Persistent poverty disparities in incidence and outcomes among oral and pharynx cancer patients.

PURPOSE: Disparities in oral cavity and pharyngeal cancer based on race/ethnicity and socioeconomic status have been reported, but the impact of living within areas that are persistently poor at the time of diagnosis and outcome is unknown. This study aimed to investigate whether the incidence, 5-year relative survival, stage at diagnosis, and mortality among patients with oral cavity and pharyngeal cancers varied by persistent poverty. METHODS: Data were drawn from the SEER database (2006-2017) and included individuals diagnosed with oral cavity and pharyngeal cancers. Persistent poverty (at census tract) is defined as areas where ≥ 20% of the population has lived below the poverty level for ~ 30 years. Age-adjusted incidence and 5-year survival rates were calculated. Multivariable logistic regression was used to estimate the association between persistent poverty and advanced stage cancer. Cumulative incidence and multivariable subdistribution hazard models were used to evaluate mortality risk. In addition, results were stratified by cancer primary site, sex, race/ethnicity, and rurality. RESULTS: Of the 90,631 patients included in the analysis (61.7% < 65 years old, 71.6% males), 8.8% lived in persistent poverty. Compared to non-persistent poverty, patients in persistent poverty had higher incidence and lower 5-year survival rates. Throughout 10 years, the cumulative incidence of cancer death was greater in patients from persistent poverty and were more likely to present with advanced-stage cancer and higher mortality risk. In the stratified analysis by primary site, patients in persistent poverty with oropharyngeal, oral cavity, and nasopharyngeal cancers had an increased risk of mortality compared to the patients in non-persistent poverty. CONCLUSION: This study found an association between oral cavity and pharyngeal cancer outcomes among patients in persistent poverty indicating a multidimensional strategy to improve survival.

Sodium Intake and Cause-Specific Mortality Among Predominantly Low-Income Black and White US Residents.

IMPORTANCE: Epidemiologic evidence regarding the outcomes of dietary sodium intake on mortality remains limited for low-income individuals, particularly Black people. OBJECTIVE: To investigate the associations of excessive dietary sodium with all-cause and cause-specific mortality among predominantly low-income Black and White Americans. DESIGN, SETTING, AND PARTICIPANTS: This cohort study included participants aged 40 to 79 years from the Southern Community Cohort Study who were recruited at Community Health Centers in 12 southeastern states from 2002 to 2009. Analyses were conducted between March 2022 and June 2023. EXPOSURES: Dietary sodium intake was assessed using a validated food frequency questionnaire at baseline. MAIN OUTCOMES AND MEASURES: Multivariable-adjusted Cox regression was used to estimate hazard ratios (HRs) and 95% CIs for mortality outcomes (all-cause, cardiovascular disease [CVD], coronary heart disease [CHD], stroke, heart failure, cancer, and other) associated with sodium intake. Nonlinear associations and population-attributable risk (PAR) of the mortality burden associated with excess sodium were further assessed. RESULTS: Among the 64 329 participants, 46 185 (71.8%) were Black, 18 144 (28.2%) were White, and 39 155 (60.9%) were female. The mean (SD) age at study enrollment was 51.3 (8.6) years for Black participants and 53.3 (9.3) years for White counterparts. Mean (SD) dietary sodium intake was 4512 (2632) mg/d in Black individuals and 4041 (2227) mg/d in White individuals; 37 482 Black individuals (81.2%) and 14 431 White individuals (79.5%) exceeded the current dietary recommendations of 2300 mg/d. During a median (IQR) follow-up of 13.8 (11.3-15.8) years, 17 811 deaths were documented, including 5701 from CVD. After adjustment for potential confounders, in Black individuals, HRs per 1000-mg increase in daily sodium intake were 1.07 (95% CI, 1.03-1.10) and 1.08 (95% CI, 1.02-1.14) for deaths from total CVD and CHD, respectively; while in White individuals, the corresponding HRs were 1.08 (95% CI, 1.02-1.14) and 1.13 (95% CI, 1.03-1.23). No significant associations were found for cancer mortality. PAR estimates suggest that sodium intake above the recommended threshold may account for 10% of total CVD, 13% of CHD, and 30% of heart failure deaths in this low-income southern population. CONCLUSIONS AND RELEVANCE: In this cohort study of 64 329 low-income Americans, nearly 80% of study participants consumed sodium exceeding the current recommended daily amount, which was associated with 10% to 30% of CVD mortality. Public health programs targeted to reduce sodium intake among this underserved population may be beneficial.

Iron homeostasis in older adults: balancing nutritional requirements and health risks.

Iron plays a crucial role in many physiological processes, including oxygen transport, bioenergetics, and immune function. Iron is assimilated from food and also recycled from senescent red blood cells. Iron exists in two dietary forms: heme (animal based) and non-heme (mostly plant based). The body uses iron for metabolic purposes, and stores the excess mainly in splenic and hepatic macrophages. Physiologically, iron excretion in humans is inefficient and not highly regulated, so regulation of intestinal absorption maintains iron homeostasis. Iron losses occur at a steady rate via turnover of the intestinal epithelium, blood loss, and exfoliation of dead skin cells, but overall iron homeostasis is tightly controlled at cellular and systemic levels. Aging can have a profound impact on iron homeostasis and induce a dyshomeostasis where iron deficiency or overload (sometimes both simultaneously) can occur, potentially leading to several disorders and pathologies. To maintain physiologically balanced iron levels, reduce risk of disease, and promote healthy aging, it is advisable for older adults to follow recommended daily intake guidelines and periodically assess iron levels. Clinicians can evaluate body iron status using different techniques but selecting an assessment method primarily depends on the condition being examined. This review provides a comprehensive overview of the forms, sources, and metabolism of dietary iron, associated disorders of iron dyshomeostasis, assessment of iron levels in older adults, and nutritional guidelines and strategies to maintain iron balance in older adults.

Associations between Plasma Tocopherols and Lung Cancer Risk: Results from the Southern Community Cohort Study.

BACKGROUND: Despite the various anticancer activities of tocopherols, little is known about tocopherols associated with lung cancer risk among low-income African Americans (AA) and European Americans (EA) who are disproportionately affected by the disease. METHODS: We conducted a nested case-control study that included 209 incident lung cancer cases and 406 matched controls within the Southern Community Cohort Study. Using biospecimens collected at cohort enrollment, plasma levels of α-, ß/γ-, δ-, and total-tocopherols were measured by high-performance liquid chromatography with photodiode array detection. Conditional logistic regression was used to estimate ORs and 95% confidence intervals (CI) for lung cancer risk after adjusting for potential confounders. Stratified analyses were also conducted. RESULTS: Plasma levels of total-tocopherols were inversely associated with lung cancer risk overall [OR (95% CI) for the highest vs. lowest tertile = 0.51 (0.30-0.90)]. The inverse association remained significant among EAs [0.20 (0.06-0.65)], men [0.43 (0.21-0.90)], current smokers [0.49 (0.26-0.93)], and cases diagnosed within 2 years of blood draw [0.36 (0.15-0.86)], though we did not find a significant risk reduction among AAs [0.75 (0.39-1.45)]. Notably, we found significant interactions between α-tocopherol and race after controlling the FDR to correct for multiple comparisons (Pinteraction = 0.02). CONCLUSIONS: Our results indicate that plasma total-tocopherols are inversely associated with lung cancer risk, but the association may differ across specific isomeric forms of tocopherols, race, or other individuals' characteristics. Further large-scale studies are warranted to confirm our findings. IMPACT: Recommendations on tocopherols for lung cancer prevention should take isomers, race, and smoking behaviors into consideration.

Lung Cancer Risk Prediction Models for Asian Ever-Smokers.

INTRODUCTION: Although lung cancer prediction models are widely used to support risk-based screening, their performance outside Western populations remains uncertain. This study aims to evaluate the performance of 11 existing risk prediction models in multiple Asian populations and to refit prediction models for Asians. METHODS: In a pooled analysis of 186,458 Asian ever-smokers from 19 prospective cohorts, we assessed calibration (expected-to-observed ratio) and discrimination (area under the receiver operating characteristic curve [AUC]) for each model. In addition, we developed the "Shanghai models" to better refine risk models for Asians on the basis of two well-characterized population-based prospective cohorts and externally validated them in other Asian cohorts. RESULTS: Among the 11 models, the Lung Cancer Death Risk Assessment Tool yielded the highest AUC (AUC [95% confidence interval (CI)] = 0.71 [0.67-0.74] for lung cancer death and 0.69 [0.67-0.72] for lung cancer incidence) and the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial Model had good calibration overall (expected-to-observed ratio [95% CI] = 1.06 [0.90-1.25]). Nevertheless, these models substantially underestimated lung cancer risk among Asians who reported less than 10 smoking pack-years or stopped smoking more than or equal to 20 years ago. The Shanghai models were found to have marginal improvement overall in discrimination (AUC [95% CI] = 0.72 [0.69-0.74] for lung cancer death and 0.70 [0.67-0.72] for lung cancer incidence) but consistently outperformed the selected Western models among low-intensity smokers and long-term quitters. CONCLUSIONS: The Shanghai models had comparable performance overall to the best existing models, but they improved much in predicting the lung cancer risk of low-intensity smokers and long-term quitters in Asia.

Calcium Intake and Lung Cancer Risk: A Pooled Analysis of 12 Prospective Cohort Studies.

BACKGROUND: Previous studies on calcium intake and lung cancer risk reported inconsistent associations, possibly due to the differences in intake amounts and contributing sources of calcium and smoking prevalence. OBJECTIVES: We investigated the associations of lung cancer risk with intake of calcium from foods and/or supplements and major calcium-rich foods in 12 studies. METHODS: Data from 12 prospective cohort studies conducted in the United States, Europe, and Asia were pooled and harmonized. We applied the DRI to categorize calcium intake based on the recommendations and quintile distribution to categorize calcium-rich food intake. We ran multivariable Cox regression by each cohort and pooled risk estimates to compute overall HR (95% CI). RESULTS: Among 1,624,244 adult men and women, 21,513 incident lung cancer cases were ascertained during a mean follow-up of 9.9 y. Overall, the dietary calcium intake was not significantly associated with lung cancer risk; the HRs (95% CI) were 1.08 (0.98-1.18) for higher (>1.5 RDA) and 1.01 (0.95-1.07) for lower intake (<0.5 RDA) comparing with recommended intake (EAR to RDA). Milk and soy food intake were positively or inversely associated with lung cancer risk [HR (95% CI) = 1.07 (1.02-1.12) and 0.92 (0.84-1.00)], respectively. The positive association with milk intake was significant only in European and North American studies (P-interaction for region = 0.04). No significant association was observed for calcium supplements. CONCLUSIONS: In this largest prospective investigation, overall, calcium intake was not associated with risk of lung cancer, but milk intake was associated with a higher risk. Our findings underscore the importance of considering food sources of calcium in studies of calcium intake.

Association of Healthy Lifestyles With Risk of Alzheimer Disease and Related Dementias in Low-Income Black and White Americans.

BACKGROUND AND OBJECTIVES: Although the importance of healthy lifestyles for preventing Alzheimer disease and related dementias (ADRD) has been recognized, epidemiologic evidence remains limited for non-White or low-income individuals who bear disproportionate burdens of ADRD. This population-based cohort study aims to investigate associations of lifestyle factors, individually and together, with the risk of ADRD among socioeconomically disadvantaged Americans. METHODS: In the Southern Community Cohort Study, comprising two-thirds self-reported Black and primarily low-income Americans, we identified incident ADRD using claims data among participants enrolled in Medicare for at least 12 consecutive months after age 65 years. Five lifestyle factors-tobacco smoking, alcohol consumption, leisure-time physical activity (LTPA), sleep hours, and diet quality-were each scored 0 (unhealthy), 1 (intermediate), or 2 (healthy) based on the health guidelines. A composite lifestyle score was created by summing all scores. Cox regression was used to estimate hazard ratios (HRs, 95% CIs) for incident ADRD, treating death as a competing risk. RESULTS: We identified 1,694 patients with newly diagnosed ADRD among 17,209 participants during a median follow-up of 4.0 years in claims data; the mean age at ADRD diagnosis was 74.0 years. Healthy lifestyles were individually associated with an 11%-25% reduced risk of ADRD: multivariable-adjusted HR (95% CI) was 0.87 (0.76-0.99) for never vs current smoking, 0.81 (0.72-0.92) for low-to-moderate vs no alcohol consumption, 0.89 (0.77-1.03) for ≥150 minutes of moderate or ≥75 minutes of vigorous LTPA each week vs none, 0.75 (0.64-0.87) for 7-9 hours vs >9 hours of sleep, and 0.85 (0.75-0.96) for the highest vs lowest tertiles of the Healthy Eating Index. The composite lifestyle score showed a dose-response association with up to 36% reduced risk of ADRD: multivariable-adjusted HRs (95% CIs) across quartiles were 1 (ref), 0.88 (0.77-0.99), 0.79 (0.70-0.90), and 0.64 (0.55-0.74); p trend <0.001. The beneficial associations were observed regardless of participants' sociodemographics (e.g., race, education, and income) and health conditions (e.g., history of cardiometabolic diseases and depression). DISCUSSION: Our findings support significant benefits of healthy lifestyles for ADRD prevention among socioeconomically disadvantaged Americans, suggesting that promoting healthy lifestyles and reducing barriers to lifestyle changes are crucial to tackling the growing burden and disparities posed by ADRD.

Prediagnosis Leisure-Time Physical Activity and Lung Cancer Survival: A Pooled Analysis of 11 Cohorts.

BACKGROUND: Little is known about the association between physical activity before cancer diagnosis and survival among lung cancer patients. In this pooled analysis of 11 prospective cohorts, we investigated associations of prediagnosis leisure-time physical activity (LTPA) with all-cause and lung cancer-specific mortality among incident lung cancer patients. METHODS: Using self-reported data on regular engagement in exercise and sports activities collected at study enrollment, we assessed metabolic equivalent hours (MET-h) of prediagnosis LTPA per week. According to the Physical Activity Guidelines for Americans, prediagnosis LTPA was classified into inactivity, less than 8.3 and at least 8.3 MET-h per week (the minimum recommended range). Cox regression was used to estimate hazard ratios (HRs) and 95% confidence interval (CIs) for all-cause and lung cancer-specific mortality after adjustment for major prognostic factors and lifetime smoking history. RESULTS: Of 20 494 incident lung cancer patients, 16 864 died, including 13 596 deaths from lung cancer (overall 5-year relative survival rate = 20.9%, 95% CI = 20.3% to 21.5%). Compared with inactivity, prediagnosis LTPA of more than 8.3 MET-h per week was associated with a lower hazard of all-cause mortality (multivariable-adjusted HR = 0.93, 95% CI = 0.88 to 0.99), but not with lung cancer-specific mortality (multivariable-adjusted HR = 0.99, 95% CI = 0.95 to 1.04), among the overall population. Additive interaction was found by tumor stage (Pinteraction = .008 for all-cause mortality and .003 for lung cancer-specific mortality). When restricted to localized cancer, prediagnosis LTPA of at least 8.3 MET-h per week linked to 20% lower mortality: multivariable-adjusted HRs were 0.80 (95% CI = 0.67 to 0.97) for all-cause mortality and 0.80 (95% CI = 0.65 to 0.99) for lung cancer-specific mortality. CONCLUSIONS: Regular participation in LTPA that met or exceeded the minimum Physical Activity Guidelines was associated with reduced hazards of mortality among lung cancer patients, especially those with early stage cancer.

Tooth Loss and Risk of Lung Cancer among Urban Chinese Adults: A Cohort Study with Meta-Analysis.

Epidemiological evidence on tooth loss and lung cancer risk remains limited, especially for smoking-specific associations. To investigate the association between tooth loss and lung cancer risk by smoking status, we first analyzed data from the Shanghai Men's Health Study (n = 49,868) and the Shanghai Women's Health Study (n = 44,309). Cox regression models were applied to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) for lung cancer risk in relation to tooth loss. We also conducted a meta-analysis to summarize epidemiologic findings to date, incorporating results from the current study and six previously published studies. For 7.3 median follow-up years, 973 incident lung cancer cases (613 men and 360 women) were ascertained. After adjustment for major covariates, tooth loss was associated with an increased risk of lung cancer among men (HR [95% CI] for >10 teeth vs. none = 1.59 [1.21−2.11]) but not among women (0.86 [0.50−1.46]). The positive association was stronger among male current smokers (1.75 [1.26−2.45], p-interaction by smoking status = 0.04). In a meta-analysis incorporating 4052 lung cancer cases and 248,126 non-cases, tooth loss was associated with a 1.64-fold increased risk of developing lung cancer (relative risk [RR, 95% CI] for the uppermost with the lowest category = 1.64 [1.44−1.86]). The positive association was more evident among current smokers (1.86 [1.41−2.46]), but no significant associations were found among never or former smokers. Our findings suggest that tooth loss may be associated with an increased risk of lung cancer, and the association could be modified by smoking status.

Obesity at early adulthood increases risk of gastric cancer from the Health Examinees-Gem (HEXA-G) study.

Emerging evidence has indicated a possible link between obesity in early life with subsequent cancer risks, but its association with gastric cancer remains unknown. This study aimed to investigate the association of obesity at ages 18-20 and 35 with the later risk of gastric cancer among the Korean population. Included were 122,724 individuals who participated in the large-scale prospective cohort study, the Health Examinees-Gem (HEXA-G) study, during 2004-2017. Multivariable Cox proportional hazards models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for gastric cancer risk associated with body mass index (BMI) at ages 18-20 and 35 years. During a mean follow-up period of 8.6±2.1 years, a total 927 gastric cancer cases (531 men and 396 women) were identified. When compared to normal BMI (18.5-23.0 kg/m2), obesity (BMI ≥30 kg/m2) at age 35 was significantly associated with increased risk of gastric cancer later in life among total participants (HR 1.94, 95% CI 1.26-2.97, p 0.01). When analyzed separately by sex, obesity at 35 years of age was significantly associated with increased risk of gastric cancer among both men (HR 1.79, 95% CI 1.02-3.13, p 0.05) and women (HR 2.35, 95% CI 1.21-4.60, p 0.02). No significant associations were found for obesity at late adolescence in both men and women. Our findings suggest that obesity in early adulthood may be associated with an increased risk of gastric cancer. The results may aid in understanding the etiology of GC in a population with a divergent trend of gastric cancer.

Reduction in total and major cause-specific mortality from tobacco smoking cessation: a pooled analysis of 16 population-based cohort studies in Asia.

BACKGROUND: Little is known about the time course of mortality reduction following smoking cessation in Asians who have smoking behaviours distinct from their Western counterparts. We evaluated the level of reduction in all-cause, cardiovascular disease (CVD) and lung cancer mortality by years since quitting smoking, in Asia. METHODS: Using Cox regression, we analysed individual participant data (n = 709 151) from 16 prospective cohorts conducted in China, Japan, Korea/Singapore, and India/Bangladesh, separately by cohorts. Cohort-specific hazard ratios (HRs) were combined using a random-effects meta-analysis. RESULTS: During a mean follow-up of 12.0 years, 108 287 deaths were ascertained-35 658 from CVD and 7546 from lung cancer. Among Asian men, a dose-response relationship of risk reduction in deaths from all causes, CVD and lung cancer was observed with an increase in years after smoking cessation. Compared with never smokers, however, all-cause and CVD mortality among former smokers remained elevated 10-14 years after quitting [multivariable-adjusted HR (95% confidence interval (CI) = 1.25 (1.13-1.37) and 1.20 (1.02-1.41), respectively]. Lung cancer mortality stayed almost 2-fold higher than among never smokers 15-19 years after smoking cessation [1.97 (1.41-2.73)], particularly among former heavy smokers [2.62 (1.71-4.00)]. Women who quitted for ≥5 years retained a significantly elevated mortality from all causes, CVD and lung cancer. Overall patterns of the cessation-mortality associations were similar across countries. CONCLUSIONS: Our findings suggest that adverse effects of tobacco smoking persist for an extended time period, even for more than two decades, which is beyond the time windows defined in current clinical guidelines for risk assessment of lung cancer and CVD.

Cholesterol and Egg Intakes with Cardiometabolic and All-Cause Mortality among Chinese and Low-Income Black and White Americans.

We examined the associations of dietary cholesterol and egg intakes with cardiometabolic and all-cause mortality among Chinese and low-income Black and White Americans. Included were 47,789 Blacks, 20,360 Whites, and 134,280 Chinese aged 40-79 years at enrollment. Multivariable Cox models with restricted cubic splines were applied to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for mortality outcomes using intakes of 150 mg cholesterol/day and 1 egg/week as the references. Cholesterol intake showed a nonlinear association with increased all-cause mortality and a linear association with increased cardiometabolic mortality among Black Americans: HRs (95% CIs) associated with 300 and 600 mg/day vs. 150 mg/day were 1.07 (1.03-1.11) and 1.13 (1.05-1.21) for all-cause mortality (P-linearity = 0.04, P-nonlinearity = 0.002, and P-overall < 0.001) and 1.10 (1.03-1.16) and 1.21 (1.08-1.36) for cardiometabolic mortality (P-linearity = 0.007, P-nonlinearity = 0.07, and P-overall = 0.005). Null associations with all-cause or cardiometabolic mortality were noted for White Americans (P-linearity ≥ 0.13, P-nonlinearity ≥ 0.06, and P-overall ≥ 0.05 for both). Nonlinear inverse associations were observed among Chinese: HR (95% CI) for 300 vs. 150 mg/day was 0.94 (0.92-0.97) for all-cause mortality and 0.91 (0.87-0.95) for cardiometabolic mortality, but the inverse associations disappeared with cholesterol intake > 500 mg/day (P-linearity ≥ 0.12; P-nonlinearity ≤ 0.001; P-overall < 0.001 for both). Similarly, we observed a positive association of egg intake with all-cause mortality in Black Americans, but a null association in White Americans and a nonlinear inverse association in Chinese. In conclusion, the associations of cholesterol and egg intakes with cardiometabolic and all-cause mortality may differ across ethnicities who have different dietary patterns and cardiometabolic risk profiles. However, residual confounding remains possible.

Associations of circulating choline and its related metabolites with cardiometabolic biomarkers: an international pooled analysis.

BACKGROUND: Choline is an essential nutrient; however, the associations of choline and its related metabolites with cardiometabolic risk remain unclear. OBJECTIVE: We examined the associations of circulating choline, betaine, carnitine, and dimethylglycine (DMG) with cardiometabolic biomarkers and their potential dietary and nondietary determinants. METHODS: The cross-sectional analyses included 32,853 participants from 17 studies, who were free of cancer, cardiovascular diseases, chronic kidney diseases, and inflammatory bowel disease. In each study, metabolites and biomarkers were log-transformed and standardized by means and SDs, and linear regression coefficients (ß) and 95% CIs were estimated with adjustments for potential confounders. Study-specific results were combined by random-effects meta-analyses. A false discovery rate <0.05 was considered significant. RESULTS: We observed moderate positive associations of circulating choline, carnitine, and DMG with creatinine [ß (95% CI): 0.136 (0.084, 0.188), 0.106 (0.045, 0.168), and 0.128 (0.087, 0.169), respectively, for each SD increase in biomarkers on the log scale], carnitine with triglycerides (ß = 0.076; 95% CI: 0.042, 0.109), homocysteine (ß = 0.064; 95% CI: 0.033, 0.095), and LDL cholesterol (ß = 0.055; 95% CI: 0.013, 0.096), DMG with homocysteine (ß = 0.068; 95% CI: 0.023, 0.114), insulin (ß = 0.068; 95% CI: 0.043, 0.093), and IL-6 (ß = 0.060; 95% CI: 0.027, 0.094), but moderate inverse associations of betaine with triglycerides (ß = -0.146; 95% CI: -0.188, -0.104), insulin (ß = -0.106; 95% CI: -0.130, -0.082), homocysteine (ß = -0.097; 95% CI: -0.149, -0.045), and total cholesterol (ß = -0.074; 95% CI: -0.102, -0.047). In the whole pooled population, no dietary factor was associated with circulating choline; red meat intake was associated with circulating carnitine [ß = 0.092 (0.042, 0.142) for a 1 serving/d increase], whereas plant protein was associated with circulating betaine [ß = 0.249 (0.110, 0.388) for a 5% energy increase]. Demographics, lifestyle, and metabolic disease history showed differential associations with these metabolites. CONCLUSIONS: Circulating choline, carnitine, and DMG were associated with unfavorable cardiometabolic risk profiles, whereas circulating betaine was associated with a favorable cardiometabolic risk profile. Future prospective studies are needed to examine the associations of these metabolites with incident cardiovascular events.

Circulating trimethylamine N-oxide in association with diet and cardiometabolic biomarkers: an international pooled analysis.

BACKGROUND: Trimethylamine N-oxide (TMAO), a diet-derived, gut microbial-host cometabolite, has been linked to cardiometabolic diseases. However, the relations remain unclear between diet, TMAO, and cardiometabolic health in general populations from different regions and ethnicities. OBJECTIVES: To examine associations of circulating TMAO with dietary and cardiometabolic factors in a pooled analysis of 16 population-based studies from the United States, Europe, and Asia. METHODS: Included were 32,166 adults (16,269 white, 13,293 Asian, 1247 Hispanic/Latino, 1236 black, and 121 others) without cardiovascular disease, cancer, chronic kidney disease, or inflammatory bowel disease. Linear regression coefficients (ß) were computed for standardized TMAO with harmonized variables. Study-specific results were combined by random-effects meta-analysis. A false discovery rate <0.10 was considered significant. RESULTS: After adjustment for potential confounders, circulating TMAO was associated with intakes of animal protein and saturated fat (ß = 0.124 and 0.058, respectively, for a 5% energy increase) and with shellfish, total fish, eggs, and red meat (ß = 0.370, 0.151, 0.081, and 0.056, respectively, for a 1 serving/d increase). Plant protein and nuts showed inverse associations (ß = -0.126 for a 5% energy increase from plant protein and -0.123 for a 1 serving/d increase of nuts). Although the animal protein-TMAO association was consistent across populations, fish and shellfish associations were stronger in Asians (ß = 0.285 and 0.578), and egg and red meat associations were more prominent in Americans (ß = 0.153 and 0.093). Besides, circulating TMAO was positively associated with creatinine (ß = 0.131 SD increase in log-TMAO), homocysteine (ß = 0.065), insulin (ß = 0.048), glycated hemoglobin (ß = 0.048), and glucose (ß = 0.023), whereas it was inversely associated with HDL cholesterol (ß = -0.047) and blood pressure (ß = -0.030). Each TMAO-biomarker association remained significant after further adjusting for creatinine and was robust in subgroup/sensitivity analyses. CONCLUSIONS: In an international, consortium-based study, animal protein was consistently associated with increased circulating TMAO, whereas TMAO associations with fish, shellfish, eggs, and red meat varied among populations. The adverse associations of TMAO with certain cardiometabolic biomarkers, independent of renal function, warrant further investigation.

Quantifying the association of low-intensity and late initiation of tobacco smoking with total and cause-specific mortality in Asia.

BACKGROUND: Little is known about the health harms associated with low-intensity smoking in Asians who, on average, smoke fewer cigarettes and start smoking at a later age than their Western counterparts. METHODS: In this pooled analysis of 738 013 Asians from 16 prospective cohorts, we quantified the associations of low-intensity (<5 cigarettes/day) and late initiation (≥35 years) of smoking with mortality outcomes. HRs and 95% CIs were estimated for each cohort by Cox regression. Cohort-specific HRs were pooled using random-effects meta-analysis. FINDINGS: During a mean follow-up of 11.3 years, 92 068 deaths were ascertained. Compared with never smokers, current smokers who consumed <5 cigarettes/day or started smoking after age 35 years had a 16%-41% increased risk of all-cause, cardiovascular disease (CVD), respiratory disease mortality and a >twofold risk of lung cancer mortality. Furthermore, current smokers who started smoking after age 35 and smoked <5 cigarettes/day had significantly elevated risks of all-cause (HRs (95% CIs)=1.14 (1.05 to 1.23)), CVD (1.27 (1.08 to 1.49)) and respiratory disease (1.54 (1.17 to 2.01)) mortality. Even smokers who smoked <5 cigarettes/day but quit smoking before the age of 45 years had a 16% elevated risk of all-cause mortality; however, the risk declined further with increasing duration of abstinence. CONCLUSIONS: Our study showed that smokers who smoked a small number of cigarettes or started smoking later in life also experienced significantly elevated all-cause and major cause-specific mortality but benefited from cessation. There is no safe way to smoke-not smoking is always the best choice.

Association of sleep duration and quality with elevated hs-CRP among healthy Korean adults.

This study aimed to investigate the association of sleep duration and quality with high-sensitivity C-reactive protein (hs-CRP) among middle-aged and elderly Koreans. Among a total of 74,867 participants (25,069 men and 49,798 women) recruited for the Health Examinees (HEXA) study, adjusted geometric means of hs-CRP level were compared across categories of sleep duration (<6, 6-7, 8-9, and ≥10 hours) and sleep quality (difficulty in initiating sleep and maintaining sleep) using ANCOVA models. Odds ratios (ORs) and 95% confidence intervals (CIs) for elevated hs-CRP (>3 mg/L) associated with sleep characteristics were estimated using multivariable-adjusted logistic regression models. Men who slept ≥10 hours per day were significantly associated with elevated hs-CRP (OR = 1.47, 95% CI 1.11-1.95). Whereas in women, difficulty in initiating sleep (OR = 1.28, 95% CI 1.04-1.57 for "Always"), and maintaining sleep was significantly associated with elevated hs-CRP levels (OR = 1.13, 95% CI 1.02-1.26 for "Often"; OR = 1.11, 95% CI 0.97-1.28 for "Always"). Additionally, women who experienced poor sleep quality presented an elevated level of hs-CRP (OR = 1.13, 95% CI 1.03-1.23). Our findings suggest that excessive sleep duration and poor sleep quality are significantly associated with the elevated inflammatory marker, specifically hs-CRP. Further research is needed to examine the effect of sleep interventions focused on these factors.

Soy Intake and Colorectal Cancer Risk: Results from a Pooled Analysis of Prospective Cohort Studies Conducted in China and Japan.

BACKGROUND: Soy is commonly consumed in east Asian countries and is suggested to reduce colorectal cancer (CRC) risk. However, results from epidemiologic studies are inconsistent, despite the anti-inflammatory and antiproliferative properties of soy isoflavones and soy protein. OBJECTIVE: We evaluated the association between soy isoflavones and soy protein and CRC risk using 4 prospective cohort studies from China and Japan. METHODS: Data were pooled from the Shanghai Women's Health Study (SWHS), Shanghai Men's Health Study (SMHS), Japan Public Health Center-based Prospective Study Cohort 1 (JPHC1), and Cohort 2 (JPHC2). Cox proportional hazards models estimated HRs and corresponding 95% CIs for the association of soy protein and isoflavone intake with CRC risk. The study included 205,060 individuals, among whom 2971 were diagnosed with incident CRC over an average follow-up of 12.7 y. RESULTS: No statistically significant associations with CRC risk were observed for soy protein or isoflavone intake. No association was observed among ever smokers consuming higher isoflavones (HRisoflavones: 0.83; 95% CI: 0.68, 1.00) and soy protein (HRsoy protein: 0.81; 95% CI: 0.39, 1.10). However, risk reductions were observed among premenopausal women with a body mass index [BMI (kg/m2)] <23.0 at baseline for higher isoflavone (HRisoflavones: 0.58, 95% CI: 0.34, 0.98). CONCLUSIONS: No evidence for an overall reduction in CRC risk by increasing soy food intake (i.e., protein or isoflavones) was observed. However, the association between soy and CRC risk may vary by BMI, smoking, and menopausal status among women. Future investigations are needed to further understand the biologic mechanisms observed.

Associations of choline-related nutrients with cardiometabolic and all-cause mortality: results from 3 prospective cohort studies of blacks, whites, and Chinese.

BACKGROUND: Choline-related nutrients are dietary precursors of a gut microbial metabolite, trimethylamine-N-oxide, which has been linked to cardiometabolic diseases and related death. However, epidemiologic evidence on dietary choline and mortality remains limited, particularly among nonwhite populations. OBJECTIVES: This study aimed to investigate the associations of choline-related nutrients with cardiometabolic and all-cause mortality among black and white Americans and Chinese adults. METHODS: Included were 49,858 blacks, 23,766 whites, and 134,001 Chinese, aged 40-79 y, who participated in 3 prospective cohorts and lived ≥1 y after enrollment. Cox regression models were used to estimate HRs and 95% CIs for cardiometabolic [e.g., ischemic heart disease (IHD), stroke, and diabetes] and all-cause deaths. To account for multiple testing, P values < 0.003 were considered significant. RESULTS: Mean choline intake among blacks, whites, and Chinese was 404.1 mg/d, 362.0 mg/d, and 296.8 mg/d, respectively. During a median follow-up of 11.7 y, 28,673 deaths were identified, including 11,141 cardiometabolic deaths. After comprehensive adjustments, including for overall diet quality and disease history, total choline intake was associated with increased cardiometabolic mortality among blacks and Chinese (HR for highest compared with lowest quintile: 1.26; 95% CI: 1.13, 1.40 and HR: 1.23; 95% CI: 1.11, 1.38, respectively; both P-trend < 0.001); among whites, the association was weaker (HR: 1.12; 95% CI: 0.95, 1.33; P-trend = 0.02). Total choline intake was also associated with diabetes and all-cause mortality in blacks (HR: 1.66; 95% CI: 1.26, 2.19 and HR: 1.20; 95% CI: 1.12, 1.29, respectively), with diabetes mortality in Chinese (HR: 2.24; 95% CI: 1.68, 2.97), and with IHD mortality in whites (HR: 1.31; 95% CI: 1.02, 1.69) (all P-trend < 0.001). The choline-mortality association was modified by alcohol consumption and appeared stronger among individuals with existing cardiometabolic disease. Betaine intake was associated with increased cardiometabolic mortality in Chinese only (HR: 1.16; 95% CI: 1.08, 1.25; P-trend < 0.001). CONCLUSIONS: High choline intake was associated with increased cardiometabolic mortality in racially diverse populations.

Associations of blood pressure categories defined by 2017 ACC/AHA guidelines with mortality in China: Pooled results from three prospective cohorts.

BACKGROUND: The recent American College of Cardiology/American Heart Association guidelines for high blood pressure lowered the hypertension criteria from systolic/diastolic blood pressure (SBP/DBP) of 140/90 mmHg or greater to 130/80 mmHg or greater, while the potential impact of the change on Chinese adults remains unclear. DESIGN: A pooled prospective cohort analysis. METHODS: Included were 154,407 Chinese adults from three prospective cohorts, which measured blood pressure at baseline and follow-up visits, and tracked death events by linkages to medical insurance system or vital statistics registries. Cox regression models were used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: During a total follow-up of 1,718,089 person-years, 14,692 deaths were documented including 5086 cardiovascular deaths (1277 ischaemic heart disease and 2509 cerebrovascular disease deaths). Compared to normal blood pressure (SBP/DBP < 120/80 mmHg), newly defined stage 1 hypertension (SBP/DBP 130-139/80-89 mmHg) was associated with increased cardiovascular mortality (HR 1.40, 95% CI 1.16-1.69; HR 1.36, 95% CI 1.12-1.65 for ischaemic heart disease mortality; HR 1.53, 95% CI 1.18-2.00 for cerebrovascular mortality), but not with all-cause mortality (HR 1.04, 95% CI 0.89-1.21). Stage 2 hypertension (SBP/DBP ≥ 140/90 mmHg) showed significant associations with cardiovascular disease and all-cause mortality, while elevated blood pressure (SBP 120-129 mmHg and DBP < 80 mmHg) showed null associations. The associations were stronger in adults younger than 65 years and adults without pre-existing cardiovascular disease compared with their counterparts (P for heterogeneity < 0.05). CONCLUSIONS: The newly defined stage 1 hypertension is associated with an increased risk of cardiovascular disease mortality in the Chinese population, particularly among younger adults and those without a history of cardiovascular disease.