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In 2008, Oregon expanded its Medicaid program using a lottery, creating a rare opportunity to study the effects of Medicaid coverage using a randomized controlled design (Oregon Health Insurance Experiment). Analysis showed that Medicaid coverage lowered the risk of depression. However, this effect may vary between individuals, and the identification of individuals likely to benefit the most has the potential to improve the effectiveness and efficiency of the Medicaid program. By applying the machine learning causal forest to data from this experiment, we found substantial heterogeneity in the effect of Medicaid coverage on depression; individuals with high predicted benefit were older and had more physical or mental health conditions at baseline. Expanding coverage to individuals with high predicted benefit generated greater reduction in depression prevalence than expanding to all eligible individuals (21.5 vs 8.8 percentage-point reduction; adjusted difference = +12.7 [95% CI, +4.6 to +20.8]; P = 0.003), at substantially lower cost per case prevented ($16 627 vs $36 048; adjusted difference = -$18 598 [95% CI, -156 953 to -3120]; P = 0.04). Medicaid coverage reduces depression substantially more in a subset of the population than others, in ways that are predictable in advance. Targeting coverage on those most likely to benefit could improve the effectiveness and efficiency of insurance expansion. This article is part of a Special Collection on Mental Health.

Research suggests that women experience greater cardiovascular ischemic effects from stress than men. Visceral adiposity is an endocrine tissue that differs by sex and interacts with stress hormones. We hypothesized that urinary cortisol would be associated with increased cardiovascular events and change in coronary artery calcium score (CAC) in women, and these relationships would vary by central obesity. In the Multi-Ethnic Study of Atherosclerosis Stress Ancillary study, cortisol was quantified by 12-h overnight urine collection. Central obesity was estimated by waist-hip ratio (WHR). Multivariable Cox models estimated the relationship between cortisol and cardiovascular events and assessed for moderation by WHR. The relationship between cortisol and change in CAC Agatston score was assessed by Tobit regression models. 918 patients were analyzed with median follow up of 11 years. There was no association between urinary cortisol and cardiovascular events in the cohort. However, in individuals with below median WHR, higher urinary cortisol levels (upper tertile) were associated with higher cardiovascular event rates in the full cohort, women, and men, but not in groups with above median WHR. There was significant moderation by WHR in women, but not men, whereby the association between elevated cortisol and increased cardiovascular events diminished as WHR increased. Urinary cortisol was associated with increased change in CAC in women (P = 0.003) but not men, without moderation by WHR. Our study highlights associations between cortisol and subclinical atherosclerosis in women, and moderation of the relationship between cortisol and cardiovascular events by central obesity in both genders.

Background Although most individuals can adapt to a large iodine load and remain euthyroid, hypothyroidism can develop after iodine exposure. Hypothyroidism is associated with adverse cardiovascular consequences, including heart failure. This study was performed to investigate the relationships between iodine-induced hypothyroidism and incident heart failure. Methods and Results This cohort study of the US Veterans Health Administration (1998-2021) included adults aged ≥18 years with a serum thyroid-stimulating hormone (thyrotropin)

CONTEXT: Although iodine-induced hyperthyroidism is a potential consequence of iodinated radiologic contrast administration, its association with long-term cardiovascular outcomes has not been previously studied. OBJECTIVE: To investigate the relationships between hyperthyroidism observed after iodine contrast administration and incident atrial fibrillation/flutter. METHODS: Retrospective cohort study of the U.S. Veterans Health Administration (1998-2021) of patients age ≥18 years with a normal baseline serum thyrotropin (TSH) concentration, subsequent TSH

BACKGROUND: In medicine, clinicians treat individuals under an implicit assumption that high-risk patients would benefit most from the treatment (high-risk approach). However, treating individuals with the highest estimated benefit using a novel machine-learning method (high-benefit approach) may improve population health outcomes. METHODS: This study included 10 672 participants who were randomized to systolic blood pressure (SBP) target of either 0) versus the high-risk approach (treating individuals with SBP ≥130 mmHg). Using transportability formula, we also estimated the effect of these approaches among 14 575 US adults from National Health and Nutrition Examination Surveys (NHANES) 1999-2018. RESULTS: We found that 78.9% of individuals with SBP ≥130 mmHg benefited from the intensive SBP control. The high-benefit approach outperformed the high-risk approach [average treatment effect (95% CI), +9.36 (8.33-10.44) vs +1.65 (0.36-2.84) percentage point; difference between these two approaches, +7.71 (6.79-8.67) percentage points, P-value

BackgroundCoronary artery calcium (CAC) has been widely recognized as an important predictor of cardiovascular disease (CVD). Given the finite resources, it is important to identify individuals who would receive the most benefit from detecting positive CAC by screening. However, the evidence is limited as to whether the burden of positive CAC on CVD differs by multidimensional individual characteristics. We sought to investigate the heterogeneity in the association between positive CAC and incident CVD.MethodsThis cohort study included adults from MESA (Multi-Ethnic Study of Atherosclerosis) ages ≥45 years and free of cardiovascular disease. After propensity score matching in a 1:1 ratio, we applied a machine learning causal forest model to (1) evaluate the heterogeneity in the association between positive CAC and incident CVD, and (2) predict the increase in CVD risk at 10-years when CAC>0 (versus CAC=0) at the individual level. We then compared the estimated increase in CVD risk when CAC>0 to the absolute 10-year atherosclerotic CVD (ASCVD) risk calculated by the 2013 American College of Cardiology/American Heart Association pooled cohort equations.ResultsAcross 3328 adults in our propensity score-matched analysis, our causal forest model showed the heterogeneity in the association between CAC>0 and incident CVD. We found a dose-response relationship of the estimated increase in CVD risk when CAC>0 with higher 10-year ASCVD risk. Almost all individuals (2293 of 2428 [94.4%]) with borderline risk of ASCVD or higher showed ≥2.5% increase in CVD risk when CAC>0. Even among 900 adults with low ASCVD risk, 689 (69.2%) showed ≥2.5% increase in CVD risk when CAC>0; these individuals were more likely to be male, Hispanic, and have unfavorable CVD risk factors than others.ConclusionsThe expected increases in CVD risk when CAC>0 were heterogeneous across individuals. Moreover, nearly 70% of people with low ASCVD risk showed a large increase in CVD risk when CAC>0, highlighting the need for CAC screening among such low-risk individuals. Future studies are needed to assess whether targeting individuals for CAC measurements based on not only the absolute ASCVD risk but also the expected increase in CVD risk when CAC>0 improves cardiovascular outcomes.

ObjectiveTo determine changes in industry marketing payments to physicians due to the covid-19 pandemic.DesignQuasi experimental, difference-in-difference study.Data sourceUS nationwide database of licensed physicians, the National Plan and Provider Enumeration System, which was linked to a database of industry marketing payments made to physicians, Open Payments.PopulationAll licensed US physicians from 2018 to 2020 and those who received payments from industry.Main outcome measuresChanges in the value and the number of monthly industry payments physician received before (January-February 2020) and during the pandemic (April-December 2020) were assessed, adjusting for physicians' characteristics (gender and specialty). As the control, data for the same months in 2019 were used. Industry payments by type of payments (eg, meals, travel, consulting fees, speaker compensation, honorariums), were also examined.ResultsAmong 880 589 US physicians included in this study, 267 463 (30.4%) physicians received a total of 4 117 482 non-research payments with $626 million ($710 per physician; £610; €708) in 2020 (40-44% decrease from $1047m in 2018 and $1115m in 2019). Industry payments decreased significantly in the months of the covid-19 pandemic (adjusted change in the value of -48.4%; 95% confidence interval -50.6 to -46.2; P

BackgroundChronic pain is the leading cause of disability worldwide and is strongly associated with the epidemic of opioid overdosing events. However, the causal links between chronic pain, opioid prescriptions, and mortality remain unclear.MethodsThis study included 13,884 US adults aged ≥20 years who provided data on chronic pain in the National Health and Nutrition Examination Survey 1999-2004 with linkage to mortality databases through 2015. We employed the generalized form of the front-door formula within the structural causal model framework to investigate the causal effect of chronic pain on all-cause mortality mediated by opioid prescriptions.ResultsWe identified a total of 718 participants at 3 years of follow-up and 1260 participants at 5 years as having died from all causes. Opioid prescriptions increased the risk of all-cause mortality with an estimated odds ratio (OR) (95% confidence interval) = 1.5 (1.1, 1.9) at 3 years and 1.3 (1.1, 1.6) at 5 years. The front-door formula revealed that chronic pain increased the risk of all-cause mortality through opioid prescriptions; OR = 1.06 (1.01, 1.11) at 3 years and 1.03 (1.01, 1.06) at 5 years. Our bias analysis showed that our findings based on the front-door formula were likely robust to plausible sources of bias from uncontrolled exposure-mediator or mediator-outcome confounding.ConclusionsChronic pain increased the risk of all-cause mortality through opioid prescriptions. Our findings highlight the importance of careful guideline-based chronic pain management to prevent death from possibly inappropriate opioid prescriptions driven by chronic pain.

BackgroundA study has shown that industry payments to physicians for drugs are associated not only with higher drug prescriptions but also with higher non-drug costs due to additional utilization of healthcare services. However, the association between industry payments to cardiologists for antiplatelet drugs and the costs and number of percutaneous coronary interventions they perform has not been investigated.ObjectiveTo examine the association between industry payments to cardiologists for antiplatelet drugs and the costs and number of percutaneous coronary interventions they perform.DesignUsing the 2016 Open Payments Database linked to the 2017 Medicare Provider Utilization and Payment Data, we examined the association between the value of industry payments related to the antiplatelet drugs prasugrel and ticagrelor and healthcare spending and volume for cardiovascular procedures, adjusted for potential cofounders.SubjectsA total of 7456 cardiologists who performed diagnostic cardiac catheterizations on Medicare beneficiaries in 2017.Main measuresPrimary outcomes included (1) healthcare spending on cardiac procedures, (2) diagnostic cardiac catheterization volumes, and (3) rates of coronary stenting. Secondary outcomes were total expenditures for all drugs and for antiplatelet drugs.Key resultsIndustry payments for antiplatelet drugs were associated with higher healthcare spending on cardiac procedures (adjusted difference, +$50.9 for additional $100 industry payments; 95% CI, +$25.5 to +$76.2; P < 0.001), diagnostic cardiac catheterizations (+0.1 procedures per cardiologist; 95% CI, +0.03 to +0.1; P=0.001), and stent use (+0.5 per 1000 diagnostic cardiac catheterizations per cardiologist; 95% CI, +0.2 to +0.9; P=0.002). Industry payments for antiplatelet drugs were associated with higher total costs for all drugs and antiplatelet drugs.ConclusionsIndustry payments to cardiologists for antiplatelet drugs were associated with both prescribing of antiplatelet drugs and the use of cardiac procedures and stents. Further research is warranted to understand whether the observed associations are causal or reflect a greater propensity for higher volume proceduralists to have relationships with industry.

BackgroundIodine and particularly its oxidated forms have long been recognized for its effective antiseptic properties. Limited in vitro and in vivo data suggest that iodine exposure may rapidly inactivate, reduce transmission, and reduce infectivity of SARS-CoV-2. We hypothesized that iodine exposure may be associated with decreased incident COVID-19 infection.MethodsA retrospective population-level cohort analysis was performed of the U.S. Veterans Health Administration between 1 March 2020 and 31 December 2020, before the widespread availability of vaccines against SARS-CoV-2. Multivariable logistic regression models estimated the adjusted odds ratios (OR) and 95% confidence intervals (CI) of the associations between iodinated contrast exposure and incident COVID-19 infection, adjusting for age, sex, race/ethnicity, place of residence, socioeconomic status, and insurance status.Results530,942 COVID-19 tests from 333,841 Veterans (mean ± SD age, 62.7 ± 15.2 years; 90.2% men; 61.9% non-Hispanic Whites) were analyzed, of whom 9% had received iodinated contrast ≤60 days of a COVID-19 test. Iodine exposure was associated with decreased incident COVID-19 test positivity (OR, 0.75 95% CI, 0.71-0.78). In stratified analyses, the associations between iodinated contrast use and decreased COVID-19 infection risk did not differ by age, sex, and race/ethnicity.ConclusionIodine exposure may be protective against incident COVID-19 infection. Weighed against the risks of supraphysiologic iodine intake, dietary, and supplemental iodine nutrition not to exceed its Tolerable Upper Limit may confer an antimicrobial benefit against SARS-CoV-2. A safe but antimicrobial level of iodine supplementation may be considered in susceptible individuals, particularly in geographic regions where effective COVID-19 vaccines are not yet readily available.

Lung cancer screening (LCS) is effective in reducing mortality, particularly when patients adhere to follow-up recommendations standardized by the Lung CT Screening Reporting & Data System (Lung-RADS). Nevertheless, patient adherence to recommended intervals varies, potentially diminishing benefit from screening. We conducted a systematic review and meta-analysis of patient adherence to Lung-RADS-recommended screening intervals. We systematically searched MEDLINE, EMBASE, Web of Science, the Cochrane Central Register of Controlled Trials, and major radiology and oncology conference archives between April 28, 2014, and December 17, 2020. Eligible studies mentioned patient adherence to the recommendations of Lung-RADS. The review protocol was registered with PROSPERO (CRD42020189326). We identified 24 eligible studies for qualitative summary, of which 21 were suitable for meta-analysis. The pooled adherence rate was 57% (95% confidence interval: 46%-69%) for defined adherence (e.g., an annual incidence screen was performed within 15 mo) among 6689 patients and 65% (95% confidence interval: 55%-75%) for anytime adherence among 5085 patients. Large heterogeneity in adherence rates between studies was observed (I2 = 99% for defined adherence, I2 = 98% for anytime adherence). Heterogeneous adherence rates were associated with Lung-RADS scores, with significantly higher adherence rates among Lung-RADS 3 to 4 than Lung-RADS 1 to 2 (p < 0.05). Patient adherence to Lung-RADS-recommended screening intervals is suboptimal across clinical LCS programs in the United States, especially among patients with results of Lung-RADS categories 1 to 2. To improve adherence rates, future research may focus on implementing tailored interventions after identifying barriers to LCS. We also propose a minimum standardized set of data elements for future pooled analyses of LCS adherence on the basis of our findings.

PurposeDiabetes and depression are risk factors for cardiovascular disease, but the evidence about their interaction effect on long-term health outcomes among Latinos is lacking. We aimed to investigate the joint association of diabetes and subsequent depressive symptoms with mortality among older Latinos, an understudied racial/ethnic group with high prevalence of diabetes.MethodsThis study included 1,495 adults from the Sacramento Area Latino Study on Aging. We employed Cox proportional-hazards models to estimate the adjusted hazard ratios [aHRs] for cardiovascular and all-cause mortality according to diabetes status at enrollment and depressive symptoms a year after the enrollment. We used marginal structural models to adjust for time-varying confounders.ResultsThe mean age (standard deviation) of participants was 70 (6.6) years. Over follow-up (median 7.7 years), diabetes and depressive symptoms were individually associated with increased risk of cardiovascular mortality (diabetes, aHR[95% CI]=2.13[1.60-2.84]; depressive symptoms, aHR[95% CI]=1.62[1.09-2.39]) and all-cause mortality (diabetes, aHR[95% CI]=1.92[1.53-2.41]; depressive symptoms, aHR[95% CI]=1.41[1.02-1.94]). After adjusting for time-varying confounders, we found a multiplicative interaction between diabetes and subsequent depressive symptoms for cardiovascular mortality (aHR[95% CI]=2.94[1.07-8.39]), but not all-cause mortality (aHR[95% CI]=1.80[0.81-4.35]).ConclusionsUsing a longitudinal cohort of community-dwelling older Latinos, we found that diabetes and subsequent depressive symptoms were jointly associated with increased risk of cardiovascular mortality.

BackgroundRandomized controlled trials (RCT) play a central role in evidence-based healthcare. However, the clinical and policy implications of implementing RCTs in clinical practice are difficult to predict as the studied population is often different from the target population where results are being applied. This study illustrates the concepts of generalizability and transportability, demonstrating their utility in interpreting results from the National Lung Screening Trial (NLST).MethodsUsing inverse-odds weighting, we demonstrate how generalizability and transportability techniques can be used to extrapolate treatment effect from (i) a subset of NLST to the entire NLST population and from (ii) the entire NLST to different target populations.ResultsOur generalizability analysis revealed that lung cancer mortality reduction by LDCT screening across the entire NLST [16% (95% confidence interval [CI]: 4-24)] could have been estimated using a smaller subset of NLST participants. Using transportability analysis, we showed that populations with a higher prevalence of females and current smokers had a greater reduction in lung cancer mortality with LDCT screening [e.g., 27% (95% CI, 11-37) for the population with 80% females and 80% current smokers] than those with lower prevalence of females and current smokers.ConclusionsThis article illustrates how generalizability and transportability methods extend estimation of RCTs' utility beyond trial participants, to external populations of interest, including those that more closely mirror real-world populations.ImpactGeneralizability and transportability approaches can be used to quantify treatment effects for populations of interest, which may be used to design future trials or adjust lung cancer screening eligibility criteria.

BackgroundType 2 diabetes is a leading contributor to the global burden of morbidity and mortality. Ozone (O3) exposure has previously been linked to diabetes.ObjectiveWe studied the impact of O3 exposure on incident diabetes risk in elderly Mexican Americans and investigated whether outdoor physical activity modifies the association.MethodsWe selected 1,090 Mexican American participants from the Sacramento Area Latino Study on Aging conducted from 1998 to 2007. Ambient O3 exposure levels were modeled with a land-use regression built with saturation monitoring data collected at 49 sites across the Sacramento metropolitan area. Using Cox proportional hazard models, we estimated the risk of developing incident diabetes based on average O3 exposure modeled for 5-y prior to incident diabetes diagnosis or last follow-up. Further, we estimated outdoor leisure-time physical activity at baseline and investigated whether higher vs. lower levels modified the association between O3 exposure and diabetes.ResultsIn total, 186 incident diabetes cases were identified during 10-y follow-up. Higher levels of physical activity were negatively associated with incident diabetes [hazard ratio (HR)=0.64 (95% CI: 0.43, 0.95)]. The estimated HRs for incident diabetes was 1.13 (95% CI: 1.00, 1.28) per 10-ppb increment of 5-y average O3 exposure; also, this association was stronger among those physically active outdoors [HR=1.52 (95% CI: 1.21, 1.90)], and close to null for those reporting lower levels of outdoor activity [HR=1.04 (95% CI: 0.90, 1.20), pinteraction=0.01].ConclusionsOur findings suggest that ambient O3 exposure contributes to the development of type 2 diabetes, particularly among those with higher levels of leisure-time outdoor physical activity. Policies and strategies are needed to reduce O3 exposure to guarantee that the health benefits of physical activity are not diminished by higher levels of O3 pollution in susceptible populations such as older Hispanics. https://doi.org/10.1289/EHP8620.

ObjectiveIt is unclear whether relatively low glycated haemoglobin (HbA1c) levels are beneficial or harmful for the long-term health outcomes among people without diabetes. We aimed to investigate the association between low HbA1c levels and mortality among the US general population.MethodsThis study includes a nationally representative sample of 39 453 US adults from the National Health and Nutrition Examination Surveys 1999-2014, linked to mortality data through 2015. We employed the parametric g-formula with pooled logistic regression models and the ensemble machine learning algorithms to estimate the time-varying risk of all-cause and cardiovascular mortality by HbA1c categories (low, 4.0 to

Several studies have reported associations between prenatal acetaminophen exposure and behavioral outcomes in young children. We aimed to evaluate the associations of prenatal and postnatal exposures to acetaminophen with behavioral problems in children at age 11 years, using behavioral measures reported by parents and children. We studied 40,934 mother-child pairs from the Danish National Birth Cohort enrolled during 1996-2002. Parent-reported and child-reported Strengths and Difficulties Questionnaire (SDQ) responses were collected during the 11-year follow-up. We estimated risk ratios for behavioral problems including total difficulties as well as internalizing or externalizing behaviors following prenatal (during pregnancy) or postnatal (within the first 18 months after birth) acetaminophen exposure. Parent-reported and child-reported SDQ scores were moderately correlated; higher for externalizing (r = 0.59) than internalizing (r = 0.49) behaviors. Prenatal acetaminophen exposure was associated with 10%-40% higher risks for total difficulties and internalizing and externalizing problems based on parent- or child-reported SDQ, with the association being stronger for greater cumulative weeks of acetaminophen use. Postnatal exposure was associated with 16%-19% higher risks for parent-reported internalizing behaviors, but the associations were weak or null for child-reported scores except for prosocial behavior. Our study corroborates published associations between prenatal exposures to acetaminophen and behavioral problems and extends the literature to early adolescence.

BackgroundThe rapidly increased spending on insulin is a major public health issue in the United States. Industry marketing might be one of the upstream determinants of physicians' prescription of long-acting insulin-the most commonly used and costly type of insulin, but the evidence is lacking. We therefore aimed to investigate the association between industry payments to physicians and subsequent prescriptions of long-acting insulin.Methods and findingsUsing the databases of Open Payments and Medicare Part D, we examined the association between the receipt of industry payments for long-acting insulin in 2016 and (1) the number of claims; (2) the costs paid for all claims; and (3) the costs per claim of long-acting insulin in 2017. We also examined the association between the receipt of payments and the change in these outcomes from 2016 to 2017. We employed propensity score matching to adjust for the physician-level characteristics (sex, years in practice, specialty, and medical school attended). Among 145,587 eligible physicians treating Medicare beneficiaries, 51,851 physicians received industry payments for long-acting insulin worth $22.3 million. In the propensity score-matched analysis including 102,590 physicians, we found that physicians who received the payments prescribed a higher number of claims (adjusted difference, 57.8; 95% CI, 55.8 to 59.7), higher costs for total claims (adjusted difference, +$22,111; 95% CI, $21,387 to $22,836), and higher costs per claim (adjusted difference, +$71.1; 95% CI, $69.0 to $73.2) of long-acting insulin, compared with physicians who did not receive the payments. The association was also found for changes in these outcomes from 2016 to 2017. Limitations to our study include limited generalizability, confounding, and possible reverse causation.ConclusionsIndustry marketing payments to physicians for long-acting insulin were associated with the physicians' prescriptions and costs of long-acting insulin in the subsequent year. Future research is needed to assess whether policy interventions on physician-industry financial relationships will help to ensure appropriate prescriptions and limit overall costs of this essential drug for diabetes care.

PurposeUrinary albumin-to-creatinine ratio (UACR) is one of the important diagnostic markers of chronic kidney disease. We aimed to investigate the association between UACR within normal range and cardiovascular or all-cause mortality.MethodsThis study included a nationally representative sample of 31,413 U.S. adults aged greater than or equal to 20 years enrolled in the National Health and Nutrition Examination Survey 1999-2014. Mortality was ascertained through 2015. We used multivariable Cox proportional models to investigate the association of UACR with all-cause and cardiovascular mortality. Stratum-specific analyses were conducted by age, sex, race, education status, and comorbidities (e.g., hypertension, diabetes, cardiovascular disease, and chronic kidney disease).ResultsOver a median follow-up of 7.6 years, 2854 all-cause deaths and 454 cardiovascular deaths were identified. Higher UACR (per 10 mg/g) was associated with increased risk of all-cause mortality (adjusted hazard ratio = 1.29, 95% confidence interval = 1.22-1.37) and cardiovascular mortality (adjusted hazard ratio = 1.34, 95% confidence interval = 1.17-1.55). The association was larger among women for both all-cause and cardiovascular mortality, and among younger and highly educated participants only for all-cause mortality. The association did not differ by the presence of comorbidities.ConclusionsElevated UACR within normal range was associated with higher all-cause and cardiovascular mortality risk across almost all subgroups including participants without comorbidities. Our findings suggest the importance of the early detection of albuminuria and careful evaluation of UACR even within normal range to reduce mortality risk.

Cognitive impairment has been linked to traffic-related air pollution and noise exposure as well as to metabolic syndrome or some of its individual components. Here, we investigate whether the presence of metabolic dysfunction modifies associations between air pollution or noise exposures and incident dementia or cognitive impairment without dementia (CIND).MethodsFor 1,612 elderly Mexican-American participants of the Sacramento Area Latino Study on Aging (SALSA) followed for up to 10 years, we estimated residential-based local traffic-related exposures relying on the California Line Source Dispersion Model version 4 (CALINE4) for nitrogen oxides (NOx) and the SoundPLAN software package (Version 8.0; NAVCON, Fullerton, CA) that implements the Federal Highway Administration Traffic Noise Model (TNM) for noise, respectively. We used Cox proportional hazard models to estimate the joint effects of NOx or noise exposures and obesity, hyperglycemia, or low high-density lipoprotein (HDL) cholesterol.ResultsThe risk of developing dementia/CIND among participants with hyperglycemia who also were exposed to high levels of NOx (≥3.44 parts per billion [ppb] [75th percentile]) or noise (≥65 dB) was 2.4 (1.4, 4.0) and 2.2 (1.7, 3.9), respectively. For participants with low HDL-cholesterol, the estimated hazard ratios for dementia/CIND were 2.5 (1.4, 4.3) and 1.8 (1.0, 3.0) for those also exposed to high levels of NOx (≥3.44 ppb) or noise (≥65 dB), respectively, compared with those without metabolic dysfunction exposed to low traffic-related air pollution or noise levels.ConclusionsExposure to traffic-related air pollution or noise most strongly increases the risk of dementia/CIND among older Mexican-Americans living in California who also exhibit hyperglycemia or low HDL-cholesterol.

Low physical activity (PA) among older adults increases the risk of cardiovascular disease (CVD) and mortality through metabolic disorders such as type 2 diabetes. We aimed to elucidate the extent to which diabetes mediates the effect of nonoccupational PA levels on CVD and mortality among older Mexican Americans. This study included 1,676 adults from the Sacramento Area Latino Study on Aging (1998-2007). We employed Cox proportional hazards regression models to investigate associations of PA level with all-cause mortality, fatal CVD, and nonfatal CVD events. Utilizing causal mediation analysis within a counterfactual framework, we decomposed the total effect of PA into natural indirect and direct effects. Over a median of 8 years of follow-up, low PA (75th percentile). Diabetes mediated 11.0%, 7.4%, and 5.2% of the total effect of PA on all-cause mortality, fatal CVD, and nonfatal CVD events, respectively. Our findings indicate that public health interventions targeting diabetes prevention and management would be a worthwhile strategy for preventing CVD and mortality among older Mexican Americans with insufficient PA levels.

Purpose of reviewReview how to use metabolomic profiling in causal mediation analysis to assess epidemiological evidence for air pollution impacts on birth outcomes.Recent findingsMaternal exposures to air pollutants have been associated with pregnancy complications and adverse pregnancy and birth outcomes. Causal mediation analysis enables us to estimate direct and indirect effects on outcomes (i.e., effect decomposition), elucidating causal mechanisms or effect pathways. Maternal metabolites and metabolic pathways are perturbed by air pollution exposures may lead to adverse pregnancy and birth outcomes, thus they can be considered mediators in the causal pathways. Metabolomic markers have been used to explain the biological mechanisms linking air pollution and respiratory function, and of arsenic exposure and birth weight. However, mediation analysis of metabolomic markers has not been used to assess air pollution effects on adverse birth outcomes. In this article, we describe the assumptions and applications of mediation analysis using metabolomic markers that elucidate the potential mechanisms of the effects of air pollution on adverse pregnancy and birth outcomes. The hypothesis of mediation along specified pathways can be assessed within the structural causal modeling framework. For causal inferences, several assumptions that go beyond the data-including no uncontrolled confounding-need to be made to justify the effect decomposition. Nevertheless, studies that integrate metabolomic information in causal mediation analysis may greatly improve our understanding of the effects of ambient air pollution on adverse pregnancy and birth outcomes as they allow us to suggest and test hypotheses about underlying biological mechanisms in studies of pregnant women.

Aldosterone is a steroid hormone regulating fluid and electrolyte homeostasis and is known to increase the risk of atherosclerosis. In this study, we examined the associations of serum aldosterone concentrations with subclinical atherosclerosis and all-cause mortality. This study included 948 adults aged 46 to 88 years from the MESA (Multi-Ethnic Study of Atherosclerosis) with measurements of serum aldosterone and plasma renin activity and not taking antihypertensive medications. Coronary calcification was longitudinally assessed using Agatston coronary artery calcium score from computed tomography scans. All-cause mortality was ascertained from the medical record. The average age (SD) was 62.3 (9.4) years and 53% were male. Among 700 subjects who had follow-up coronary artery calcium score (median follow-up of 6.4 years), higher aldosterone levels (per 100 pg/mL) were associated with higher coronary artery calcium (relative ratio, 1.17 [95% CI, 1.04-1.32]), with the association being stronger in individuals with suppressed plasma renin activity (≤0.5 μg/L/hr). Systolic or diastolic blood pressure mediated around 45% of the total effect of aldosterone on coronary artery calcium. Over a median follow-up of 12.5 years (120 deaths identified among 948 subjects), aldosterone was associated with the increased risk of all-cause mortality when plasma renin activity was suppressed; hazard ratio per 100 pg/mL, 1.70 (95% CI, 1.10-2.63). In this study, we found that higher aldosterone levels were associated with the increased risk of subclinical coronary atherosclerosis and all-cause mortality particularly when renin was suppressed. Our findings indicate the importance of aldosterone levels (even within the reference range) with respect to the cardiovascular system and overall health.