysis according to age (12-14, 15-17 years old) and sex, and adjusted by smoking, alcohol consumption, physical inactivity, sedentary behavior, socioeconomic status, and Tanner stage; (3) Results: The FIeqs for obesity were greater than those for overweight and elevated waist circumference for both TG/HDL and TyG in early adolescence. The FIeqs for elevated WC were greater than those for obesity and overweight in adolescents aged 15 to 17 years; (4) Conclusions: Our study suggests that WC measurements might be useful to identify adolescents with insulin resistance, particularly in late adolescence.

Racial and Ethnic Differences in All-Cause and Cardiovascular Disease Mortality: The MESA Study.

BACKGROUND: Despite improvements in population health, marked racial and ethnic disparities in longevity and cardiovascular disease (CVD) mortality persist. This study aimed to describe risks for all-cause and CVD mortality by race and ethnicity, before and after accounting for socioeconomic status (SES) and other factors, in the MESA study (Multi-Ethnic Study of Atherosclerosis). METHODS: MESA recruited 6814 US adults, 45 to 84 years of age, free of clinical CVD at baseline, including Black, White, Hispanic, and Chinese individuals (2000-2002). Using Cox proportional hazards modeling with time-updated covariates, we evaluated the association of self-reported race and ethnicity with all-cause and adjudicated CVD mortality, with progressive adjustments for age and sex, SES (neighborhood SES, income, education, and health insurance), lifestyle and psychosocial risk factors, clinical risk factors, and immigration history. RESULTS: During a median of 15.8 years of follow-up, 22.8% of participants (n=1552) died, of which 5.3% (n=364) died of CVD. After adjusting for age and sex, Black participants had a 34% higher mortality hazard (hazard ratio [HR], 1.34 [95% CI, 1.19-1.51]), Chinese participants had a 21% lower mortality hazard (HR, 0.79 [95% CI, 0.66-0.95]), and there was no mortality difference in Hispanic participants (HR, 0.99 [95% CI, 0.86-1.14]) compared with White participants. After adjusting for SES, the mortality HR for Black participants compared with White participants was reduced (HR, 1.16 [95% CI, 1.01-1.34]) but still statistically significant. With adjustment for SES, the mortality hazards for Chinese and Hispanic participants also decreased in comparison with White participants. After further adjustment for additional risk factors and immigration history, Hispanic participants (HR, 0.77 [95% CI, 0.63-0.94]) had a lower mortality risk than White participants, and hazard ratios for Black participants (HR, 1.08 [95% CI, 0.92-1.26]) and Chinese participants (HR, 0.81 [95% CI, 0.60-1.08]) were not significantly different from those of White participants. Similar trends were seen for CVD mortality, although the age- and sex-adjusted HR for CVD mortality for Black participants compared with White participants was greater than all-cause mortality (HR, 1.72 [95% CI, 1.34-2.21] compared with HR, 1.34 [95% CI, 1.19-1.51]). CONCLUSIONS: These results highlight persistent racial and ethnic differences in overall and CVD mortality, largely attributable to social determinants of health, and support the need to identify and act on systemic factors that shape differences in health across racial and ethnic groups.

Self-reported marijuana use and cardiac arrhythmias (from the Multiethnic Study of Atherosclerosis).

Marijuana use among all age groups has been increasing, including among older adults aged ≥65 years. There is a lack of epidemiologic data examining arrhythmia risk among users of marijuana. We evaluated cross-sectional associations between current and past marijuana smoking and arrhythmias among 1485 participants from the Multiethnic Study of Atherosclerosis who underwent extended ambulatory electrocardiographic monitoring with the Zio Patch XT. Outcomes included premature atrial contractions, runs of supraventricular tachycardia, premature ventricular contractions, and runs of nonsustained ventricular tachycardia (NSVT). Compared with never users, participants reporting current use of marijuana (n = 40, 3%) had more supraventricular tachycardia/day (adjusted geometric mean ratio [GMR] 1.42, 95% confidence interval [CI] 0.87 to 2.32), more premature atrial contractions/hour (GMR 1.22, 95% CI 0.72, 2.13), and more NSVT/day (GMR 1.28, 95% CI 0.95 to 1.73); although, CIs overlapped 1. Additionally, more frequent marijuana use was associated with more runs of NSVT/day (GMR 1.56, 95% CI 1.13, 2.17). In conclusion, our results suggest that current marijuana use may be associated with a greater burden of arrhythmias. There is a need for additional research, mainly using a prospective design, to clarify if marijuana use causes atrial and ventricular arrhythmias or other cardiovascular complications among older adults.

Higher Leptin Levels Are Associated with Coronary Artery Calcium Progression: the Multi-Ethnic Study of Atherosclerosis (MESA).

BACKGROUND: Adipokines play a role in cardiometabolic pathways. Coronary artery calcium (CAC) progression prognosticates cardiovascular disease (CVD) risk. However, the association of adipokines with CAC progression is not well established. We examined the association of adipokines with CAC progression in a multi-ethnic cohort free of CVD at baseline. METHODS: We included 1,904 randomly-selected adults enrolled in the Multi-Ethnic Study of Atherosclerosis who had both adipokine levels [leptin, resistin, adiponectin] and CAC by CT measured at either exam 2 (2002-2004) or exam 3 (2004-2005). CAC was previously measured at exam 1 (2000-2002) and a subset (n=566) had CAC measured at exam 5 (2010-2012). We used logistic regression to examine odds of CAC progression between exam 1 and 2/3 (defined as >0 Agatston units of change/year). We used linear mixed effect models to examine CAC progression from exam 2/3 to 5. RESULTS: At exam 2/3, the mean age was 65(10) yrs; 50% women. In models adjusted for sociodemographic factors and BMI, the highest tertile of leptin, compared to lowest, was associated with an increased odds of CAC progression over the preceding 2.6yrs [OR 1.60 (95% CI: 1.10-2.33)]. In models further adjusted for visceral fat and CVD risk factors, the highest tertile of leptin was statistically significantly associated with a 4% (1-7%) greater CAC progression over an average of 7yrs. No associations were seen for resistin and adiponectin. CONCLUSIONS: Higher leptin levels were independently, but modestly, associated with CAC progression. Atherosclerosis progression may be one mechanism through which leptin confers increased CVD risk.

Determinants of Incident Atherosclerotic Cardiovascular Disease Events Among Those With Absent Coronary Artery Calcium: Multi-Ethnic Study of Atherosclerosis.

BACKGROUND: The 2018 American Heart Association/American College of Cardiology/Multisociety cholesterol guideline states that statin therapy may be withheld or delayed among intermediate-risk individuals in the absence of coronary artery calcium (CAC=0). We evaluated whether traditional cardiovascular risk factors are associated with incident atherosclerotic cardiovascular disease (ASCVD) events among individuals with CAC=0 over long-term follow-up. METHODS: We included participants with CAC=0 at baseline from the MESA (Multi-Ethnic Study of Atherosclerosis), a prospective cohort study of individuals free of clinical ASCVD at baseline. We used multivariable-adjusted Cox proportional hazards models to study the association between cardiovascular risk factors (cigarette smoking, diabetes, hypertension, preventive medication use [aspirin and statin], family history of premature ASCVD, chronic kidney disease, waist circumference, lipid and inflammatory markers) and adjudicated incident ASCVD outcomes. RESULTS: We studied 3416 individuals (mean [SD] age 58 [9] years; 63% were female, 33% White, 31% Black, 12% Chinese American, and 24% Hispanic). Over a median follow-up of 16 years, there were 189 ASCVD events (composite of coronary heart disease and stroke) of which 91 were coronary heart disease, 88 were stroke, and 10 were both coronary heart disease and stroke events. The unadjusted event rates of ASCVD were ≤5 per 1000 person-years among individuals with CAC=0 for most risk factors with the exception of current cigarette smoking (7.3), diabetes (8.9), hypertension (5.4), and chronic kidney disease (6.8). After multivariable adjustment, risk factors that were significantly associated with ASCVD included current cigarette smoking: hazard ratio, 2.12 (95% CI, 1.32-3.42); diabetes: hazard ratio, 1.68 (95% CI, 1.01-2.80); and hypertension: hazard ratio, 1.57 (95% CI, 1.06-2.33). CONCLUSIONS: Current cigarette smoking, diabetes, and hypertension are independently associated with incident ASCVD over a 16-year follow-up among those with CAC=0.

Association of Physical Activity With Maximal and Submaximal Tests of Exercise Capacity in Middle- and Older-Aged Adults.

Although physical activity (PA) is an important determinant of exercise capacity, the association between these constructs is modest. The authors investigated the associations of self-reported and objectively measured PA with maximal and submaximal tests of exercise capacity. Participants aged ≥40 years (N = 413; 49.6% female) completed a PA questionnaire, wore a uniaxial accelerometer (5.2 ± 1.1 days), and performed maximal (cardiopulmonary exercise test [CPET]) and submaximal (long-distance corridor walk) tests with indirect calorimetry (oxygen consumption, V˙O2). Linear regression models were fitted to assess the variation in exercise capacity explained (partial eta squared, η2) by PA variables. Accelerometer-measured vigorous (η2 = 22% female; η2 = 16% male) and total PA (η2 = 17% female; η2 = 13% male) explained the most variance in CPET V˙O2 (p < .001). All η2 values were lower for long-distance corridor walk V˙O2 (η2 ≤ 11%). Age contributed more to CPET V˙O2 than any PA variable in males (η2 = 32%), but not in females (η2 = 19%). Vigorous and total PA play important roles in CPET V˙O2 in mid to late life.

Personality disorders and cause-specific mortality: a nationwide study of 2 million adolescents.

BACKGROUND: Personality disorders are prevalent in 6-10% of the population, but their risk for cause-specific mortality is unclear. The aim of the study was to assess the association between personality disorders diagnosed in late adolescence and all-cause as well as cause-specific (cardiovascular-related, external-related) mortality. METHODS: We performed a longitudinal study on a historical prospective cohort based on nationwide screening prior to recruitment to the Israeli army. The study participants were 16-19-year-old persons who attended the army screening (medical and cognitive, including screening for psychiatric disorders) between 1967 and 2006. Participants were followed from 1967 till 2011. RESULTS: The study included 2 051 606 subjects, of whom 1 229 252 (59.9%) were men and 822 354 (40.1%) were women, mean age 17.36 years. There were 55 508 (4.5%) men and 8237 (1.0%) women diagnosed with personality disorders. The adjusted hazard ratio (HRs) for coronary, stroke, cardiovascular, external-related causes and all-cause mortality among men with personality disorders were 1.34 (1.03-1.74), 1.82 (1.20-2.76), 1.45 (1.23-1.71), 1.41 (1.30-1.53) and 1.44 (1.36-1.51), respectively. The absolute rate difference for all-cause mortality was 56.07 and 13.19 per 105 person-years among men and women, respectively. Among women with personality disorders, the adjusted HRs for external-related causes and all-cause mortality were 2.74 (1.87-4.00) and 2.01 (1.56-2.58). Associations were already evident within 10 years of follow-up. CONCLUSIONS: Personality disorder in late adolescence is associated with increased risk of cardiovascular, external- and all-cause mortality. Increased cardiovascular mortality is evident before the age of 40 years and may point to the importance of lifestyle education already in youth.

Birth weight, life course factors and excess weight among schoolchildren in Niterói, Rio de Janeiro, Brazil in 2010

Abstract Objective: To investigate the association between birth weight and excess weight among students aged 6-14 years, adjusted for life course confounding factors. Methods: Cross-sectional study with 6-14-year-old schoolchildren in 2010; 795 school children from two public schools. In addition, a sub-sample was selected using a case-cohort study approach. Sociodemographic, breastfeeding, food introduction, previous weight gain, family history, current clinical and behavioral variables as well as maternal variables related to pregnancy, were collected. Multivariable weighted logistic regression was used to evaluate the association between birth weight and overweight. All prevalent cases of overweight (n = 160) were selected to compose the case group and a random sub-sample of all students participating in the study (n = 276 students, of whom 88 were cases) were the control group. Results: An unadjusted 6% increase in the excess weight prevalence ratio (p-value = 0.004) was found for each 100 g increase in birth weight. With adjustment for age, sex and behavioral variables (models 1 and 2), the association of birth weight with excess weight was positive and statistically significant, but it was no longer significant in the final model (model 3) when clinical variables were considered. Conclusions: Although some of the secondary associations were statistically significant, we could not identify a significant association between birthweight and excess weight in adolescents.

Chronic Stress Burden, Visceral Adipose Tissue, and Adiposity-Related Inflammation: The Multi-Ethnic Study of Atherosclerosis.

OBJECTIVE: We investigated the role of chronic stress burden on adiposity and adiposity-related inflammation with two hypotheses: a) greater chronic stress is associated with higher central adiposity and selective accumulation of visceral adipose tissue (VAT) compared with subcutaneous adipose tissue (SAT), and b) associations between VAT and inflammatory biomarkers are exacerbated when chronic stress is high. METHODS: Data come from 1809 participants included in a Multi-Ethnic Study of Atherosclerosis ancillary study of body composition and adiposity-related inflammation. Chronic psychosocial stress was measured with a five-item version of the Chronic Stress Burden Scale. First, we tested associations between chronic stress (three-level categorical variable) and VAT, SAT, and VAT/SAT ratio. Second, we tested whether associations between VAT and inflammatory biomarkers varied by level of chronic stress. RESULTS: Participants were approximately 65 years, 50% female, and 40.5% White, 25.6% Hispanic, 21.2% African American, and 12.8% Chinese American. About half of the sample reported little to no stress, and a quarter and a fifth of the sample reported medium and high levels of stress. Higher levels of chronic stress were associated with greater VAT and SAT, but not VAT/SAT ratio. Greater levels of VAT were associated with increased levels of adiposity-related inflammation in a graded pattern. These associations did not vary by stress level. CONCLUSIONS: Greater chronic stress burden is associated with both central and subcutaneous adiposity. We found no evidence that the associations between VAT and inflammatory biomarkers are exacerbated by chronic stress. Findings contribute to ongoing literature untangling pathways in which psychosocial stress contributes to adiposity-related inflammation.