Significant Additive Interaction Research Articles

Association patterns of ketone bodies with the risk of adverse outcomes according to diabetes status.

To investigate the associations between ketone bodies (KB) and multiple adverse outcomes including cardiovascular disease (CVD), chronic kidney disease (CKD) and all-cause mortality according to diabetes status. This prospective study included 222 824 participants free from CVD and CKD at baseline from the UK Biobank. Total KB including β-hydroxybutyrate, acetoacetate and acetone were measured by nuclear magnetic resonance. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between KB and adverse outcomes among participants with normoglycaemia, prediabetes and type 2 diabetes, respectively. During a mean follow-up of 14.1 years, 24 088 incident CVD events (including 17 303 coronary heart disease events, 5172 stroke events and 5881 heart failure [HF] events), 8605 CKD events and 15 813 deaths, were documented. Higher total KB significantly increased the risk of HF among participants with normoglycaemia (HR, 1.32 [95% CI, 1.17-1.49], per 10-fold increase in total KB) and prediabetes (1.35 [1.04-1.76]), and increased the risk of CKD among those with normoglycaemia (1.20 [1.09-1.33]). Elevated KB levels were associated with an increased risk of all-cause mortality across the glycaemic spectrum (1.32 [1.23-1.42] for normoglycaemia, 1.45 [1.24-1.71] for prediabetes and 1.47 [1.11-1.94] for diabetes). Moreover, a significant additive interaction between KB and diabetes status was observed on the risk of death (P = .009), with 4.9% of deaths attributed to the interactive effects. Our study underscored the variation in association patterns between KB and adverse outcomes according to diabetes status and suggested that KB could interact with diabetes status in an additive manner to increase the risk of mortality.

Relationships between sarcopenia, depressive symptoms, and the risk of cardiovascular disease in Chinese population

BackgroundPrevious studies had indicated that sarcopenia and depressive symptoms were associated with increased risk of cardiovascular disease (CVD). The aim of present study was to evaluate the combined effect of sarcopenia and depressive symptoms on the CVD risk. MethodsA total of 11,011 participants from the China Health and Retirement Longitudinal Study 2011–2020 were included. Multivariate Cox proportional hazards regression model was used to explore the associations between sarcopenia, depressive symptoms and new-onset CVD, stroke and cardiac events. ResultsDuring the 7-year follow-up, a total of 2,388 respondents experienced CVD (including 812 stroke and 1,831 cardiac events). There is a significant additive and multiplicative interactions of sarcopenia and depressive symptoms on risk of CVD, stroke and cardiac events. Compared with those without sarcopenia and depressive symptoms, individuals with depressive sarcopenia had the highest risk of CVD, stroke and cardiac events, with the corresponding hazard ratios (95% confidence interval) were 1.43 (1.26–1.63), 1.45 (1.15–1.82) and 1.50 (1.29−1.74), respectively. ConclusionOur study indicated that there was a combined effect of sarcopenia and depressive symptoms on the risk of CVD, stroke and cardiac events. Our findings highlighted the importance of identifying sarcopenia and depressive symptoms, and intervening much earlier both in older and younger population.

Sleep and liver function biomarkers in relation to risk of incident liver cancer: a nationwide prospective cohort study

BackgroundTo assess the largely undetermined separate and joint effects of sleep and liver function biomarkers on liver cancer.MethodsData of 356,894 participants without cancer at baseline in the UK Biobank were analyzed. Sleep score was evaluated using five sleep traits (sleep duration, chronotype, insomnia, snoring, and excessive daytime sleepiness) and dichotomized into healthy or unhealthy sleep. Circulating liver function biomarkers were measured. Cox proportional hazard model was performed to investigate the independent and joint associations of sleep and liver function biomarkers with liver cancer incidence.ResultsAfter a median follow-up time of 13.1 years, 394 cases of incident liver cancer were documented. The multivariable-adjusted hazard ratio (HR) for liver cancer was 1.46 (95% confidence interval: 1.15–1.85) associated with unhealthy sleep (vs. healthy sleep), and was 1.17 (1.15–1.20), 1.20 (1.18–1.22), 1.69 (1.47–1.93), 1.06 (1.06–1.07), 1.08 (1.07–1.09), 1.81 (1.37–2.39), or 0.29 (0.18–0.46) associated with each 10-unit increase in alanine transaminase (ALT), aspartate transaminase (AST), total bilirubin (TBIL), gamma-glutamyl transferase (GGT), alkaline phosphatase (ALP), total protein (TP), or albumin (ALB), respectively. Individuals with unhealthy sleep and high (≥ median) ALT, AST, TBIL, GGT, ALP, or TP or low (< median) ALB level had the highest HR of 3.65 (2.43–5.48), 4.03 (2.69–6.03), 1.97 (1.40–2.77), 4.69 (2.98–7.37), 2.51 (1.75–3.59), 2.09 (1.51–2.89), or 2.22 (1.55–3.17) for liver cancer, respectively. Significant additive interaction of unhealthy sleep with high TP level on liver cancer was observed with relative excess risk due to an interaction of 0.80 (0.19–1.41).ConclusionsUnhealthy sleep was associated with an increased risk of liver cancer, especially in participants with lower ALB levels or higher levels of ALT, AST, TBIL, GGT, ALP, or particularly TP.

Unveiling Statins and Genetics in Age-Related Macular Degeneration: The Coimbra Eye Study-Report 9.

To assess the association of age-related macular degeneration (AMD) progression and statins, connected with AMD genetic risk, and if there is an interplay between statins and genetics. In this analysis, 682 subjects made two visits (6.5-year follow-up) of the Coimbra Eye Study. Subjects who started taking statins at any time point between the two visits were considered. Progressors were defined as not having AMD at baseline and having any AMD at follow-up. Genetic risk scores (GRSs) were calculated individually with 52 independent variants associated with AMD. Time to progression was estimated using unadjusted Kaplan-Meier curves. An extended Cox model was used for the association between statins and GRS with the risk for AMD progression. Multiplicative and additive interactions were assessed. Median survival time was 7.50 years for subjects not taking statins and 7.62 for subjects taking statins (P < 0.001). Statin intake reduced the risk for progression to AMD in 48%, adjusting for age, sex, body mass index, smoking, and diabetes (model 1) and GRS (model 2). The combined effects of not taking statins and having high GRS increased the progression risk fourfold compared to taking statins and having low GRS (hazard ratio [HR] = 4.25; 95% confidence interval [CI], 1.62-11.16; P = 0.003). For subjects not taking statins, an increased risk of progression was found for those subjects with high GRS compared to subjects with low GRS (HR = 1.80; 95% CI, 1.13-2.85; P = 0.013). No statistically significant multiplicative or additive interactions were found. Statins seem to be protective against AMD progression, and genetics may play a role in treatment response.

The role of familial factors and neuroticism in the association between exposure to offensive behaviors at work and long-term sickness absence due to common mental disorders - a prospective twin study

ObjectivesThe aim of this study was to investigate associations between exposure to work-related violence/threats and harassment, and future sickness absence (SA) due to common mental disorders (CMDs), taking familial factors (shared genetics and early-life environment) and neuroticism into account.MethodsThe study sample included 8795 twin individuals from the Swedish Twin Project of Disability Pension and Sickness Absence (STODS), including survey data from the Study of Twin Adults: Genes and Environment (STAGE). Self-reported work-related violence and/or threats as well as work-related harassment (including bullying) and national register data on SA due to CMDs were analyzed using standard logistic regression, and conditional logistic regression among complete twin pairs discordant on exposures. Individuals were followed for a maximum of 13 years. Interactions between neuroticism and exposures were assessed using both multiplicative and additive interaction analyses.ResultsExposure to work-related violence/threats was associated with higher odds of SA due to CMDs when adjusting for age, sex, marital status, children, education, type of living area, work characteristics, and symptoms of depression and burnout (OR 2.11, 95% CI 1.52–2.95). Higher odds of SA due to CMDs were also found for exposure to harassment (OR 1.52, 95% CI 1.10–2.11) and a combined indicator of exposure to violence/threats and/or harassment (OR 1.98, 95% CI 1.52–2.59), compared with the unexposed. Analyses of twins discordant on exposure, using the unexposed co-twin as reference, showed reduced ORs. These ORs were still elevated but no longer statistically significant, potentially due to a lack of statistical power. No multiplicative interaction was found between neuroticism and exposure to work-related violence/threats, or harassment. However, a statistically significant additive interaction was found between neuroticism and exposure to violence/threats, indicating higher odds of SA due to CMDs in the group scoring lower on neuroticism.ConclusionsExposure to work-related offensive behaviors was associated with SA due to CMDs. However, the results indicated that these associations may be partly confounded by familial factors. In addition, an interaction between exposure and neuroticism was suggested. Thus, when possible, future studies investigating associations and causality between offensive behaviors at work and mental health-related outcomes, should consider familial factors and neuroticism.

Secondhand tobacco smoke and risk of atrial fibrillation: an observational epidemiologic and gene-environment interaction analysis

Abstract Background Second-hand tobacco smoke (SHS) is related to coronary artery disease and increases susceptibility to arrhythmia inducibility including atrial fibrillation (AF). However, epidemiologic evidence on the relationship between SHS and the risk of incident AF remains controversial. Purpose To evaluate the effect of SHS exposure on the long-term risk of AF and assess whether gene-environment interaction (synergism) exists by utilising the population-based data from the UK biobank. Methods We performed a nationwide population-based cohort study using the UK Biobank database. Participants with previous AF or current smokers were excluded. Participants were categorised into SHS-exposure and non-exposure groups. The risk of incident AF was assessed using the multivariable Cox proportional hazards model. We also evaluated the synergistic effect of SHS exposure and the polygenic risk score (PRS) of AF. Results Out of 400,493 participants, AF occurred in 23,471 (5.9%) during a median follow-up of 12.5 years. The SHS-exposure group (mean exposure 2.2 ± 5.2 hours/week) had a higher proportion of male participants with a younger age. The risk of incident AF was significantly increased in the SHS-exposure group (multivariable-adjusted hazard ratio [aHR] 1.06, 95% confidence interval 1.03-1.10, P &amp;lt;0.001) compared to the non-exposure group, suggesting a dose-dependent manner (aHR of severe SHS-exposure group, 1.11 [1.03-1.20], P = 0.005). The risk of AF increases regardless of the exposure location (home, outside, or workplace). When SHS-exposure was combined with the high genetic risk of AF, significant additive interaction was observed on the risk AF (Synergy Index of SHS-exposure with 3rdtertile of AF PRS, 1.13 [1.02-1.25], P = 0.024). Conclusion Exposure to SHS is a significant predictor for an increased risk of AF, with a synergistic effect when combined with genetic predisposition. Minimising SHS exposure, especially in individuals with a heightened genetic susceptibility to AF, may hold potential benefits for reducing the future risk of AF.

Examining the relationship between social determinants of health, measures of structural racism and county-level overdose deaths from 2017-2020.

Despite being an important determinant of health outcomes, measures of structural racism are lacking in studies examining the relationship between the social determinants of health (SDOH) and overdose deaths. The aim of this study is to examine the association between per capita revenue generated from fines and forfeitures, a novel measure of structural racism, and other SDOH with county-level overdose deaths from 2017-2020. This longitudinal analysis of 2,846 counties from 2017-2020 used bivariate and multivariate Generalized Estimating Equations models to estimate associations between county overdose mortality rates and SDOH characteristics, including the fines and forfeitures measure. In our multivariate model, higher per capita fine and forfeiture revenue (5.76; CI: 4.76, 6.78), households receiving food stamps (1.15; CI: 0.77, 1.53), residents that are veterans (1.07; CI: 0.52, 1.63), substance use treatment availability (4.69; CI: 3.03, 6.33) and lower population density (-0.002; CI: -0.004, -0.001) and percent of Black residents (-0.7`; CI: -1.01, -0.42) were significantly associated with higher overdose death rates. There was a significant additive interaction between the fines and forfeitures measure (0.10; CI: 0.03, 0.17) and the percent of Black residents. Our findings suggest that structural racism, along with other SDOH, is associated with overdose deaths. Future research should focus on connecting individual-level data on fines and forfeitures to overdose deaths and other health outcomes, include measures of justice-related fines, such as court fees, and assess whether interventions aimed at increasing economic vitality in disadvantaged communities impact overdose deaths in a meaningful way.

Combined use of Donepezil and Memantine increases the probability of five-year survival of Alzheimer’s disease patients

BackgroundAlzheimer’s disease (AD) is the most common neurodegenerative disease. Studying the effects of drug treatments on multiple health outcomes related to AD could be beneficial in demonstrating which drugs reduce the disease burden and increase survival.MethodsWe conducted a comprehensive causal inference study implementing doubly robust estimators and using one of the largest high-quality medical databases, the Oracle Electronic Health Records (EHR) Real-World Data. Our work was focused on the estimation of the effects of the two common Alzheimer’s disease drugs, Donepezil and Memantine, and their combined use on the five-year survival since initial diagnosis of AD patients. Also, we formally tested for the presence of interaction between these drugs.ResultsHere, we show that the combined use of Donepezil and Memantine significantly elevates the probability of five-year survival. In particular, their combined use increases the probability of five-year survival by 0.050 (0.021, 0.078) (6.4%), 0.049 (0.012, 0.085), (6.3%), 0.065 (0.035, 0.095) (8.3%) compared to no drug treatment, the Memantine monotherapy, and the Donepezil monotherapy respectively. We also identify a significant beneficial additive drug-drug interaction effect between Donepezil and Memantine of 0.064 (0.030, 0.098).ConclusionsBased on our findings, adopting combined treatment of Memantine and Donepezil could extend the lives of approximately 303,000 people with AD living in the USA to be beyond five-years from diagnosis. If these patients instead have no drug treatment, Memantine monotherapy or Donepezil monotherapy they would be expected to die within five years.

Insulin resistance and its relationship with long-term exposure to ozone: Data based on a national population cohort

The relationship of ozone (O3), particularly the long-term exposure, with impacting metabolic homeostasis in population was understudied and under-recognised. Here, we used data from ChinaHEART, a nationwide, population-based cohort study, combined with O3 and PM2.5 concentration data with high spatiotemporal resolution, to explore the independent association of exposure to O3 with the prevalence of insulin resistance (IR). Among the 271 540 participants included, the crude prevalence of IR was 39.1%, while the age and sex standardized prevalence stood at 33.0%. Higher IR prevalence was observed with each increase of 10.0 μg/m3 in long-term O3 exposure, yielding adjusted odds ratios (OR) of 1.084 (95% CI: 1.079–1.089) in the one-pollutant model and 1.073 (95% CI: 1.067–1.079) in the two-pollutant model. Notably, a significant additive interaction between O3 and PM2.5 on the prevalence of IR was observed (P for additive interaction < 0.001). Our main findings remained consistent and robust in the sensitivity analyses. Our study suggests long-term exposure to O3 was independently and positively associated with prevalence of IR. It emphasized the benefits of policy interventions to reduce O3 and PM2.5 exposure jointly, which could ultimately alleviate the health and economic burden related to DM.

Association of levonorgestrel-releasing intrauterine device with gynecologic and breast cancers: a national cohort study in Sweden

BackgroundThe levonorgestrel-releasing intrauterine device (LNG-IUD) is widely used for the treatment of menorrhagia, dysmenorrhea, and for contraception. However, the association between the use of LNG-IUD and the risk of site-specific gynecologic and breast cancers remains inconclusive. ObjectiveWe aim to address this knowledge gap by investigating whether the use of LNG-IUD is associated with a significant risk of site-specific gynecologic and breast cancers. This will be achieved by accessing the nationwide Swedish Registers, with consideration given to the influence and potential interaction of family history of cancer. Study DesignA total of 514719 women aged 18 to 50 years who have used LNG-IUD between July 2005 and December 2018 were identified from the Swedish Prescribed Drug Register and randomly matched with 1544157 comparisons who did not use LNG-IUD at a ratio of 1:3. The propensity score was calculated and matched among women who used LNG-IUD and the matched comparisons. The follow-up period started from the date of the first prescription of LNG-IUD for users as well as for their matched comparisons and ended at the date of diagnosis of gynecologic and breast cancers, date of death from any cause, and the end of the study period, whichever came first. The Cox proportional hazard model with a competing risk analysis was used to calculate hazard ratios and 95% confidence intervals. Additive interaction was calculated as the relative excess risk for interaction, while multiplicative interaction was calculated by including a product term in the regression model. ResultsThe use of LNG-IUD was associated with a 13% higher risk of breast cancer (adjusted HR, 1.13; 95% CI, 1.10-1.17), a 33% lower risk of endometrial cancer (adjusted HR, 0.67; 95% CI, 0.56-0.80), a 14% lower risk of ovarian cancer (adjusted HR, 0.86; 95% CI, 0.75-0.99) and a 9% reduced risk of cervical cancer (adjusted HR, 0.91; 95% CI, 0.84-0.99) compared to women who did not use LNG-IUD. A significant additive interaction between LNG-IUD use and family history of cancer was observed in breast cancer, indicating a relative 19% excess risk for interaction (P < 0.002), and 1.63 additional cases per 10,000 person-years. ConclusionsThe risk of gynecologic and breast cancers exhibits a site-specific effect among LNG-IUD users. It's important to note that the observed effect is small for breast cancer and the results are limited by the observational study design. Clinical recommendations regarding the use of LNG-IUD should carefully weigh its potential benefits and risks. Close monitoring is advisable for the potential development of breast cancer, particularly among women with a family history of breast cancer.

Association of cognitive impairment with the interaction between chronic kidney disease and depression: findings from NHANES 2011–2014

BackgroundCognitive impairment (CoI), chronic kidney disease (CKD), and depression are prevalent among older adults and are interrelated, imposing a significant disease burden. This study evaluates the association of CKD and depression with CoI and explores their potential interactions.MethodData for this study were sourced from the 2011–2014 National Health and Nutritional Examination Survey (NHANES). Multiple binary logistic regression models assessed the relationship between CKD, depression, and CoI while controlling for confounders. The interactions were measured using the relative excess risk of interaction (RERI), the attributable proportion of interaction (AP), and the synergy index (S).ResultsA total of 2,666 participants (weighted n = 49,251,515) were included in the study, of which 700 (16.00%) had CoI. After adjusting for confounding factors, the risk of CoI was higher in patients with CKD compared to non-CKD participants (odds ratio [OR] = 1.49, 95% confidence interval [CI]:1.12–1.99). The risk of CoI was significantly increased in patients with depression compared to those without (OR = 2.29, 95% CI: 1.73–3.03). Furthermore, there was a significant additive interaction between CKD and depression in terms of the increased risk of CoI (adjusted RERI = 2.01, [95% CI: 0.31–3.71], adjusted AP = 0.50 [95% CI: 0.25–0.75], adjusted S = 2.97 [95% CI: 1.27–6.92]).ConclusionCKD and depression synergistically affect CoI, particularly when moderate-to-severe depression co-occurs with CKD. Clinicians should be mindful of the combined impact on patients with CoI. Further research is needed to elucidate the underlying mechanisms and assess the effects specific to different CKD stages.

Association of hypertension and depression with mortality: an exploratory study with interaction and mediation models

BackgroundThe association of hypertension and depression with mortality has not been fully understood. We aimed to explore the possible independent or joint association of hypertension and depression with mortality. Their interaction effects on mortality and possible mediating role were also investigated.MethodsAssociations of hypertension, depression, and their interaction with all-cause and cardiovascular disease (CVD) mortality were evaluated using multivariate Cox proportional hazards regression models. The mediation analysis was conducted with a Sobel test.ResultsA total of 35152 participants were included in the final analysis. Hypertension and depression were independently associated with increased risk of all-cause and CVD mortality. The co-existence of hypertension and depression resulted in a 1.7-fold [95% confidence interval (CI): 1.3-2.1] increase in all-cause mortality and a 2.3-fold (95% CI: 1.4-3.7) increase in CVD mortality compared to those with neither of them. Hypertension and depression showed no significant multiplicative (P for interaction, 0.587) and additive interaction (P for relative excess risk of interaction, 0.243; P for Interaction on additive scale, 0.654) on all-cause mortality, as well as on CVD mortality. Depression did not mediate the relationship between hypertension and all-cause (Z=1.704, P=0.088) and CVD mortality (Z=1.547, P=0.122). Hypertension did not mediate the relationship between all-cause and CVD mortality as well.ConclusionHypertension and depression were related to all-cause and CVD mortality independently and the co-existence of them increased the risk of mortality. However, there is no interaction effect of them on mortality, and hypertension or depression did not mediate the association of each other with mortality.

Association Between Composite Dietary Antioxidant Index and the Risk of Endometriosis-Related Rheumatoid Arthritis in Women of Childbearing Age: A Cross-Sectional Study Based on the National Health and Nutrition Examination Survey Database.

To evaluate the association between Composite Dietary Antioxidant Index (CDAI) and the risk of endometriosis (EM)-related rheumatoid arthritis (RA) in women of childbearing age. Using the data from the National Health and Nutrition Examination Survey database, this cross-sectional study included women of childbearing age. The CDAI was obtained by summing the standardized Z-values of the dietary intakes. EM was diagnosed based on a questionnaire-based survey. The outcome of this study was the presence of RA, which was defined by a questionnaire. The associations of CDAI and EM with the risk of RA were determined using weighted logistic analysis. Additive interaction was evaluated using the relative excess risk due to interaction (RERI), the attributable proportion due to interaction (AP), and the synergy index (S). In total, 3803 patients were included, of which 74 patients (1.99%) were with RA. A lower CDAI [odds ratio (OR): 1.85, 95% confidence interval (CI): 1.12 to 3.04, P= 0.015] and the presence of EM (OR: 3.05, 95% CI: 1.19 to 7.81, P= 0.023) was associated with the risk of RA. The result demonstrated an additive interaction of a lower CDAI and the presence of EM on the risk of RA (OR: 6.19, 95% CI: 2.33 to 16.43, P <0.001, P of trend =0.007). Nevertheless, there was no significant additive interaction after being assessed by the RERI, AP, and S. However, a joint effect of a lower CDAI and EM on the risk of RA (OR: 3.94, 95% CI: 1.35 to 11.51, P= 0.013) was observed. Our study identified EM, and lower CDAI, was related to the risk of RA. Lower CDAI score was also associated with the risk of EM-related RA. This study indicates the importance of antioxidant intake in daily diet for the management of EM-related RA.

Association between sleep quality, depressive symptoms, and suicidal ideation in college students

ABSTRACT Suicide among college students is a challenging problem globally. Yet, the association between sleep quality, depressive symptoms, and suicidal ideation remains unclear. This study aims to understand if depressive symptoms mediate the relationship between sleep quality and suicide ideation and whether the interaction between depressive symptoms and sleep quality on suicidal ideation is additive. A total of 1182 college students were recruited, and sleep quality, depressive symptoms, and suicidal ideation were assessed using questionnaires. Univariate analysis, logistic regression analysis, linear regression models, and the Sobel test were performed. The results showed that, among college students, poor sleep quality was positively associated with suicidal ideation, and the association was mediated through depressive symptoms. Moreover, there was a significant additive interaction between poor sleep quality and depressive symptoms on suicidal ideation. These findings suggest that, in the process of preventing and treating suicidal ideation in college students with sleep disorders, we should focus on the evaluation and intervention of depressive symptoms and adopt multidisciplinary team interventions for college students with sleep disorders and depression.

Abstract P421: Smoking Timing, Healthy Diet, and Risk of Incident CKD Among Smokers: A Cohort Study in UK Biobank

Introduction: While smoking is a recognized risk factor for chronic kidney disease (CKD), the relationship between the smoking timing and CKD remains largely unstudied. Hypothesis: We assessed the hypothesis that there is an association between the smoking timing and the risk of CKD. Method: A total of 32,776 participants with complete data on the time from waking to the first cigarette and free of prevalent CKD from UK Biobank were included in this prospective study. The Cox proportional hazard model was used to investigate the associations between smoking timing and risk of CKD. The potential interactions of smoking timing with risk factors in relation to CKD risk were assessed on both multiplicative and additive scales. Results: During a median follow-up of 12 years, 940 incident CKD cases were reported. Shorter time from waking to the first cigarette was significantly associated with a higher risk of incident CKD ( P -trend=0.012). The adjusted hazard ratio (HR) associated with smoking timing was 1.28 (95% CI: 0.92-1.80) for 61-120 minutes, 1.48 (95% CI: 1.11-1.96) for 30-60 minutes, 1.36 (95% CI: 1.01-1.88) for 5-15 minutes, and 1.70 (95% CI: 1.22-2.37) for &lt;5 minutes, respectively. Those who smoke within 5 minutes of waking had a 70% increased risk of CKD incident compared to those who delayed for over 120 minutes. Furthermore, there was a significant positive additive interaction between the timing of smoking and a healthy diet score ( P for additive interaction=0.01). Conclusion: Our findings indicate a significant association between the shorter time from waking to the first cigarette and a higher CKD risk; and the associations are exacerbated in the presence of an unhealthy diet.

Air pollution and serious bleeding events in high-risk older adults

ImportanceDespite biological plausibility, very few epidemiologic studies have investigated the risks of clinically significant bleeding events due to particulate air pollution. ObjectiveTo measure the independent and synergistic effects of PM2.5 exposure and anticoagulant use on serious bleeding events. DesignRetrospective cohort study (2008–2016). SettingNationwide Medicare population. ParticipantsA 50% random sample of Medicare Part D-eligible Fee-for-Service beneficiaries at high risk for cardiovascular and thromboembolic events. ExposuresFine particulate matter (PM2.5) and anticoagulant drugs (apixaban, dabigatran, edoxaban, rivaroxaban, or warfarin). Main outcomes and measuresThe outcomes were acute hospitalizations for gastrointestinal bleeding, intracranial bleeding, or epistaxis. Hazard ratios and 95% CIs for PM2.5 exposure were estimated by fitting inverse probability weighted marginal structural Cox proportional hazards models. The relative excess risk due to interaction was used to assess additive-scale interaction between PM2.5 exposure and anticoagulant use. ResultsThe study cohort included 1.86 million high-risk older adults (mean age 77, 60% male, 87% White, 8% Black, 30% anticoagulant users, mean PM2.5 exposure 8.81 μg/m3). A 10 μg/m3 increase in PM2.5 was associated with a 48% (95% CI: 45%–52%), 58% (95% CI: 49%–68%) and 55% (95% CI: 37%–76%) increased risk of gastrointestinal bleeding, intracranial bleeding, and epistaxis, respectively. Significant additive interaction between PM2.5 exposure and anticoagulant use was observed for gastrointestinal and intracranial bleeding. ConclusionsAmong older adults at high risk for cardiovascular and thromboembolic events, increasing PM2.5 exposure was significantly associated with increased risk of gastrointestinal bleeding, intracranial bleeding, and epistaxis. In addition, PM2.5 exposure and anticoagulant use may act together to increase risks of severe gastrointestinal and intracranial bleeding. Thus, clinicians may recommend that high-risk individuals limit their outdoor air pollution exposure during periods of increased PM2.5 concentrations. Our findings may inform environmental policies to protect the health of vulnerable populations.

Association of a low-inflammatory diet with survival among adults: The role of cardiometabolic diseases and lifestyle

Background and aimsEvidence on the association between dietary inflammation and longevity is limited. We aimed to examine the association of a low-inflammatory diet with mortality and longevity, and to explore whether cardiometabolic diseases (CMDs) and lifestyle factors may play a role in this association. MethodsWithin the UK Biobank, 188,443 participants aged 39-72 years (mean 56.07) were followed for up to 16 years to detect survival status from the death registry. At baseline, dietary intake was assessed with a 24-hour dietary record. An inflammatory diet index (IDI) was calculated as weighted sum of 31 food groups (including 14 anti-inflammatory and 17 pro-inflammatory) based on plasma high-sensitivity C-reactive protein levels, and tertiled as low, moderate, and high IDI scores. Baseline lifestyle beyond diet was assessed by summing the number of healthy lifestyle factors (i.e., never smoking, regular physical activity, and normal BMI) and categorized as unfavorable (≤1) and favorable (≥2). Presence of CMDs was defined as having any one of type 2 diabetes, ischemic heart disease, atrial fibrillation, heart failure, and stroke. Data were analyzed using Cox regression, Laplace regression, and generalized structural equation modelling. ResultsDuring the follow-up (median 9.79 years, interquartile range: 9.68 to 10.57 years), 9,178 (4.9%) participants died. In multi-adjusted Cox regression models, a low-inflammatory diet (i.e. low IDI score) was associated with lower risk of all-cause mortality [hazard ratio (HR)=0.82, 95% confidence interval (CI): 0.78 to 0.86]. Laplace regression analysis showed that the multi-adjusted 10th percentile difference (10th PD, 95% CI) of death time was delayed by 0.80 (0.55, 1.06; P<0.001) years for participants with a low IDI score compared to those with a high IDI score. In mediation analysis, 21.48% of the association between IDI and mortality was mediated by CMDs. In joint effect analysis, participants with a low IDI score and favorable lifestyle had a 42% lower risk of death (HR=0.58, 95% CI: 0.54, 0.62) compared to those with a high IDI score and unfavorable lifestyle. There was a significant additive interaction between low IDI score and favorable lifestyle on decreased mortality. ConclusionsA low-inflammatory diet is associated with a lower risk of death and could prolong survival time. CMDs may partially mediate the IDI-mortality association. A favorable lifestyle beyond diet may augment the positive effect of a low-inflammatory diet on longevity.

Combined effects of vitamin D deficiency and systemic inflammation on all-cause mortality and cause-specific mortality in older adults

BackgroundVitamin D deficiency and systemic inflammation share common pathological mechanisms in muscle loss, cardio-pulmonary function decline, and abnormal metabolism, which are linked to chronic conditions, senescence, and early mortality. However, their combined effect on mortality in older adults has not been well established. This study longitudinal aimed to explore the independent and combined associations of serum 25-hydroxyvitamin D [25(OH)D] and high sensitivity C-reactive protein (hs-CRP) with mortality risk in Chinese community-based older people.Methods3072 older adults (86.07 ± 11.87 years, 54.52% female) from the Chinese Longitudinal Healthy Longevity Survey (2012–2018) were enrolled. Baseline 25(OH)D and hs-CRP levels were collected, and survival information was recorded in the 2014 and 2018 follow-up waves. Cox proportional hazard regressions were conducted to explore the associations between 25(OH)D, hs-CRP, and mortality. Demographic characteristics, health behaviors, and chronic disease biomarkers were adjusted.ResultsDuring 10,622.3 person-years of follow-up (median: 3.51 years), 1321 older adults died, including 448 deaths due to cardiovascular disease (CVD). Increased mortality risk was associated with lower 25(OH)D and higher hs-CRP quantiles, even after adjusting for each other and multiple covariates (all P-trend < 0.05). In combined analyses, the highest all-cause mortality (HR: 2.18, 95% CI: 1.73 ~ 2.56), CVD mortality (HR: 2.30, 95% CI: 1.64 ~ 3.21), and non-CVD mortality (HR: 2.19, 95% CI: 1.79 ~ 2.49) were obtained in participants with both 25(OH)D deficiency (< 50 nmol/L) and high hs-CRP (≥ 3.0 mg/L), respectively. We observed significant additive interactions of 25(OH)D and hs-CRP on all-cause mortality and non-CVD mortality (RERIS>0).ConclusionsLow 25(OH)D and high hs-CRP, both independently and jointly, increase mortality risk in Chinese community-dwelling older adults. Thus, priority should be given to early detection and appropriate intervention in older individuals with combined vitamin D deficiency and systemic inflammation. Molecular mechanisms of related adverse health effect are worthy of further investigation.

Interaction between sleep duration and trouble sleeping on depressive symptoms among U.S. adults, NHANES 2015-2018

BackgroundThis study aims to examine the associations and interaction effects of sleep duration and trouble sleeping on depressive symptoms among U.S. adults. MethodsNational Health and Nutrition Examination Survey (NHANES) data from 2015 to 2018 were analyzed (N = 10,044). Trouble sleeping and sleep duration were self-reported. Sleep duration was defined as short (≤6 h) or long (≥9 h), compared with normal (>6 and < 9 h). Depressive symptoms were determined by the Patient Health Questionnaire-9 score ≥ 10. Both multiplicative interaction and additive interaction were reported. ResultsThere was a significant positive additive interaction between short sleep duration and trouble sleeping on depressive symptoms in the fully adjusted model (Relative excess risk due to interaction, RERIOR = 4.42, 95 % CI: 1.12, 7.73), with 43 % of the association with depressive symptoms attributed to the interaction (attributable proportion of interaction, AP = 0.43, 95 % CI: 0.22, 0.64). Similarly, a significant positive additive interaction between long sleep duration and trouble sleeping on depressive symptoms was found (RERIOR = 4.17, 95 % CI: 0.96, 7.38), with 41 % of the association with depressive symptoms attributed to the interaction (AP = 0.41, 95 % CI: 0.21, 0.60). No multiplicative interaction was detected between short or long sleep duration and trouble sleeping. LimitationsThe cross-sectional design limits the ability to draw causal inferences. ConclusionsFindings suggest that different aspects of sleep health interact synergistically, accounting for a substantial portion of the association with depressive symptoms. This underscores the importance of simultaneously considering multiple dimensions of sleep health in relation to depressive symptoms.

Interacting and joint effects of triglyceride-glucose index (TyG) and body mass index on stroke risk and the mediating role of TyG in middle-aged and older Chinese adults: a nationwide prospective cohort study

BackgroundIndividuals who are overweight or obese often develop insulin resistance, mediation of the association between body mass index (BMI) and stroke risk through the triglyceride-glucose index (TyG) seems plausible but has not been investigated. This study aims to examine whether TyG mediates associations of BMI with stroke risk and the extent of interaction or joint relations of TyG and BMI with stroke outcome.MethodsThe China Health and Retirement Longitudinal Study, initiated in 2011, is a nationally representative, ongoing prospective cohort study involving 8 231 middle-aged and older Chinese adults without a stroke history at baseline. Exposures examined include BMI and the TyG, the latter being the logarithmized product of fasting triglyceride and glucose concentrations. The primary study outcome is stroke incidence, as determined through self-reports, with a follow-up period extending from June 1, 2011, to June 30, 2018.ResultsOf the 8 231 participants, 3 815 (46.3%) were men; mean (SD) age was 59.23 (9.32) years. During a median follow-up of 7.1 years, 585 (7.1%) participants developed stroke. The TyG was found to mediate the association between BMI and incident stroke, proportions mediated were 16.3% for BMI in the 24.0–27.9 kg/m2 group and 53.8% for BMI ≥ 28.0 kg/m2 group. No significant multiplicative and additive interactions were found between BMI and TyG on incident stroke (Additive: RERI = 1.78, 95% CI − 1.29–4.86; Multiplicative, HR = 1.40, 95% CI 0.86–2.27). HRs for individuals with BMI ≥ 28.0 kg/m2 and quartile 4 of TyG compared with those with BMI < 24.0 kg/m2 and quartile 1 of TyG were 2.05 (95% CI 1.37–3.06) for incident stroke. Combining BMI and TyG enhanced predictive performance for stroke when compared to their individual (AUCBMI+TyGvs AUCBMIvs AUCTyG, 0.602 vs 0.581 vs 0.583).ConclusionsTyG appeared to be associated with stroke risk and mediates more than 50% of the total association between BMI and stroke in middle-aged and older Chinese adults. Public health efforts aiming at the reduction of body weight might decrease the stroke risk due to insulin resistance and the burden of stroke.