The environmental epidemiology of atrial Arrhythmogenesis

Atrial fibrillation (AF) is the most common cardiac arrhythmia seen in clinical practice, and makes an important contribution to cardiovascular disease (CVD) and all-cause mortality. The focus of AF research has recently shifted, from concentrating on treatments and complications, to the evaluation of putative risk factors including ambient air pollution. Although the present study pertains specifically to AF, much of its content is drawn from, and therefore is applicable to, the study of other arrhythmias, the conduct of which is confronted by many of the same challenges. Meeting these challenges involves recognising the collective importance of 1. large, ethnically and geographically diverse, clinically well-characterised populations; 2. methods for reducing uncertainty in outcome ascertainment, distinguishing effects of pervasive environmental exposures and improving their estimation; 3. approaches to evaluation of susceptibility; and 4. strategies for informing regulatory policies designed to help control population-level risks for CVD

Trends in US Cancer and Heart Disease Mortality, 1999-2018

Since initial reports documenting an increase in midlife US mortality rates were first published, numerous studies have examined the resulting demographic, economic, and policy implications; however, fewer studies have examined trends for the 2 major drivers of US mortality: heart disease and cancer. Here, we used 2 decades (1999–2018) of death certificate data to further inform understanding of contemporary US cancer and heart disease mortality trends overall and by sex, race, ethnicity, and age group

Comparison of 20-Year Obesity-Associated Cancer Mortality Trends with Heart Disease Mortality Trends in the US

Importance: Heart disease and cancer are the 2 major diseases associated with mortality risk in the United States. Four decades of improvements in heart disease mortality slowed after 2011; this slowing has been associated with the obesity epidemic. The same pattern has not been observed for total cancer mortality. However, trends in total cancer mortality may obscure patterns specific to obesity-associated cancers. Objective: To investigate whether trends in obesity-associated cancer mortality mirror the slowed mortality improvements observed for heart disease associated with the obesity epidemic. Design, Setting, and Participants: This cross-sectional study compared US mortality trends for International Statistical Classification of Diseases and Related Health Problems, Tenth Revision-defined cancer (total cancer, obesity-associated cancer, and cancer not associated with obesity) and heart disease deaths from January 1, 1999, to December 31, 2018. Data were included on decedents with complete information on the underlying cause of death, age, sex, race, and ethnicity. Exposures: Changes in age-adjusted cause-specific mortality rates between 1999-2011 and 2011-2018 were compared. Main Outcomes and Measures: Annual relative rates of change in age-adjusted mortality rates (AAMRs) in the overall population and stratified by sex, race, and ethnicity were estimated using Poisson regression. Differences in AAMR annual relative rates of change before and after 2011 were evaluated using Wald tests. Results: A total of 50163483 decedents met the inclusion criteria (50.1% female decedents, 79.9% non-Hispanic White decedents, and 11.7% non-Hispanic Black decedents; mean [SD] age, 72.8 [18.5] years). In contrast with heart disease mortality, for which improvements slowed between 1999-2011 and 2011-2018, decreases in total cancer AAMR relative change accelerated between 1999-2011 (-1.48 [95% CI, -1.43 to -1.52]) and 2011-2018 (-1.77 [95% CI, -1.67 to -1.86]) (P <.001). For obesity-associated cancer mortality, which accounted for approximately 33% of total cancer deaths annually, decreases in annual AAMR relative change decelerated from -1.19 (95% CI, -1.13 to -1.26) in 1999-2011 to -0.83 (95% CI, -0.70 to -0.96) in 2011-2018 (P <.001). The largest decelerations in obesity-associated cancer mortality were observed for female decedents (-1.45 [95% CI, -1.36 to -1.53] in 1999-2011 and -0.91 [95% CI, -0.75 to -1.07] in 2011-2018; P <.001) and non-Hispanic White individuals (-1.16 [95% CI, -1.09 to -1.22] in 1999-2011 and -0.68 [95% CI, -0.55 to -0.81] in 2011-2018; P <.001). Conclusions and Relevance: Slowing improvements in obesity-associated cancer mortality were obscured when considering total cancer mortality. These findings potentially signal a changing profile of cancer-associated mortality that may parallel trends previously observed for heart disease as the consequences of the obesity epidemic are understood

US acculturation and poor sleep among an intergenerational cohort of adult Latinos in Sacramento, California

Acculturation may shape the disproportionate burden of poor sleep among Latinos in the United States. Existing studies are limited by unidimensional acculturation proxies that are incapable of capturing cultural complexities across generations. Understanding how acculturation relates to sleep may lead to the identification of modifiable intervention targets. We used multivariable regression and latent class methods to examine cross-sectional associations between a validated multidimensional scale of US acculturation and self-reported poor sleep measures. We analyzed an intergenerational cohort: first-generation (GEN1) older Latinos (Sacramento Area Latino Study on Aging; N = 1,716; median age: 69.5) and second-generation (GEN2) middle-aged offspring and relatives of GEN1 (Niños Lifestyle and Diabetes Study; N = 670; median age: 54.0) in Sacramento, California. GEN1 with high US acculturation, compared with high acculturation towards another origin/ancestral country, had less restless sleep (prevalence ratio [PR] [95% confidence interval (CI)]: 0.67 [0.54, 0.84]) and a higher likelihood of being in the best sleep class than the worst (OR [95% CI]: 1.62 [1.09, 2.40]), but among nonmanual occupations, high intergenerational US acculturation was associated with more general fatigue (PR [95% CI: 1.86 [1.11, 3.10]). GEN2 with high intergenerational US acculturation reported shorter sleep (PR [95% CI]: 2.86 [1.02, 7.99]). High US acculturation shaped sleep differentially by generation, socioeconomic context, and intergenerational acculturative status. High US acculturation was associated with better sleep among older, lower socioeconomic Latinos, but with shorter sleep duration among middle-aged, higher socioeconomic Latinos; results also differed by parental acculturation status. Upon replication, future studies should incorporate prospective and intergenerational designs to uncover sociobehavioral pathways by which acculturation may shape sleep to ultimately inform intervention efforts

Rapid detection of identity-by-descent tracts for mega-scale datasets

The ability to identify segments of genomes identical-by-descent (IBD) is a part of standard workflows in both statistical and population genetics. However, traditional methods for finding local IBD across all pairs of individuals scale poorly leading to a lack of adoption in very large-scale datasets. Here, we present iLASH, an algorithm based on similarity detection techniques that shows equal or improved accuracy in simulations compared to current leading methods and speeds up analysis by several orders of magnitude on genomic datasets, making IBD estimation tractable for millions of individuals. We apply iLASH to the PAGE dataset of ~52,000 multi-ethnic participants, including several founder populations with elevated IBD sharing, identifying IBD segments in ~3 minutes per chromosome compared to over 6 days for a state-of-the-art algorithm. iLASH enables efficient analysis of very large-scale datasets, as we demonstrate by computing IBD across the UK Biobank (~500,000 individuals), detecting 12.9 billion pairwise connections

Primary prevention of chronic kidney disease through population-based strategies for blood pressure control: The ARIC study

While much of the chronic kidney disease (CKD) literature focuses on the role of blood pressure reduction in delaying CKD progression, little is known about the benefits of modest population-wide decrements in blood pressure on incident CKD. The authors used multivariable linear regression to characterize the impact on incident CKD of two approaches for blood pressure management: (1) a 1-mm Hg reduction in systolic BP across the entire study population; and (2) a 10% reduction in participants with unaware, untreated, and uncontrolled BP above goal as defined by the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7) thresholds. Over a mean of 20 years of follow-up (ARIC [Atherosclerosis Risk in Communities] study, n = 15 390), 3852 incident CKD events were ascertained. After adjustment, a 1-mm Hg decrement in systolic BP across the population was associated with an estimated 11.7 (95% confidence interval [CI], 6.2–17.3) and 13.4 (95% CI, 10.3–16.6) fewer CKD events per 100 000 person-years in blacks and whites, respectively. Among participants with BP above JNC 7 goal, a 10% decrease in unaware, untreated, or uncontrolled BP was associated with 3.2 (95% CI, 2.0–4.9), 2.8 (95% CI, 1.8–4.3), and 5.8 (95% CI, 3.6–8.8) fewer CKD events per 100 000 person-years in blacks and 3.1 (95% CI, 2.3–4.1), 0.7 (95% CI, 0.5–0.9), and 1.0 (95% CI, 1.3–2.4) fewer CKD events per 100 000 person-years in whites. Modest population-wide reductions in systolic BP hold potential for the primary prevention of CKD

Comparison of adaptive multiple phenotype association tests using summary statistics in genome-wide association studies

Genome-wide association studies have been successful mapping loci for individual phenotypes, but few studies have comprehensively interrogated evidence of shared genetic effects across multiple phenotypes simultaneously. Statistical methods have been proposed for analyzing multiple phenotypes using summary statistics, which enables studies of shared genetic effects while avoiding challenges associated with individual-level data sharing. Adaptive tests have been developed to maintain power against multiple alternative hypotheses because the most powerful single-alternative test depends on the underlying structure of the associations between the multiple phenotypes and a single nucleotide polymorphism (SNP). Here we compare the performance of six such adaptive tests: two adaptive sum of powered scores (aSPU) tests, the unified score association test (metaUSAT), the adaptive test in a mixed-models framework (mixAda) and two principal-component-based adaptive tests (PCAQ and PCO). Our simulations highlight practical challenges that arise when multivariate distributions of phenotypes do not satisfy assumptions of multivariate normality. Previous reports in this context focus on low minor allele count (MAC) and omit the aSPU test, which relies less than other methods on asymptotic and distributional assumptions. When these assumptions are not satisfied, particularly when MAC is low and/or phenotype covariance matrices are singular or nearly singular, aSPU better preserves type I error, sometimes at the cost of decreased power. We illustrate this trade-off with multiple phenotype analyses of six quantitative electrocardiogram traits in the Population Architecture using Genomics and Epidemiology (PAGE) study

Waist Circumference Change is Associated with Blood Pressure Change Independent of BMI Change

Objective: This study aimed to understand how an increase in abdominal adiposity relative to overall adiposity is associated with blood pressure (BP) change. Methods: A sex-stratified mixed linear model was used to examine the association (95% CI) between annual changes in waist circumference (WC) and systolic blood pressure and diastolic blood pressure, estimated from two to eight repeated measures across the 1993-2015 China Health and Nutrition Survey, among 5,742 men and 5,972 women (18-66 years) with no history of antihypertension medication use. Results: The association between annual WC change and BP change remained statistically significant but was attenuated after controlling for annual BMI change, regardless of baseline abdominal obesity or overweight status. Each 10-cm annual WC gain in men and women was associated with a 0.98-mm Hg (95% CI: 0.61-1.35) and a 0.97-mm Hg (95% CI: 0.62-1.32) annual increase in systolic blood pressure and a 1.13-mm Hg (95% CI: 0.87-1.38) and a 0.74-mm Hg (95% CI: 0.51-0.97) annual increase in diastolic blood pressure, respectively, independent of annual BMI change. Conclusions: WC gain may elevate BP even in the absence of BMI gain. BP management that addresses only BMI gain could overlook individuals at risk of elevated BP who have increased WC but not BMI

Dietary quality and cardiometabolic indicators in the USA: A comparison of the Planetary Health Diet Index, Healthy Eating Index-2015, and Dietary Approaches to Stop Hypertension

Background The Planetary Health Diet Index (PHDI) measures adherence to the sustainable dietary guidance proposed by the EAT-Lancet Commission on Food, Planet, Health. To justify incorporating sustainable dietary guidance such as the PHDI in the US, the index needs to be compared to health-focused dietary recommendations already in use. The objectives of this study were to compare the how the Planetary Health Diet Index (PHDI), the Healthy Eating Index-2015 (HEI-2015) and Dietary Approaches to Stop Hypertension (DASH) relate to cardiometabolic risk factors. Methods and findings Participants from the National Health and Nutrition Examination Survey (2015–2018) were assigned a score for each dietary index. We examined disparities in dietary quality for each index. We used linear and logistic regression to assess the association of standardized dietary index values with waist circumference, blood pressure, HDL-C, fasting plasma glucose (FPG) and triglycerides (TG). We also dichotomized the cardiometabolic indicators using the cutoffs for the Metabolic Syndrome and used logistic regression to assess the relationship of the standardized dietary index values with binary cardiometabolic risk factors. We observed diet quality disparities for populations that were Black, Hispanic, low-income, and low-education. Higher diet quality was associated with improved continuous and binary cardiometabolic risk factors, although higher PHDI was not associated with high FPG and was the only index associated with lower TG. These patterns remained consistent in sensitivity analyses.; Conclusions Sustainability-focused dietary recommendations such as the PHDI have similar cross-sectional associations with cardiometabolic risk as HEI-2015 or DASH. Health-focused dietary guidelines such as the forthcoming 2025–2030 Dietary Guidelines for Americans can consider the environmental impact of diet and still promote cardiometabolic health

Leisure-time physical activity volume, intensity, and duration from mid-to late-life in U.S. subpopulations by race and sex. The Atherosclerosis Risk in communities (ARIC) study

Mitigating age-related disease and disability presents challenges. Physical activity (PA) may be influential for prolonging health and functioning, warranting characterization of its patterns over the life course in population-based data. With the availability of up to three self-reported assessments of past year leisuretime PA (LTPA) over multiple decades in 15,036 participants (26% African American; 55% women; mean baseline age=54; median follow-up=23 years) from the Atherosclerosis Risk in Communities (ARIC) Study sampled from four U.S. communities, race-sex-stratified trajectories of average weekly intensity (metabolic equivalent of task (MET), duration (hours), and energy expenditure or volume (MET-h) of LTPA were developed from age 45 to 90 using joint models to accommodate expected non-ignorable attrition. Declines in weekly LTPA intensity, duration, and volume from age 70 to 90 were observed in white women (2.9 to 1.2 MET; 2.5 to 0.6 h; 11.1 to 2.6 MET-h), white men (2.5 to 1.0 MET; 3.5 to 1.8 h; 15.5 to 6.4 MET-h), African American women (2.5 to 2.4 MET; 0.8 to 0.1 h; 6.7 to 6.0 MET-h), and African American men (2.3 to 1.4 MET; 1.5 to 0.6 h; 8.0 to 2.3 MET-h). These data reveal population-wide shifts towards less active lifestyles in older adulthood