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

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

Is a Hypertension Diagnosis Associated With Improved Dietary Outcomes Within 2 to 4 Years? A Fixed-Effects Analysis From the China Health and Nutrition Survey

Background: Evidence shows that dietary factors play an important role in blood pressure. However, there is no clear understanding of whether hypertension diagnosis is associated with dietary modifications. The aim of this study is to estimate the longitudinal association between hypertension diagnosis and subsequent changes (within 2–4 years) in dietary sodium, potassium, and sodium-potassium (Na/K) ratio. Methods and Results: We included adults (18–75 years, n=16 264) from up to 9 waves (1991–2015) of the China Health and Nutrition Survey. Diet data were collected using three 24-hour dietary recalls and a household food inventory. We used fixed-effects models to estimate the association between newly self-reported diagnosed hypertension and subsequent within-individual changes in sodium, potassium, and Na/K ratio. We also examined changes among couples and at the household level. Results suggest that on average, men who were diagnosed with hypertension decreased their sodium intake by 251 mg/d and their Na/K ratio by 0.19 within 2 to 4 years after diagnosis (P<0.005). Among spouse pairs, sodium intake and Na/K ratio of women decreased when their husbands were diagnosed (P<0.05). Household average sodium density and Na/K ratio decreased, and household average potassium density increased after a man was diagnosed. In contrast, changes were not statistically significant when women were diagnosed. Conclusions: Our findings suggest that hypertension diagnosis for a man may result in modest dietary improvements for him, his wife, and other household members. Yet, diagnosis for a woman does not seem to result in dietary changes for her or her household members

Strengthening Causal Inference in Exposomics Research: Application of Genetic Data and Methods

Advances in technologies to measure a broad set of exposures have led to a range of exposome research efforts. Yet, these efforts have insufficiently integrated methods that incorporate genetic data to strengthen causal inference, despite evidence that many exposome-associated phenotypes are heritable. OBJECTIVE: We demonstrate how integration of methods and study designs that incorporate genetic data can strengthen causal inference in exposomics research by helping address six challenges: reverse causation and unmeasured confounding, comprehensive examination of phenotypic effects, low efficiency, replication, multilevel data integration, and characterization of tissue-specific effects. Examples are drawn from studies of biomarkers and health behaviors, exposure domains where the causal inference methods we describe are most often applied. DISCUSSION: Technological, computational, and statistical advances in genotyping, imputation, and analysis, combined with broad data sharing and cross-study collaborations, offer multiple opportunities to strengthen causal inference in exposomics research. Full application of these opportunities will require an expanded understanding of genetic variants that predict exposome phenotypes as well as an appreciation that the utility of genetic variants for causal inference will vary by exposure and may depend on large sample sizes. However, several of these challenges can be addressed through international scientific collaborations that prioritize data sharing. Ultimately, we anticipate that efforts to better integrate methods that incorporate genetic data will extend the reach of exposomics research by helping address the challenges of comprehensively measuring the exposome and its health effects across studies, the life course, and in varied contexts and diverse populations

Large-scale pharmacogenomic study of sulfonylureas and the QT, JT and QRS intervals: CHARGE Pharmacogenomics Working Group

Sulfonylureas, a commonly used class of medication used to treat type 2 diabetes, have been associated with an increased risk of cardiovascular disease. Their effects on QT interval duration and related electrocardiographic phenotypes are potential mechanisms for this adverse effect. In 11 ethnically diverse cohorts that included 71 857 European, African-American and Hispanic/Latino ancestry individuals with repeated measures of medication use and electrocardiogram (ECG) measurements, we conducted a pharmacogenomic genome-wide association study of sulfonylurea use and three ECG phenotypes: QT, JT and QRS intervals. In ancestry-specific meta-analyses, eight novel pharmacogenomic loci met the threshold for genome-wide significance (P&lt;5 × 10−8), and a pharmacokinetic variant in CYP2C9 (rs1057910) that has been associated with sulfonylurea-related treatment effects and other adverse drug reactions in previous studies was replicated. Additional research is needed to replicate the novel findings and to understand their biological basis

Circulating short-chain fatty acids are positively associated with adiposity measures in chinese adults

Epidemiological studies suggest a positive association between obesity and fecal short-chain fatty acids (SCFAs) produced by microbial fermentation of dietary carbohydrates, while animal models suggest increased energy harvest through colonic SCFA production in obesity. However, there is a lack of human population-based studies with dietary intake data, plasma SCFAs, gut microbial, and anthropometric data. In 490 Chinese adults aged 30–68 years, we examined the associations between key plasma SCFAs (butyrate/isobutyrate, isovalerate, and valerate measured by non-targeted plasma metabolomics) with body mass index (BMI) using multivariable-adjusted linear regression. We then assessed whether overweight (BMI ≥ 24 kg/m2 ) modified the association between dietary-precursors of SCFAs (insoluble fiber, total carbohydrates, and high-fiber foods) with plasma SCFAs. In a sub-sample (n = 209) with gut metagenome data, we examined the association between gut microbial SCFA-producers with BMI. We found positive associations between butyrate/isobutyrate and BMI (p-value < 0.05). The associations between insoluble fiber and butyrate/isobutyrate differed by overweight (p-value < 0.10). There was no statistical evidence for an association between microbial SCFA-producers and BMI. In sum, plasma SCFAs were positively associated with BMI and that the colonic fermentation of fiber may differ for adults with versus without overweight

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

Associations of sodium and potassium consumption with the gut microbiota and host metabolites in a population-based study in Chinese adults

Background: There is increasing evidence that sodium consumption alters the gut microbiota and host metabolome in murine models and small studies in humans. However, there is a lack of population-based studies that capture large variations in sodium consumption as well as potassium consumption. Objective: We examined the associations of energy-adjusted dietary sodium (milligrams/kilocalorie), potassium, and sodium-to-potassium (Na/K) ratio with the microbiota and plasma metabolome in a well-characterized Chinese cohort with habitual excessive sodium and deficient potassium consumption. Methods: We estimated dietary intakes from 3 consecutive validated 24-h recalls and household inventories. In 2833 adults (18-80 y old, 51.2% females), we analyzed microbial (genus-level 16S ribosomal RNA) between-person diversity, using distance-based redundancy analysis (dbRDA), and within-person diversity and taxa abundance using linear regression, accounting for geographic variation in both. In a subsample (n = 392), we analyzed the overall metabolome (dbRDA) and individual metabolites (linear regression). P values for specific taxa and metabolites were false discovery rate adjusted (q-value). Results: Sodium, potassium, and Na/K ratio were associated with microbial between-person diversity (dbRDA P < 0.01) and several specific taxa with large geographic variation, including pathogenic Staphylococcus and Moraxellaceae, and SCFA-producing Phascolarctobacterium and Lachnospiraceae (q-value < 0.05). For example, sodium and Na/K ratio were positively associated with Staphylococcus and Moraxellaceae in Liaoning, whereas potassium was positively associated with 2 genera from Lachnospiraceae in Shanghai. Additionally, sodium, potassium, and Na/K ratio were associated with the overall metabolome (dbRDA P ≤ 0.01) and several individual metabolites, including butyrate/isobutyrate and gut-derived phenolics such as 1,2,3-benzenetriol sulfate, which was negatively associated with sodium in Guizhou (q-value < 0.05). Conclusions: Our findings suggest that sodium and potassium consumption is associated with taxa and metabolites that have been implicated in cardiometabolic health, providing insights into the potential roles of gut microbiota and host metabolites in the pathogenesis of sodium- and potassium-associated diseases. More studies are needed to confirm our results