Dietary quality and dietary greenhouse gas emissions 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 dietary pattern presented by the EAT-Lancet Commission, which aligns health and sustainability targets. There is a need to understand how PHDI scores correlate with dietary greenhouse gas emissions (GHGE) and how this differs from the carbon footprints of scores on established dietary recommendations. The objectives of this study were to compare how the PHDI, Healthy Eating Index-2015 (HEI-2015) and Dietary Approaches to Stop Hypertension (DASH) relate to (a) dietary GHGE and (b) to examine the influence of PHDI food components on dietary GHGE. METHODS: We used life cycle assessment data from the Database of Food Recall Impacts on the Environment for Nutrition and Dietary Studies to calculate the mean dietary GHGE of 8,128 adult participants in the 2015-2016 and 2017-2018 cycles of the National Health and Nutrition Examination Survey (NHANES). Poisson regression was used to estimate the association of (a) quintiles of diet score and (b) standardized dietary index Z-scores with dietary GHGE for PHDI, HEI-2015, and DASH scores. In secondary analyses, we used Poisson regression to assess the influence of individual PHDI component scores on dietary GHGE. RESULTS: We found that higher dietary quality on all three indices was correlated with lower dietary GHGE. The magnitude of the dietary quality-dietary GHGE relationship was larger for PHDI [-0.4, 95% CI (-0.5, -0.3) kg CO2 equivalents per one standard deviation change] and for DASH [-0.5, (-0.4, -0.6) kg CO2-equivalents] than for HEI-2015 [-0.2, (-0.2, -0.3) kg CO2-equivalents]. When examining PHDI component scores, we found that diet-related GHGE were driven largely by red and processed meat intake. CONCLUSIONS: Improved dietary quality has the potential to lower the emissions impacts of US diets. Future efforts to promote healthy, sustainable diets could apply the recommendations of the established DASH guidelines as well as the new guidance provided by the PHDI to increase their environmental benefits.

Adherence to the Planetary Health Diet Index and correlation with nutrients of public health concern: an analysis of NHANES 2003-2018.

BACKGROUND: The Planetary Health Diet Index (PHDI) is a novel measure adapted to quantify alignment with the dietary evidence presented by the EAT-Lancet Commission on Food, Planet, Health. OBJECTIVES: To examine how population-level health and sustainability of diet as measured by the PHDI changed from 2003 to 2018, and to assess how PHDI correlated with inadequacy for nutrients of public health concern (iron, calcium, potassium, and fiber) in the United States. METHODS: We estimated survey-weighted trends in PHDI scores and median intake of PHDI components in a nationally representative sample of 33,859 adults aged 20+ y from 8 cycles (2003-2018) of the National Health and Nutrition Examination Survey with 2 d of dietary recall data. We used the National Cancer Institute method to examine how PHDI correlated with inadequate intake of iron, calcium, potassium, and fiber. RESULTS: Out of a theoretical range of 0-140, the median PHDI value increased by 4.2 points over the study period, from 62.7 (95% confidence interval [CI]: 62.0, 63.4) points in 2003-2004 to 66.9 (66.2, 67.7) points in 2017-2018 (P-trend < 0.001), although most of this change occurred before 2011-2012 and plateaued thereafter. For adequacy components that are encouraged for consumption, nonstarchy vegetable intake significantly decreased over time, whereas whole grains, nuts and seeds, and unsaturated oils increased. For moderation components with recommended limits for consumption, poultry and egg intake increased, but red and processed meat, added sugars, saturated fats, and starchy vegetables decreased over time. Higher PHDI values were associated with a lower probability of iron, fiber, and potassium inadequacy. CONCLUSIONS: Although there have been positive changes over the past 20 y, there is substantial room for improving the health and sustainability of the United States diet. Shifting diets toward EAT-Lancet recommendations would improve nutrient adequacy for iron, fiber, and potassium. Policy action is needed to support healthier, more sustainable diets in the United States and globally.

2024 Heart Disease and Stroke Statistics: A Report of US and Global Data From the American Heart Association.

BACKGROUND: The American Heart Association (AHA), in conjunction with the National Institutes of Health, annually reports the most up-to-date statistics related to heart disease, stroke, and cardiovascular risk factors, including core health behaviors (smoking, physical activity, nutrition, sleep, and obesity) and health factors (cholesterol, blood pressure, glucose control, and metabolic syndrome) that contribute to cardiovascular health. The AHA Heart Disease and Stroke Statistical Update presents the latest data on a range of major clinical heart and circulatory disease conditions (including stroke, brain health, complications of pregnancy, kidney disease, congenital heart disease, rhythm disorders, sudden cardiac arrest, subclinical atherosclerosis, coronary heart disease, cardiomyopathy, heart failure, valvular disease, venous thromboembolism, and peripheral artery disease) and the associated outcomes (including quality of care, procedures, and economic costs). METHODS: The AHA, through its Epidemiology and Prevention Statistics Committee, continuously monitors and evaluates sources of data on heart disease and stroke in the United States and globally to provide the most current information available in the annual Statistical Update with review of published literature through the year before writing. The 2024 AHA Statistical Update is the product of a full year's worth of effort in 2023 by dedicated volunteer clinicians and scientists, committed government professionals, and AHA staff members. The AHA strives to further understand and help heal health problems inflicted by structural racism, a public health crisis that can significantly damage physical and mental health and perpetuate disparities in access to health care, education, income, housing, and several other factors vital to healthy lives. This year's edition includes additional global data, as well as data on the monitoring and benefits of cardiovascular health in the population, with an enhanced focus on health equity across several key domains. RESULTS: Each of the chapters in the Statistical Update focuses on a different topic related to heart disease and stroke statistics. CONCLUSIONS: The Statistical Update represents a critical resource for the lay public, policymakers, media professionals, clinicians, health care administrators, researchers, health advocates, and others seeking the best available data on these factors and conditions.

Branched chain amino acids harbor distinct and often opposing effects on health and disease.

BACKGROUND: The branched chain amino acids (BCAA) leucine, isoleucine, and valine are essential nutrients that have been associated with diabetes, cancers, and cardiovascular diseases. Observational studies suggest that BCAAs exert homogeneous phenotypic effects, but these findings are inconsistent with results from experimental human and animal studies. METHODS: Hypothesizing that inconsistencies between observational and experimental BCAA studies reflect bias from shared lifestyle and genetic factors in observational studies, we used data from the UK Biobank and applied multivariable Mendelian randomization causal inference methods designed to address these biases. RESULTS: In n = 97,469 participants of European ancestry (mean age = 56.7 years; 54.1% female), we estimate distinct and often opposing total causal effects for each BCAA. For example, of the 117 phenotypes with evidence of a statistically significant total causal effect for at least one BCAA, almost half (44%, n = 52) are associated with only one BCAA. These 52 associations include total causal effects of valine on diabetic eye disease [odds ratio = 1.51, 95% confidence interval (CI) = 1.31, 1.76], valine on albuminuria (odds ratio = 1.14, 95% CI = 1.08, 1.20), and isoleucine on angina (odds ratio = 1.17, 95% CI = 1.31, 1.76). CONCLUSIONS: Our results suggest that the observational literature provides a flawed picture of BCAA phenotypic effects that is inconsistent with experimental studies and could mislead efforts developing novel therapeutics. More broadly, these findings motivate the development and application of causal inference approaches that enable 'omics studies conducted in observational settings to account for the biasing effects of shared genetic and lifestyle factors.

The three branched chain amino acids (BCAAs) leucine, isoleucine, and valine are important building blocks of muscle proteins that are obtained from the diet. Many studies in human populations have examined whether BCAAs affect health and disease. These human studies report results that are inconsistent with results from highly controlled animal studies. Because interest in the therapeutic targeting of BCAAs is growing, we wanted to better understand these discrepancies. Briefly, we used data from a large database that captured many diseases (e.g., cardiovascular disease, cancers, and respiratory disease) and new statistical methods. Our results showed that discrepancies between human studies and animal studies may reflect errors in the ways human studies were designed and conducted. As a result, these human studies may provide a flawed picture of BCAA effects that could mislead efforts developing novel therapeutics.

Heart Disease and Stroke Statistics-2023 Update: A Report From the American Heart Association.

BACKGROUND: The American Heart Association, in conjunction with the National Institutes of Health, annually reports the most up-to-date statistics related to heart disease, stroke, and cardiovascular risk factors, including core health behaviors (smoking, physical activity, diet, and weight) and health factors (cholesterol, blood pressure, and glucose control) that contribute to cardiovascular health. The Statistical Update presents the latest data on a range of major clinical heart and circulatory disease conditions (including stroke, congenital heart disease, rhythm disorders, subclinical atherosclerosis, coronary heart disease, heart failure, valvular disease, venous disease, and peripheral artery disease) and the associated outcomes (including quality of care, procedures, and economic costs). METHODS: The American Heart Association, through its Epidemiology and Prevention Statistics Committee, continuously monitors and evaluates sources of data on heart disease and stroke in the United States to provide the most current information available in the annual Statistical Update with review of published literature through the year before writing. The 2023 Statistical Update is the product of a full year's worth of effort in 2022 by dedicated volunteer clinicians and scientists, committed government professionals, and American Heart Association staff members. The American Heart Association strives to further understand and help heal health problems inflicted by structural racism, a public health crisis that can significantly damage physical and mental health and perpetuate disparities in access to health care, education, income, housing, and several other factors vital to healthy lives. This year's edition includes additional COVID-19 (coronavirus disease 2019) publications, as well as data on the monitoring and benefits of cardiovascular health in the population, with an enhanced focus on health equity across several key domains. RESULTS: Each of the chapters in the Statistical Update focuses on a different topic related to heart disease and stroke statistics. CONCLUSIONS: The Statistical Update represents a critical resource for the lay public, policymakers, media professionals, clinicians, health care administrators, researchers, health advocates, and others seeking the best available data on these factors and conditions.

Large-scale genome-wide association study of coronary artery disease in genetically diverse populations.

We report a genome-wide association study (GWAS) of coronary artery disease (CAD) incorporating nearly a quarter of a million cases, in which existing studies are integrated with data from cohorts of white, Black and Hispanic individuals from the Million Veteran Program. We document near equivalent heritability of CAD across multiple ancestral groups, identify 95 novel loci, including nine on the X chromosome, detect eight loci of genome-wide significance in Black and Hispanic individuals, and demonstrate that two common haplotypes at the 9p21 locus are responsible for risk stratification in all populations except those of African origin, in which these haplotypes are virtually absent. Moreover, in the largest GWAS for angiographically derived coronary atherosclerosis performed to date, we find 15 loci of genome-wide significance that robustly overlap with established loci for clinical CAD. Phenome-wide association analyses of novel loci and polygenic risk scores (PRSs) augment signals related to insulin resistance, extend pleiotropic associations of these loci to include smoking and family history, and precisely document the markedly reduced transferability of existing PRSs to Black individuals. Downstream integrative analyses reinforce the critical roles of vascular endothelial, fibroblast, and smooth muscle cells in CAD susceptibility, but also point to a shared biology between atherosclerosis and oncogenesis. This study highlights the value of diverse populations in further characterizing the genetic architecture of CAD.

Changes in nonnutritive sweetener intake in a cohort of preschoolers after the implementation of Chile's Law of Food Labelling and Advertising.

BACKGROUND: The first phase of Chile's Law of Food Labelling and Advertising showed important declines in the sugar content of packaged foods, but it is unknown whether the law led to an increase in nonnutritive sweetener (NNS) intake, particularly among preschool children. OBJECTIVES: Estimate the changes in preschoolers' NNS intake after the first phase of the Chilean law. METHODS: We used 24-h dietary recalls collected in 2016 (pre-law) and 2017 (post-law) from a cohort of preschoolers (n = 875). The primary caretaker was the respondent of the recalls. Information on NNS was obtained from nutrition facts panels collected annually and linked to dietary data. We used logistic regression to estimate the changes in the proportion of preschoolers who consume NNS and two-part models to estimate the changes in mean intake. We determined the percentage of children that surpassed the acceptable daily intake (ADI) of each NNS using the National Cancer Institute method. RESULTS: The proportion of consumers of at least one NNS increased from 77.9% to 92.0% (p-value < 0.01). The mean intake increased for sucralose, aspartame, acesulfame-K and steviol glycosides (+20.3, +15.1, +6.1 and +3.3 mg/day, respectively). In addition, NNS dietary sources changed for sucralose and steviol glycosides, becoming industrialized juices and dairy beverages more relevant while tabletop NNS became less relevant. None of the children surpassed the ADI. CONCLUSIONS: NNS intake increased in preschoolers after the first phase of a national policy that promoted sugar reformulation.

Do Genetic Variants Modify the Effect of Smoking on Risk of Preeclampsia in Pregnancy?

OBJECTIVE: Maternal smoking is associated with as much as a 50% reduced risk of preeclampsia, despite increasing risk of other poor pregnancy outcomes that often co-occur with preeclampsia, such as preterm birth and fetal growth restriction. Researchers have long sought to understand whether this perplexing association is biologically based, or a result of noncausal mechanisms. We examined whether smoking-response genes modify the smoking-preeclampsia association to investigate potential biological explanations. STUDY DESIGN: We conducted a nested case-control study within the Norwegian Mother, Father and Child Birth Cohort (1999-2008) of 2,596 mother-child dyads. We used family-based log-linear Poisson regression to examine modification of the maternal smoking-preeclampsia relationship by maternal and fetal single nucleotide polymorphisms involved in cellular processes related to components of cigarette smoke (n = 1,915 with minor allele frequency ≥10%). We further investigated the influence of smoking cessation during pregnancy. RESULTS: Three polymorphisms showed overall (p < 0.001) multiplicative interaction between smoking and maternal genotype. For rs3765692 (TP73) and rs10770343 (PIK3C2G), protection associated with smoking was reduced with two maternal copies of the risk allele and was stronger in continuers than quitters (interaction p = 0.02 for both loci, based on testing 3-level smoking by 3-level genotype). For rs2278361 (APAF1) the inverse smoking-preeclampsia association was eliminated by the presence of a single risk allele, and again the trend was stronger in continuers than in quitters (interaction p = 0.01). CONCLUSION: Evidence for gene-smoking interaction was limited, but differences by smoking cessation warrant further investigation. We demonstrate the potential utility of expanded dyad methods and gene-environment interaction analyses for outcomes with complex relationships between maternal and fetal genotypes and exposures. KEY POINTS: · Maternal and fetal genotype may differentially influence preeclampsia.. · Smoking-related genes did not strongly modify smoking-preeclampsia association.. · Smoking cessation reduced strength of gene by smoking interactions..

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 50 163 483 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.

Gut Microbiota and Host Plasma Metabolites in Association with Blood Pressure in Chinese Adults.

Animal studies have revealed gut microbial and metabolic pathways of blood pressure (BP) regulation, yet few epidemiological studies have collected microbiota and metabolomics data in the same individuals. In a population-based, Chinese cohort who did not report antihypertension medication use (30-69 years, 54% women), thus minimizing BP treatment effects, we examined multivariable-adjusted (eg, diet, physical activity, smoking, kidney function), cross-sectional associations between measures of gut microbiota (16S rRNA [ribosomal ribonucleic acid], N=1003), and plasma metabolome (liquid chromatography-mass spectrometry, N=434) with systolic (SBP, mean [SD]=126.0 [17.4] mm Hg) and diastolic BP (DBP [80.7 (10.7) mm Hg]). We found that the overall microbial community assessed by principal coordinate analysis varied by SBP and DBP (permutational multivariate ANOVA P<0.05). To account for strong correlations across metabolites, we first examined metabolite patterns derived from principal component analysis and found that a lipid pattern was positively associated with SBP (linear regression coefficient [95% CI] per 1 SD pattern score: 2.23 [0.72-3.74] mm Hg) and DBP (1.72 [0.81-2.63] mm Hg). Among 1104 individual metabolites, 34 and 39 metabolites were positively associated with SBP and DBP (false discovery rate-adjusted linear model P<0.05), respectively, including linoleate, palmitate, dihomolinolenate, 8 sphingomyelins, 4 acyl-carnitines, and 2 phosphatidylinositols. Subsequent pathway analysis showed that metabolic pathways of long-chain saturated acylcarnitine, phosphatidylinositol, and sphingomyelins were associated with SBP and DBP (false discovery rate-adjusted Fisher exact test P<0.05). Our results suggest potential roles of microbiota and metabolites in BP regulation to be followed up in prospective and clinical studies.

Diagnostic accuracy and prediction increment of markers of epithelial-mesenchymal transition to assess cancer cell detachment from primary tumors.

BACKGROUND: Metastases play a role in about 90% of cancer deaths. Markers of epithelial-mesenchymal transition (EMT) measured in primary tumor cancer cells might provide diagnostic information about the likelihood that cancer cells have detached from the primary tumor. Used together with established diagnostic tests of detachment-lymph node evaluation and radiologic imaging-EMT marker measurements might improve the ability of clinicians to assess the patient's risk of metastatic disease. Translation of EMT markers to clinical use has been hampered by a lack of valid analyses of clinically-informative parameters. Here, we demonstrate a rigorous approach to estimating the sensitivity, specificity, and prediction increment of an EMT marker to assess cancer cell detachment from primary tumors. METHODS: We illustrate the approach using immunohistochemical measurements of the EMT marker E-cadherin in a set of colorectal primary tumors from a population-based prospective cohort in North Carolina. Bayesian latent class analysis was used to estimate sensitivity and specificity in a setting of multiple imperfect diagnostic tests and no gold standard. Risk reclassification analysis was used to assess the extent to which addition of the marker to the panel of established diagnostic tests would improve mortality prediction. We explored how changing the latent class conditional dependence assumptions and definition of marker positivity would impact the results. RESULTS: All diagnostic accuracy and prediction increment statistics varied with the choice of cut point to define marker positivity. When comparing different definitions of marker positivity to each other, numerous trade-offs were observed in terms of sensitivity, specificity, predictive discrimination, and prediction model calibration. We then discussed several implementation considerations and the plausibility of analytic assumptions. CONCLUSIONS: The approaches presented here can be extended to any EMT marker, to most forms of cancer, and to different kinds of EMT marker measurements, such as RNA or gene methylation data. These methods provide valid, clinically-informative assessment of whether and how to use a given EMT marker to refine tumor staging and consequent treatment decisions.

GWAS of the electrocardiographic QT interval in Hispanics/Latinos generalizes previously identified loci and identifies population-specific signals.

QT interval prolongation is a heritable risk factor for ventricular arrhythmias and can predispose to sudden death. Most genome-wide association studies (GWAS) of QT were performed in European ancestral populations, leaving other groups uncharacterized. Herein we present the first QT GWAS of Hispanic/Latinos using data on 15,997 participants from four studies. Study-specific summary results of the association between 1000 Genomes Project (1000G) imputed SNPs and electrocardiographically measured QT were combined using fixed-effects meta-analysis. We identified 41 genome-wide significant SNPs that mapped to 13 previously identified QT loci. Conditional analyses distinguished six secondary signals at NOS1AP (n = 2), ATP1B1 (n = 2), SCN5A (n = 1), and KCNQ1 (n = 1). Comparison of linkage disequilibrium patterns between the 13 lead SNPs and six secondary signals with previously reported index SNPs in 1000G super populations suggested that the SCN5A and KCNE1 lead SNPs were potentially novel and population-specific. Finally, of the 42 suggestively associated loci, AJAP1 was suggestively associated with QT in a prior East Asian GWAS; in contrast BVES and CAP2 murine knockouts caused cardiac conduction defects. Our results indicate that whereas the same loci influence QT across populations, population-specific variation exists, motivating future trans-ethnic and ancestrally diverse QT GWAS.

Targeting physical activity interventions for adults: When should intervention occur?

Understanding demographic differences in transitions across physical activity (PA) levels is important for informing PA-promoting interventions, yet few studies have examined these transitions in contemporary multi-ethnic adult populations. We estimated age-, race/ethnicity-, and sex-specific 1-year net transition probabilities (NTPs) for National Health and Nutrition Examination Survey (2007-2012, n=11,556) and Hispanic Community Health Study/Study of Latinos (2008-2011, n=15,585) adult participants using novel Markov-type state transition models developed for cross-sectional data. Among populations with ideal PA (≥150min/week; ranging from 56% (non-Hispanic black females) to 88% (non-Hispanic white males) at age 20), NTPs to intermediate PA (>0-<149min/week) generally increased with age, particularly for non-Hispanic black females for whom a net 0.0% (95% confidence interval (CI): 0.0, 0.2) transitioned from ideal to intermediate PA at age 20; by age 70, the NTP rose to 3.6% (95% CI: 2.3, 4.8). Heterogeneity in intermediate to poor (0min/week) PA NTPs also was observed, with NTPs peaking at age 20 for Hispanic/Latino males and females [age 20 NTP=3.7% (95% CI: 2.0, 5.5) for females and 5.0% (1.2, 8.7) for males], but increasing throughout adulthood for non-Hispanic blacks and whites [e.g. age 70 NTP=7.8% (95% CI: 6.1, 9.6%) for black females and 8.1% (4.7, 11.6) for black males]. Demographic differences in PA net transitions across adulthood justify further development of tailored interventions. However, innovative efforts may be required for populations in which large proportions have already transitioned from ideal PA by early adulthood.

Genome-wide association of trajectories of systolic blood pressure change.

BACKGROUND: There is great interindividual variation in systolic blood pressure (SBP) as a result of the influences of several factors, including sex, ancestry, smoking status, medication use, and, especially, age. The majority of genetic studies have examined SBP measured cross-sectionally; however, SBP changes over time, and not necessarily in a linear fashion. Therefore, this study conducted a genome-wide association (GWA) study of SBP change trajectories using data available through the Genetic Analysis Workshop 19 (GAW19) of 959 individuals from 20 extended Mexican American families from the San Antonio Family Studies with up to 4 measures of SBP. We performed structural equation modeling (SEM) while taking into account potential genetic effects to identify how, if at all, to include covariates in estimating the SBP change trajectories using a mixture model based latent class growth modeling (LCGM) approach for use in the GWA analyses. RESULTS: The semiparametric LCGM approach identified 5 trajectory classes that captured SBP changes across age. Each LCGM identified trajectory group was ranked based on the average number of cumulative years as hypertensive. Using a pairwise comparison of these classes the heritability estimates range from 12 to 94 % (SE = 17 to 40 %). CONCLUSION: These identified trajectories are significantly heritable, and we identified a total of 8 promising loci that influence one's trajectory in SBP change across age. Our results demonstrate the potential utility of capitalizing on extant genetic data and longitudinal SBP assessments available through GAW19 to explore novel analytical methods with promising results.

Evaluating markers of epithelial-mesenchymal transition to identify cancer patients at risk for metastatic disease.

Most cancer deaths are due to metastases. Markers of epithelial-mesenchymal transition (EMT) measured in primary tumor cancer cells could be helpful to assess patient risk of metastatic disease, even among those otherwise diagnosed with local disease. Previous studies of EMT markers and patient outcomes used inconsistent methods and did not compare the clinical impact of different expression cut points for the same marker. Using digital image analysis, we measured the EMT markers Snail and E-cadherin in primary tumor specimens from 190 subjects in tissue microarrays from a population-based prospective cohort of colorectal cancer patients and estimated their associations with time-to-death. After measuring continuous marker expression data, we performed a systematic search for the cut point for each marker with the best model fit between dichotomous marker expression and time-to-death. We also assessed the potential clinical impact of different cut points for the same marker. After dichotomizing expression status at the statistically-optimal cut point, we found that Snail expression was not associated with time-to-death. When measured as a weighted average of tumor cores, low E-cadherin expression was associated with a greater risk of dying within 5 years of surgery than high expression (risk difference = 33 %, 95 % confidence interval 3-62 %). Identifying a clinically-optimal cut point for an EMT marker requires trade-offs between strength and precision of the association with patient outcomes, as well as consideration of the number of patients whose treatments might change based on using the marker at a given cut point.

American Heart Association's Life's Simple 7: Avoiding Heart Failure and Preserving Cardiac Structure and Function.

BACKGROUND: Many people may underappreciate the role of lifestyle in avoiding heart failure. We estimated whether greater adherence in middle age to American Heart Association's Life's Simple 7 guidelines­on smoking, body mass, physical activity, diet, cholesterol, blood pressure, and glucose­is associated with lower lifetime risk of heart failure and greater preservation of cardiac structure and function in old age. METHODS: We studied the population-based Atherosclerosis Risk in Communities Study cohort of 13,462 adults ages 45-64 years in 1987-1989. From the 1987-1989 risk factor measurements, we created a Life's Simple 7 score (range 0-14, giving 2 points for ideal, 1 point for intermediate, and 0 points for poor components). We identified 2218 incident heart failure events using surveillance of hospital discharge and death codes through 2011. In addition, in 4855 participants free of clinical cardiovascular disease in 2011-2013, we performed echocardiography from which we quantified left ventricular hypertrophy and diastolic dysfunction. RESULTS: One in four participants (25.5%) developed heart failure through age 85 years. Yet, this lifetime heart failure risk was 14.4% for those with a middle-age Life's Simple 7 score of 10-14 (optimal), 26.8% for a score of 5-9 (average), and 48.6% for a score of 0-4 (inadequate). Among those with no clinical cardiovascular event, the prevalence of left ventricular hypertrophy in late life was approximately 40% as common, and diastolic dysfunction was approximately 60% as common, among those with an optimal middle-age Life's Simple 7 score, compared with an inadequate score. CONCLUSIONS: Greater achievement of American Heart Association's Life's Simple 7 in middle age is associated with a lower lifetime occurrence of heart failure and greater preservation of cardiac structure and function.

Polymorphisms in inflammatory genes are associated with term small for gestational age and preeclampsia.

PROBLEM: Inflammatory biomarkers are associated with preeclampsia (PE) and poor fetal growth; however, genetic epidemiologic studies have been limited by reduced gene coverage and the exclusion of African American mothers. METHOD OF STUDY: Cases and controls (N = 1646) from a pregnancy cohort were genotyped for 503 tagSNPs in 40 genes related to inflammation. Gene-set analyses were stratified by race and were followed by a single SNP analysis within significant gene sets. RESULTS: Gene-level associations were found for IL6 and KLRD1 for term small for gestational age (SGA) among African Americans. LTA/TNF and TBX21 were associated with PE among European Americans. The strongest association was for PE among European Americans for an upstream regulator of TNF with RR = 1.8 (95% CI 1.1-2.7). CONCLUSION: Although previous studies have suggested null associations, increased tagging and stratification by genetic ancestry suggests important associations between IL6 and term SGA for African Americans, and a TNF regulator and PE among European Americans (N = 149).

Single nucleotide polymorphisms in nucleotide excision repair genes, cancer treatment, and head and neck cancer survival.

PURPOSE: Head and neck cancers (HNC) are commonly treated with radiation and platinum-based chemotherapy, which produce bulky DNA adducts to eradicate cancerous cells. Because nucleotide excision repair (NER) enzymes remove adducts, variants in NER genes may be associated with survival among HNC cases both independently and jointly with treatment. METHODS: Cox proportional hazards models were used to estimate race-stratified (White, African American) hazard ratios (HRs) and 95 % confidence intervals for overall (OS) and disease-specific (DS) survival based on treatment (combinations of surgery, radiation, and chemotherapy) and 84 single nucleotide polymorphisms (SNPs) in 15 NER genes among 1,227 HNC cases from the Carolina Head and Neck Cancer Epidemiology Study. RESULTS: None of the NER variants evaluated were associated with survival at a Bonferroni-corrected alpha of 0.0006. However, rs3136038 [OS HR = 0.79 (0.65, 0.97), DS HR = 0.69 (0.51, 0.93)] and rs3136130 [OS HR = 0.78 (0.64, 0.96), DS HR = 0.68 (0.50, 0.92)] of ERCC4 and rs50871 [OS HR = 0.80 (0.64, 1.00), DS HR = 0.67 (0.48, 0.92)] of ERCC2 among Whites, and rs2607755 [OS HR = 0.62 (0.45, 0.86), DS HR = 0.51 (0.30, 0.86)] of XPC among African Americans were suggestively associated with survival at an uncorrected alpha of 0.05. Three SNP-treatment joint effects showed possible departures from additivity among Whites. CONCLUSIONS: Our study, a large and extensive evaluation of SNPs in NER genes and HNC survival, identified mostly null associations, though a few variants were suggestively associated with survival and potentially interacted additively with treatment.

Pleiotropic effects of genetic risk variants for other cancers on colorectal cancer risk: PAGE, GECCO and CCFR consortia.

OBJECTIVE: Genome-wide association studies have identified a large number of single nucleotide polymorphisms (SNPs) associated with a wide array of cancer sites. Several of these variants demonstrate associations with multiple cancers, suggesting pleiotropic effects and shared biological mechanisms across some cancers. We hypothesised that SNPs previously associated with other cancers may additionally be associated with colorectal cancer. In a large-scale study, we examined 171 SNPs previously associated with 18 different cancers for their associations with colorectal cancer. DESIGN: We examined 13 338 colorectal cancer cases and 40 967 controls from three consortia: Population Architecture using Genomics and Epidemiology (PAGE), Genetic Epidemiology of Colorectal Cancer (GECCO), and the Colon Cancer Family Registry (CCFR). Study-specific logistic regression results, adjusted for age, sex, principal components of genetic ancestry, and/or study specific factors (as relevant) were combined using fixed-effect meta-analyses to evaluate the association between each SNP and colorectal cancer risk. A Bonferroni-corrected p value of 2.92×10(-4) was used to determine statistical significance of the associations. RESULTS: Two correlated SNPs--rs10090154 and rs4242382--in Region 1 of chromosome 8q24, a prostate cancer susceptibility region, demonstrated statistically significant associations with colorectal cancer risk. The most significant association was observed with rs4242382 (meta-analysis OR=1.12; 95% CI 1.07 to 1.18; p=1.74×10(-5)), which also demonstrated similar associations across racial/ethnic populations and anatomical sub-sites. CONCLUSIONS: This is the first study to clearly demonstrate Region 1 of chromosome 8q24 as a susceptibility locus for colorectal cancer; thus, adding colorectal cancer to the list of cancer sites linked to this particular multicancer risk region at 8q24.