Association of lifestyle with reduced stroke risk in 41 314 individuals with diabetes: Two prospective cohort studies in China.

AIM: To investigate the associations of individual and combined healthy lifestyle factors (HLS) with the risk of stroke in individuals with diabetes in China. METHODS: This prospective analysis included 41 314 individuals with diabetes [15 191 from the Comprehensive Research on the Prevention and Control of the Diabetes (CRPCD) project and 26 123 from the China Kadoorie Biobank (CKB) study]. Associations of lifestyle factors, including cigarette smoking, alcohol consumption, physical activity, diet, body shape and sleep duration, with the risk of stroke, intracerebral haemorrhage (ICH) and ischaemic stroke (IS) were assessed using Cox proportional hazard models. RESULTS: During median follow-up periods of 8.02 and 9.05 years, 2499 and 4578 cases of stroke, 2147 and 4024 of IS, and 160 and 728 of ICH were documented in individuals with diabetes in the CRPCD and CKB cohorts, respectively. In the CRPCD cohort, patients with ≥5 HLS had a 14% lower risk of stroke (hazard ratio (HR): 0.86, 95% confidence interval (CI): 0.75-0.98) than those with ≤2 HLS. In the CKB cohort, the adjusted HR (95% CI) for patients with ≥5 HLS were 0.74 (0.66-0.83) for stroke, 0.74 (0.66-0.83) for IS, and 0.57 (0.42-0.78) for ICH compared with those with ≤2 HLS. The pooled adjusted HR (95% CI) comparing patients with ≥5 HLS versus ≤2 HLS was 0.79 (0.69-0.92) for stroke, 0.80 (0.68-0.93) for IS, and 0.60 (0.46-0.78) for ICH. CONCLUSIONS: Maintaining a healthy lifestyle was associated with a lower risk of stroke, IS and ICH among individuals with diabetes.

Association of Serum Calcium with the Risk of Chronic Obstructive Pulmonary Disease: A Prospective Study from UK Biobank.

BACKGROUND: Although intracellular calcium had been demonstrated to involve in the pathogenesis of chronic obstructive pulmonary disease (COPD), the association between serum calcium and COPD risk remains unclear. METHODS: We included 386,844 participants with serum calcium measurements and without airway obstruction at the baseline from UK Biobank. The restricted cubic splines were used to assess the dose-response relationship. Multivariable cox regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the associations of albumin-corrected calcium concentrations with the risk of COPD incidence and mortality. RESULTS: During a median of 12.3 years of follow-up, 10,582 incident COPD cases were documented. A linear positive association was observed between serum calcium concentrations and the risk of COPD incidence. Compared to participants with normal serum calcium (2.19-2.56 mmol/L), a 14% higher risk of COPD was observed in hypercalcemic participants (≥2.56 mmol/L, HR = 1.14; 95% CI: 1.02-1.27). No significant effect modifications were observed in stratified variables. In survival analysis, 215 COPD-specific deaths were documented after a median survival time of 3.8 years. Compared to participants with normal serum calcium, hypercalcemic participants had a 109% (HR = 2.09, 95% CI: 1.15-3.81) increased risk for COPD-specific mortality. CONCLUSION: Our study indicated that hypercalcemia was associated with an elevated risk of COPD incidence and mortality in the European population, and suggested that serum calcium may have a potential impact on the progression of COPD.

Association between glycated haemoglobin and the risk of chronic obstructive pulmonary disease: A prospective cohort study in UK biobank.

AIMS: To investigate the association between glycated haemoglobin (HbA1c) levels and chronic obstructive pulmonary disease (COPD) incidents in the general population, and the association between HbA1c levels and mortality in patients with COPD. MATERIALS AND METHODS: We investigated the association of HbA1c levels with COPD risk in the general population in the UK Biobank, using data from 420 065 participants. Survival analysis was conducted for 18 854 patients with COPD. We used restricted cubic spline analysis to assess the dose-response relationship between HbA1c levels and COPD risk and survival. Cox proportional hazards regression models were used to estimate hazard ratios (HRs) with 95% confidence intervals (CIs). RESULTS: During a median follow-up of 12.3 years, 11 556 COPD cases were recorded. HbA1c had a non-linear relationship with COPD risk (p for non-linearity < .05). Compared with the quintile 2 (32.2-<34.3 mmol/mol), those with HbA1c levels above 38.7 mmol/mol (quintile 5) had a 22% (HR, 1.22, 95% CI: 1.15-1.30) higher risk of COPD. Compared with the HbA1c decile 2 (30.5-<32.2 mmol/mol), the HRs (95% CI) of COPD risk were 1.16 (1.03-1.30) and 1.36 (1.24-1.50) in the lowest HbA1c decile (<30.5 mmol/mol) and highest decile (≥41.0 mmol/mol), respectively. The increased COPD risk associated with HbA1c was more pronounced in younger, current smokers, passive smokers, and participants with a higher Townsend deprivation index (all p for interaction < .05). Among patients with COPD, 4569 COPD cases died (488 because of COPD) during a median follow-up of 5.4 years. Regarding COPD survival, HbA1c had a non-linear relationship with all-cause death (p for non-linearity < .05). Those with HbA1c quintile 5 (≥38.7 mmol/mol) had a 23% (HR, 1.23, 95% CI: 1.10-1.37) higher risk of all-cause death compared with the quintile 2 (32.2-<34.3 mmol/mol). Compared with the HbA1c decile 4 (33.3-<34.3 mmol/mol), those in the lowest HbA1c decile (<30.5 mmol/mol) and highest HbA1c decile (≥41.0 mmol/mol) had 22% (HR, 1.22; 95% CI: 1.01-1.47) and 28% (HR, 1.28; 95% CI: 1.11-1.48) higher risk for overall death. However, no significant association was observed between HbA1c levels and the risk of COPD-specific death. CONCLUSIONS: Our findings indicated that lower and higher HbA1c levels were associated with a higher risk of COPD. In COPD cases, lower and higher HbA1c levels were associated with a higher COPD all-cause death risk.

Associations of serum aminotransferase and the risk of all-cause and cause-specific mortality in Chinese type 2 diabetes: a community-based cohort study.

OBJECTIVE: Investigating the associations of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) with all-cause, cardiovascular disease (CVD) and cancer mortality in a large cohort of community-dwelling patients with type 2 diabetes mellitus (T2DM). DESIGN: Community-based prospective cohort study conducted between 2013 and 2014. SETTING: 44 selected townships in Changshu and Huai'an City, Jiangsu province, China. PARTICIPANTS: 20340 participants with T2DM were recruited in Jiangsu province, China. METHODS: We use Cox proportional hazard models to estimate the HR and 95% CIs of associations of serum ALT and AST levels with all-cause and cause-specific mortality. Restricted cubic splines were used to explore the dose-response relationships between ALT and AST levels with mortality. RESULTS: ALT and AST levels were inversely associated with CVD mortality, compared with the lowest quintile (Q1), the multivariable HRs of the highest quintile (Q5) was 0.82 (95% CI: 0.66 to 1.01, p for trend=0.022) and 0.78 (95% CI: 0.63 to 0.96, p for trend=0.022), respectively. Furthermore, the HRs for ALT levels in all-cause mortality were 0.90 (95% CI: 0.79 to 1.01, p for trend=0.018), and the HRs for AST levels in cancer mortality were 1.29 (95% CI: 1.02 to 1.63, p for trend=0.023). Stronger inverse effects of ALT and AST levels on all-cause mortality were observed in the older subgroup and in those with dyslipidaemia (all p for interaction <0.05). Further analysis based on gender showed that the associations between serum aminotransferases and the mortality risk were more significant in women and substantially attenuated in men. CONCLUSION: Our findings suggested patients with T2DM with lower levels of ALT and AST had an increased risk of CVD mortality, which needs confirmation in future clinical trials.

Vitamin D status and chronic obstructive pulmonary disease risk: a prospective UK Biobank study.

BACKGROUND: Low vitamin D status has been linked to an increased risk for various inflammatory diseases. Conflicting results have been reported regarding chronic obstructive pulmonary disease (COPD). This study aims to investigate the associations of serum 25-hydroxyvitamin D (25(OH)D) concentrations with COPD risk and survival. METHODS: We included 403 648 participants with serum 25(OH)D measurements and free of COPD at baseline from UK Biobank. Follow-up was until 30 September 2021. Multivariable-adjusted cox regression models were applied to estimate HRs and 95% CIs for the associations of season-standardised 25(OH)D concentrations with COPD risk and survival. The restricted cubic splines were used to assess dose-response relationship. Kaplan-Meier estimation was used to create graphs of the survival curves. RESULTS: During a median follow-up of 12.3 (IQR: 11.4-13.2) years, 11 008 cases of COPD were recorded. We observed a non-linear inverse association between 25(OH)D concentrations and COPD risk. Compared with participants in the fourth quintile of 25(OH)D, those in the lowest quintile were associated with a 23% higher risk (HR, 1.23; 95% CI, 1.16 to 1.31). Stronger associations were observed for the risk in men and current smokers (Both p for interaction <0.05). In survival analyses, compared with the fourth quintile, cases in the lowest quintile had a 38% higher risk for overall death (HR, 1.38; 95% CI, 1.22 to 1.56). CONCLUSION: Our findings indicate that serum 25(OH)D concentrations are non-linearly negatively associated with incidence and mortality of COPD, suggesting a potential protective role of vitamin D in the pathogenesis of COPD.

Association of gamma-glutamyl transferase concentrations with all-cause and cause-specific mortality in Chinese adults with type 2 diabetes.

BACKGROUND: Evidence links gamma-glutamyl transferase (GGT) to mortality in the general population. However, the relationship of GGT with all-cause and cause-specific mortality risk has been little explored in type 2 diabetes mellitus (T2DM) patients. METHODS: We recruited 20 340 community-dwelling T2DM patients between 2013 and 2014 in Jiangsu, China. Cox regression models were used to assess associations of GGT with all-cause and specific-cause mortality. Restricted cubic splines were used to analyze dose-response relationships between GGT and mortality. Stratified analysis was conducted to examine potential interaction effects by age, sex, smoking status, body mass index (BMI), diabetes duration, and dyslipidemia. RESULTS: During a median follow-up period of 7.04 years (interquartile range: 6.98-7.08), 2728 deaths occurred, including 902 (33.09%) due to cardiovascular disease (CVD), and 754 (27.58%) due to cancer. GGT concentrations were positively associated with all-cause, CVD, and cancer mortality. Multivariable hazard ratios (HRs) for the highest (Q5) vs. the lowest quintile (Q1) were 1.63 (95% confidence intervals [CI]: 1.44-1.84) for all-cause mortality, 1.87 (95% CI: 1.49-2.35) for CVD mortality, and 1.43 (95% CI: 1.13-1.81) for cancer mortality. Effect modification by BMI and dyslipidemia was observed for all-cause mortality (both p for interaction <.05), and HRs were stronger in the BMI <25 kg/m2 group and those without dyslipidemia. CONCLUSIONS: Our findings suggest that, in Chinese T2DM patients, elevated serum GGT concentrations were associated with mortality for all-cause, CVD, and cancer, and further research is needed to elucidate the role of obesity, nonalcoholic fatty liver disease, and lipids in this association.

Associations of diabetes, prediabetes and diabetes duration with the risk of chronic obstructive pulmonary disease: A prospective UK Biobank study.

AIM: To investigate the associations of diabetes, prediabetes and diabetes duration with chronic obstructive pulmonary disease (COPD) risk and survival in the UK Biobank. MATERIALS AND METHODS: We conducted a prospective analysis among 452 680 participants without COPD at baseline using UK Biobank data. Multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated from Cox regression models. The dose-response relationship was explored using restricted cubic splines. A separate survival analysis was conducted for 12 595 patients with incident COPD. RESULTS: Over a median follow-up of 12.3 years, 12 595 cases of COPD were documented. Compared with the reference group, those with prediabetes and diabetes were associated with an 18% (HR 1.18 [95% CI: 1.13-1.24]) and 35% (HR 1.35 [95% CI: 1.24-1.47]) higher risk of COPD, respectively. Diabetes duration was associated with COPD risk, with multivariable HRs (95% CIs) of 1.23 (1.05-1.44), 1.20 (1.04-1.39) and 1.18 (1.01-1.37) for diabetes duration of 7 years or longer, 3 to less than 7 years, and 1 to less than 3 years versus less than 1 year, respectively. Dose-response analysis revealed a non-linear relationship between diabetes duration and COPD risk. Regarding COPD survival, COPD patients with prediabetes and diabetes had a 9% (HR 1.09 [95% CI: 1.00-1.19]) and 21% (HR 1.21 [95% CI: 1.05-1.41]) higher risk of overall death, respectively. Compared with the cases with a diabetes duration of less than 1 year, those with a diabetes duration of 7 years or longer were associated with a 46% higher risk of overall death (HR 1.46 [95% CI: 1.11-1.92]). CONCLUSIONS: Our findings indicate that diabetes, prediabetes and a longer diabetes duration are associated with a higher risk of and worse survival for COPD. Future studies are warranted to determine the optimal way of diabetes control that might reduce COPD risk.

Circulating liver function markers and the risk of COPD in the UK Biobank.

Objective: To investigate the associations of circulating liver function marker levels with the risk of chronic obstructive pulmonary disease (COPD). Methods: We leveraged the data of 372,056 participants from the UK Biobank between 2006 and 2010. The assessed circulating liver function markers included alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT), alkaline phosphatase (ALP), total bilirubin (TBIL), albumin (ALB), and total protein (TP). Incident COPD was identified through linkage to the National Health Service registries. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Results: During a median follow-up period of 12.3 (interquartile range:11.4-13.2) years, we documented 10,001 newly diagnosed COPD cases. Lower levels of ALT, TBIL, ALB, and TP and higher levels of GGT and ALP were nonlinearly associated with elevated COPD risk. The HR (95% CI) for decile 10 vs. 1 was 0.92 (0.84-1.01) for ALT, 0.82 (0.75-0.89) for TBIL, 0.74 (0.67-0.81) for ALB, 0.96 (0.88-1.04) for TP, 1.45 (1.31-1.62) for GGT, and 1.31 (1.19-1.45) for ALP. Restricted cubic spline analyses suggested a U-shaped relationship between AST levels and COPD risk (P for nonlinearity <0.05). Conclusion: We observed that all seven circulating liver function markers were nonlinearly associated with the risk of COPD, indicating the importance of liver function in COPD.

Association of healthy lifestyle with incident cardiovascular diseases among hypertensive and normotensive Chinese adults.

Background: Whether lifestyle improvement benefits in reducing cardiovascular diseases (CVD) events extend to hypertensive patients and whether these benefits differ between hypertensive and normotensive individuals is unclear. This study aimed to investigate the associations of an overall healthy lifestyle with the subsequent development of CVD among participants with hypertension and normotension. Methods: Using data from the Suzhou subcohort of the China Kadoorie Biobank study of 51,929 participants, this study defined five healthy lifestyle factors as nonsmoking or quitting for reasons other than illness; nonexcessive alcohol intake; relatively higher physical activity level; a relatively healthy diet; and having a standard waist circumference and body mass index. We estimated the associations of these lifestyle factors with CVD, ischemic heart disease (IHD) and ischemic stroke (IS). Results: During a follow-up of 10.1 years, this study documented 6,151 CVD incidence events, 1,304 IHD incidence events, and 2,243 IS incidence events. Compared to those with 0-1 healthy lifestyle factors, HRs for those with 4-5 healthy factors were 0.71 (95% CI: 0.62, 0.81) for CVD, 0.56 (95% CI: 0.42, 0.75) for IHD, and 0.63 (95% CI: 0.51, 0.79) for IS among hypertensive participants. However, we did not observe this association among normotensive participants. Stratified analyses showed that the association between a healthy lifestyle and IHD risk was stronger among younger participants, and the association with IS risk was stronger among hypertensive individuals with lower household incomes. Conclusion: Adherence to a healthy lifestyle pattern is associated with a lower risk of cardiovascular diseases among hypertensive patients, but this benefit is not as pronounced among normotensive patients.

Serum Calcium Concentrations and Risk of All-Cause and Cause-Specific Mortality: Results From 2 Prospective Cohorts.

CONTEXT: Calcium plays a critical role in various physiological activities. However, the association between circulating calcium concentrations and mortality in a general healthy population remains undetermined. OBJECTIVE: To examine the association of serum calcium concentrations with all-cause and cause-specific mortality. METHODS: Leveraging data from the UK Biobank (n = 361 662) and the US National Health and Nutrition Examination Survey (NHANES, n = 36 985), we prospectively examined the association of serum calcium concentrations with all-cause and cause-specific mortality using Cox proportional hazard and restricted cubic spline models. RESULTS: During a median follow-up of 12.0 years, UK Biobank documented 18 327 deaths, including 3119 (17.0%) from cardiovascular disease (CVD) and 9599 (52.4%) from cancer. We found a U-shaped relationship of albumin-adjusted calcium concentrations with all-cause and CVD mortality. Compared with participants with moderate calcium levels (the third quintile, Q3), those with low and high levels had an increased risk of all-cause (hazard ratio [HR] 1.02 for Q1 vs Q3; 1.10 for Q5 vs Q3) and CVD mortality (HR 1.11 for Q1 vs Q3; 1.25 for Q5 vs Q3). In contrast, there was a linear positive relationship with cancer mortality (HR 1.09 for Q5 vs Q1). Similar results for all-cause, CVD, and cancer mortality were observed in US NHANES. CONCLUSION: Our findings provide novel insights into the association between serum calcium concentrations and mortality in the general healthy population.

Particulate air pollution and cardiovascular disease mortality in Jiangsu Province, China: a time-series analysis between 2015 and 2021.

Introduction: Previous time-series studies have revealed a positive association between particulate matter (PM) and acute cardiovascular effects. However, the evidence mostly comes from developed countries and regions, while the majority of air-pollution-related deaths occur in developing countries. To assess the effect of short-term exposure to PM on daily cause-specific cardiovascular disease (CVD) mortality in Jiangsu Province, China, we investigated 1,417,773 CVD deaths from 2015 to 2021 in Jiangsu. Methods: The city-specific association was estimated using generalized additive models with quasi-Poisson regression, and then, random effects meta-analysis was performed to estimate the pooled provincial-average associations between acute exposure to PM2.5 and PM10 and cardiovascular disease mortality. To test the independence of PM from gaseous pollutants, we fitted two-pollutant models. Mortality data were also stratified by sex, age, and region to investigate the modification of associations. The exposure-response (E-R) curve from each city was combined using meta-analysis to drive the provincial-level E-R curve. Results: The results showed that each 10-µg/m3 increase in the PM2.5 concentration was associated with a 0.723% [95% confidence interval (CI): 0.512, 0.935] increase in daily total CVD mortality, a 0.669% (95% CI: 0.461, 0.878) increase in CHD mortality, a 0.758% (95% CI: 0.584, 0.931) increase in stroke mortality, a 0.512% (95% CI: 0.245, 0.780) increase in ICH mortality, and a 0.876% (95% CI: 0.637, 1.116) increase in CI mortality. The corresponding increases in daily mortality rates for the same increase in the PM10 concentration were 0.424% (95% CI: 0.293, 0.556), 0.415% (95% CI: 0.228, 0.602), 0.444% (95% CI: 0.330, 0.559), 0.276% (95% CI: 0.026, 0.526), and 0.510% (95% CI: 0.353, 0.667), respectively. The association between PM and total CVD mortality remained significant after adjusting for gaseous pollutants. Females, older adults and districts with lower average PM levels are more sensitive, especially for PM10. The E-R curve for PM on CVD mortality is steeper at lower concentrations and flattens out at higher concentrations. The estimates remained generally consistent in sensitivity analyses when excluding the data during the COVID-19 pandemic period. Discussion: Our time-series study provides evidence of positive associations between acute exposure to PM2.5 and PM10 and total and cause-specific cardiovascular disease mortality in developing countries.

Association between physical activity and cancer risk among Chinese adults: a 10-year prospective study.

BACKGROUND: In China, the quantity of physical activity differs from that in Western countries. Substantial uncertainty remains about the relevance of physical activity for cancer subtypes among Chinese adults. OBJECTIVE: This study aimed to investigate the association between total daily physical activity and the incidence of common types of cancer. METHODS: A total of 53,269 participants aged 30-79 years were derived from the Wuzhong subcohort of the China Kadoorie Biobank study during 2004-2008. We included 52,938 cancer-free participants in the final analysis. Incident cancers were identified through linkage with the health insurance system and death registries. Cox proportional hazard models were introduced to assess the associations of total daily physical activity with the incidence of 6 common types of cancer. RESULTS: During a follow-up of 10.1 years, 3,674 cases of cancer were identified, including 794 (21.6%) from stomach cancer, 722 (19.7%) from lung cancer, 458 (12.5%) from colorectal cancer, 338 (9.2%) from liver cancer, 250 (6.8%) from breast cancer, and 231 (6.3%) from oesophageal cancer. Compared to the participants in the lowest quartile of physical activity levels, those in the highest quartile had an 11% lower risk for total cancer incidence (hazard ratio [HR]: 0.89, 95% confidence interval [CI]: 0.81-0.99), 25% lower risk for lung cancer incidence (HR: 0.75, 95% CI: 0.60-0.94), and 26% lower risk for colorectal cancer incidence (HR: 0.74, 95% CI: 0.55-1.00). There were significant interactions of physical activity with sex and smoking on total cancer (both P for interaction < 0.005), showing a lower risk for females and never smokers (HR: 0.92, 95% CI: 0.87-0.98 and HR: 0.93, 95% CI: 0.87-0.98, respectively). CONCLUSIONS: Higher physical activity levels are associated with a reduced risk of total, lung, and colorectal cancer.

Trends and predictions of lung cancer incidence in Jiangsu Province, China, 2009-2030: a bayesian age-period-cohort modelling study.

BACKGROUND: Lung cancer is currently the most frequent cancer in Jiangsu Province, China, and the features of cancer distribution have changed continuously in the last decade. The aim of this study was to analyse the trend of the incidence of lung cancer in Jiangsu from 2009 to 2018 and predict the incidence from 2019 to 2030. METHODS: Data on lung cancer incidence in Jiangsu from 2009 to 2018 were retrieved from the Jiangsu Cancer Registry. The average annual percentage change (AAPC) was used to quantify the trend of the lung cancer age-standardized rate (ASR) using Joinpoint software. Bayesian age-period-cohort models were used to predict lung cancer incidence up to 2030. RESULTS: In Jiangsu, the lung cancer crude rate increased from 45.73 per 100,000 in 2009 to 69.93 per 100,000 in 2018. The lung cancer ASR increased from 29.03 per 100,000 to 34.22 per 100,000 during the same period (AAPC = 2.17%, 95% confidence interval [CI], 1.54%, 2.80%). Between 2019 and 2030, the lung cancer ASR is predicted to decrease slightly to 32.14 per 100,000 (95% highest density interval [HDI], 24.99, 40.22). Meanwhile, the ASR showed a downward trend in males and rural regions while remaining stable in females and urban regions. CONCLUSION: We predict that the incidence of lung cancer in Jiangsu will decrease in the next 12 years, mainly due to the decrease in males and rural areas. Therefore, future lung cancer prevention and control efforts should be focused on females and urban regions.

Association Between Neuroticism and Risk of Lung Cancer: Results From Observational and Mendelian Randomization Analyses.

BACKGROUND: It remains undetermined whether neuroticism affects the risk of lung cancer. Therefore, we performed complementary observational and Mendelian randomization (MR) analyses to investigate the association between neuroticism and lung cancer risk. METHODS: We included 364,451 UK Biobank participants free of cancer at baseline. Neuroticism was ascertained using the 12-item of Eysenck Personality Inventory Neuroticism Scale. Multivariable Cox regression models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). Two-sample MR analysis was carried out with summary genetic data from UK Biobank (374,323 individuals) and International Lung Cancer Consortium (29,266 lung cancer cases and 56,450 controls). Furthermore, we calculated a polygenic risk score of lung cancer, and examined the joint-effect and interaction between neuroticism and genetic susceptibility on lung cancer risk. RESULTS: During a median follow-up of 7.13 years, 1573 lung cancer cases were documented. After adjusting for smoking and other confounders, higher neuroticism was associated with an increased risk of lung cancer (HR per 1 SD=1.07, 95% CI: 1.02-1.12). Consistently, MR analysis suggested a causal effect of neuroticism on lung cancer risk (OR IVW=1.10, 95% CI: 1.03-1.17). Compared to individuals with low neuroticism and low PRS, those with both high neuroticism and high PRS had the greatest risk of lung cancer (HR=1.82, 95%CI: 1.51-2.20). Furthermore, there was a positive additive but no multiplicative interaction between neuroticism and genetic risk. CONCLUSIONS: Our findings suggest that neuroticism is associated with an elevated risk of incident lung cancer, which is strengthened by the genetic susceptibility to lung cancer. Further studies are necessary to elucidate underlying mechanisms.

Association between circulating insulin-like growth factor 1 and risk of all-cause and cause-specific mortality.

BACKGROUND: Insulin-like growth factor 1 (IGF1) is an important growth factor modulating development, homeostasis, and aging. However, whether and how circulating IGF1 concentrations influence early death risk in the general population remains largely unknown. METHODS: We included 380 997 participants who had serum IGF1 measurement and no history of cancer, cardiovascular disease (CVD), or diabetes at baseline from UK Biobank, a prospective cohort study initiated in 2006-2010. Restricted cubic splines and Cox proportional hazards regression models were used to assess the association between baseline IGF-1 concentrations and all-cause and cause-specific mortality. RESULTS: Over a median follow-up of 8.8 years, 10 753 of the participants died, including 6110 from cancer and 1949 from CVD. Dose-response analysis showed a U-shaped relationship between IGF1 levels and mortality. Compared to the fifth decile of IGF1, the lowest decile was associated with 39% (95% CI: 29-50%), 20% (95% CI: 8-34%), and 39% (95% CI: 14-68%) higher risk of all-cause, cancer, and CVD mortality, respectively, while the highest decile was associated with 17% (95% CI: 7-28%) and 38% (95% CI: 11-71%) higher risk of all-cause and CVD mortality, respectively. The results remained stable in detailed stratified and sensitivity analyses. CONCLUSIONS: Our findings indicate that both low and high concentrations of serum IGF1 are associated with increased risk of mortality in the general population. Our study provides a basis for future interrogation of underlying mechanisms of IGF1 in early death occurrence and possible implications for mitigating the risk.

Birth Weight and Adult Obesity Index in Relation to the Risk of Hypertension: A Prospective Cohort Study in the UK Biobank.

Objectives: To investigate the association between birth weight and the risk of hypertension, and to examine the interaction between birth weight and the adult obesity index. Methods: We included 199,893 participants who had birth weight data and no history of hypertension at baseline (2006-2010) from the UK Biobank. A multivariate cubic regression spline was used to visually explore the dose-response relationship. Multivariate Cox proportional hazard regression models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). Results: We observed a nonlinear inverse association between birth weight and hypertension. The risk for hypertension decreased as birth weight increased up to approximately 3.80 kg. Compared with the participants with the fourth quintile of birth weight (3.43-3.80 kg), those with the first quartile of birth weight (<2.88 kg) were associated with a 25% higher risk of hypertension [HR 1.25; 95% CI (1.18-1.32)]. In addition, the participants with birth weight <2.88 kg and body mass index ≥30 kg/m2 had the highest risk [HR 3.54; 95% CI (3.16-3.97); p for interaction <0.0001], as compared with those with birth weight between 3.43-3.80 kg and body mass index between 18.5-25.0 kg/m2. These associations were largely consistent in the stratified and sensitivity analyses. Conclusion: Our findings indicate that lower birth weight is nonlinearly correlated with higher risk of hypertension, and birth weight between 3.43-3.80 kg might represent an intervention threshold. Moreover, lower birth weight may interact with adult obesity to significantly increase hypertension risk.

Association between birth weight and risk of cardiovascular disease: Evidence from UK Biobank.

BACKGROUND AND AIMS: Birth weight has been linked to cardiovascular disease (CVD) risk in adulthood, but no consensus has emerged on the threshold of birth weight for the lowest CVD risk and few studies have examined potential interaction between birth weight and adult adiposity. METHODS AND RESULTS: A total of 256,787 participants, who had birth weight data and were free of CVD at baseline, were included from UK Biobank. Multivariate restricted cubic splines and Cox regression models were used to assess the association between birth weight and CVD. We observed nonlinear inverse associations of birth weight with the risk of coronary heart disease (CHD), stroke, and heart failure. Participants with the first quintile of birth weight (≤2.85 kg) had higher risks for CHD (hazard ratio [HR] = 1.23, 95% confidence interval [CI]: 1.15-1.32), stroke (HR = 1.19, 95% CI: 1.03-1.37), and heart failure (HR = 1.28, 95% CI: 1.11-1.48), as compared to the fourth quintile (3.41-3.79 kg). There was a significant interaction between birth weight and adult body mass index (BMI) on CHD and heart failure (both P for interaction <0.001), showing the highest risk for those who had birth weight ≤2.85 kg and BMI ≥30 kg/m2 (HR = 1.96, 95% CI: 1.70-2.25 and HR = 2.39, 95% CI: 1.77-3.22, respectively). CONCLUSIONS: Our findings indicate nonlinear inverse associations between birth weight and CVD risk, with a threshold of 3.41-3.79 kg for the lowest risk. Moreover, low birth weight may interact with adult obesity to increase the risk of CHD and heart failure.

Associations of vitamin D status with colorectal cancer risk and survival.

Biological evidence suggests that vitamin D has numerous anticancer functions, but the associations between vitamin D status and colorectal cancer (CRC) risk and survival remain inconclusive. Based on UK Biobank, we prospectively evaluated the associations of season-standardized 25-hydroxyvitamin D (25(OH)D) concentrations with CRC risk among 360 061 participants, and with survival among 2509 CRC cases. We observed an inverse linear relationship between 25(OH)D concentrations and CRC risk (P for linearity = .01; HR per 1-SD increment, 0.95; 95% CI, 0.91-0.99). Compared to the lowest quartile of 25(OH)D, the highest quartile was associated with a 13% (HR, 0.87; 95% CI, 0.77-0.98) lower risk of CRC. For CRC survival, compared to those in the lowest quartile of 25(OH)D, cases in the highest quartile had a 20% (HR, 0.80; 95% CI, 0.65-0.99) lower risk for overall death. Our findings indicate that higher concentrations of serum 25(OH)D are associated with lower incidence and improved survival of CRC, suggesting a role of vitamin D in the pathogenesis of CRC.

Sex-specific associations of circulating testosterone levels with all-cause and cause-specific mortality.

OBJECTIVE: Testosterone is a critical determinant of health in both genders. However, the relationship between circulating levels of testosterone and mortality remains undetermined. METHODS: We examined the associations of serum total testosterone (TT) and free testosterone (FT) with all-cause and cause-specific mortality in 154 965 men and 93 314 postmenopausal women from UK Biobank. Cox regression models were used to calculate the hazard ratios (HR) and 95% CIs. Given multiple testing, P < 0.005 was considered statistically significant. RESULTS: Over a median follow-up of 8.9 (inter-quartile range: 8.3-9.5) years, we documented 5754 deaths in men, including 1243 (21.6%) from CVD and 2987 (51.9%) from cancer. In postmenopausal women, 2435 deaths occurred, including 346 (14.2%) from CVD and 1583 (65.0%) from cancer. TT and FT concentrations were inversely associated with all-cause mortality in men, with the multivariable HR of 0.82 (95% CI: 0.75-0.91) and 0.80 (95% CI: 0.73-0.87) for the highest (Q5) vs the lowest quintile (Q1), respectively. In postmenopausal women, TT concentrations showed a positive association with all-cause mortality (HR for Q5 vs Q1 = 1.20, 95% CI: 1.06-1.37). Furthermore, higher TT and FT concentrations were associated with a lower risk of cancer mortality in men (both P for trend = 0.001), whereas TT concentrations were suggestively associated with a higher risk of cancer mortality in postmenopausal women (P for trend = 0.03). CONCLUSIONS: Our findings suggest that high levels of circulating testosterone may be beneficial for all-cause and cancer mortality in men but detrimental in postmenopausal women.

Pre-diagnostic circulating concentrations of insulin-like growth factor-1 and risk of COVID-19 mortality: results from UK Biobank.

Coronavirus disease 2019 (COVID-19) deteriorates suddenly primarily due to excessive inflammatory injury, and insulin-like growth factor-1 (IGF-1) is implicated in endocrine control of the immune system. However, the effect of IGF-1 levels on COVID-19 prognosis remains unknown. Using UK Biobank resource, we investigated the association between circulating IGF-1 concentrations and mortality risk (available death data updated on 07 Sep 2020) among COVID-19 patients who had pre-diagnostic serum IGF-1 measurements at baseline (2006-2010). Unconditional logistic regression was performed to estimate the odds ratio (OR) and 95% confidence intervals (CIs) of mortality. Among 1670 COVID-19 patients, 415 deaths occurred due to COVID-19. Compared to the lowest quartile of IGF-1 concentrations, the highest quartile was associated with a 41% lower risk of mortality (OR = 0.59, 95% CI 0.41-0.86, P-trend = 0.01). In the continuous model, per 1-standard deviation increment in log-transformed IGF-1 was associated with a 15% reduction in the risk (intraclass correlation coefficients corrected OR = 0.85, 95% CI 0.73-0.99). The association was largely consistent in the various stratified and sensitivity analyses. In conclusion, our data suggest that higher IGF-1 concentrations are associated with a lower risk of COVID-19 mortality. Further studies are required to determine whether and how targeting IGF-1 pathway might improve COVID-19 prognosis.