Linear Dose-response Manner Research Articles

Longitudinal association of objectively measured physical activity and bioimpedance phase angle in older adults

Background & AimsThe benefits of physical activity, including exercise and daily and household chores, on the bioimpedance phase angle remain unclear. We aimed to examine the longitudinal association between objectively measured physical activity and bioimpedance phase angle among community-dwelling older adults. MethodsThis community-based cohort study enrolled individuals aged 65 years or older without any disability in the basic activities of daily living. The exposure was physical activity level measured objectively using a tri-axial accelerometer at baseline. The outcome was a whole body phase angle at 50 kHz obtained from a bioelectrical impedance analyzer at a one-year follow-up. The linear regression model was fitted to estimate the continuous associations of physical activity level and phase angle with adjustment of confounders, including age, sex, body mass index, physical performance, and phase angle at baseline. ResultsThe primary analysis included 229 individuals (mean age = 72.6 years [standard deviation = 4.9], 62.9% females). In the multivariable linear regression model, physical activity level at baseline is associated with a greater phase angle at follow-up (mean difference per 1 increase, 0.53° [95%CI, 0.23–0.83]). Subgroup analysis by sex showed similar trends. Restricted cubic spline analysis indicated a linear association between phase angle at follow-up and physical activity level at baseline (p = 0.66 for non-linearity). ConclusionsHigher physical activity level was associated with greater phase angle at one-year follow-up in a linear dose-response manner, independent of demographics, physical performance, and phase angle at baseline, in community-dwelling older adults.

Exposure to volatile organic compounds and mortality in US adults: A population-based prospective cohort study

Volatile organic compounds (VOCs) are ubiquitous in both indoor and outdoor environments. Evidence on the associations of individual and joint VOC exposure with all-cause and cause-specific mortality is limited. Measurements of 15 urinary VOC metabolites were available to estimate exposure to 12 VOCs in the National Health and Nutritional Examination Survey (NHANES) 2005–2006 and 2011–2018. The environment risk score (ERS) was calculated using LASSO regression to reflect joint exposure to VOCs. Follow-up data on death were obtained from the NHANES Public-Use Linked Mortality File through December 31, 2019. Cox proportional hazard models and restricted cubic spline models were applied to evaluate the associations of individual and joint VOC exposures with all-cause and cause-specific mortality. Population attributable fractions were calculated to assess the death burden attributable to VOC exposure. During a median follow-up of 6.17 years, 734 (8.34 %) deaths occurred among 8799 adults. Urinary metabolites of acrolein, acrylonitrile, 1,3-butadiene, and ethylbenzene/styrene were significantly associated with all-cause, cardiovascular disease (CVD), respiratory disease (RD), and cancer mortality in a linear dose-response manner. Linear and robust dose-response relationships were also observed between ERS and all-cause and cause-specific mortality. Each 1-unit increase in ERS was associated with a 33.6 %, 39.1 %, 109.8 %, and 67.8 % increase for all-cause, CVD, RD, and cancer mortality risk, respectively. Moreover, joint exposure to VOCs contributed to 17.95 % of all-cause deaths, 13.49 % of CVD deaths, 35.65 % of RD deaths, and 33.85 % of cancer deaths. Individual and joint exposure to VOCs may enhance the risk of all-cause and cause-specific mortality. Reducing exposure to VOCs may alleviate the all-cause and cause-specific death burden.

Abstract 14359: Life’s Essential 8 and Cardiovascular Health of Veterans: The Million Veteran Program

Background and Hypothesis: The American Heart Association (AHA) recently proposed the Life’s Essential 8 (LE8) score as an enhanced measurement tool for cardiovascular health. No studies to date have estimated its association with the risk for atherosclerotic cardiovascular disease (ASCVD) incidence and prognosis. Methods: A prospective cohort study of 384,518 Veterans enrolled in the VA Million Veteran Program (MVP) (2011-2021). LE8 score was developed using AHA guidelines. Primary outcome was total ASCVD. Secondary outcome was hard ASCVD which included non-fatal myocardial infarction, non-fatal stroke, and fatal CVD. Results: Based on 1.16 million person-years of follow-up among Veterans with no ASCVD at baseline, 46,295 Veterans had ASCVD events during follow-up. LE8 score was associated with ASCVD and its subtypes in a linear dose-response manner (Figure 1A). The overall population-attributable fractions for all non-ideal LE8 scores was 59% (95%CI: 51%-66%) for ASCVD, where non-ideal blood pressure was most influential (Figure 1B). Based on 0.6 million person-years of follow-up among patients with ASCVD at baseline, the hazard ratio for incident or recurrent hard ASCVD was 0.52 (95%CI: 0.48-0.56) comparing veterans with ≥650 to those with LE8 score <350, with a dose-response linear association pattern. Conclusions: Based on 1.76 million person years of follow-up among Veterans, a high LE8 score was associated with a significantly lower ASCVD risk and a lower likelihood of developing adverse cardiovascular events regardless of ASCVD status at baseline. Theoretically, an ideal LE8 could potentially prevent almost 59% of ASCVD in this study. Our results support the importance of AHA’s promotion of LE8.

Adherence to diabetes risk reduction diet and the risk of head and neck cancer: a prospective study of 101,755 American adults.

Adherence to the diabetes risk reduction diet (DRRD) may potentially reduce the risk of developing head and neck cancer (HNC) as the diet includes fruits and limits red and processed meats, known risk factors for HNC. However, there is currently no epidemiological research to investigate this potential association. The present study utilized data on demographics, lifestyles, medications, and diets of participants from the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial to explore the potential association between adherence to DRRD and the risk of HNC. We used a DRRD score to evaluate adherence to the dietary pattern and employed Cox regression analysis to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for HNC risk. Several subgroup analyses were carried out to identify potential effect modifiers, and multiple sensitivity analyses were performed to evaluate the stability of the correlation. The nine components of the DRRD was assessed separately for its association with the risk of HNC. During a mean follow up of 8.84 years, 279 cases of HNC were observed. DDRD score was found to be inversely associated with the risk of HNC (HR Q4 vs. Q1: 0.582; 95% CI: 0.396, 0.856; p = 0.005 for trend) in a linear dose-response manner (p = 0.211 for non-linearity). Subgroup analysis indicated this inverse correlation was more pronounced among participants who had never smoked (HRQ4 vs. Q1: 0.193; 95% CI: 0.073, 0.511; p < 0.001 for trend) compared to current or former smokers (p = 0.044 for interaction). The primary association of DDRD and HNC risk remained robust after several sensitivity analyses. Regarding the individual components of DRRD, an inverse association was also observed between the risk of HNC and increased intake of cereal fiber and whole fruit (all p < 0.05 for trend). Our findings provide evidence that following the DRRD pattern may reduce the risk of NHC, especially for non-smokers.

Short-term exposure to multiple metals mixture and mitochondrial DNA copy number among children: A panel study

BackgroundLittle is known regarding the individual and overall associations of short-term co-exposure to metals mixture with mitochondrial DNA copy number (mtDNAcn) among healthy children. MethodsWe conducted a panel study across three seasons among 144 children aged 4 to 12 years in Guangzhou. For each season, we collected the first-morning urine for four consecutive days and fasting blood on the 4th day to detect 23 urinary metals and blood leukocyte mtDNAcn, respectively. Linear mixed-effect (LME) models and multiple informant models were used to examine the relations of individual metals with mtDNAcn over different lag days, and the least absolute shrinkage and selection operator (LASSO) regression was applied to determine the most important metal. We further employed weighted quantile sum (WQS) regression to investigate the overall association of metals mixture with mtDNAcn. ResultsNickel (Ni), manganese (Mn) and antimony (Sb) were independently associated with mtDNAcn in a linear dose-response manner. Each 1-fold increase in Ni at lag 0 day, Mn and Sb at lag 2 day was associated with respective decrements of 8.74 %, 6.93 % and 3.98 % in mtDNAcn in multi-metal LME models. LASSO regression also selected Ni, Mn and Sb as the most significant metals at the corresponding lag day. WQS regression showed overall inverse associations between metals mixture and mtDNAcn both at lag 0 and lag 2 day, with mtDNAcn decreased by 2.75 % and 3.14 % in response to a quartile increase in the WQS index. Additionally, the associations of Ni and Mn with decreased mtDNAcn were stronger among children younger than 7 years, girls and those having less vegetables and fruit intake. ConclusionWe found an overall association between metals mixture and decreased mtDNAcn among healthy children, in which Ni, Mn and Sb were the major contributors. Younger children, girls and those with less vegetables and fruit intake were more susceptible.

Associations of serum vitamin C concentrations with risk of all-cause and cause-specific mortality among individuals with and without type 2 diabetes.

Compared with people without diabetes, people with type 2 diabetes (T2D) are at higher risk of both subnormal vitamin C status and increased oxidative stress. We aimed to investigate the associations of serum vitamin C concentrations with all-cause and cause-specific mortality among adults with and without T2D. The current analysis included 20,045 adults (2691 people with T2D and 17,354 without T2D) from the Third National Health and Nutrition Examination Survey (NHANES III) and NHANES 2003-2006. Cox proportional hazards regression models were applied to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Restricted cubic spline analyses were used to examine the dose-response relationship. After a median follow-up of 17.3years, 5211 deaths were documented. Individuals with T2D had a lower level of serum vitamin C concentrations compared with those without T2D (the median value: 40.1 vs. 44.9μmol/L). Furthermore, the dose-response relationship between serum vitamin C and mortality showed different patterns between participants with and without T2D. In individuals without T2D, there was a nonlinear association of serum vitamin C concentrations with all-cause, cancer, and CVD mortality, with the lowest risk around a serum vitamin C concentration of 48.0μmol/L (all Poverall < 0.05, Pnonlinearity < 0.05). In contrast, among those with T2D in the similar concentration range, higher serum vitamin C levels (ranged from 0.46 to 116.26μmol/L) were linearly associated with lower all-cause and cancer mortality (both Poverall < 0.05, Pnonlinearity > 0.05). Significant additive interaction was observed between diabetes status and serum vitamin C levels with regard to all-cause and cancer mortality (P < 0.001). In addition, C-reactive protein, gamma-glutamyl transpeptidase, and HbA1c explained 14.08, 8.96, and 5.60% of the association between serum vitamin C and all-cause mortality among individuals with T2D, respectively. Higher serum vitamin C concentrations were significantly associated with lower risk of mortality in participants with T2D in a linear dose-response manner, while a nonlinear association was observed in participants without T2D, with an apparent threshold around 48.0μmol/L. These findings suggest that the optimal vitamin C requirement may differ in individuals with and without T2D.

142 Short-Term Exposure to Nanomaterials and Effect Biomarkers at Local and Systemic Levels: dose-Response Modelling Results from the Nanoexplore Project

Abstract We aimed at analyzing dose-response relationship between occupational exposure to a mixture of nanomaterials (NMs) and effect biomarkers measured according to the NanoExplore protocol in exhaled breath condensate (EBC, local pulmonary level)) and urine (systemic level) of 141 workers. Two exposure metrics: particle number concentration (PNC) and lung deposited surface area (LDSA) were monitored using DiSCMini for 2-4 8h-workshifts. Biological samples were collected twice, before and after exposure monitoring. We assumed that current or short-term exposure to NMs is associated in a linear dose-response manner to the effect biomarker concentration. We analyzed each biomarker separately, using the multilevel mixed-effects interval regression models to properly manage the biomarker concentrations the LOD or in the interval between the LOD and the limit of quantification. We used directed acyclic graphs to identify all potential confounders: age, smoking status, medication status, and study center. Center and the participant’s ID were modeled as random effect variables. For IL-10, IL-1β and TNF-α in EBC we observed consistent positive dose-response relationships with both PNC and LDSA. For urinary Total Antioxidant Power the relationship was consistently negative. For MDA, KL-6, hs-CRP or NOTyr in EBC and urinary MDA and 8-Isoprostane, no relationship was found. These results suggest an activation of the innate immune response rather than oxidative stress as the main effect of the mixture of NM investigated. This study offers new insights into the dose-response relationship between exposure to NMs and possible indicators of early and long-term biological alterations in the cohort of recruited workers.

24-Hour Urinary Sodium Excretion Association with Cardiovascular Events: A Systematic Review and Dose-Response Meta-Analysis

ObjectiveThe relationship between sodium intake and cardiovascular (CV) events remains unconfirmed. Therefore, we carried out a systematic review and dose-response meta-analysis for evaluating the potential impact of 24-hour sodium excretion on CV risk. Besides, 24-hour sodium excretion was used to replace daily sodium diet intake. MethodsWe searched ISI Web of Science, Embase, PubMed, and the Cochrane Library. Our study included cohort studies reporting hazard ratio (HR). The random-effects model was used for summarizing the total relative risks (RRs) between the included studies. In addition, the generalized least-squares regression was employed to fit the study model. ResultsA total of 9 studies involving 645,006 participants were included in this study. A significant non-linear relationship was observed between sodium excretion and CV events (Pnon-linearity < 0.001). In studies collecting 24-h urine samples, the sodium excretion and CV events risk were associated linearly (RR: 1.04; 95% CI: 1.01, 1.07). ConclusionIn a linear dose-response manner, every 1 g increase in sodium intake was associated with an increased risk of CV events up to 4%. Further studies are required to validate our conclusions further.

Ultra-processed food consumption and the risk of pancreatic cancer in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial.

Whether ultra-processed food consumption is associated with the risk of pancreatic cancer has not been determined. We performed a prospective study to fill this gap. A population-based cohort of 98 265 American adults was identified from the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. Ultra-processed foods were defined by the NOVA classification. Cox regression was used to estimate hazard ratios (HRs) for pancreatic cancer incidence. Subgroup analysis was performed to identify the potential effect modifiers. During a mean follow-up of 8.86 years, 387 pancreatic cancer cases occurred. High consumption of ultra-processed foods was found to be associated with an increased risk of pancreatic cancer (fully adjusted HRquartile 4 vs 1 :1.49; 95% confidence interval [CI]: 1.07-2.07; Ptrend =.021) in a linear dose-response manner (Pnonlinearity =.075). Subgroup analysis further found that the positive association of ultra-processed food consumption with the risk of pancreatic cancer was more pronounced in subjects aged <65 years (HRquartile 4 vs 1 :2.17; 95% CI: 1.14-4.15) than in those aged ≥65 years (HRquartile 4 vs 1 :1.32; 95% CI: 0.88-1.94), though the interaction test failed to achieve the statistical significance (Pinteraction =.061). These findings suggest that reducing ultra-processed food consumption may be beneficial in decreasing pancreatic cancer incidence.

The Association between Aortic Calcification Index and Urinary Stones: A Cross-Sectional Study.

Background: It is believed that vascular calcification and urinary stones may possibly have a shared mechanism. However, the association between vascular calcification and urinary stones is largely unexplored. Using the aortic calcification index (ACI) as a clinical indicator of vascular calcification, the present study aimed to examine the association between the ACI and urinary stones. Methods: This cross-sectional study included 282 patients hospitalized for either urinary stones or other urological diseases from January 2020 to December 2021 at the Department of Urology and Lithotripsy in Peking University People’s Hospital. Among them, 137 and 145 patients were divided into the stone group and the non-stone group. Multivariable logistic regression analysis was performed to examine the association between the ACI and urinary stones. The restricted cubic splines model was used to further explore the dose–response relationship between the ACI and urinary stones. Results: The median (Q1–Q3) age of the study population was 59.0 (47.0–67.0) years. After adjusting coronary heart disease, triglycerides, glucose, serum creatinine, uric acid, urea, calcium, and eGFR, the ACI was independently associated with urinary stones (odds ratio [OR], 1.07; 95% confidence interval [CI], 1.03–1.11) in a linear dose–response pattern (p for non-linearity =0.153). Age was found to interact with the effect of the ACI on urinary stones (p for interaction <0.001). Conclusions: This study found that the ACI was independently associated with urinary stones in a linear dose–response manner. Our results indicate that the ACI might be a helpful indicator for identifying populations at risk for urinary stones.

Biomarkers of dairy fat intake, incident cardiovascular disease, and all-cause mortality: A cohort study, systematic review, and meta-analysis.

We aimed to investigate the association of serum pentadecanoic acid (15:0), a biomarker of dairy fat intake, with incident cardiovascular disease (CVD) and all-cause mortality in a Swedish cohort study. We also systematically reviewed studies of the association of dairy fat biomarkers (circulating or adipose tissue levels of 15:0, heptadecanoic acid [17:0], and trans-palmitoleic acid [t16:1n-7]) with CVD outcomes or all-cause mortality. We measured 15:0 in serum cholesterol esters at baseline in 4,150 Swedish adults (51% female, median age 60.5 years). During a median follow-up of 16.6 years, 578 incident CVD events and 676 deaths were identified using Swedish registers. In multivariable-adjusted models, higher 15:0 was associated with lower incident CVD risk in a linear dose-response manner (hazard ratio 0.75 per interquintile range; 95% confidence interval 0.61, 0.93, P = 0.009) and nonlinearly with all-cause mortality (P for nonlinearity = 0.03), with a nadir of mortality risk around median 15:0. In meta-analyses including our Swedish cohort and 17 cohort, case-cohort, or nested case-control studies, higher 15:0 and 17:0 but not t16:1n-7 were inversely associated with total CVD, with the relative risk of highest versus lowest tertile being 0.88 (0.78, 0.99), 0.86 (0.79, 0.93), and 1.01 (0.91, 1.12), respectively. Dairy fat biomarkers were not associated with all-cause mortality in meta-analyses, although there were ≤3 studies for each biomarker. Study limitations include the inability of the biomarkers to distinguish different types of dairy foods and that most studies in the meta-analyses (including our novel cohort study) only assessed biomarkers at baseline, which may increase the risk of misclassification of exposure levels. In a meta-analysis of 18 observational studies including our new cohort study, higher levels of 15:0 and 17:0 were associated with lower CVD risk. Our findings support the need for clinical and experimental studies to elucidate the causality of these relationships and relevant biological mechanisms.

Abstract 026: Biomarkers Of Dairy Fat Intake Associated With Lower Cardiovascular Disease Risk: A Cohort Study And Meta-analysis

Introduction: Dietary recommendations promote low-fat rather than full fat dairy consumption. Emerging evidence, however, has raised doubts if avoidance of dairy fat will lower CVD risk. Traditionally, self-reported estimates of dairy fat intake were used to study its relationship with CVD, which are subject to recall biases and measurement error. Here, we employed circulating levels of pentadecanoic acid [15:0] as a biomarker of dairy fat intake to examine its association with CVD incidence and all-cause mortality in a Swedish population-based cohort. We also conducted a systematic review of prospective studies that assessed 15:0, and other dairy fat biomarkers (heptadecanoic acid [17:0] and trans -palmitoleic acid [ t 16n-7]) and their associations with CVD and all-cause mortality. Hypothesis: We assessed the hypothesis that higher levels of dairy fat biomarkers 15:0, 17:0 and t 16n-7 would be associated with lower risk of incident CVD events and all-cause mortality. Methods: In a cohort of 60-year old Swedish women (n=2133) and men (n=2017), we measured 15:0 in serum cholesterol esters at baseline in 1997-99. Cox proportional hazard models were used to assess the associations between serum 15:0 with CVD outcomes and all-cause mortality, after adjusting for demographics and CVD risk factors. In the meta-analysis, five databases were searched to include prospective observational studies that examined the associations between circulating or adipose tissues levels of 15:0, 17:0 and t 16n-7 and CVD and mortality risks. Pooled associations of each dairy fat biomarker with incidence of CVD and all-cause mortality were estimated using a random-effects model. Results: During a median follow-up of 16.6 years, 578 incident CVD events and 676 deaths were identified using national registers. In multivariable-adjusted models, higher serum 15:0 was associated with lower incidence of CVD in a linear dose-response manner [HR: 0.75 per interquintile range; 95% CI: 0.61, 0.93), but in a non-linear relationship with all-cause mortality (P nonlinearity = 0.03); with a nadir of mortality risk around the median level of 15:0. In the meta-analysis including our Swedish cohort and 17 other studies, the relative risk of total CVD comparing the highest versus the lowest tertile was 0.88 (0.78, 0.99) for 15:0 (n=17), 0.86 (0.79, 0.93) for 17:0 (n=12), and 1.01 (0.91, 1.12) for t16n-7 (n=6). In meta-analyses of ≤3 studies, there was little evidence that dairy fat biomarkers were associated with all-cause mortality. Conclusion: In conclusion, our de novo Swedish cohort study and an updated systematic review including 18 studies suggests that higher levels of dairy fat biomarkers (15:0 and 17:0) were associated with a lower risk of CVD incidence. These results justify further investigation in interventional and experimental studies to elucidate the potential causality of these relationships and relevant mechanisms.

Adherence to the 2018 World Cancer Research Fund/American Institute for Cancer Research cancer prevention recommendations and pancreatic cancer incidence and mortality: A prospective cohort study.

BackgroundWhether adherence to the World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) cancer prevention recommendations is associated with a reduced risk of pancreatic cancer remains controversial. Additionally, no study has investigated this association in the US population. Hence, we investigated the association of adherence to the 2018 WCRF/AICR cancer prevention recommendations with pancreatic cancer incidence and mortality in a US population.MethodsA population‐based cohort of 95 962 participants was identified. A score incorporating eight WCRF/AICR components was constructed to reflect adherence to the WCRF/AICR guidelines, with higher scores representing greater adherence to the guidelines. Cox and competing risk regression were used to calculate risk estimates for pancreatic cancer incidence and mortality, respectively. Restricted cubic spline functions were used to test nonlinearity.ResultsIn the fully adjusted model, higher overall WCRF/AICR scores were shown to be associated with lower risks of developing pancreatic cancer (hazard ratiotertile 3 vs 1:0.67; 95% confidence interval: 0.49, 0.90; P trend = .0099) and mortality due to this cancer (subdistribution hazard ratiotertile 3 vs 1 0.65; 95% confidence interval: 0.47, 0.89; P trend = .0108) in a linear dose–response manner (all P nonlinearity > .05). The component “be physically active” was shown to be a key contributor to the observed associations. No association of the diet‐specific WCRF/AICR score with pancreatic incidence and mortality was found.ConclusionsAdherence to the 2018 WCRF/AICR guidelines, especially “be physically active,” confers reduced risks of pancreatic cancer incidence and mortality in the US population; however, adherence to dietary components alone does not confer such beneficial effects.

Dose-Response Association Between Accelerometer-Assessed Physical Activity and Incidence of Functional Disability in Older Japanese Adults: A 6-Year Prospective Study.

BackgroundIt is unknown whether moderate-to-vigorous physical activity (MVPA) in bouts of <10 minutes protects against disability risks or if only 10 minutes bouts of MVPA is critical. Additionally, it is unclear whether light physical activity (LPA) or its accumulation patterns is associated with functional disability.MethodsA total of 1,687 adults aged ≥65 years and without functional disability at baseline were followed up for 6 years. Functional disability was identified using the database of Japan’s Long-term Care Insurance System. Physical activity was measured using a tri-axial accelerometer secured to the waist.ResultsFunctional disability was identified in 274 participants (16.2%). When examined as quartiles, higher levels of all MVPA measures were dose-dependently associated with lower risk of functional disability. Associations of MVPA in ≥10 and <10 minutes bouts remained significant in a mutually adjusted model. Neither total LPA nor LPA in bout of ≥10 minutes, but LPA in bouts of <10 minutes was associated with functional disability. Analyses using restricted cubic spline functions showed that associations of all MVPA measures and LPA in bouts of <10 minutes with functional disability were linear (p for nonlinear >.05). The hazard ratios (HRs; 95% confidence interval [CI]) for functional disability per 10 minutes increment of total MVPA and LPA in bout of <10 minutes were 0.86 (0.81–0.92) and 0.96 (0.93–0.99), respectively.ConclusionsHigher MVPA, regardless accumulation patterns, or LPA in bouts of <10 minutes was associated with lower risk of functional disability in a linear dose–response manner in older adults.

Exposure to organochlorine pesticides and the risk of type 2 diabetes in the population of East China

Organochlorine pesticides (OCPs) have been reported to be associated with an elevated risk of type 2 diabetes, although no study has focused on such associations in Chinese populations. In this case-control study, we aimed to explore the associations between OCPs and type 2 diabetes and their potential mechanisms in a population from East China. Participants diagnosed with type 2 diabetes and nondiabetic participants from Shandong Province, East China, were enrolled in this case-control study. Six OCPs (β-HCH, trans-chlordane, trans-nonachlor, p,p'-DDE, p,p'-DDT and mirex/kepone) were detected in more than 75% of serum samples. Logistic regression analysis and multiple linear regression analysis were used to assess the associations between OCP exposure and the outcomes. After adjusting for potential confounding factors such as age, sex and body mass index, all six OCPs showed positive associations with type 2 diabetes in a linear dose-response manner. Serum concentrations of β-HCH and p,p'-DDE were associated with higher levels of fasting plasma glucose in participants without diabetes, although no OCPs showed significant associations with hemoglobin A1c. In addition, certain OCPs showed significantly positive associations with triglycerides, total cholesterol, and low-density lipoprotein cholesterol and negative relationships with high-density lipoprotein cholesterol in nondiabetics, indicating that OCP exposure may disrupt lipid metabolism. Findings in the current study indicated that OCPs may be a diabetogenic factor in the population of this study. To our knowledge, this is the first study to investigate the associations between OCP exposure and type 2 diabetes in a Chinese population.

A dose–response meta-analysis of coffee consumption and thyroid cancer occurrence

The relationship between coffee consumption and thyroid cancer (TC) occurrence has been evaluated in several observational studies with controversial results. The study aims to examine the associations between coffee consumption and TC occurrence. Systematic searches up to February 2019 were conducted. We estimated summary adjusted relative risks (RRs) and the corresponding 95% confidence intervals (CIs). The dose–response analysis was conducted by using generalised least square trend estimation. A total of ten studies involving 379,825 participants and 1,254 TC cases were included. The total summary RR showed that high coffee consumption was a protection factor of TC (RR = 0.75; 95% CI, 0.62–0.91). With the linear cubic spline model, the occurrence of TC was reduced by 5% with each one cup/day increment of coffee consumption (RR = 0.95; 95% CI, 0.91–0.99).This meta-analysis provides quantitative evidence that coffee consumption was inversely associated with the TC occurrence in a linear dose–response manner.

Plasma oxylipins respond in a linear dose-response manner with increased intake of EPA and DHA: results from a randomized controlled trial in healthy humans

The health effects of long-chain omega-3 polyunsaturated fatty acids (n-3 PUFAs) are partly mediated by their oxidized metabolites, i.e., eicosanoids and other oxylipins. Some intervention studies have demonstrated that eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) increase systemic concentrations of n-3 PUFA-derived oxylipins and moderately decrease arachidonic acid-derived oxylipins. There is no information on the dose-response of oxylipin concentrations after n-3 PUFA intake. The aim of this study was to quantify oxylipins in human plasma samples from an intervention study in which participants were randomly assigned to different daily intakes of EPA and DHA for 12 mo. Healthy adult men and women with low habitual fish consumption (n=121) were randomly assigned to receive capsules providing doses of n-3 PUFAs reflecting 3 patterns of consumption of oily fish [1, 2, or 4 portions/wk with 3.27 g EPA+DHA (1:1.2, wt:wt) per portion] or placebo. Oxylipins were quantified in plasma after 3 and 12 mo. Relative and absolute changes of individual oxylipins were calculated and concentrations were correlated with the dose and the content of EPA and DHA in blood lipid pools. Seventy-three oxylipins, mostly hydroxy-, dihydroxy-, and epoxy-PUFAs, were quantified in the plasma samples. After 3 and 12 mo a linear increase with dose was observed for all EPA- and DHA-derived oxylipins. Cytochrome-P450-derived anti-inflammatory and cardioprotective epoxy-PUFAs increased linearly with n-3 PUFA dose and showed low interindividual variance (r2>0.95). Similarly, 5, 12-, and 15-lipoxygenase-derived hydroxy-PUFAs as well as those formed autoxidatively increased linearly. These include the precursors of so-called specialized pro-resolving lipid mediators (SPMs), e.g., 17-hydroxy-DHA and 18-hydroxy-EPA. Plasma concentrations of biologically active oxylipins derived from n-3 PUFAs, including epoxy-PUFAs and SPM-precursors, increase linearly with elevated intake of EPA and DHA. Interindividual differences in resulting plasma concentrations are low. This trial was registered at controlled-trials.com as ISRCTN48398526.

Dietary approach to stop hypertension diet and risk of coronary artery disease: a meta-analysis of prospective cohort studies

Adherence to the Dietary Approaches to Stop Hypertension (DASH) diet can lower blood pressure, but its role in preventing coronary artery disease (CAD) remains in debate. Thus, we performed a meta-analysis of prospective cohort studies to address this issue. We carried out a systematical search in databases of PubMed and Embase to screen out eligible publications. Relative risks (RRs) of CAD in the included studies were summarised using random-effect meta-analysis. Dose-response association between DASH diet score and CAD risk was also evaluated. Seven prospective studies were finally included, with a total of 377,725 participants and 15,074 CAD cases. Compared to lower adherence, higher adherence to the DASH diet was associated a decreased risk of CAD (RR 0.82, 95% confidence interval [CI]: 0.78–0.87). Subgroup and sensitivity analyses supported the preventive effects of DASH diet against CAD, and there was no indication of publication bias. For a curvilinear dose-response pattern, the RRs (95% CIs) of CAD for the 4 knots (5th, 35th, 65th and 95th percentiles) of DASH diet score were 0.93 (0.89–0.98), 0.87 (0.80–0.95), 0.81 (0.72–0.90) and 0.74 (0.68–0.82), respectively. For a linear dose-response manner, each 4-point increase in the DASH diet score could reduce the risk of CAD by 5% (RR 0.95, 95% CI: 0.94–0.97). The results of our study indicate that higher adherence to the DASH diet confers a reduced risk of developing CAD.

Meta-Analysis of Adiponectin as a Biomarker for the Detection of Metabolic Syndrome

Previous studies revealed the potential significance of circulating adiponectin levels with respect to the diagnosis and prediction of metabolic syndrome, but uncertainty has been noted across different cohorts. Systematic evaluation was performed for diagnostic accuracy and predictivity of adiponectin variation for metabolic syndrome in enrolled studies including 1,248 and 6,020 subjects, respectively. Adiponectin can identify metabolic syndrome with moderate accuracy (area under the curve = 0.81, 95% CI: 0.77–0.84). Heterogeneity analysis revealed that an increasing index of insulin resistance was independently associated with improving the performance of adiponectin upon metabolic syndrome diagnosis (ratio of diagnostic odds ratio = 3.89, 95% CI: 1.13–13.9). In addition, reductions in adiponectin were associated with increasing metabolic syndrome incidence in a linear dose-response manner. The risk of hypoadiponectinemia with metabolic syndrome was especially increased in men (P < 0.05). Further Mendelian randomization analysis identified that the amplified risk could be attributed to increased susceptibility (up to 7%) to insulin resistance compared with women. In conclusion, adiponectin measurement might have potential benefits in the detection of metabolic syndrome. Factors that affect insulin resistance should be considered for adjustment in future assessments.

Inverse association between serum albumin and future risk of venous thromboembolism: interrelationship with high sensitivity C-reactive protein

Purpose: We aimed to assess the prospective association of serum albumin with venous thromboembolism (VTE) risk and evaluate if the association is independent of or modified by inflammation, as measured by high sensitivity C-reactive protein (hsCRP).Design: We analysed data of 2176 men aged 42–61 years free from VTE in the Kuopio Ischemic Heart Disease study, with serum albumin concentrations measured at baseline using Coulter’s bromocresol purple colorimetric assays. Hazard ratios (HRs) (95% confidence intervals [CI]) were calculated for VTE.Results: There were 109 validated cases of VTE recorded during a median follow-up of 24.9 years. The risk of VTE increased linearly below a serum albumin concentration of ∼48 g/l. In Cox regression analysis adjusted for established risk factors and other potential confounders, the HR (95% CI) for VTE per 1 standard deviation lower serum albumin was 1.23 (1.02–1.47). The association remained persistent on further adjustment for hsCRP 1.22 (1.01–1.46). Furthermore, the association was not modified by hsCRP and persisted on exclusion of men with elevated hsCRP levels.Conclusions: In middle-aged Caucasian men, low serum albumin is associated with an increased risk of VTE, consistent with a linear dose-response relationship. The association is independent of and not modified by inflammation.Key messages • Serum albumin may be associated with future risk of venous thromboembolism (VTE); however, the shape, nature, magnitude and consistency of the association is uncertain. • In a population-based prospective cohort study, low serum albumin was associated with an increased risk of VTE in a linear dose-response manner and this association was independent of and not modified by inflammation. • Serum albumin concentrations may play a role in the development of VTE.