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Abstract Background Dysglycemia and insulin resistance increase type 2 diabetes (T2D) and cardiovascular disease (CVD) risk, yet associations with specific glucose-insulin homeostatic biomarkers have been inconsistent. Vitamin D and marine omega-3 fatty acids (n-3 FA) may improve insulin resistance. We sought to examine the association between baseline levels of insulin, C-peptide, HbA1c, and a novel insulin resistance score (IRS) with incident cardiometabolic diseases, and whether randomized vitamin D or n-3 FA modify these associations. Methods VITamin D and OmegA-3 TriaL (NCT01169259) was a randomized clinical trial testing vitamin D and n-3 FA for the prevention of CVD and cancer over a median of 5.3 years. Incident cases of T2D and CVD (including cardiovascular death, myocardial infarction, stroke, and coronary revascularization) were matched 1:1 on age, sex, and fasting status to controls. Conditional logistic regressions adjusted for demographic, clinical, and adiposity-related factors were used to assess the adjusted odds ratio (aOR) per-standard deviation (SD) and 95%CI of baseline insulin, C-peptide, HbA1c, and IRS (Insulin×0.0295 + C-peptide×0.00372) with risk of T2D, CVD, and coronary heart disease (CHD). Results We identified 218 T2D case-control pairs and 715 CVD case-control pairs including 423 with incident CHD. Each of the four biomarkers at baseline was separately associated with incident T2D, aOR (95%CI) per SD increment: insulin 1.46 (1.03, 2.06), C-peptide 2.04 (1.35, 3.09), IRS 1.72 (1.28, 2.31) and HbA1c 7.00 (3.76, 13.02), though only HbA1c remained statistically significant with mutual adjustments. For cardiovascular diseases, we only observed significant associations of HbA1c with CVD (1.19 [1.02, 1.39]), and IRS with CHD (1.25 [1.04, 1.50]), which persisted after mutual adjustment. Randomization to vitamin D and/or n-3 FA did not modify the association of these biomarkers with the endpoints. Conclusions Each of insulin, C-peptide, IRS, and HbA1c were associated with incident T2D with the strongest association noted for HbA1c. While HbA1c was significantly associated with CVD risk, a novel IRS appears to be associated with CHD risk. Neither vitamin D nor n-3 FA modified the associations between these biomarkers and cardiometabolic outcomes.

Abstract Background and aims Understanding the amounts of intensity-specific movement needed to attenuate the association between sedentary time and mortality may help to inform personalized prescription and behavioral counselling. Herein, we examined the joint associations of sedentary time and intensity-specific physical activity with all-cause and cardiovascular disease (CVD) mortality. Methods Prospective cohort study including 73,729 adults from the UK Biobank who wore an Axivity AX3 accelerometer on their dominant wrist for at least 3 days, being one a weekend day, between June 2013 and December 2015. We considered the median tertile values of sedentary time and physical activity in each intensity band to determine the amount of physical activity needed to attenuate the association between sedentary time and mortality. Results During a median of 6.9 years of follow-up (628,807 person-years), we documented 1521 deaths, including 388 from CVD. Physical activity of any intensity attenuated the detrimental association of sedentary time with mortality. Overall, at least a median of 6 min/day of vigorous physical activity, 30 min/day of MVPA, 64 min/day of moderate physical activity, or 163 min/day of light physical activity (mutually-adjusted for other intensities) attenuated the association between sedentary time and mortality. High sedentary time was associated with higher risk of CVD mortality only among participants with low MVPA (HR 1.96; 95% CI 1.23 to 3.14). Conclusions Different amounts of each physical activity intensity may attenuate the association between high sedentary time and mortality.

Background: Patterns of physical activity and sedentary behavior among postmenopausal women are not well characterized. Objectives: To describe the patterns of accelerometer-assessed physical activity and sedentary behavior among postmenopausal women. Design: Cross-sectional study. Methods: Women 63–97 years (n = 6126) wore an ActiGraph GT3X + accelerometer on their hip for 1 week. Latent class analysis was used to classify women by patterns of percent of wake time in physical activity and sedentary behavior over the week. Results: On average, participants spent two-thirds of their day in sedentary behavior (62.3%), 21.1% in light low, 11.0% in light high, and 5.6% in moderate-to-vigorous physical activity. Five classes emerged for each single-component model for sedentary behavior and light low, light high, and moderate-to-vigorous physical activity. Six classes emerged for the multi-component model that simultaneously considered the four behaviors together. Conclusion: Unique profiles were identified in both single- and multi-component models that can provide new insights into habitual patterns of physical activity and sedentary behavior among postmenopausal women. Implications: The multi-component approach can contribute to refining public health guidelines that integrate recommendations for both enhancing age-appropriate physical activity levels and reducing time spent in sedentary behavior.

BackgroundDescribing correlates of physical activity (PA) and sedentary behavior (SB) among postmenopausal cancer survivors can help identify risk profiles and can be used to support development of targeted interventions to improve PA and reduce SB in this population.ObjectiveTo describe PA/SB and identify correlates of PA/SB among cancer and cancer-free post-menopausal women.MethodsWomen from the Women's Health Study (N = 16,629) and Women's Health Initiative/Objective Physical Activity and Cardiovascular Health Study (N = 6,079) were asked to wear an accelerometer on the hip for 7 days. Multiple mixed-effects linear regression models were used to identify sociodemographic-, health-, and chronic condition-related correlates (independent variables) associated with PA and SB (dependent variables) among women with (n = 2,554) and without (n = 20,154) a history of cancer. All correlates were mutually adjusted for each other.ResultsIn unadjusted analyses, women with a history of cancer took fewer mean daily steps (4,572 (standard deviation 2557) vs 5,029 (2679) steps/day) and had lower mean moderate-to-vigorous PA (74.9 (45.0) vs. 81.6 (46.7) minutes/day) than cancer-free women. In adjusted analyses, for cancer and cancer-free women, age, diabetes, overweight, and obesity were inversely associated with all metrics of PA (average vector magnitude, time in moderate-to-vigorous PA, step volume, time at ≥40 steps/minutes, and peak 30-minute step cadence). In unadjusted analyses, mean SB was similar for those with and without cancer (529.7 (98.1) vs. 521.7 (101.2) minutes/day). In adjusted analyses, for cancer and cancer-free women, age, diabetes, cardiovascular disease, current smoking, overweight, and obesity were positive correlates of SB, while Black or Hispanic race/ethnicity, weekly/daily alcohol intake, and excellent/very good/good self-rated health were inverse correlates of SB.ConclusionSeveral sociodemographic, health, and chronic conditions were correlates of PA/SB for postmenopausal women with and without cancer. Future studies should examine longitudinal relationships to gain insight into potential determinants of PA/SB.

Evidence suggests that individuals diagnosed with Parkinson’s Disease (PD) spend less time in moderate-to-vigorous intensity physical activity (MVPA) compared to those without PD. However, prior studies primarily included men and did not consider movement across the entire intensity spectrum. To address these gaps, the association of PD status with total volume physical activity and time spent in sedentary, low light-intensity physical activity (LLPA), high light-intensity physical activity (HLPA), and MVPA among older women was examined. This is a cross-sectional analysis of 17,466 ambulatory women enrolled in the Women’s Health Study (WHS) with a median (IQR) age of 70 (67–75) years who were asked to wear an accelerometer for 7 days from 2011 to 2015 for the ancillary study. Reported PD status was assessed via annual mail-in questionnaires prior to device wear. Compared to those without PD (n = 16,661), PD (n = 80) was associated with 98,400 fewer vector magnitude (VM) counts per day and with spending an average of 23.2 more minutes per day sedentary and 10.5 more minutes per day in LLPA. Further, PD was associated with spending 6.4 and 27.3 fewer minutes per day in HLPA and MVPA, respectively, compared to women without PD. PD in women is associated with more daily sedentary time and less time spent in health-enhancing physical activity. Prevention strategies to promote physical activity should be emphasized to enhance health and limit progression of disability in women living with PD.

Background & Aims: Incidence rates of liver cancer in most populations are two to three times higher among men than women. The higher rates among men have led to the suggestion that androgens are related to increased risk whereas oestrogens are related to decreased risk. This hypothesis was investigated in the present study via a nested case-control analysis of pre-diagnostic sex steroid hormone levels among men in five US cohorts. Methods: Concentrations of sex steroid hormones and sex hormone-binding globulin were quantitated using gas chromatography–mass spectrometry and a competitive electrochemiluminescence immunoassay, respectively. Multivariable conditional logistic regression was used to calculate odds ratios (ORs) and 95% CIs for associations between hormones and liver cancer among 275 men who subsequently developed liver cancer and 768 comparison men. Results: Higher concentrations of total testosterone (OR per one-unit increase in log2 = 1.77, 95% CI = 1.38–2.29), dihydrotestosterone (OR = 1.76, 95% CI = 1.21–2.57), oestrone (OR = 1.74, 95% CI = 1.08-2.79), total oestradiol (OR = 1.58, 95% CI=1.22–20.05), and sex hormone-binding globulin (OR = 1.63, 95% CI = 1.27–2.11) were associated with increased risk. Higher concentrations of dehydroepiandrosterone (DHEA), however, were associated with a 53% decreased risk (OR = 0.47, 95% CI = 0.33–0.68). Conclusions: Higher concentrations of both androgens (testosterone, dihydrotestosterone) and their aromatised oestrogenic metabolites (oestrone, oestradiol) were observed among men who subsequently developed liver cancer compared with men who did not. As DHEA is an adrenal precursor of both androgens and oestrogens, these results may suggest that a lower capacity to convert DHEA to androgens, and their subsequent conversion to oestrogens, confers a lower risk of liver cancer, whereas a greater capacity to convert DHEA confers a greater risk. Impact and implications: This study does not fully support the current hormone hypothesis as both androgen and oestrogen levels were associated with increased risk of liver cancer among men. The study also found that higher DHEA levels were associated with lower risk, thus suggesting the hypothesis that greater capacity to convert DHEA could be associated with increased liver cancer risk among men.

Background Few studies have investigated associations of acclerometer‐based assessments of physical activity (PA) and sedentary behavior (SB) with incidence of cardiovascular disease (CVD) and its components. This prospective cohort study assessed the associations of accelerometer‐measured PA and SB with total CVD, myocardial infarction, and ischemic stroke (IS). Methods and Results The authors included 16 031 women aged 62 years and older, free of CVD, with adherent accelerometer wear (≥10 hours/day for ≥4 days) from the Women's Health Study (mean age, 71.4 years [SD, 5.6 years]). Hip‐worn ActiGraph GT3X+ accelerometers measured total volume of PA (total average daily vector magnitude), minutes per day of high‐light PA and moderate to vigorous PA (MVPA), and SB. Women reported diagnoses of CVD, which were adjudicated using medical records and death certificates. Hazard ratios (HRs) were estimated for each exposure, and 95% CIs using Cox proportional hazards models were adjusted for accelerometer wear time, age, self‐reported general health, postmenopausal hormone therapy, smoking status, and alcohol use. The hypothetical effect of replacing 10 minutes/day of SB or high‐light PA with MVPA on CVD incidence was assessed using adjusted isotemporal substitution Cox models. Over a mean of 7.1 years (SD, 1.6 years) of follow‐up, 482 total CVD cases, 107 myocardial infarction cases, and 181 IS cases were diagnosed. Compared with the lowest quartiles of total average daily vector magnitude and MVPA (≤60 minutes), women who were in the highest quartiles (>120 minutes of MVPA) had a 43% (95% CI, 24%–58%) and 38% (95% CI, 18%–54%) lower hazard of total CVD, respectively. Estimates were similar for total average daily vector magnitude and MVPA with IS, but PA was not associated with myocardial infarction overall. High‐light PA was not associated with any CVD outcomes. Women who spent

This study aimed to investigate whether n−3 fatty acid supplementation reduced cardiovascular disease (CVD) events in a novel analysis using hierarchical composite CVD outcomes based on win ratio in the VITamin D and OmegA-3 TriaL (VITAL). This was a secondary analysis of our VITAL randomized trial, which assessed the effects of marine n−3 fatty acids (1 g/day) and vitamin D3 on incident CVD and cancer among healthy older adults (n = 25,871). The primary analysis estimated win ratios of a composite of major CVD outcomes prioritized as fatal coronary heart disease, other fatal CVD including stroke, non-fatal myocardial infarction (MI), and non-fatal stroke, comparing n−3 fatty acids to placebo. The primary result was a nonsignificant benefit of this supplementation for the prioritized primary CVD outcome (reciprocal win ratio [95% confidence interval]: 0.90 [0.78–1.04]), similar to the 0.92 (0.80–1.06) hazard ratio in our original time-to-first event analysis without outcome prioritization. Its benefits came from reducing MI (0.71 [0.57–0.88]) but not stroke (1.01 [0.80 to 1.28]) components. For the primary CVD outcome, participants with low fish consumption at baseline benefited (0.79 [0.65–0.96]) more than those with high consumption (1.05 [0.85–1.30]). These results are consistent with, but slightly stronger than, those without outcome prioritization.

Background Vitamin D supplementation leads to regression of left ventricular (LV) hypertrophy and improves LV function in animal models. However, limited data exist from prospective human studies. We examined whether vitamin D supplementation improved cardiac structure and function in midlife/older individuals in a large randomized trial. Methods and Results The VITAL (Vitamin D and OmegA‐3 Trial) was a nationwide double‐blind, placebo‐controlled randomized trial that tested the effects of vitamin D3 (2000 IU/d) and n−3 fatty acids (1 g/d) on cardiovascular and cancer risk in 25 871 individuals aged ≥50 years. We conducted a substudy of VITAL in which participants underwent echocardiography at baseline and 2 years. Images were interpreted by a blinded investigator at a central core laboratory. The primary end point was change in LV mass. Among 1054 Greater Boston–area participants attending in‐clinic visits, we enrolled 1025 into this study. Seventy‐nine percent returned for follow‐up and had analyzable echocardiograms at both visits. At baseline, the median age was 64 years (interquartile range, 60–69 years), 52% were men, and 43% had hypertension. After 2 years, the change in LV mass did not significantly differ between the vitamin D and placebo arms (median +1.4 g versus +2.6 g, respectively; P=0.32). Changes in systolic and diastolic LV function also did not differ significantly between arms. There were no significant changes in cardiac structure and function between the n−3 fatty acids and placebo arms. Conclusions Among adults aged ≥50 years, neither vitamin D3 nor n−3 fatty acids supplementation had significant effects on cardiac structure and function after 2 years. Registration URL: https://clinicaltrials.gov/; Unique identifiers: NCT01169259 (VITAL) and NCT01630213 (VITAL‐Echo)

Abstract Background While physical activity has consistently been associated with decreased mortality rates, it remains unknown if there is a single “ideal” combination of time in physical activities of different intensities and sedentary behavior (SB) associated with the lowest rate. This study examined the associations of combinations of time in moderate-to-vigorous intensity (MVPA), higher-light intensity (HLPA), lower-light intensity activities (LLPA), and SB with mortality rates in older women. Methods This prospective cohort study included 16,676 older women from throughout the United States enrolled in the Women’s Health Study. Women wore accelerometers on their hip from 2011 to 2015 and were followed through 2017 (mean (SD) of 4.3 (1.1) years). Deaths were confirmed with medical records, death certificates, or the National Death Index. Compositional Cox regression models were used. Results The mean (SD) age was 72 (5.7) years at accelerometer wear; 503 women died. Compared to the least active women (mean, 3 min/day MVPA, 27 min/day HLPA, 162 min/day LLPA, and 701 min/day SB): compositional models showed an inverse L-shaped dose-response association of MVPA replacing other behaviors with mortality rates mortality rates (P = .02); SB relative to LLPA, HLPA, and MVPA was directly associated with mortality rates in a curvilinear dose-response manner (P

Background Few data exist on long‐term steps and their relation to changes in cardiovascular disease risk factors. We aimed to examine the associations using long‐term smartphone‐recorded steps. Methods and Results The present analysis made use of data from 2 national databases and a commercial app database. We evaluated the associations between smartphone‐recorded daily steps over 2 years and 2‐year changes in the cardiovascular disease risk factors. A total of 15 708 participants with mean (SD) age of 44.1 (9.5) and 23.5% women were included. After adjustment for potential confounders, differences in weight were almost linearly associated with 2‐year steps in men (estimate [SE] per 1000 steps/d: −0.33 [0.029] kg), and inversely related only above 5000 steps/d in women (−0.18 [0.054] kg). An inverse linear association with systolic blood pressure was observed in men (−0.34 [0.097] mm Hg) but not in women. Greater steps were associated with change in high‐density lipoprotein cholesterol and triglycerides (0.61 [0.068] and −3.4 [0.61] mg/dL in men; 0.64 [0.17] and −2.3 [0.67] mg/dL in women), while changes in low‐density lipoprotein cholesterol were evident in men only (−0.59 [0.17] mg/dL). A significant negative association with hemoglobin A1c was observed only in women (−0.012 [0.0043] %). Conclusions In a large cohort of Japanese adults, smartphone‐recorded steps over years were associated with beneficial changes in cardiovascular disease risk factors, with some differences between men and women in the associational patterns. The findings support the benefit of long‐term physical activity for cardiovascular disease health and suggest a useful role of smartphone‐recorded steps for monitoring cardiovascular disease risk over the long term.

Summary: Background: Although 10 000 steps per day is widely promoted to have health benefits, there is little evidence to support this recommendation. We aimed to determine the association between number of steps per day and stepping rate with all-cause mortality. Methods: In this meta-analysis, we identified studies investigating the effect of daily step count on all-cause mortality in adults (aged ≥18 years), via a previously published systematic review and expert knowledge of the field. We asked participating study investigators to process their participant-level data following a standardised protocol. The primary outcome was all-cause mortality collected from death certificates and country registries. We analysed the dose–response association of steps per day and stepping rate with all-cause mortality. We did Cox proportional hazards regression analyses using study-specific quartiles of steps per day and calculated hazard ratios (HRs) with inverse-variance weighted random effects models. Findings: We identified 15 studies, of which seven were published and eight were unpublished, with study start dates between 1999 and 2018. The total sample included 47 471 adults, among whom there were 3013 deaths (10·1 per 1000 participant-years) over a median follow-up of 7·1 years ([IQR 4·3–9·9]; total sum of follow-up across studies was 297 837 person-years). Quartile median steps per day were 3553 for quartile 1, 5801 for quartile 2, 7842 for quartile 3, and 10 901 for quartile 4. Compared with the lowest quartile, the adjusted HR for all-cause mortality was 0·60 (95% CI 0·51–0·71) for quartile 2, 0·55 (0·49–0·62) for quartile 3, and 0·47 (0·39–0·57) for quartile 4. Restricted cubic splines showed progressively decreasing risk of mortality among adults aged 60 years and older with increasing number of steps per day until 6000–8000 steps per day and among adults younger than 60 years until 8000–10 000 steps per day. Adjusting for number of steps per day, comparing quartile 1 with quartile 4, the association between higher stepping rates and mortality was attenuated but remained significant for a peak of 30 min (HR 0·67 [95% CI 0·56–0·83]) and a peak of 60 min (0·67 [0·50–0·90]), but not significant for time (min per day) spent walking at 40 steps per min or faster (1·12 [0·96–1·32]) and 100 steps per min or faster (0·86 [0·58–1·28]). Interpretation: Taking more steps per day was associated with a progressively lower risk of all-cause mortality, up to a level that varied by age. The findings from this meta-analysis can be used to inform step guidelines for public health promotion of physical activity. Funding: US Centers for Disease Control and Prevention.

Abstract Background Daily step counts is an intuitive metric that has demonstrated success in motivating physical activity in adults and may hold potential for future public health physical activity recommendations. This review seeks to clarify the pattern of the associations between daily steps and subsequent all-cause mortality, cardiovascular disease (CVD) morbidity and mortality, and dysglycemia, as well as the number of daily steps needed for health outcomes. Methods A systematic review was conducted to identify prospective studies assessing daily step count measured by pedometer or accelerometer and their associations with all-cause mortality, CVD morbidity or mortality, and dysglycemia (dysglycemia or diabetes incidence, insulin sensitivity, fasting glucose, HbA1c). The search was performed across the Medline, Embase, CINAHL, and the Cochrane Library databases from inception to August 1, 2019. Eligibility criteria included longitudinal design with health outcomes assessed at baseline and subsequent timepoints; defining steps per day as the exposure; reporting all-cause mortality, CVD morbidity or mortality, and/or dysglycemia outcomes; adults ≥18 years old; and non-patient populations. Results Seventeen prospective studies involving over 30,000 adults were identified. Five studies reported on all-cause mortality (follow-up time 4–10 years), four on cardiovascular risk or events (6 months to 6 years), and eight on dysglycemia outcomes (3 months to 5 years). For each 1000 daily step count increase at baseline, risk reductions in all-cause mortality (6–36%) and CVD (5–21%) at follow-up were estimated across a subsample of included studies. There was no evidence of significant interaction by age, sex, health conditions or behaviors (e.g., alcohol use, smoking status, diet) among studies that tested for interactions. Studies examining dysglycemia outcomes report inconsistent findings, partially due to heterogeneity across studies of glycemia-related biomarker outcomes, analytic approaches, and sample characteristics. Conclusions Evidence from longitudinal data consistently demonstrated that walking an additional 1000 steps per day can help lower the risk of all-cause mortality, and CVD morbidity and mortality in adults, and that health benefits are present below 10,000 steps per day. However, the shape of the dose-response relation is not yet clear. Data are currently lacking to identify a specific minimum threshold of daily step counts needed to obtain overall health benefit.

Abstract Introduction : Few large, randomized trials have evaluated marine n‐3 supplements and cognition in healthy older adults. Methods : Healthy community‐dwelling participants aged 60+ years (mean [standard deviation] = 70.9 [5.8] years) in VITAL (randomized trial of n‐3 fats [1 g/day, including 840 mg of eicosapentaenoic acid + docosahexaenoic acid] and vitamin D) were included: 3424 whose cognition was assessed by phone (VITAL‐Cog; eight neuropsychological tests; 2.8 years) and 794 evaluated in person (CTSC‐Cog; nine tests; 2.0 years). The primary outcome was a global score (average of test z‐scores) of change over two assessments. We used multivariable‐adjusted linear mixed models; substudy‐specific results were meta‐analyzed. Results : We observed no significant effect of n‐3 supplementation: the mean difference in annual rate of cognitive change for the n‐3 versus placebo group was –0.01 standard units (95% confidence interval [CI]: –0.02, 0.003) in VITAL‐Cog and –0.002 (95% CI: –0.04, 0.03) in CTSC‐Cog; the pooled difference was –0.01 (95% CI: –0.02, 0.003; P = .15). Discussion : Marine n‐3 supplementation (1 g/day) did not confer cognitive benefits over 2 to 3 years in community‐dwelling older adults.

Background: The VITAL study was a nationwide, randomized, double-blind, placebo-controlled, 2 × 2 factorial trial of vitamin D3 (2000 IU/day) and marine n-3 FAs (1 g/day) supplements. We recently reported that vitamin D supplementation with or without omega 3 fatty acids reduced autoimmune disease by 22% in the VITAL study. Objective: To investigate the effects of vitamin D3 and/or n-3 FAs on changes in systemic inflammatory biomarkers including pro- and anti-inflammatory cytokines over a 4-year period in the VITAL sub-cohort with in-person evaluations at the Center for Clinical Investigations (CCI) in Boston. Design: Serum levels of four inflammatory biomarkers (high-sensitivity C-reactive protein [hs-CRP], interleukin-6, interleukin-10, and tumor necrosis factor-α) were measured in a total of 2713 samples from those 1054 VITAL/CCI participants (aged 64.9 ± 6.5 years, 49% female, 84% white, and 9% black) at baseline, year 2, and year 4 follow-up visits. Results: In multiple-adjusted models, vitamin D3 supplementation decreased serum hs-CRP levels by 19% at 2-year follow-up (nominal p = 0.007; p-value after multiple comparison adjustment = 0.028), but not at 4-year follow-up (nominal and adjusted p-values > 0.05). The effects of vitamin D3 on other inflammatory markers were not statistically significant either at year 2 or year 4 (all adjusted p-values > 0.05). Marine n-3 FAs were not significantly associated with changes of all the above inflammatory markers either at years 2 and 4, after multiple comparison adjustment (all p-values > 0.05). Conclusions: Vitamin D3 supplementation with or without n-3 FAs decreased hs-CRP by 19% at year 2, but not other inflammatory biomarkers at year 2 or year 4, while n-3 FAs with or without vitamin D3 did not significantly affect these biomarkers at either time point. Our findings support a potential role of vitamin D supplementation in modulating the chronic inflammatory process, systemic inflammation, and possibly autoimmune disease progression.

Purpose This paper describes the Women’s Health Accelerometry Collaboration, a consortium of two prospective cohort studies of women age 62 years or older, harmonised to explore the association of accelerometer-assessed physical activity and sedentary behaviour with cancer incidence and mortality.Participants A total of 23 443 women (age mean 73.4, SD 6.8) living in the USA and participating in an observational study were included; 17 061 from the Women’s Health Study (WHS) and 6382 from the Women’s Health Initiative Objective Physical Activity and Cardiovascular Health (WHI/OPACH) Study.Findings to date Accelerometry, cancer outcomes and covariate harmonisation was conducted to align the two cohort studies. Physical activity and sedentary behaviour were measured using similar procedures with an ActiGraph GT3X+ accelerometer, worn at the hip for 1 week, during 2011–2014 for WHS and 2012–2014 for WHI/OPACH. Cancer outcomes were ascertained via ongoing surveillance using physician adjudicated cancer diagnosis. Relevant covariates were measured using questionnaire or physical assessments. Among 23 443 women who wore the accelerometer for at least 10 hours on a single day, 22 868 women wore the accelerometer at least 10 hours/day on ≥4 of 7 days. The analytical sample (n=22 852) averaged 4976 (SD 2669) steps/day and engaged in an average of 80.8 (SD 46.5) min/day of moderate-to-vigorous, 105.5 (SD 33.3) min/day of light high and 182.1 (SD 46.1) min/day of light low physical activity. A mean of 8.7 (SD 1.7) hours/day were spent in sedentary behaviour. Overall, 11.8% of the cohort had a cancer diagnosis (other than non-melanoma skin cancer) at the time of accelerometry measurement. During an average of 5.9 (SD 1.6) years of follow-up, 1378 cancer events among which 414 were fatal have occurred.Future plans Using the harmonised cohort, we will access ongoing cancer surveillance to quantify the associations of physical activity and sedentary behaviour with cancer incidence and mortality.

Abstract Aims/Introduction To investigate the relationship between combined aerobic and resistance training, and the incidence of type 2 diabetes mellitus. Materials and Methods The present study included 10,680 Japanese women. Participants enrolled between 2005 and 2010, and were followed up until 2014. The frequency of combined training was counted for the first 3 months, the 6th month and the 9th month. In 2014, women reported whether or not they had diabetes, as well as the year of developing diabetes. Hazard ratios and 95% confidence intervals (CI) for the incidence of type 2 diabetes were obtained using Cox proportional hazard models. Results The median duration of follow up was 5 years, with 166 women developing type 2 diabetes. Using the lowest frequency of training group (1st quartile) as the reference, the hazard ratios for the second through fourth quartiles was as follows: 0.95 (95% CI 0.64–1.41), 0.73 (95% CI 0.48–1.13) and 0.69 (95% CI 0.44–1.07), respectively (P for trend = 0.116). After adjustment for age, body mass index and thigh circumference, the hazard ratios were: 0.84 (95% CI 0.56–1.26), 0.69 (95% CI 0.45–1.06) and 0.61 (95% CI 0.39–0.95), respectively (P for trend = 0.040). Conclusions A higher frequency of combined aerobic and resistance training is associated with a lower risk of developing type 2 diabetes in Japanese women.

Background: Red and processed meat consumption has been consistently associated with increased risk of colorectal cancer (CRC), but the association for fish intake is unclear. Evidence using objective dietary assessment approaches to evaluate these associations is sparse. Objectives: We aim to investigate the plasma metabolite profiles related to red meat, poultry, and fish consumption and examine their associations with CRC risk. Methods: We measured plasma metabolites among 5269 participants from the Nurses’ Health Study (NHS), NHSII, and Health Professionals Follow-Up study (HPFS). We calculated partial Spearman correlations between each metabolite and self-reported intake of seven red meat, poultry, and fish groups. Metabolite profile scores correlated to self-reported dietary intakes were developed using elastic net regression. Associations between self-reported intakes, metabolite profile scores, and subsequent CRC risk were further evaluated using conditional logistic regression among 559 matched (1:1) case-control pairs in NHS/HPFS and replicated among 266 pairs in Women’s Health Study. Results: Plasma metabolites, especially highly unsaturated lipids, were differentially associated with red meat and fish groups. Metabolite profile scores for each food group were significantly correlated with the corresponding self-reported dietary intake. A higher dietary intake of processed red meat was associated with a higher risk of CRC (pooled OR per 1 SD, 1.15; 95% CI: 1.03, 1.29). In contrast, higher metabolite profile scores for all fish groups, not dietary intakes, were consistently associated with a lower CRC risk: the pooled OR per 1 SD was 0.86 (95% CI: 0.78, 0.96) for total fish, 0.86 (95% CI: 0.77, 0.96) for dark meat fish, and 0.87 (95% CI: 0.78, 0.97) for canned tuna fish. No significant associations were found for other food groups. Conclusions: Red meat and fish intake exhibited systematically different plasma metabolite profiles. Plasma metabolite profile of fish intake was inversely associated with CRC risk.

Background: We sought to examine the association between cardiorespiratory fitness (CRF) and incidence of type 2 diabetes considering the follow-up period in a cohort of Japanese men with a maximum follow-up period of 23 years. Methods: This study enrolled 7,804 male workers free of diabetes in 1986. CRF was measured using a cycle ergometer, and maximal oxygen uptake was estimated. During 1986–2009, participants were followed for development of type 2 diabetes, which was diagnosed using fasting blood tests, self-administered questionnaires, or oral glucose tolerance tests after urinary tests from annual health checkups. Hazard ratios for the incidence of type 2 diabetes were estimated using Cox proportional hazards models. Results: During the follow-up period, 1,047 men developed type 2 diabetes. In analyses by follow-up periods (1986–1993, 1994–2001, and 2002–2009), there was an inverse dose-response relationship between CRF and the development of type 2 diabetes for all three follow-up periods (P for trend 0.019, 20 years among men.

Abstract Background This study aimed to examine the relationship between pedometer-assessed daily step count and all-cause mortality in a sample of elderly Japanese people. Methods Participants included 419 (228 males and 191 females) physically independent, community-dwelling 71-year-old Japanese people. The number of steps per day was measured by a waist-mounted pedometer for seven consecutive days at baseline. Participants were divided into quartiles based on their average number of steps/day (first quartile, 7972 steps/day) and were followed up over a mean period of 9.8 years (1999–2010) for mortality. Results Seventy-six participants (18.1%) died during the follow-up period. The hazard ratios (adjusted for sex, body mass index, cigarette smoking, alcohol intake, and medication use) for mortality across the quartiles of daily step count (lowest to highest) were 1.00 (reference), 0.81 (95%CI, 0.43–1.54), 1.26 (95%CI, 0.70–2.26), and 0.46 (95%CI, 0.22–0.96) (P for trend = 0.149). Participants in the highest quartile had a significantly lower risk of death compared with participants in the lowest quartile. Conclusion This study suggested that a high daily step count is associated with a lower risk of all-cause mortality in physically independent Japanese elderly people.

This study describes relationships between awareness of physical activity (PA) promotion and duration of PA and sedentary behavior (SB) in elderly Japanese. Following a community-wide intervention, 874 individuals 65 years or over were selected via population-based random sampling of 3,000 adults aged 20 years or over living in Fujisawa City, and asked to complete self-administered questionnaires; 550 responded and 373 with data on pertinent variables were included. Forty-eight percent (179/373) stated that they recognized elements of the Japanese PA guidelines such as the “Active Guide” and “+10 (plus ten).” The median duration of PA, of intensity at least equal to walking, and SB among all participants were 100 minutes/day and 300 minutes/day, respectively. Duration of PA did not significantly differ by promotion awareness (Odds Ratio (OR) for ≥100 minutes/day among those aware = 1.02, 95% Confidence Interval (CI) = 0.65-1.62); however, duration of SB did (OR for

Abstract Background The work of The Global Observatory for Physical Activity-GoPA! is the first global effort to compile standardized country-level surveillance, policy and research data for physical activity in order to better understand how countries and regions address promoting physical activity. GoPA! developed standardized country-specific physical activity profiles (“Country Cards”) to summarize country-level data through 2013. The aim of this study was to assess use of the Country Cards, identify the factors associated with their use, and develop recommendations for supporting country-level physical activity promotion. Methods Cross sectional internet-based survey conducted between August–October 2016. Target study participants were national physical activity leaders and advocates in academia, government and practice from the GoPA! countries, and members of the International Society of Physical Activity and Health. A Country Card use composite score was created based on the diversity and frequency of use. Statistical analyses on the associations between the composite score and respondent characteristics, country characteristics, barriers and opinions were conducted (including descriptive analyses and a logistic regression with robust standard errors). Results One hundred forty three participants from 68 countries completed the survey. Use of the Country Cards was associated with being part of the GoPA! network, knowing about the Country Cards, and on the stage of country capacity for physical activity promotion. Country Card knowledge varied by country income group, region and the country specific context. More diverse and frequent use of the cards (highest tertile of the composite score for use) was associated with: 1. Being a country contact vs general participant (OR 18.32–95% CI 5.63–59.55, p = 0.002), and 2. Collaborating with a government representative working in NCDs on a monthly or more frequent contact vs less frequent contact (OR 3.39–95% CI 1.00–11.54, P

The stability of the relative order of cardiorespiratory fitness (CRF) during adulthood has not been sufficiently investigated. This study investigated the tracking of CRF over a 7-year follow-up period in Japanese male adults aged 18-53 years. A total of 3,718 male workers who underwent three submaximal exercise tests (a first test and again 3 and 7 years later for a second and third test) were included. CRF was defined as the maximal oxygen uptake estimated from a submaximal exercise test using a cycle ergometer. Spearman correlation coefficients for CRF in the first and second tests, the second and third tests and the first and third tests were 0.61, 0.62 and 0.54, respectively. A moderate kappa coefficient, indicating the degree of agreement for quartiles, was obtained for all follow-up periods (kappa coefficient = 0.43-0.53). The changes in quartiles for all three time measurements indicated that approximately 70% of participants had stable (participants in the same quartile for all three measurements) or moderately stable (participants who exhibited changes varying by one quartile from the initial quartile) CRF levels. These findings showed moderate CRF tracking during adulthood over a period of up to 7 years.

Risk for renal cell carcinoma (RCC) is higher when there are first-degree family members with the disease. Here, Scelo and colleagues perform a genome-wide association meta-analysis and new genome-wide scan to identify seven new loci with significant RCC association.

Abstract Background Limited evidence exists to inform physical activity (PA) and sedentary behavior guidelines for older people, especially women. Rigorous evidence on the amounts, intensities, and movement patterns associated with better health in later life is needed. Methods/Design The Objective PA and Cardiovascular Health (OPACH) Study is an ancillary study to the Women’s Health Initiative (WHI) Program that examines associations of accelerometer-assessed PA and sedentary behavior with cardiovascular and fall events. Between 2012 and 2014, 7048 women aged 63–99 were provided with an ActiGraph GT3X+ (Pensacola, Florida) triaxial accelerometer, a sleep log, and an OPACH PA Questionnaire; 6489 have accelerometer data. Most women were in their 70s (40%) or 80s (46%), while approximately 10% were in their 60s and 4% were age 90 years or older. Non-Hispanic Black or Hispanic/Latina women comprise half of the cohort. Follow-up includes 1-year of falls surveillance with monthly calendars and telephone interviews of fallers, and annual follow-up for outcomes with adjudication of incident cardiovascular disease (CVD) events through 2020. Over 63,600 months of calendar pages were returned by 5,776 women, who reported 5,980 falls. Telephone interviews were completed for 1,492 women to ascertain the circumstances, injuries and medical care associated with falling. The dataset contains extensive information on phenotypes related to healthy aging, including inflammatory and CVD biomarkers, breast and colon cancer, hip and other fractures, diabetes, and physical disability. Discussion This paper describes the study design, methods, and baseline data for a diverse cohort of postmenopausal women who wore accelerometers under free-living conditions as part of the OPACH Study. By using accelerometers to collect more precise and complete data on PA and sedentary behavior in a large cohort of older women, this study will contribute crucial new evidence about how much, how vigorous, and what patterns of PA are necessary to maintain optimal cardiovascular health and to avoid falls in later life. Clinical trials registration ClinicalTrials.gov identifier NCT00000611 . Registered 27 October 1999.

To evaluate the association between numbers of floors climbed (per week) and all-cause and cardiovascular (CVD) mortality in men. A prospective study was conducted in 8874 men (Median [interquartile range] age: 65 years [60–71.6 years]) from the Harvard Alumni Health Study. Participants reported the number of floors habitually climbed, physical activity in their leisure time, other health related behaviours and any physician diagnosed disease in 1988. Men were followed for mortality through December 2008. Multivariate Cox hazard models to examine the association between weekly number of floors climbed and all-cause and CVD mortality adjusted for participation in total physical activity and other confounders.During a median follow-up of 12.4 years, 4063 men died (1195 from CVD). After adjusting for confounders (age, walking, sports/recreation, body mass index, alcohol intake, and smoking, diagnoses of hypertension or diabetes or high cholesterol) number of stairs habitually climbed was inversely associated with all-cause mortality (p trend

BackgroundSeveral obesity-related factors have been associated with renal cell carcinoma (RCC), but it is unclear which individual factors directly influence risk. We addressed this question using genetic markers as proxies for putative risk factors and evaluated their relation to RCC risk in a mendelian randomization (MR) framework. This methodology limits bias due to confounding and is not affected by reverse causation.Methods and findingsGenetic markers associated with obesity measures, blood pressure, lipids, type 2 diabetes, insulin, and glucose were initially identified as instrumental variables, and their association with RCC risk was subsequently evaluated in a genome-wide association study (GWAS) of 10,784 RCC patients and 20,406 control participants in a 2-sample MR framework. The effect on RCC risk was estimated by calculating odds ratios (ORSD) for a standard deviation (SD) increment in each risk factor. The MR analysis indicated that higher body mass index increases the risk of RCC (ORSD: 1.56, 95% confidence interval [CI] 1.44-1.70), with comparable results for waist-to-hip ratio (ORSD: 1.63, 95% CI 1.40-1.90) and body fat percentage (ORSD: 1.66, 95% CI 1.44-1.90). This analysis further indicated that higher fasting insulin (ORSD: 1.82, 95% CI 1.30-2.55) and diastolic blood pressure (DBP; ORSD: 1.28, 95% CI 1.11-1.47), but not systolic blood pressure (ORSD: 0.98, 95% CI 0.84-1.14), increase the risk for RCC. No association with RCC risk was seen for lipids, overall type 2 diabetes, or fasting glucose.ConclusionsThis study provides novel evidence for an etiological role of insulin in RCC, as well as confirmatory evidence that obesity and DBP influence RCC risk.

Objective: We conducted a laboratory-based calibration study to determine relevant cutpoints for a hip-worn accelerometer among women ≥60 years, considering both type and filtering of counts. Methods: Two hundred women wore an ActiGraph GT3X+ accelerometer on their hip while performing eight laboratory-based activities. Oxygen uptake was measured using an Oxycon portable calorimeter. Accelerometer data were analyzed in 15-second epochs for both normal and low frequency extension (LFE) filters. Receiver operating characteristic (ROC) curve analyses were used to calculate cutpoints for sedentary, light (low and high), and moderate to vigorous physical activity (MVPA) using the vertical axis and vector magnitude (VM) counts. Results: Mean age was 75.5 years (standard deviation 7.7). The Spearman correlation between oxygen uptake and accelerometry ranged from 0.77 to 0.85 for the normal and LFE filters and for both the vertical axis and VM. The area under the ROC curve was generally higher for VM compared to the vertical axis, and higher for cutpoints distinguishing MVPA compared to sedentary and light low activities. The VM better discriminated sedentary from light low activities compared to the vertical axis. The area under the ROC curves were better for the LFE filter compared to the normal filter for the vertical axis counts, but no meaningful differences were found by filter type for VM counts. Conclusion: The cutpoints derived for this study among women ≥60 years can be applied to ongoing epidemiologic studies to define a range of physical activity intensities.

BackgroundFew data exist on the association between strength training and mortality rates. We sought to examine the association between strength training and all‐cause, cardiovascular disease, and cancer mortality. Methods and ResultsBeginning in 2001 to 2005, 28 879 women throughout the United States (average baseline age, 62.2 years) from the Women's Health Study who were free of cardiovascular disease, diabetes mellitus, and cancer reported their physical activities, including strength training. During follow‐up (average, 12.0 years) through 2015, investigators documented 3055 deaths (411 from cardiovascular disease and 748 from cancer). After adjusting for covariables, including aerobic activity, time in strength training showed a quadratic association with all‐cause mortality (P=0.36 for linear trend; P1.00 for ≥146 min/wk of strength training. However, confidence intervals were wide at higher levels of strength training. ConclusionsTime in strength training showed a J‐shaped association with all‐cause mortality in older women. A moderate amount of time in strength training seemed beneficial for longevity, independent of aerobic activity; however, any potential risk with more time (≈≥150 min/wk) should be further investigated.

BackgroundThe relationship between light intensity physical activity (PA), which is common in older adults, and cardiovascular disease (CVD) risk factors is unclear. This study examined associations of accelerometer‐measured PA intensity with CVD risk factors in older women of different race‐ethnicities. Methods and ResultsCross‐sectional analyses were conducted in 4832 women (mean age 78.9 years; 52.5% white, 30.5% black, 17.1% Hispanic) who were without known CVD and wore triaxial accelerometers a minimum of 4 of 7 days with ≥10 hours/d awake wear‐time. Vector magnitude counts per 15‐s epoch were used to define time spent in low light (19–225 counts/15 s), high light (226–518), and moderate‐to‐vigorous; ≥519) intensity PA. Fasting CVD biomarkers, resting blood pressure, waist girth, body mass index, and 10‐year predicted CVD risk (Reynolds Risk Score) were measured. After adjusting for age, wear time, race‐ethnicity, and potential confounders, each PA measure was favorably associated with mean high‐density lipoprotein, triglyceride, glucose, C‐reactive protein, body mass index, waist girth, and Reynolds Risk Score (P

BACKGROUND:The purpose of this study was to examine the impact of combined cardiorespiratory fitness and waist-to-height ratio in the form of a fit-fat index on incident diabetes risk. Additionally, the independent predictive performance of cardiorespiratory fitness, waist-to-height ratio, and body mass index also were estimated and compared. METHODS:This was a prospective cohort study of 10,381 men who had a normal electrocardiogram and no history of major chronic disease at baseline from 1979 to 2005. Random survival forest models and traditional Cox proportional hazards models were used to predict diabetes at 5-, 10-, and 15-year incidence horizons. RESULTS:Overall, 4.8% of the participants developed diabetes. Receiver operating characteristic curve analyses for incidence risk demonstrated good discrimination using random survival forest models across fitness and fatness measures; Cox models were poor to fair. The differences between fitness and fatness measures across horizons were clinically negligible. Smoothed random survival forest estimates demonstrated the impact of each fitness and fatness measure on incident diabetes was intuitive and graded. CONCLUSIONS:Although fitness and fatness measures showed a similar discriminative ability in predicting incident diabetes, unique to the study was the ability of the fit-fat index to demonstrate a better indication of incident risk when compared to fitness or fatness alone. A single index combining cardiorespiratory fitness and waist-to-height ratio may be more useful because it can indicate improvements in either or both of the measures.

Acute phase proteins highlight the dynamic interaction between inflammation and oncogenesis. GlycA, a novel nuclear magnetic resonance (NMR) inflammatory marker that identifies primarily circulating N-acetyl glycan groups attached to acute phase proteins, may be a future CRC risk biomarker.We examined the association between GlycA and incident CRC and mortality in two prospective cohorts (N = 34,320); Discovery cohort: 27,495 participants from Women's Health Study (WHS); Replication cohort: 6,784 participants from Multi-Ethnic Study of Atherosclerosis (MESA). Multivariable Cox models were adjusted for clinical risk factors and compared GlycA to acute phase proteins (high-sensitivity C-reactive protein [hsCRP], fibrinogen, and soluble intercellular adhesion molecule-1 [sICAM-1]).In WHS (median follow-up 19 years, 337 cases, 103 deaths), adjusted HRs (95% CIs) per SD increment of GlycA for CRC incidence and mortality were 1.19 (1.06-1.35; p = 0.004) and 1.24 (1.00-1.55; p = 0.05), respectively. We replicated findings in MESA (median follow-up 11 years, 70 cases, 23 deaths); HRs (95% CIs) per SD of GlycA for CRC incidence and mortality were 1.32 (1.06-1.65; p = 0.01) and 1.54 (1.06-2.23; p = 0.02), respectively, adjusting for age, sex, and race. Pooled analysis, adjusted HR (95% CI) per SD of GlycA for CRC incidence and mortality was 1.26 (1.15-1.39; p = 1 x 10-6). Other acute phase proteins (hsCRP, fibrinogen, and sICAM-1) had weaker or no association with CRC incidence, while only fibrinogen and GlycA were associated with CRC mortality.The clinical utility of GlycA to personalize CRC therapies or prevention warrants further study.ClinicalTrials.gov: WHS NCT00000479, MESA NCT00005487.

Self-reported physical activity measures continue to be validated against accelerometers; however, the absence of standardized, accelerometer moderate-to-vigorous physical activity (MVPA) definitions has made comparisons across studies difficult. Furthermore, recent accelerometer models assess accelerations in three axes, instead of only the vertical axis, but validation studies have yet to take incorporate triaxial data.Participants (n = 10 115) from the Women's Health Study wore a hip-worn accelerometer (ActiGraph GT3X+) for seven days during waking hours (2011-2014). Women then completed a physical activity questionnaire. We compared self-reported with accelerometer-assessed MVPA, using four established cutpoints for MVPA: three using only vertical axis data (760, 1041 and 1952 counts per minute (cpm)) and one using triaxial data (2690 cpm).According to self-reported physical activity, 66.6% of women met the US federal physical activity guidelines, engaging in ≥150 minutes per week of MVPA. The percent of women who met guidelines varied widely depending on the accelerometer MVPA definition (760 cpm: 50.0%, 1041 cpm: 33.0%, 1952 cpm: 13.4%, and 2690 cpm: 19.3%).Triaxial count data do not substantially reduce the difference between self-reported and accelerometer-assessed MVPA.

BackgroundLeisure time physical activity reduces the risk of premature mortality, but the years of life expectancy gained at different levels remains unclear. Our objective was to determine the years of life gained after age 40 associated with various levels of physical activity, both overall and according to body mass index (BMI) groups, in a large pooled analysis.Methods and findingsWe examined the association of leisure time physical activity with mortality during follow-up in pooled data from six prospective cohort studies in the National Cancer Institute Cohort Consortium, comprising 654,827 individuals, 21-90 y of age. Physical activity was categorized by metabolic equivalent hours per week (MET-h/wk). Life expectancies and years of life gained/lost were calculated using direct adjusted survival curves (for participants 40+ years of age), with 95% confidence intervals (CIs) derived by bootstrap. The study includes a median 10 y of follow-up and 82,465 deaths. A physical activity level of 0.1-3.74 MET-h/wk, equivalent to brisk walking for up to 75 min/wk, was associated with a gain of 1.8 (95% CI: 1.6-2.0) y in life expectancy relative to no leisure time activity (0 MET-h/wk). Higher levels of physical activity were associated with greater gains in life expectancy, with a gain of 4.5 (95% CI: 4.3-4.7) y at the highest level (22.5+ MET-h/wk, equivalent to brisk walking for 450+ min/wk). Substantial gains were also observed in each BMI group. In joint analyses, being active (7.5+ MET-h/wk) and normal weight (BMI 18.5-24.9) was associated with a gain of 7.2 (95% CI: 6.5-7.9) y of life compared to being inactive (0 MET-h/wk) and obese (BMI 35.0+). A limitation was that physical activity and BMI were ascertained by self report.ConclusionsMore leisure time physical activity was associated with longer life expectancy across a range of activity levels and BMI groups. Please see later in the article for the Editors' Summary.

BackgroundBetter information on lung cancer occurrence in lifelong nonsmokers is needed to understand gender and racial disparities and to examine how factors other than active smoking influence risk in different time periods and geographic regions.Methods and findingsWe pooled information on lung cancer incidence and/or death rates among self-reported never-smokers from 13 large cohort studies, representing over 630,000 and 1.8 million persons for incidence and mortality, respectively. We also abstracted population-based data for women from 22 cancer registries and ten countries in time periods and geographic regions where few women smoked. Our main findings were: (1) Men had higher death rates from lung cancer than women in all age and racial groups studied; (2) male and female incidence rates were similar when standardized across all ages 40+ y, albeit with some variation by age; (3) African Americans and Asians living in Korea and Japan (but not in the US) had higher death rates from lung cancer than individuals of European descent; (4) no temporal trends were seen when comparing incidence and death rates among US women age 40-69 y during the 1930s to contemporary populations where few women smoke, or in temporal comparisons of never-smokers in two large American Cancer Society cohorts from 1959 to 2004; and (5) lung cancer incidence rates were higher and more variable among women in East Asia than in other geographic areas with low female smoking.ConclusionsThese comprehensive analyses support claims that the death rate from lung cancer among never-smokers is higher in men than in women, and in African Americans and Asians residing in Asia than in individuals of European descent, but contradict assertions that risk is increasing or that women have a higher incidence rate than men. Further research is needed on the high and variable lung cancer rates among women in Pacific Rim countries.

Background: We examined the joint associations of diet and device-measured intensity-specific physical activity (PA) with all-cause mortality (ACM), cardiovascular disease (CVD), and cancer incidence. Methods: We used data from 79,988 participants from the UK Biobank, a population-based prospective cohort study. Light PA (LPA), moderate-to-vigorous PA (MVPA), vigorous PA (VPA), and total PA (TPA) were measured using a wrist-worn accelerometer. Diet quality score (DQS) was based on 10 foods and ranged from 0 (unhealthiest) to 100 (healthiest) points. We derived joint PA and diet variables. Outcomes were ACM, CVD, and cancer incidence including PA, diet and adiposity-related (PDAR) cancer. Results: During a median follow-up of 8 years, 2,863 deaths occurred, 11,053 participants developed CVD, 7,005 developed cancer, and 3,400 developed PDAR cancer. Compared with the least favorable referent group (bottom PA tertile/low DQS), participants with middle and high (total and intensity specific) PA, except for LPA, had lower ACM risk and incident CVD risk, regardless of DQS. For example, among middle and high VPA and high DQS groups, CVD HR were 0.79 (95% CI, 0.74-0.86) and 0.75 (95% CI, 0.69-0.82), respectively. The pattern of cancer results was less pronounced but in agreement with the ACM and CVD incidence findings (e.g., HR, 0.90, 95% CI, 0.81-0.99; 0.88, 0.79-0.98; and 0.82, 0.74-0.92 among high VPA for low, moderate, and high DQS groups, respectively). Conclusions: Device-measured PA reveals novel joint associations with diet on health outcomes. [ABSTRACT FROM AUTHOR]