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Association of Major Dietary Protein Sources With All-Cause and Cause-Specific Mortality: Prospective Cohort Study.
Sun, Y, Liu, B, Snetselaar, LG, Wallace, RB, Shadyab, AH, Kroenke, CH, Haring, B, Howard, BV, Shikany, JM, Valdiviezo, C, et al
Journal of the American Heart Association. 2021;10(5):e015553
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Dietary recommendations for human health focusing on total protein intake without considering specific protein sources may be simplistic and insufficient. The aim of this study was to investigate whether different dietary protein sources would be differentially associated with mortality risk. The study is based on data from a large prospective cohort study with up to 18-years of follow-up to investigate the risks of all-cause and cause-specific mortality in relation to animal and plant protein intake, and major sources of dietary protein. Results indicate that intake of plant protein and substitution of animal protein with plant protein, were associated with lower risk of all-cause, cardiovascular disease, and dementia mortality. Furthermore, substitution of red meat, eggs, dairy products, or legumes with nuts was associated with lower risk of all-cause mortality. Authors conclude that their findings support the need for consideration of protein sources, in addition to the amount of protein intake, in future dietary guidelines.
Abstract
Background Dietary recommendations regarding protein intake have been focused on the amount of protein. However, such recommendations without considering specific protein sources may be simplistic and insufficient. Methods and Results We included 102 521 postmenopausal women enrolled in the Women's Health Initiative between 1993 and 1998, and followed them through February 2017. During 1 876 205 person-years of follow-up, 25 976 deaths occurred. Comparing the highest with the lowest quintile, plant protein intake was inversely associated with all-cause mortality (hazard ratio [HR], 0.91 [0.86, 0.96]), cardiovascular disease mortality (HR, 0.88 [0.79, 0.97]), and dementia mortality (HR, 0.79 [0.67, 0.94]). Among major protein sources, comparing the highest with the lowest quintile of consumption, processed red meat (HR, 1.06 [1.01, 1.10]) or eggs (HR, 1.14 [1.10, 1.19]) was associated with higher risk of all-cause mortality. Unprocessed red meat (HR, 1.12 [1.02, 1.23]), eggs (HR, 1.24 [1.14, 1.34]), or dairy products (HR, 1.11 [1.02, 1.22]) was associated with higher risk of cardiovascular disease mortality. Egg consumption was associated with higher risk of cancer mortality (HR, 1.10 [1.02, 1.19]). Processed red meat consumption was associated with higher risk of dementia mortality (HR, 1.20 [1.05, 1.32]), while consumption of poultry (HR, 0.85 [0.75, 0.97]) or eggs (HR, 0.86 [0.75, 0.98]) was associated with lower risk of dementia mortality. In substitution analysis, substituting of animal protein with plant protein was associated with a lower risk of all-cause mortality, cardiovascular disease mortality, and dementia mortality, and substitution of total red meat, eggs, or dairy products with nuts was associated with a lower risk of all-cause mortality. Conclusions Different dietary protein sources have varying associations with all-cause mortality, cardiovascular disease mortality, and dementia mortality. Our findings support the need for consideration of protein sources in future dietary guidelines.
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Association of Body Fat and Risk of Breast Cancer in Postmenopausal Women With Normal Body Mass Index: A Secondary Analysis of a Randomized Clinical Trial and Observational Study.
Iyengar, NM, Arthur, R, Manson, JE, Chlebowski, RT, Kroenke, CH, Peterson, L, Cheng, TD, Feliciano, EC, Lane, D, Luo, J, et al
JAMA oncology. 2019;(2):155-163
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Abstract
IMPORTANCE Obesity is associated with an increased risk of breast cancer, including the estrogen receptor (ER)-positive subtype in postmenopausal women. Whether excess adiposity is associated with increased risk in women with a normal body mass index (BMI; calculated as weight in kilograms divided by height in meters squared) is unknown. OBJECTIVE To investigate the association between body fat and breast cancer risk in women with normal BMI. DESIGN, SETTING, AND PARTICIPANTS This ad hoc secondary analysis of the Women's Health Initiative (WHI) clinical trial and observational study cohorts was restricted to postmenopausal participants with a BMI ranging from 18.5 to 24.9. Women aged 50 to 79 years were enrolled from October 1, 1993, through December 31, 1998. Of these, 3460 participants underwent body fat measurement with dual-energy x-ray absorptiometry (DXA) at 3 US designated centers with follow-up. At a median follow-up of 16 years (range, 9-20 years), 182 incident breast cancers had been ascertained, and 146 were ER positive. Follow-up was complete on September 30, 2016, and data from October 1, 1993, through September 30, 2016, was analyzed August 2, 2017, through August 21, 2018. MAIN OUTCOMES AND MEASURES Body fat levels were measured at baseline and years 1, 3, 6, and 9 using DXA. Information on demographic data, medical history, and lifestyle factors was collected at baseline. Invasive breast cancers were confirmed via central review of medical records by physician adjudicators. Blood analyte levels were measured in subsets of participants. RESULTS Among the 3460 women included in the analysis (mean [SD] age, 63.6 [7.6] years), multivariable-adjusted hazard ratios for the risk of invasive breast cancer were 1.89 (95% CI, 1.21-2.95) for the highest quartile of whole-body fat and 1.88 (95% CI, 1.18-2.98) for the highest quartile of trunk fat mass. The corresponding adjusted hazard ratios for ER-positive breast cancer were 2.21 (95% CI, 1.23-3.67) and 1.98 (95% CI, 1.18-3.31), respectively. Similar positive associations were observed for serial DXA measurements in time-dependent covariate analyses. Circulating levels of insulin, C-reactive protein, interleukin 6, leptin, and triglycerides were higher, whereas levels of high-density lipoprotein cholesterol and sex hormone-binding globulin were lower in those in the uppermost vs lowest quartiles of trunk fat mass. CONCLUSIONS AND RELEVANCE In postmenopausal women with normal BMI, relatively high body fat levels were associated with an elevated risk of invasive breast cancer and altered levels of circulating metabolic and inflammatory factors. Normal BMI categorization may be an inadequate proxy for the risk of breast cancer in postmenopausal women. TRIAL REGISTRATION ClinicalTrials.gov identifier: NCT00000611.
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Muscle radiodensity and mortality in patients with colorectal cancer.
Kroenke, CH, Prado, CM, Meyerhardt, JA, Weltzien, EK, Xiao, J, Cespedes Feliciano, EM, Caan, BJ
Cancer. 2018;(14):3008-3015
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Abstract
BACKGROUND Low skeletal muscle radiodensity (SMD) is related to higher mortality in several cancers, but the association with colorectal cancer (CRC) prognosis is unclear. METHODS This observational study included 3262 men and women from the Kaiser Permanente Northern California population diagnosed between 2006 and 2011 with AJCC stages I to III CRC. The authors evaluated hazard ratios (HRs) of low SMD for all-cause and CRC-specific mortality, assessed by computed tomography using optimal stratification, compared with patients with normal SMD. They also evaluated the cross-classification of categories of low versus normal SMD and muscle mass (MM) with outcomes. RESULTS The median follow-up was 6.9 years. Optimal stratification cutpoints for SMD were 32.5 in women and 35.5 in men. In multivariate-adjusted analyses, among patients with CRC, those with low SMD demonstrated higher overall (HR, 1.61; 95% confidence interval [95% CI], 1.36-1.90) and CRC-specific (HR, 1.74; 95% CI, 1.38-2.21) mortality when compared with those with normal SMD levels. Patients with low SMD and low MM (ie, sarcopenia) were found to have the highest overall (HR, 2.02; 95% CI, 1.65-2.47) and CRC-specific (HR, 2.54; 95% CI, 1.91-3.37) mortality rates. CONCLUSIONS In patients with CRC, those with low SMD were found to have elevated risks of disease-specific and overall mortality, independent of MM or adiposity. Clinical practice should incorporate body composition measures into the evaluation of the health status of patients with CRC. Cancer 2018;124:3008-15. © 2018 American Cancer Society.
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Association between Post-Cancer Diagnosis Dietary Inflammatory Potential and Mortality among Invasive Breast Cancer Survivors in the Women's Health Initiative.
Zheng, J, Tabung, FK, Zhang, J, Liese, AD, Shivappa, N, Ockene, JK, Caan, B, Kroenke, CH, Hébert, JR, Steck, SE
Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology. 2018;(4):454-463
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Abstract
Background: Inflammation is important in chronic disease and can be modulated by dietary exposures. Our aim was to examine whether the inflammatory potential of diet after cancer diagnosis, assessed using the dietary inflammatory index (DII), is associated with all-cause and cause-specific mortality among women diagnosed with invasive breast cancer in the Women's Health Initiative (WHI).Methods: Our analytic cohort included 2,150 postmenopausal women, ages 50 to 79 years at baseline, who developed invasive breast cancer during follow-up and completed a food frequency questionnaire (FFQ) on average 1.5 years after diagnosis. Women were followed from breast cancer diagnosis until death or the end of follow-up by October 2014. Energy-adjusted DII (E-DII) scores were calculated from food plus supplements using a nutrient-density approach. Cox proportional hazards models were fit to estimate multivariable-adjusted HRs and 95% confidence intervals (CIs) for all-cause, breast cancer-specific, and cardiovascular disease (CVD) mortality.Results: After a median 13.3 years of follow-up, 580 deaths from any cause occurred, including 212 breast cancer deaths and 103 CVD deaths. Lower (i.e., more anti-inflammatory) E-DII scores were associated with a lower risk of CVD mortality (HRQ1VSQ4 = 0.44; 95% CI, 0.24-0.82; Ptrend = 0.005), but not with breast cancer-specific mortality (HRQ1VSQ4 = 0.96; 95% CI, 0.62-1.49; Ptrend = 0.96) or all-cause mortality (HRQ1VSQ4 = 0.82; 95% CI, 0.63-1.05; Ptrend = 0.17).Conclusions: Consuming a more anti-inflammatory diet after breast cancer diagnosis may be a means for reducing risk of death from CVD.Impact: Survival after invasive breast cancer diagnosis may be improved by consumption of an anti-inflammatory diet. Cancer Epidemiol Biomarkers Prev; 27(4); 454-63. ©2018 AACR.
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Association of Muscle and Adiposity Measured by Computed Tomography With Survival in Patients With Nonmetastatic Breast Cancer.
Caan, BJ, Cespedes Feliciano, EM, Prado, CM, Alexeeff, S, Kroenke, CH, Bradshaw, P, Quesenberry, CP, Weltzien, EK, Castillo, AL, Olobatuyi, TA, et al
JAMA oncology. 2018;(6):798-804
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IMPORTANCE Sarcopenia (low muscle mass), poor muscle quality (low muscle radiodensity), and excess adiposity derived from computed tomography (CT) has been related to higher mortality in patients with metastatic breast cancer, but the association with prognosis in patients with nonmetastatic breast cancer is unknown. OBJECTIVE To evaluate associations of all 3 body composition measures, derived from clinically acquired CT at diagnosis, with overall mortality in nonmetastatic breast cancer. DESIGN, SETTING, AND PARTICIPANTS This observational study included 3241 women from Kaiser Permanente of Northern California and Dana Farber Cancer Institute diagnosed from January 2000 to December 2013 with stages II or III breast cancer. We calculated hazard ratios (HRs) to evaluate the associations of all-cause mortality with sarcopenia, low muscle radiodensity, and total adipose tissue (TAT). Models were adjusted for sociodemographics, tumor characteristics, treatment, body mass index (BMI; calculated as weight in kilograms divided by height in meters squared), and other body composition measures. We also evaluated the cross-classification of categories of sarcopenia (yes/no) and tertiles of TAT, with outcomes. MAIN OUTCOMES AND MEASURES Overall survival time and all-cause mortality. RESULTS Median (range) age of 3241 women included in this study was 54 (18-80) years, and median follow-up was 6.0 years; 1086 patients (34%) presented with sarcopenia, and 1199 patients (37%) had low muscle radiodensity. Among patients with nonmetastatic breast cancer, those with sarcopenia showed higher overall mortality (HR, 1.41; 95% CI, 1.18-1.69) compared with those without sarcopenia. Patients in the highest tertile of TAT also showed higher overall mortality (HR, 1.35; 95% CI, 1.08-1.69) compared with those in the lowest tertile. Low radiodensity was not associated with survival. In analyses of sarcopenia and TAT, highest mortality was seen in patients with sarcopenia and high TAT (HR, 1.89; 95% CI, 1.30-2.73); BMI alone was not significantly related to overall mortality and did not appropriately identify patients at risk of death owing to their body composition. CONCLUSIONS AND RELEVANCE Sarcopenia is underrecognized in nonmetastatic breast cancer and occurs in over one-third of newly diagnosed patients. Measures of both sarcopenia and adiposity from clinically acquired CT scans in nonmetastatic patients provide significant prognostic information that outperform BMI and will help to guide interventions to optimize survival outcomes.
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Impact of Body Weight and Body Composition on Ovarian Cancer Prognosis.
Purcell, SA, Elliott, SA, Kroenke, CH, Sawyer, MB, Prado, CM
Current oncology reports. 2016;(2):8
Abstract
Measures of body weight and anthropometrics such as body mass index (BMI) are commonly used to assess nutritional status in clinical conditions including cancer. Extensive research has evaluated associations between body weight and prognosis in ovarian cancer patients, yet little is known about the potential impact of body composition (fat mass (FM) and fat-free mass (FFM)) in these patients. Thus, the purpose of this publication was to review the literature (using PubMed and EMBASE) evaluating the impact of body weight and particularly body composition on surgical complications, morbidity, chemotherapy dosing and toxicity (as predictors of prognosis), and survival in ovarian cancer patients. Body weight is rarely associated with intra-operative complications, but obesity predicts higher rates of venous thromboembolism and wound complications post-operatively in ovarian cancer patients. Low levels of FM and FFM are superior predictors of length of hospital stay compared to measures of body weight alone, but the role of body composition on other surgical morbidities is unknown. Obesity complicates chemotherapy dosing due to altered pharmacokinetics, imprecise dosing strategies, and wide variability in FM and FFM. Measurement of body composition has the potential to reduce toxicity if the results are incorporated into chemotherapy dosing calculations. Some findings suggest that excess body weight adversely affects survival, while others find no such association. Limited studies indicate that FM is a better predictor of survival than body weight in ovarian cancer patients, but the direction of this relationship has not been determined. In conclusion, body composition as an indicator of nutritional status is a better prognostic tool than body weight or BMI alone in ovarian cancer patients.
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Analysis of Body Mass Index and Mortality in Patients With Colorectal Cancer Using Causal Diagrams.
Kroenke, CH, Neugebauer, R, Meyerhardt, J, Prado, CM, Weltzien, E, Kwan, ML, Xiao, J, Caan, BJ
JAMA oncology. 2016;(9):1137-45
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IMPORTANCE Physicians and investigators have sought to determine the relationship between body mass index (BMI [calculated as weight in kilograms divided by height in meters squared]) and colorectal cancer (CRC) outcomes, but methodologic limitations including sampling selection bias, reverse causality, and collider bias have prevented the ability to draw definitive conclusions. OBJECTIVE To evaluate the association of BMI at the time of, and following, colorectal cancer (CRC) diagnosis with mortality in a complete population using causal diagrams. DESIGN, SETTING, AND PARTICIPANTS This retrospective observational study with prospectively collected data included a cohort of 3408 men and women, ages 18 to 80 years, from the Kaiser Permanente Northern California population, who were diagnosed with stage I to III CRC between 2006 and 2011 and who also had surgery. EXPOSURES Body mass index at diagnosis and 15 months following diagnosis. MAIN OUTCOMES AND MEASURES Hazard ratios (HRs) for all-cause mortality and CRC-specific mortality compared with normal-weight patients, adjusted for sociodemographics, disease severity, treatment, and prediagnosis BMI. RESULTS This study investigated a cohort of 3408 men and women ages 18 to 80 years diagnosed with stage I to III CRC between 2006 and 2011 who also had surgery. At-diagnosis BMI was associated with all-cause mortality in a nonlinear fashion, with patients who were underweight (BMI <18.5; HR, 2.65; 95% CI, 1.63-4.31) and patients who were class II or III obese (BMI ≥35; HR, 1.33; 95% CI, 0.89-1.98) exhibiting elevated mortality risks, compared with patients who were low-normal weight (BMI 18.5 to <23). In contrast, patients who were high-normal weight (BMI 23 to <25; HR, 0.77; 95% CI, 0.56-1.06), low-overweight (BMI 25 to <28; HR, 0.75; 95% CI, 0.55-1.04), and high-overweight (BMI 28 to <30; HR, 0.52; 95% CI, 0.35-0.77) had lower mortality risks, and patients who were class I obese (BMI 30 to <35) showed no difference in risk. Spline analysis confirmed a U-shaped relationship in participants with lowest mortality at a BMI of 28. Associations with CRC-specific mortality were similar. Associations of postdiagnosis BMI and mortality were also similar, but patients who were class I obese had significantly lower all-cause and cancer-specific mortality risks. CONCLUSIONS AND RELEVANCE In this study, body mass index at the time of diagnosis and following diagnosis of CRC was associated with mortality risk. Though evidence shows that exercise in patients with cancer should be encouraged, findings suggest that recommendations for weight loss in the immediate postdiagnosis period among patients with CRC who are overweight may be unwarranted.
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Breastfeeding, PAM50 tumor subtype, and breast cancer prognosis and survival.
Kwan, ML, Bernard, PS, Kroenke, CH, Factor, RE, Habel, LA, Weltzien, EK, Castillo, A, Gunderson, EP, Maxfield, KS, Stijleman, IJ, et al
Journal of the National Cancer Institute. 2015;(7)
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BACKGROUND Breastfeeding is associated with decreased breast cancer risk, yet associations with prognosis and survival by tumor subtype are largely unknown. METHODS We conducted a cohort study of 1636 women from two prospective breast cancer cohorts. Intrinsic tumor subtype (luminal A, luminal B, human epidermal growth factor receptor 2 [HER2]-enriched, basal-like) was determined by the PAM50 gene expression assay. Breastfeeding history was obtained from participant questionnaires. Questionnaires and medical record reviews documented 383 recurrences and 290 breast cancer deaths during a median follow-up of nine years. Multinomial logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) between breastfeeding and tumor subtype. Cox regression was used to estimate hazard ratios (HRs) for breast cancer recurrence or death. Statistical significance tests were two-sided. RESULTS Breast cancer patients with basal-like tumors were less likely to have previously breastfed than those with luminal A tumors (OR = 0.56, 95% CI = 0.39 to 0.80). Among all patients, ever breastfeeding was associated with decreased risk of recurrence (HR = 0.70, 95% CI = 0.53 to 0.93), especially breastfeeding for six months or more (HR = 0.63, 95% CI = 0.46 to 0.87, P trend = .01). Similar associations were observed for breast cancer death. Among women with luminal A subtype, ever breastfeeding was associated with decreased risks of recurrence (HR = 0.52, 95% CI = 0.31 to 0.89) and breast cancer death (HR = 0.52, 95% CI = 0.29 to 0.93), yet no statistically significant associations were observed among the other subtypes. Effects appeared to be limited to tumors with lower expression of proliferation genes. CONCLUSIONS History of breastfeeding might affect prognosis and survival by establishing a luminal tumor environment with lower proliferative activity.
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Associations of stressful life events and social strain with incident cardiovascular disease in the Women's Health Initiative.
Kershaw, KN, Brenes, GA, Charles, LE, Coday, M, Daviglus, ML, Denburg, NL, Kroenke, CH, Safford, MM, Savla, T, Tindle, HA, et al
Journal of the American Heart Association. 2014;(3):e000687
Abstract
BACKGROUND Epidemiologic studies have yielded mixed findings on the association of psychosocial stressors with cardiovascular disease (CVD) risk. In this study, we examined associations of stressful life events (SLE) and social strain with incident coronary heart disease (CHD) and stroke (overall, and for hemorrhagic and ischemic strokes) independent of sociodemographic characteristics, and we evaluated whether these relationships were explained by traditional behavioral and biological risk factors. METHODS AND RESULTS Data from approximately 82 000 Women's Health Initiative Observational Study participants were used for the SLE and social strain analyses, respectively. Participants were followed for events for up to 18.0 years (median, 14.0). Separate Cox proportional hazards models were generated to estimate associations of each stress measure with incident CVD. After adjusting for sociodemographic characteristics and depressive symptoms, higher SLE and social strain were associated with higher incident CHD and stroke (each P trend <0.05). Hazard ratios and 95% confidence intervals were 1.12 (1.01, 1.25) for incident CHD and 1.14 (1.01, 1.28) for incident stroke among participants reporting high versus low SLE. Findings were similar for social strain. Associations were attenuated with further adjustment for mediating behavioral and biological risk factors. Findings were similar for associations of SLE with ischemic stroke and hemorrhagic stroke, but social strain was only associated with ischemic stroke. CONCLUSIONS Higher SLE and social strain were associated with higher incident CVD independent of sociodemographic factors and depressive symptoms, but not behavioral and biological risk factors.
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Beyond treatment: lifestyle choices after breast cancer to enhance quality of life and survival.
Holmes, MD, Kroenke, CH
Women's health issues : official publication of the Jacobs Institute of Women's Health. 2004;(1):11-3