Practical Guide to Honest Causal Forests for Identifying Heterogeneous Treatment Effects.

"Heterogeneous treatment effects" is a term which refers to conditional average treatment effects (i.e., CATEs) that vary across population subgroups. Epidemiologists are often interested in estimating such effects because they can help detect populations that may particularly benefit from or be harmed by a treatment. However, standard regression approaches for estimating heterogeneous effects are limited by preexisting hypotheses, test a single effect modifier at a time, and are subject to the multiple-comparisons problem. In this article, we aim to offer a practical guide to honest causal forests, an ensemble tree-based learning method which can discover as well as estimate heterogeneous treatment effects using a data-driven approach. We discuss the fundamentals of tree-based methods, describe how honest causal forests can identify and estimate heterogeneous effects, and demonstrate an implementation of this method using simulated data. Our implementation highlights the steps required to simulate data sets, build honest causal forests, and assess model performance across a variety of simulation scenarios. Overall, this paper is intended for epidemiologists and other population health researchers who lack an extensive background in machine learning yet are interested in utilizing an emerging method for identifying and estimating heterogeneous treatment effects.

Statin Use and Reduced Hepatocellular Carcinoma Risk in Patients With Nonalcoholic Fatty Liver Disease.

BACKGROUND & AIMS: Recent evidence suggests potential clinical benefits of statin in cancer chemoprevention and treatment. Nonalcoholic fatty liver disease (NAFLD) is expected to become the leading cause of hepatocellular carcinoma (HCC). We aimed to investigate the association between statin initiation and the risk of HCC among patients with NAFLD. METHODS: In this study using the Optum de-identified Clinformatics database, Cox proportional hazards regression model was performed to determine the risk of HCC in statin initiators versus nonusers. We incorporated inverse probability of treatment weighting (IPTW) to minimize potential confounding. RESULTS: Among 272,431 adults with NAFLD diagnosis, IPTW model shows that statin initiators had 53% less risk of developing HCC compared with nonusers (hazard ratio [HR], 0.47; 95% confidence interval, 0.36-0.60). In the subcohort with fibrosis-4 index data available, statin initiation was associated with 56% hazard reduction of developing HCC in NAFLD after adjusting for fibrosis-4 index score (HR, 0.44; 0.30-0.65). The association between statin initiation and lower risk of HCC development was observed for both lipophilic statin (HR, 0.49; 0.37-0.65) and hydrophilic statin (HR, 0.40; 0.21-0.76). Moreover, we observed greater hazards reduction as the dose and duration of statin use increased. NAFLD patients with more than 600 cumulative defined daily doses of statin had 70% reduction in hazards of developing HCC (HR, 0.30; 0.20-0.43). CONCLUSIONS: Our study provides strong evidence for the association between statin initiation and reduced risk of HCC development in NAFLD patients. These findings imply that statin can be used as a protective medication for NAFLD patients to reduce the risk of HCC.

Racial and Ethnic Disparities in Years of Potential Life Loss Among Patients With Cirrhosis During the COVID-19 Pandemic in the United States.

INTRODUCTION: Our aim was to evaluate the impact of race/ethnicity on cirrhosis-related premature death during the COVID-19 pandemic. METHODS: We obtained cirrhosis-related death data (n = 872,965, January 1, 2012-December 31, 2021) from the US National Vital Statistic System to calculate age-standardized mortality rates and years of potential life lost (YPLL) for premature death aged 25-64 years. RESULTS: Significant racial/ethnic disparity in cirrhosis-related age-standardized mortality rates was noted prepandemic but widened during the pandemic, with the highest excess YPLL for the non-Hispanic American Indian/American Native (2020: 41.0%; 2021: 68.8%) followed by other minority groups (28.7%-45.1%), and the non-Hispanic White the lowest (2020: 20.7%; 2021: 31.6%). COVID-19 constituted >30% of the excess YPLLs for Hispanic and non-Hispanic American Indian/American Native in 2020, compared with 11.1% for non-Hispanic White. DISCUSSION: Ethnic minorities with cirrhosis experienced a disproportionate excess death and YPLLs in 2020-2021.

Scientific opportunities in resilience research for cardiovascular health and wellness. Report from a National Heart, Lung, and Blood Institute workshop.

Exposure of biological systems to acute or chronic insults triggers a host of molecular and physiological responses to either tolerate, adapt, or fully restore homeostasis; these responses constitute the hallmarks of resilience. Given the many facets, dimensions, and discipline-specific focus, gaining a shared understanding of "resilience" has been identified as a priority for supporting advances in cardiovascular health. This report is based on the working definition: "Resilience is the ability of living systems to successfully maintain or return to homeostasis in response to physical, molecular, individual, social, societal, or environmental stressors or challenges," developed after considering many factors contributing to cardiovascular resilience through deliberations of multidisciplinary experts convened by the National Heart, Lung, and Blood Institute during a workshop entitled: "Enhancing Resilience for Cardiovascular Health and Wellness." Some of the main emerging themes that support the possibility of enhancing resilience for cardiovascular health include optimal energy management and substrate diversity, a robust immune system that safeguards tissue homeostasis, and social and community support. The report also highlights existing research challenges, along with immediate and long-term opportunities for resilience research. Certain immediate opportunities identified are based on leveraging existing high-dimensional data from longitudinal clinical studies to identify vascular resilience measures, create a 'resilience index,' and adopt a life-course approach. Long-term opportunities include developing quantitative cell/organ/system/community models to identify resilience factors and mechanisms at these various levels, designing experimental and clinical interventions that specifically assess resilience, adopting global sharing of resilience-related data, and cross-domain training of next-generation researchers in this field.

Regression discontinuity design to evaluate the effect of statins on myocardial infarction in electronic health records.

Regression discontinuity design (RDD) is a quasi-experimental method intended for causal inference in observational settings. While RDD is gaining popularity in clinical studies, there are limited real-world studies examining the performance on estimating known trial casual effects. The goal of this paper is to estimate the effect of statins on myocardial infarction (MI) using RDD and compare with propensity score matching and Cox regression. For the RDD, we leveraged a 2008 UK guideline that recommends statins if a patient's 10-year cardiovascular disease (CVD) risk score > 20%. We used UK electronic health record data from the Health Improvement Network on 49,242 patients aged 65 + in 2008-2011 (baseline) without a history of CVD and no statin use in the two years prior to the CVD risk score assessment. Both the regression discontinuity (n = 19,432) and the propensity score matched populations (n = 24,814) demonstrated good balance of confounders. Using RDD, the adjusted point estimate for statins on MI was in the protective direction and similar to the statin effect observed in clinical trials, although the confidence interval included the null (HR = 0.8, 95% CI 0.4, 1.4). Conversely, the adjusted estimates using propensity score matching and Cox regression remained in the harmful direction: HR = 2.42 (95% CI 1.96, 2.99) and 2.51 (2.12, 2.97). RDD appeared superior to other methods in replicating the known protective effect of statins with MI, although precision was poor. Our findings suggest that, when used appropriately, RDD can expand the scope of clinical investigations aimed at causal inference by leveraging treatment rules from everyday clinical practice.

Serum NfL and GFAP are associated with incident dementia and dementia mortality in older adults: The cardiovascular health study.

INTRODUCTION: Circulating neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) have been independently associated with dementia risk. Their additive association, and their associations with dementia-specific mortality, have not been investigated. METHODS: We associated serum NfL, GFAP, total tau ,and ubiquitin carboxyl-terminal hydrolase-L1, measured in 1712 dementia-free adults, with 19-year incident dementia and dementia-specific mortality risk, and with 3-year cognitive decline. RESULTS: In adjusted models, being in the highest versus lowest tertile of NfL or GFAP associated with a hazard ratio (HR) of 1.49 (1.20-1.84) and 1.38 (1.15-1.66) for incident dementia, and 2.87 (1.79-4.61) and 2.76 (1.73-4.40) for dementia-specific mortality. Joint third versus first tertile exposure further increased risk; HR = 2.06 (1.60-2.67) and 9.22 (4.48-18.9). NfL was independently associated with accelerated cognitive decline. DISCUSSION: Circulating NfL and GFAP may, independently and jointly, provide useful clinical insight regarding dementia risk and prognosis.

Discrimination, Mediating Psychosocial or Economic Factors, and Antihypertensive Treatment: A 4-Way Decomposition Analysis in the Health and Retirement Study.

Untested psychosocial or economic factors mediate associations between perceived discrimination and suboptimal antihypertensive therapy. This study included 2 waves of data from Health and Retirement Study participants with self-reported hypertension (n = 8,557, 75% non-Hispanic White, 15% non-Hispanic Black, and 10% Hispanic/Latino) over 4 years (baselines of 2008 and 2010, United States). Our primary exposures were frequency of experiencing discrimination, in everyday life or across 7 lifetime circumstances. Candidate mediators were self-reported depressive symptoms, subjective social standing, and household wealth. We evaluated with causal mediation methods the interactive and mediating associations between each discrimination measure and reported antihypertensive use at the subsequent wave. In unmediated analyses, everyday (odds ratio (OR) = 0.86, 95% confidence interval (CI): 0.78, 0.95) and lifetime (OR = 0.91, 95% CI: 0.85, 0.98) discrimination were associated with a lower likelihood of antihypertensive use. Discrimination was associated with lower wealth, greater depressive symptoms, and decreased subjective social standing. Estimates for associations due to neither interaction nor mediation resembled unmediated associations for most discrimination-mediator combinations. Lifetime discrimination was indirectly associated with reduced antihypertensive use via depressive symptomatology (OR = 0.99, 95% CI: 0.98, 1.00). In conclusion, the impact of lifetime discrimination on the underuse of antihypertensive therapy appears partially mediated by depressive symptoms.

Racial Residential Segregation in Young Adulthood and Brain Integrity in Middle Age: Can We Learn From Small Samples?

Racial residential segregation is associated with multiple adverse health outcomes in Black individuals. Yet, the influence of structural racism and racial residential segregation on brain aging is less understood. In this study, we investigated the association between cumulative exposure to racial residential segregation over 25 years (1985-2010) in young adulthood, as measured by the Getis-Ord Gi* statistic, and year 25 measures of brain volume (cerebral, gray matter, white matter, and hippocampal volumes) in midlife. We studied 290 Black participants with available brain imaging data who were enrolled in the Coronary Artery Risk Development in Young Adults (CARDIA) Study, a prospective cohort study. CARDIA investigators originally recruited 2,637 Black participants aged 18-30 years from 4 field centers across the United States. We conducted analyses using marginal structural models, incorporating inverse probability of treatment weighting and inverse probability of censoring weighting. We found that compared with low/medium segregation, greater cumulative exposure to a high level of racial residential segregation throughout young adulthood was associated with smaller brain volumes in general (e.g., for cerebral volume, ß = -0.08, 95% confidence interval: -0.15, -0.02) and with a more pronounced reduction in hippocampal volume, though results were not statistically significant. Our findings suggest that exposure to segregated neighborhoods may be associated with worse brain aging.

Associations of Modifiable Behavioral Risk Factor Combinations at 65 to 74 Years Old With Cognitive Health Span for 20 Years.

OBJECTIVE: Behavioral risk factors for dementia tend to co-occur and interrelate, especially poor diet, physical inactivity, sleep disturbances, and depression. Having multiple of these modifiable behavioral risk factors (MBRFs) may predict a particularly shortened cognitive health span and therefore may signal high-risk status/high intervention need. METHODS: These secondary analyses of data from the Cardiovascular Health Study included 3149 participants aged 65 to 74 years (mean [standard deviation {SD}] age = 69.5 [2.5] years; 59.6% female). MBRF exposures were self-reports regarding a) diet, b) activity, c) sleep, and d) depression symptoms. We primarily analyzed MBRF counts. For up to 26 years of follow-up, we assessed the a) number of remaining cognitively healthy life-years (CHLYs) and b) percentage of remaining life-years (LYs) that were CHLYs (%CHLY). We estimated CHLYs as time before a dementia diagnosis, cognitive screener scores indicating impairment, proxy report indicating significant cognitive decline, or dementia medication use. RESULTS: Participants averaged a remaining 16 LYs (SD = 7 LYs), 12.2 CHLYs (SD = 6.6 CHLYs), and 78.1% of LYs being CHLYs (SD = 25.6 CHLYs). Compared with having no MBRFs, having one was associated with ~1 less LY and CHLY, but not a relatively lower %CHLY. In contrast, having 3+ MBRFs was associated with about 2 to 3 fewer LYs and CHLYs as well as about 6% lower %CHLY (95% confidence interval = -9.0 to -2.5 %CHLYs; p = .001). CONCLUSIONS: MBRF-related reductions in the cognitive health span are most apparent when people have multiple MBRFs. Future research is needed to determine if/how behavioral risks converge mechanistically and if dementia prevention efficacy improves when targeting MBRF combinations.

Intensive Versus Standard Blood Pressure Lowering and Days Free of Cardiovascular Events and Serious Adverse Events: a Post Hoc Analysis of Systolic Blood Pressure Intervention Trial.

BACKGROUND: Communication of the benefits and harms of blood pressure lowering strategy is crucial for shared decision-making. OBJECTIVES: To quantify the effect of intensive versus standard systolic blood pressure lowering in terms of the number of event-free days DESIGN: Post hoc analysis of the Systolic Blood Pressure Intervention Trial PARTICIPANTS: A total of 9361 adults 50 years or older without diabetes or stroke who had a systolic blood pressure of 130-180 mmHg and elevated cardiovascular risk INTERVENTIONS: Intensive (systolic blood pressure goal <120 mmHg) versus standard blood pressure lowering (<140 mmHg) MAIN MEASURES: Days free of major adverse cardiovascular events (MACE), serious adverse events (SAE), and monitored adverse events (hypotension, syncope, bradycardia, electrolyte abnormalities, injurious falls, or acute kidney injury) over a median follow-up of 3.33 years KEY RESULTS: The intensive treatment group gained 14.7 more MACE-free days over 4 years (difference, 14.7 [95% confidence interval: 5.1, 24.4] days) than the standard treatment group. The benefit of the intensive treatment varied by cognitive function (normal: difference, 40.7 [13.0, 68.4] days; moderate-to-severe impairment: difference, -15.0 [-56.5, 26.4] days; p-for-interaction=0.009) and self-rated health (excellent: difference, -22.7 [-51.5, 6.1] days; poor: difference, 156.1 [31.1, 281.2] days; p-for-interaction=0.001). The mean overall SAE-free days were not significantly different between the treatments (difference, -14.8 [-35.3, 5.7] days). However, the intensive treatment group had 28.5 fewer monitored adverse event-free days than the standard treatment group (difference, -28.5 [-40.3, -16.7] days), with significant variations by frailty status (non-frail: difference, 38.8 [8.4, 69.2] days; frail: difference, -15.5 [-46.6, 15.7] days) and self-rated health (excellent: difference, -12.9 [-45.5, 19.7] days; poor: difference, 180.6 [72.9, 288.4] days; p-for-interaction <0.001). CONCLUSIONS: Over 4 years, intensive systolic blood pressure lowering provides, on average, 14.7 more MACE-free days than standard treatment, without any difference in SAE-free days. Whether this time-based effect summary improves shared decision-making remains to be elucidated. TRIAL REGISTRATION: ClinicalTrials.gov Registration: NCT01206062.

Proteomics and Population Biology in the Cardiovascular Health Study (CHS): design of a study with mentored access and active data sharing.

BACKGROUND: In the last decade, genomic studies have identified and replicated thousands of genetic associations with measures of health and disease and contributed to the understanding of the etiology of a variety of health conditions. Proteins are key biomarkers in clinical medicine and often drug-therapy targets. Like genomics, proteomics can advance our understanding of biology. METHODS AND RESULTS: In the setting of the Cardiovascular Health Study (CHS), a cohort study of older adults, an aptamer-based method that has high sensitivity for low-abundance proteins was used to assay 4979 proteins in frozen, stored plasma from 3188 participants (61% women, mean age 74 years). CHS provides active support, including central analysis, for seven phenotype-specific working groups (WGs). Each CHS WG is led by one or two senior investigators and includes 10 to 20 early or mid-career scientists. In this setting of mentored access, the proteomic data and analytic methods are widely shared with the WGs and investigators so that they may evaluate associations between baseline levels of circulating proteins and the incidence of a variety of health outcomes in prospective cohort analyses. We describe the design of CHS, the CHS Proteomics Study, characteristics of participants, quality control measures, and structural characteristics of the data provided to CHS WGs. We additionally highlight plans for validation and replication of novel proteomic associations. CONCLUSION: The CHS Proteomics Study offers an opportunity for collaborative data sharing to improve our understanding of the etiology of a variety of health conditions in older adults.

The association of hearing problems with social network strength and depressive symptoms: the cardiovascular health study.

BACKGROUND: research on the association between hearing impairment and psychosocial outcomes is not only limited but also yielded mixed results. METHODS: we investigated associations between annual self-reports of hearing problems, depressive symptoms and social network strength among 5,888 adults from the Cardiovascular Health Study over a period of 9 years. Social network strength and depressive symptoms were defined using the Lubben Social Network Scale (LSNS), and the Center for Epidemiological Studies Depression Scale (CES-D). RESULTS: hearing problems were associated with weaker social networks and more depressive symptoms. These association differed for prevalent versus incident hearing problems. Participants with prevalent hearing problems scored an adjusted 0.47 points lower (95% CI: -2.20, -0.71) on the LSNS and 0.71 points higher (95% CI: 0.23, 1.19) on the CES-D than those without hearing problems. Participants with incident hearing problems had a greater decline of 0.12 points (95% CI: -0.12, -0.03) per year in social network score than individuals with no hearing problems after adjusting for confounders. Females appeared to be more vulnerable to changes in social network strength than males (P-value for interaction = 0.02), but not for changes in depressive score. Accounting for social network score did not appear to attenuate the association between hearing problems and depressive score. CONCLUSION: findings suggest that older adults with prevalent hearing problems may be more at risk for depression, but individuals with incident hearing problems may be at greater risk for a winnowing of their social network.

Aging Hearts in a Hotter, More Turbulent World: The Impacts of Climate Change on the Cardiovascular Health of Older Adults.

PURPOSE OF REVIEW: Climate change has manifested itself in multiple environmental hazards to human health. Older adults and those living with cardiovascular diseases are particularly susceptible to poor outcomes due to unique social, economic, and physiologic vulnerabilities. This review aims to summarize those vulnerabilities and the resultant impacts of climate-mediated disasters on the heart health of the aging population. RECENT FINDINGS: Analyses incorporating a wide variety of environmental data sources have identified increases in cardiovascular risk factors, hospitalizations, and mortality from intensified air pollution, wildfires, heat waves, extreme weather events, rising sea levels, and pandemic disease. Older adults, especially those of low socioeconomic status or belonging to ethnic minority groups, bear a disproportionate health burden from these hazards. The worldwide trends responsible for global warming continue to worsen climate change-mediated natural disasters. As such, additional investigation will be necessary to develop personal and policy-level interventions to protect the cardiovascular wellbeing of our aging population.

Subclinical Vascular Disease Burden and Premature Mortality Among Middle-aged Adults: the Atherosclerosis Risk in Communities Study.

BACKGROUND: Whether high burden of subclinical vascular disease (SVD) is associated with increased premature mortality among middle-aged adults is not adequately understood. The association of midlife SVD burden with premature mortality among middle-aged adults free of clinical cardiovascular disease (CVD) could provide further insights into stratifying premature death beyond clinical CVD. OBJECTIVE: To determine whether high burden of subclinical vascular disease is associated with increased premature mortality among middle-aged adults. DESIGN: We leveraged data from the Atherosclerosis Risk in Communities Study. PARTICIPANTS: Thirteen thousand eight hundred seventy-six community-dwelling blacks and whites aged 45-64 years from the Atherosclerosis Risk in Communities Study. MAIN MEASURES: Each SVD measure-ankle-brachial index, carotid intima-media thickness, and electrocardiogram-was scored 0 (no abnormalities), 1 (minor abnormalities), or 2 (major abnormalities). An index was constructed as the sum of three measures, ranging from 0 (lowest burden) to 6 (highest burden). We used the Cox proportional-hazards model to determine the association of SVD burden with premature mortality (death before age 70) among persons free of clinical CVD. We then tested the difference in point estimates between SVD and clinical CVD. KEY RESULTS: Among persons without CVD, the premature death was 1.7, 2.1, 2.5, and 3.8 per 1000 person-years among those with an SVD score of 0 (lowest burden), 1, 2, and 3-6 (highest burden), respectively. After multivariable-adjustment, highest SVD burden (score = 3-6; HR = 1.47) was significantly associated with premature death among persons initially without CVD. In the model where persons with and without CVD were included, high SVD burden (score: 3-6 vs. 0) and CVD did not have hugely different association with premature death (HR = 1.49 vs. 1.68; P = 0.32 for comparison). CONCLUSIONS: Midlife SVD burden was associated with premature mortality and it could stratify premature death beyond clinical CVD. It is important to take SVD into account when designing interventions for reducing premature mortality.

Balance and cognitive decline in older adults in the cardiovascular health study.

BACKGROUND: Previous studies have demonstrated an association between gait speed and cognitive function. However, the relationship between balance and cognition remains less well explored. This study examined the cross-sectional and longitudinal relationship of balance and cognitive decline in older adults. METHODS: A cohort of 4,811 adults, aged ≥65 years, participating in the Cardiovascular Health Study was followed for 6 years. Modified Mini-Mental State Examination (3MSE) and Digit Symbol Substitution Test (DSST) were used to measure cognition. Tandem balance measures were used to evaluate balance. Regression models were adjusted for demographics, behavioural and disease factors. RESULTS: Worse balance was independently associated with worse cognition in cross-sectional analysis. Longitudinally, participants aged ≥76 years with poorer balance had a faster rate of decline after adjustment for co-variates: -0.97 points faster decline in 3MSE per year (95% confidence interval (CI): -1.32, -0.63) compared to the participants with good balance. There was no association of balance and change in 3MSE among adults aged <76 years (P value for balance and age interaction < 0.0001). DSST scores reflected -0.21 (95% CI: -0.37, -0.05) points greater decline when adjusted for co-variates. In Cox proportional hazard models, participants with worse balance had a higher risk of being cognitively impaired over the 6 years of follow-up visits (adjusted HR:1.72, 95% CI: 1.30, 2.29). CONCLUSIONS: Future studies should evaluate standing balance as a potential screening technique to identify individuals at risk of cognitive decline. Furthermore, a better understanding of the pathophysiological link between balance and cognition may inform strategies to prevent cognitive decline.

Creation and validation of a polysocial score for mortality among community-dwelling older adults in the USA: the health and retirement study.

BACKGROUND: the interrelatedness between social determinants of health impedes researchers to identify important social factors for health investment. A new approach is needed to quantify the aggregate effect of social factors and develop person- centred social interventions. METHODS: participants ([n = 7,383], 54.5% female) were aged 65 years or above who complete an additional psychosocial questionnaire in the health and retirement study in 2006 or 2008. Social determinants of health encompassed five social domains: economic stability, neighbourhood and physical environment, education, community and social context, and healthcare system. We used the forward stepwise logistic regression to derive a polysocial score model for 5-year mortality. Indices of goodness-of-fit, discrimination and reclassification were used to assess model performance. We used logistic regression to identify the association between polysocial score and mortality. Subgroup analyses were conducted to examine sex- and race-specific association. RESULTS: polysocial score was created using 14 social determinants of health. In the training cohort, the C-statistic was 0.71 for the reference model (only age, sex and race/ethnicity) and increased to 0.75 for the continuous and categorical polysocial score. Compared with the reference model, the integrated discrimination index for adding the continuous or categorical polysocial score was both 0.03 (P values < 0.001). Participants with an intermediate (odds ratio [OR] = 0.69; 95% confidence interval [CI], 0.51-0.82) or high (OR = 0.48; 95% CI, 0.38-0.60) polysocial score had lower odds of death than those in the low category in the fully adjusted model, respectively. CONCLUSIONS: the polysocial approach may offer possible solutions to monitor social environments and suggestions for older people to improve their social status for specific health outcomes.

Daily linkages among high and low arousal affect and subjective cognitive complaints.

Objectives: Subjective cognitive complaints may be an early indicator of Alzheimer's disease pathology and related dementias that can be detectable prior to objective, performance-based decline. Negative and positive affective states (NA and PA, respectively) are established psychosocial correlates of cognition in older adulthood and have demonstrated capacity for meaningful within-person fluctuations based on person-environment interactions, age, and measurement approach.Method: We utilized data from a 100-day, microlongitudinal study of 105 community-dwelling older adults (Mage = 63.19, SD = 7.80, Range = 52-88) to explore within- and between-person associations between high and low arousal NA and PA, and memory- and attention-related complaints.Results: For memory-related complaints, those who reported experiencing greater NA-high arousal had increased forgetfulness (OR = 2.23, 95%CI: 1.11-4.49, p < .05). Within persons, reporting more NA-high arousal than usual was associated with increased forgetfulness (OR = 1.01, 95%CI: 1.004-1.018, p < .01). For attention-related complaints, those who reported experiencing greater NA-low arousal had increased trouble staying focused (OR = 2.34, 95%CI: 1.17-4.66, p < .05). Within persons, reporting more NA-low arousal (OR = 1.02, 95%CI: 1.01-1.03, p < .001) and less PA-high arousal (OR = 0.96, 95%CI: 0.95-0.97, p < .001) than usual was associated with increased trouble staying focused. Additionally, reporting more PA-low arousal than usual was associated with decreased trouble staying focused among those with higher levels of conscientiousness (OR = 0.72, 95%CI: 0.57-0.92, p < .01).Conclusion: Results from this study offer a means to maximize resource allocation and personalized cognitive health efforts by pinpointing for whom and on which days boosting PA and/or reducing NA may both serve as pathways to benefit daily subjective cognition.

Potential Cardiovascular Disease Events Prevented with Adoption of the 2017 American College of Cardiology/American Heart Association Blood Pressure Guideline.

BACKGROUND: Over 10 years, achieving and maintaining 2017 ACC/AHA guideline goals could prevent 3.0 million (UR, 1.1-5.1 million), 0.5 million (UR, 0.2-0.7 million), and 1.4 million (UR, 0.6-2.0 million) cardiovascular disease (CVD) events compared with maintaining current blood pressure (BP) levels, achieving 2003 Seventh Joint National Committee Report goals, and achieving 2014 Eighth Joint National Committee goals, respectively. We estimated the number of cardiovascular disease events prevented and treatment-related serious adverse events incurred over 10 years among US adults with hypertension by achieving 2017 ACC/AHA guideline-recommended BP goals compared with (1) current BP levels, (2) achieving 2003 Seventh Joint National Committee Report BP goals, and (3) achieving 2014 Eighth Joint National Committee panel member report BP goals. METHODS: US adults aged ≥45 years with an indication for BP treatment were grouped according to recommendations for antihypertensive drug therapy in the 2017 ACC/AHA guideline, 2003 Seventh Joint National Committee Report, and 2014 Eighth Joint National Committee. Population sizes were estimated from the 2011 to 2014 National Health and Nutrition Examination Surveys. Rates for fatal and nonfatal CVD events (stroke, coronary heart disease, or heart failure) were estimated from the REGARDS (REasons for Geographic And Racial Differences in Stroke) study, weighted to the US population. CVD risk reductions with treatment to BP goals and risk for serious adverse events were obtained from meta-analyses of BP-lowering trials. CVD events prevented and treatment-related nonfatal serious adverse events over 10 years were calculated. Uncertainty surrounding main data inputs was expressed in uncertainty ranges (UR). RESULTS: Over ten years, achieving and maintaining 2017 ACC/AHA guideline goals compared with current BP levels, achieving 2003 Seventh Joint National Committee Report goals, or achieving 2014 Eighth Joint National Committee goals could prevent 3.0 million (UR, 1.1-5.1 million), 0.5 million (UR, 0.2-0.7 million), or 1.4 million (UR, 0.6-2.0 million) CVD events, respectively. Compared with current BP levels, achieving and maintaining 2017 goals could prevent 71.9 (UR, 26.6-122.3) CVD events per 1000 treated. Achieving 2017 guideline BP goals compared with current BP levels could also lead to nearly 3.3 million more serious adverse events over 10 years (UR, 2.2-4.4 million). CONCLUSIONS: Achieving and maintaining 2017 ACC/AHA BP goals could prevent a greater number of CVD events than achieving 2003 Seventh Joint National Committee Report or 2014 Eighth Joint National Committee BP goals but could also lead to more serious adverse events.

Heterogeneous Exposure Associations in Observational Cohort Studies: The Example of Blood Pressure in Older Adults.

Heterogeneous exposure associations (HEAs) can be defined as differences in the association of an exposure with an outcome among subgroups that differ by a set of characteristics. In this article, we intend to foster discussion of HEAs in the epidemiologic literature and present a variant of the random forest algorithm that can be used to identify HEAs. We demonstrate the use of this algorithm in the setting of the association between systolic blood pressure and death in older adults. The training set included pooled data from the baseline examination of the Cardiovascular Health Study (1989-1993), the Health, Aging, and Body Composition Study (1997-1998), and the Sacramento Area Latino Study on Aging (1998-1999). The test set included data from the National Health and Nutrition Examination Survey (1999-2002). The hazard ratios ranged from 1.25 (95% confidence interval: 1.13, 1.37) per 10-mm Hg increase in systolic blood pressure among men aged ≤67 years with diastolic blood pressure greater than 80 mm Hg to 1.00 (95% confidence interval: 0.96, 1.03) among women with creatinine concentration ≤0.7 mg/dL and a history of hypertension. HEAs have the potential to improve our understanding of disease mechanisms in diverse populations and guide the design of randomized controlled trials to control exposures in heterogeneous populations.

Results of the CARDIA study suggest that higher dietary potassium may be kidney protective.

The association between dietary sodium and potassium intake with the development of kidney disease remains unclear, particularly among younger individuals. Here, we determined whether dietary sodium and potassium intake are associated with incident chronic kidney disease (CKD) using data from 1,030 adults (age 23-35 in 1990-1991) from the Coronary Artery Risk Development In Young Adults study, based on repeated measurements of estimated glomerular filtration rate (eGFR) and urinary albumin to creatinine ratio (ACR) from 1995 through 2015. Urinary sodium and potassium excretion (mg/day), calculated from three 24-hour urine collections in 1990-1991, were averaged to measure sodium and potassium intake. Serum creatinine was used to calculate eGFR using the CKD EPI equation; spot urine albumin and creatinine were used to calculate ACR, each at five visits from 1995-1996 through 2015-2016. CKD was defined as decreased eGFR (under 60 ml/min/1.73m2) or the development of albuminuria (ACR over 30 mg/g). We used log binomial regression models adjusted for socio-demographic, behavioral, and clinical factors to determine whether sodium and potassium intake were associated with incident CKD (decreased eGFR or developed albuminuria) among those free of CKD in 1995. Dietary sodium intake was not significantly associated with incident CKD. However, every 1,000 mg/day increment of potassium intake in 1990 was significantly associated with a 29% lower risk of incident albuminuria (relative risk 0.71, 95% confidence interval 0.53, 0.95), but not eGFR. Thus, higher dietary potassium intake may protect against the development of kidney damage, particularly albuminuria.