Publications by authors named "Bernard Rosner"

538 Publications

HDL Containing Apolipoprotein C-III is Associated with Insulin Sensitivity: a Multi-Center Cohort Study.

J Clin Endocrinol Metab 2021 Apr 11. Epub 2021 Apr 11.

Department of Nutrition, Harvard T.H. Chan School of Public Health, 665 Huntington Avenue, Boston, MA, United States of America.

Context: HDL in humans is composed of a heterogeneous group of particles varying in protein composition as well as biological effects.

Objective: We investigated the prospective associations between HDL subspecies containing and lacking apoC-III at baseline and insulin sensitivity at year 3.

Design, Setting, And Participants: A prospective cohort study of 864 healthy volunteers drawn from the RISC study, a multi-center European clinical investigation, whose recruitment initiated in 2002 with a follow-up of 3 years.

Main Measures: Insulin sensitivity was estimated from an oral glucose tolerance test (OGTT) at baseline and year 3, and by euglycemic-hyperinsulinemic clamp at baseline only. The apolipoprotein concentrations were measured at baseline by a sandwich ELISA-based method.

Results: The two HDL subspecies demonstrated significantly opposite associations with insulin sensitivity at year 3 (p-heterogeneity=0.004). The highest quintile of HDL containing apoC-III was associated with a 1.2% reduction in insulin sensitivity (p-trend=0.02), while the highest quintile of HDL lacking apoC-III was associated with a 1.3% increase (p-trend=0.01), compared to the lowest quintile. No significant association was observed for total HDL, and VLDL and LDL containing apoC-III. ApoC-III contained in HDL was associated with a decrease in insulin sensitivity even more strongly than plasma total apoC-III.

Conclusion: Both HDL containing apoC-III and apoC-III in HDL adversely affect the beneficial properties of HDL on insulin response to glucose. Our results support the potential of HDL-associated apoC-III as a promising target for diabetes prevention and treatment.
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http://dx.doi.org/10.1210/clinem/dgab234DOI Listing
April 2021

Post-diagnostic coffee and tea consumption and breast cancer survival.

Br J Cancer 2021 Mar 24. Epub 2021 Mar 24.

Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA.

Background: We examined the role of post-diagnostic coffee and tea consumption in relation to breast cancer-specific and all-cause mortality among women with breast cancer in prospective cohort studies.

Methods: We identified 8900 women with stage I-III breast cancer from 1980 through 2010 in the Nurses' Health Study (NHS) and from 1991 through 2011 in the NHSII. Post-diagnostic coffee and tea consumption was assessed by a validated food frequency questionnaire every 4 years after diagnosis.

Results: During up to 30 years of follow-up, we documented 1054 breast cancer-specific deaths and 2501 total deaths. Higher post-diagnostic coffee consumption was associated with a lower breast cancer-specific mortality: compared with non-drinkers, >3 cups/day of coffee was associated with a 25% lower risk (hazard ratio (HR) = 0.75, 95% confidence interval (CI) = 0.59-0.96; P = 0.002). We also observed a lower all-cause mortality with coffee consumption: compared with non-drinkers, >2 to 3 cups/day was associated with a 24% lower risk (HR = 0.76, 95% CI = 0.66-0.87) and >3 cups/day was associated with a 26% lower risk (HR = 0.74, 95% CI = 0.63-0.87, P < 0.0001). Post-diagnostic tea consumption was associated with a lower all-cause mortality: compared with non-drinkers, >3 cups/day was associated with a 26% lower risk (HR = 0.74, 95% CI = 0.58-0.95; P = 0.04).

Conclusions: Among breast cancer survivors, higher post-diagnostic coffee consumption was associated with better breast cancer and overall survival. Higher post-diagnostic tea consumption may be related to better overall survival.
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http://dx.doi.org/10.1038/s41416-021-01277-1DOI Listing
March 2021

Hypertensive Disorders of Pregnancy and Subsequent Risk of Premature Mortality.

J Am Coll Cardiol 2021 Mar;77(10):1302-1312

Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA; Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA. Electronic address:

Background: Hypertensive disorders of pregnancy (HDPs) are leading causes of maternal and perinatal morbidity and mortality. However, it is uncertain whether HDPs are associated with long-term risk of premature mortality (before age 70 years).

Objectives: The objective of this study was to evaluate whether HDPs were associated with premature mortality.

Methods: Between 1989 and 2017, the authors followed 88,395 parous female nurses participating in the Nurses' Health Study II. The study focused on gestational hypertension and pre-eclampsia within the term HDPs. Hazard ratios (HRs) and 95% confidence intervals (CIs) for the associations between HDPs and premature mortality were estimated by using Cox proportional hazards models, with adjustment for relevant confounders.

Results: The authors documented that 2,387 women died before age 70 years, including 1,141 cancer deaths and 212 CVD deaths. The occurrence of HDPs, either gestational hypertension or pre-eclampsia, was associated with an HR of 1.31 (95% CI: 1.18 to 1.46) for premature death during follow-up. When specific causes of death were examined, these relations were strongest for CVD-related mortality (HR: 2.26; 95% CI: 1.67 to 3.07). The association between HDPs and all-cause premature death persisted, regardless of the subsequent development of chronic hypertension (HR: 1.20 [95% CI: 1.02 to 1.40] for HDPs only and HR: 2.02 [95% CI: 1.75 to 2.33] for both HDPs and subsequent chronic hypertension).

Conclusions: An occurrence of HDPs, either gestational hypertension or pre-eclampsia, was associated with an increased risk of premature mortality, particularly CVD mortality, even in the absence of chronic hypertension.
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http://dx.doi.org/10.1016/j.jacc.2021.01.018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7959184PMC
March 2021

Fruit and Vegetable Intake and Mortality: Results From 2 Prospective Cohort Studies of US Men and Women and a Meta-Analysis of 26 Cohort Studies.

Circulation 2021 Mar 1. Epub 2021 Mar 1.

Channing Division for Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA; Departments of Nutrition and Epidemiology, Harvard T. H. Chan School of Public Health, Boston, MA.

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http://dx.doi.org/10.1161/CIRCULATIONAHA.120.048996DOI Listing
March 2021

THE RELATIONSHIP BETWEEN INFLAMMATORY DIETARY PATTERN AND INCIDENCE OF PERIODONTITIS.

Br J Nutr 2021 Jan 8:1-36. Epub 2021 Jan 8.

Department of Epidemiology, Harvard T.H. Chan School of Public Health 677 Huntington Ave, Boston, MA02115, USA.

The long-term inflammatory impact of diet could potentially elevate the risk of periodontal disease through modification of systemic inflammation. The aim of the present study was to prospectively investigate the associations between a food based, reduced rank regression (RRR) derived, empirical dietary inflammatory pattern (EDIP) and incidence of periodontitis. The study population was composed of 34,940 men from the Health Professionals Follow-Up Study, who were free of periodontal disease and major illnesses at baseline (1986). Participants provided medical and dental history through mailed questionnaires every 2 years, and dietary data through validated semi-quantitative food frequency questionnaires every 4 years. We used Cox proportional hazard models to examine the associations between EDIP scores and validated self-reported incidence of periodontal disease over a 24-year follow-up period. No overall association between EDIP and the risk of periodontitis was observed; the hazard ratio comparing the highest EDIP quintile (most proinflammatory diet) to the lowest quintile was 0.99 (95% confidence interval: 0.89 -1.10, p-value for trend = 0.97). A secondary analysis showed that among obese non-smokers (i.e. never and former smokers at baseline), the hazard ratio for periodontitis comparing the highest EDIP quintile to the lowest was 1.39 (95% confidence interval: 0.98 -1.96, p-value for trend = 0.03). In conclusion, no overall association was detected between EDIP and incidence of self-reported periodontitis in the study population. From the subgroups evaluated EDIP was significantly associated with increased risk of periodontitis only among nonsmokers who were obese. Hence, this association must be interpreted with caution.
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http://dx.doi.org/10.1017/S0007114520005231DOI Listing
January 2021

Rare and Common Genetic Variants, Smoking, and Body Mass Index: Progression and Earlier Age of Developing Advanced Age-Related Macular Degeneration.

Invest Ophthalmol Vis Sci 2020 Dec;61(14):32

Channing Division of Network Medicine, Harvard Medical School, Boston, Massachusetts, United States.

Purpose: To determine behavioral and genetic factors associated with incidence and age of progression to advanced age-related macular degeneration (AMD), geographic atrophy (GA), and neovascular disease (NV), and to quantify these effects.

Methods: Longitudinal analyses were conducted among 5421 eyes with nonadvanced AMD at baseline in 2976 participants in the Age-Related Eye Disease Study (mean age of 68.8 (±5.0), 56.1% female). Progression was confirmed based on two consecutive visits on the AMD severity scale. Separate analyses for progression and age of progression were performed. All analyses adjusted for correlation between eyes, demographic and behavioral covariates, baseline severity scale, and genetic variants.

Results: A higher genetic risk score (GRS) including eight genetic variants was associated with a higher rate of progression to advanced AMD within each baseline severity scale, especially for the highest risk intermediate level AMD category, and smoking further increased this risk. When assessing age when progression to advanced disease occurred, smoking reduced age of onset by 3.9 years (P < 0.001), and higher body mass index (BMI) led to earlier onset by 1.7 years (P = 0.003), with similar results for GA and NV. Genetic variants associated with earlier age of progression were CFH R1201C (4.3 years), C3 K155Q (2.15 years), and ARMS2/HTRA1 (0.8 years per allele).

Conclusions: Rare variants in the complement pathway and a common risk allele in ARMS2/HTRA1, smoking, and higher BMI can lead to as much as 11.5 additional years of disease and treatment burden. Closer adherence to healthy lifestyles could reduce years of visual impairment.
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http://dx.doi.org/10.1167/iovs.61.14.32DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7774056PMC
December 2020

Central adiposity and subsequent risk of breast cancer by menopause status.

J Natl Cancer Inst 2020 Dec 26. Epub 2020 Dec 26.

Department of Biostatistics and Epidemiology, University of Massachusetts Amherst, MA, USA.

Background: Increased body mass index (BMI) is associated with higher postmenopausal breast cancer risk and lower premenopausal breast cancer risk. Less is known about the central adiposity-breast cancer risk association, particularly for tumor subtypes.

Methods: We used prospective waist (WC) and hip circumference (HC) measures in the Nurses' Health Studies. We examined associations of WC, HC and waist-to-hip ratio (WHR) with breast cancer independent of BMI, by menopausal status. Cox proportional hazards models estimated the hazard ratio (HR) and 95% confidence intervals (CI) adjusting for breast cancer risk factors, with and without BMI.

Results: Adjusting for BMI, WC, and HC were not associated and WHR was positively associated with premenopausal breast cancer risk (WHR, quintile 5 vs. 1: HRQ5vQ1, BMI-adjusted=1.27, 95%CI = 1.04-1.54, p-trend = 0.01); particularly for, estrogen receptor-negative (ER-)/ progesterone receptor-negative (PR-) and basal-like breast cancers. Premenopausal WC, HC, and WHR were not associated with postmenopausal breast cancer risk, with or without BMI adjustment. Postmenopausal WC, HC, and WHR were each positively associated with postmenopausal breast cancer (eg, WC HRQ5vsQ1=1.59, 95%CI = 1.36-1.86); after adjustment for BMI, only WC remained statistically significant (HRQ5vsQ1, BMI-adjusted=1.38, 95%CI = 1.15-1.64, p-trend = 0.002). In postmenopausal women, associations were stronger among never users of hormone therapy and for ER+/PR+ breast cancers.

Conclusions: Central adiposity was positively associated with pre- and postmenopausal breast cancers independent of BMI. This suggests that mechanisms other than estrogen may also play a role in the relationship between central adiposity and breast cancer. Maintaining a healthy waist circumference may decrease pre- and postmenopausal breast cancer risk.
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http://dx.doi.org/10.1093/jnci/djaa197DOI Listing
December 2020

Reproducibility and Validity of a Semi-quantitative Food Frequency Questionnaire in Men Assessed by Multiple Methods.

Am J Epidemiol 2020 Dec 22. Epub 2020 Dec 22.

Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.

Among 626 participants of the Men's Lifestyle Validation Study (2011-2013), we evaluated the validity and reproducibility of a self-administered 152-item semiquantitative food frequency questionnaire (SFFQ) using two 7-day dietary records (7DDRs), four automated self-administered 24-hour dietary recalls (ASA24s), four 24-hour urine samples, one doubly-labeled water measurement (repeated in 104 participants), and two fasting blood samples, collected over 15 months. Compared to 7DDRs, SFFQs underestimated energy intake, macronutrients, and sodium intake, but overestimated some micronutrients. The mean of Spearman correlation coefficients was 0.66 (range 0.38 to 0.88) between 46 energy-adjusted nutrients estimated from 7DDRs and the final SFFQ, de-attenuated for within-person variation in the 7DDRs. These deattenuated correlations were similar using ASA24s as the comparison. Relative to biomarkers, SFFQs underestimated energy, sodium, and protein intakes, and the sodium:potassium ratio. The energy-adjusted correlations between the final SFFQ and the biomarkers were slightly lower than the correlations between the SFFQ and 7DDRs. Using method of triads to calculate validity coefficients (VC), the median VC between SFFQ and true intake was 0.65 and 0.69 using 7DDRs or ASA24s as the third method. These data indicate that this SFFQ provided reasonably valid estimates for a wide range of nutrients when evaluated by multiple comparison methods.
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http://dx.doi.org/10.1093/aje/kwaa280DOI Listing
December 2020

Adolescent alcohol, nuts, and fiber: combined effects on benign breast disease risk in young women.

NPJ Breast Cancer 2020 Nov 23;6(1):61. Epub 2020 Nov 23.

Alvin J. Siteman Cancer Center, Washington University School of Medicine, St. Louis, MO, USA.

Adolescent drinking is associated with higher risks of proliferative benign breast disease (BBD) and invasive breast cancer (BC). Furthermore, adolescent nut and fiber consumptions are associated with lower risks of benign lesions and premenopausal BC. We hypothesize that diet (nuts, fiber) may mitigate the elevated BBD risk associated with alcohol. A prospective cohort of 9031 females, 9-15 years at baseline, completed questionnaires in 1996-2001, 2003, 2005, 2007, 2010, 2013, and 2014. Participants completed food frequency questionnaires in 1996-2001. In 2005, participants (>=18 years) began reporting biopsy-confirmed BBD (N = 173 cases). Multivariable logistic regression estimated associations between BBD and cross-classified intakes (14-17 years) of alcohol and peanut butter/nuts (separately, total dietary fiber). Only 19% of participants drank in high school; drinking was associated with elevated BBD risk (OR = 1.75, 95% CI: 1.20-2.56; p = 0.004) compared to nondrinkers. Participants consuming any nuts/butter had lower BBD risk (OR = 0.64, 95% CI: 0.45-0.90; p = 0.01) compared to those consuming none. Participants in top 75% fiber intake had lower risk (OR = 0.57, 95% CI: 0.40-0.81; p = 0.002) compared to bottom quartile. Testing our hypothesis that consuming nuts/butter mitigates the elevated alcohol risk, analyzing alcohol and nuts combined found that those who consumed both had lower risk (RR = 0.47, 95% CI: 0.24-0.89; p = 0.02) compared to drinkers eating no nuts. Our analysis of alcohol and fiber together did not demonstrate risk mitigation by fiber. For high school females who drink, their BBD risk may be attenuated by consuming nuts. Due to modest numbers, future studies need to replicate our findings in adolescent/adult females. However, high school students may be encouraged to eat nuts and fiber, and to avoid alcohol, to reduce risk of BBD and for general health benefits.
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http://dx.doi.org/10.1038/s41523-020-00206-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7683739PMC
November 2020

Early-Life and Adult Adiposity, Adult Height, and Benign Breast Tissue Composition.

Cancer Epidemiol Biomarkers Prev 2021 Apr 7;30(4):608-615. Epub 2020 Dec 7.

Department of Population Health Sciences, Weill Cornell Medicine, New York, New York.

Background: Early-life and adult anthropometrics are associated with breast density and breast cancer risk. However, little is known about whether these factors also influence breast tissue composition beyond what is captured by breast density among women with benign breast disease (BBD).

Methods: This analysis included 788 controls from a nested case-control study of breast cancer within the Nurses' Health Study BBD subcohorts. Body fatness at ages 5 and 10 years was recalled using a 9-level pictogram. Weight at age 18, current weight, and height were reported via questionnaires. A deep-learning image analysis was used to quantify the percentages of epithelial, fibrous stromal, and adipose tissue areas within BBD slides. We performed linear mixed models to estimate beta coefficients (β) and 95% confidence intervals (CI) for the relationships between anthropometrics and the log-transformed percentages of individual tissue type, adjusting for confounders.

Results: Childhood body fatness (level ≥ 4.5 vs. 1), BMI at age 18 (≥23 vs. <19 kg/m), and current adult BMI (≥30 vs. <21 kg/m) were associated with higher proportions of adipose tissue [β (95% CI) = 0.34 (0.03, 0.65), 0.19 (-0.04-0.42), 0.40 (0.12, 0.68), respectively] and lower proportions of fibrous stromal tissue [-0.05 (-0.10, 0.002), -0.03 (-0.07, 0.003), -0.12 (-0.16, -0.07), respectively] during adulthood (all < 0.04). BMI at age 18 was also inversely associated with epithelial tissue ( = 0.03). Adult height was not associated with any of the individual tissue types.

Conclusions: Our data suggest that body fatness has long-term impacts on breast tissue composition.

Impact: This study contributes to our understanding of the link between body fatness and breast cancer risk..
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http://dx.doi.org/10.1158/1055-9965.EPI-20-1348DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8026662PMC
April 2021

The contact Lens risk survey to assess risk of soft contact lens-related inflammatory events.

Cont Lens Anterior Eye 2021 Feb 4;44(1):35-41. Epub 2020 Dec 4.

University of Houston, College of Optometry, Houston, TX, USA.

Purpose: To test the Contact Lens Assessment in Youth Contact Lens Risk Survey (CLRS) scoring algorithm in soft contact lens (SCL) wearers presenting with SCL-related adverse events and healthy matched controls.

Methods: This prospective case-control study compared CLRS responses in SCL wearers presenting with symptomatic red eyes (Cases) with age-, sex- and site-matched healthy SCL wearers (Controls) at six locations across North America. Responses to individual questions from Cases and Controls were analyzed using either the Pearson, Mantel-Haenszel chi-square, or Fisher's exact test. Differences in the CLRS scores were compared using t-tests.

Results: A total of 171 SCL wearers were enrolled (n = 57 Cases, 114 Controls). Cases were adjudicated to consensus and classified as contact lens-related serious and significant (S&S) or non-serious events. S&S Cases scored significantly higher on the CLRS (56.1 ± 11.1) than either their matched Controls (44.3 ± 11.1) (P <  0.001) or the non-Serious Cases (44.8± 12.8 P =  0.002). Scores of non-serious Cases were not significantly different than scores of their Controls (43.4 ± 10.7, P = 0.33) CONCLUSIONS: The CLRS scoring algorithm discriminated between SCL wearers presenting with S&S CL-related adverse events from healthy SCL wearers and those with non-serious events. This survey and scoring system could help practitioners identify patients at greatest risk for CL-related adverse events and support targeted interventions aimed at reducing risk behaviors.
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http://dx.doi.org/10.1016/j.clae.2020.11.013DOI Listing
February 2021

Development of a contact Lens risk survey.

Cont Lens Anterior Eye 2020 Dec 3:101383. Epub 2020 Dec 3.

Harvard University, T. H Chan School of Public Health, Boston, MA, United States.

Purpose: To describe the development and report psychometric properties of the Contact Lens Risk Survey (CLRS) to identify patients at risk for soft contact lens-related complications.

Methods: Psychometric properties of the CLRS, a web-based survey with branching logic, were determined using data from 5 multi-site fieldings (n = 1059), including re-fielding to sub groups. Responses from participants with and without an active red eye were used to identify risk factors of a red eye event and calculate an overall risk score. A 6th fielding of the CLRS (n = 171) was used to assess discriminate validity.

Results: Participants needed 11-12 min to complete the survey with a negligible difference by age. Internal consistency was excellent (Cronbach's α ≥ 0.70) for 3 of the 5 constructs identified by factor analysis. Twelve of the 17 survey items exhibited excellent within-subject repeatability (Kappa ≥ 0.61). Between-subject agreement, assessed in 18-25 year olds, was high for the majority of items, suggesting good generalizability across different populations of SCL wearers. The ability of the model using individual items of the CLRS to discriminate Controls and participants with a red eye was good with an area under the curve of 0.779.

Conclusion: The CLRS tool is a repeatable and valid instrument to standardize documentation of demographic, behavior, and exposure factors which appear to drive the greatest risk of a contact lens related red eye event.
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http://dx.doi.org/10.1016/j.clae.2020.11.003DOI Listing
December 2020

Simplified Breast Risk Tool Integrating Questionnaire Risk Factors, Mammographic Density, and Polygenic Risk Score: Development and Validation.

Cancer Epidemiol Biomarkers Prev 2021 Apr 4;30(4):600-607. Epub 2020 Dec 4.

Alvin J. Siteman Cancer Center and Department of Surgery, Division of Public Health Sciences, School of Medicine, Washington University in St. Louis, St. Louis, Missouri.

Background: Clinical use of breast cancer risk prediction requires simplified models. We evaluate a simplified version of the validated Rosner-Colditz model and add percent mammographic density (MD) and polygenic risk score (PRS), to assess performance from ages 45-74. We validate using the Mayo Mammography Health Study (MMHS).

Methods: We derived the model in the Nurses' Health Study (NHS) based on: MD, 77 SNP PRS and a questionnaire score (QS; lifestyle and reproductive factors). A total of 2,799 invasive breast cancer cases were diagnosed from 1990-2000. MD (using Cumulus software) and PRS were assessed in a nested case-control study. We assess model performance using this case-control dataset and evaluate 10-year absolute breast cancer risk. The prospective MMHS validation dataset includes 21.8% of women age <50, and 434 incident cases identified over 10 years of follow-up.

Results: In the NHS, MD has the highest odds ratio (OR) for 10-year risk prediction: OR = 1.48 [95% confidence interval (CI): 1.31-1.68], followed by PRS, OR = 1.37 (95% CI: 1.21-1.55) and QS, OR = 1.25 (95% CI: 1.11-1.41). In MMHS, the AUC adjusted for age + MD + QS 0.650; for age + MD + QS + PRS 0.687, and the NRI was 6% in cases and 16% in controls.

Conclusion: A simplified assessment of QS, MD, and PRS performs consistently to discriminate those at high 10-year breast cancer risk.

Impact: This simplified model provides accurate estimation of 10-year risk of invasive breast cancer that can be used in a clinical setting to identify women who may benefit from chemopreventive intervention..
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http://dx.doi.org/10.1158/1055-9965.EPI-20-0900DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8026588PMC
April 2021

Circulating carotenoids and breast cancer among high-risk individuals.

Am J Clin Nutr 2021 03;113(3):525-533

Department of Epidemiology, Harvard TH Chan School of Public Health, Boston, MA, USA.

Background: Carotenoids represent 1 of few modifiable factors to reduce breast cancer risk. Elucidation of interactions between circulating carotenoids and genetic predispositions or mammographic density (MD) may help inform more effective primary preventive strategies in high-risk populations.

Objectives: We tested whether women at high risk for breast cancer due to genetic predispositions or high MD would experience meaningful and greater risk reduction from higher circulating levels of carotenoids in a nested case-control study in the Nurses' Health Studies (NHS and NHSII).

Methods: This study included 1919 cases and 1695 controls in a nested case-control study in the NHS and NHSII. We assessed both multiplicative and additive interactions. RR reductions and 95% CIs were calculated using unconditional logistic regressions, adjusting for matching factors and breast cancer risk factors. Absolute risk reductions (ARR) were calculated based on Surveillance, Epidemiology, and End Results incidence rates.

Results: We showed that compared with women at low genetic risk or low MD, those with higher genetic risk scores or high MD had greater ARRs for breast cancer as circulating carotenoid levels increase (additive P-interaction = 0.05). Among women with a high polygenic risk score, those in the highest quartile of circulating carotenoids had a significant ARR (28.6%; 95% CI, 14.8-42.1%) compared to those in the lowest quartile of carotenoids. For women with a high percentage MD (≥50%), circulating carotenoids were associated with a 37.1% ARR (95% CI, 21.7-52.1%) when comparing the highest to the lowest quartiles of circulating carotenoids.

Conclusions: The inverse associations between circulating carotenoids and breast cancer risk appeared to be more pronounced in high-risk women, as defined by germline genetic makeup or MD.
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http://dx.doi.org/10.1093/ajcn/nqaa316DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7948839PMC
March 2021

Postdiagnostic Dietary Glycemic Index, Glycemic Load, Dietary Insulin Index, and Insulin Load and Breast Cancer Survival.

Cancer Epidemiol Biomarkers Prev 2021 Feb 20;30(2):335-343. Epub 2020 Nov 20.

Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.

Background: We investigated the associations of postdiagnostic dietary glycemic index (GI), glycemic load (GL), insulin index (II), and insulin load (IL) with breast cancer-specific and all-cause mortality.

Methods: Among 8,932 women with stage I-III breast cancer identified in the Nurses' Health Study (NHS; 1980-2010) and NHSII (1991-2011), we prospectively evaluated the associations between postdiagnostic GI, GL, II, and IL, and breast cancer-specific and all-cause mortality. Participants completed a validated food frequency questionnaire every 4 years after diagnosis.

Results: During follow-up by 2014 in the NHS and 2015 in the NHSII, 2,523 deaths, including 1,071 from breast cancer, were documented. Higher postdiagnostic GL was associated with higher risk of both breast cancer-specific mortality [HR = 1.33; 95% confidence interval (CI) = 1.09-1.63; = 0.008] and all-cause mortality (HR = 1.26; 95% CI = 1.10-1.45; = 0.0006). Higher all-cause mortality was also observed with higher postdiagnostic GI (HR = 1.23; 95% CI = 1.08-1.40; = 0.001), II (HR = 1.20; 95% CI = 1.04-1.38; = 0.005), and IL (HR = 1.23; 95% CI = 1.07-1.42; = 0.0003). The associations were not modified by insulin receptor or estrogen receptor status of the tumor, or body mass index.

Conclusions: We found that higher dietary GL, reflecting postprandial glucose response, after a breast cancer diagnosis was associated with higher risk of breast cancer-specific mortality. Higher dietary GI, GL, II, and IL after a breast cancer diagnosis were associated with higher risk of death from any cause.

Impact: These results suggest that carbohydrate quantity and quality may be important in breast cancer prognosis..
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http://dx.doi.org/10.1158/1055-9965.EPI-20-0764DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7984717PMC
February 2021

Postdiagnostic Fruit and Vegetable Consumption and Breast Cancer Survival: Prospective Analyses in the Nurses' Health Studies.

Cancer Res 2020 11;80(22):5134-5143

Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.

Fruits and vegetables contain many bioactive components that may contribute to improved survival after diagnosis of breast cancer, however, evidence to date is insufficient. We prospectively assessed the associations of postdiagnostic fruit and vegetable consumption with breast cancer-specific and all-cause mortality among 8,927 women with stage I-III breast cancer identified during follow-up of the Nurses' Health Study (NHS; 1980-2010) and NHSII (1991-2011), using a validated food frequency questionnaire completed every 4 years after diagnosis. We prospectively documented 2,521 deaths, including 1,070 from breast cancer through follow-up until 2014 in the NHS and 2015 in the NHSII. Total fruit and vegetable and total vegetable consumption was related to lower all-cause [HR, 0.82; 95% confidence interval (CI), 0.71-0.94; = 0.004, and HR, 0.84; 95% CI, 0.72-0.97; = 0.001, respectively], but not breast cancer-specific mortality. Total fruit consumption was not related to breast cancer-specific or all-cause mortality. Greater intake of green leafy and cruciferous vegetables was associated with lower all-cause mortality. Each 2 servings/week of blueberries was associated with a 25% (HR, 0.75; 95% CI, 0.60-0.94) lower breast cancer-specific and a 17% (HR, 0.83; 95% CI, 0.72-0.96) lower all-cause mortality. In contrast, higher fruit juice consumption was associated with higher breast cancer-specific (HR, 1.33; 95% CI, 1.09-1.63; = 0.002) and all-cause mortality (HR, 1.19; 95% CI, 1.04-1.36; = 0.003). Apple juice largely accounted for these higher risks and orange juice was not associated with risk. Higher postdiagnostic fruit and vegetable consumption among breast cancer survivors was not associated with breast cancer-specific mortality. However, our findings suggest that higher vegetable consumption, particularly green leafy and cruciferous vegetables, was associated with better overall survival among patients with breast cancer. Higher fruit juice consumption, but not orange juice, was associated with poorer breast cancer-specific and all-cause survival. SIGNIFICANCE: A large-scale study shows that high fruit and vegetable consumption may be associated with better overall survival among breast cancer patients, while high fruit juice consumption may be associated with poorer porgnosis.
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http://dx.doi.org/10.1158/0008-5472.CAN-18-3515DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7932849PMC
November 2020

Prospective study of a diabetes risk reduction diet and the risk of breast cancer.

Am J Clin Nutr 2020 12;112(6):1492-1503

Channing Division of Network Medicine, Department of Medicine, Brigham & Women's Hospital, Boston, MA, USA.

Background: Hyperinsulinemia and higher insulin-like growth factors may increase breast cancer risk. We evaluated a diabetes risk reduction diet (DRRD) and breast cancer risk.

Objectives: We prospectively evaluated the association between adherence to a DRRD and the incidence of breast cancer.

Methods: We followed 88,739 women from the Nurses' Health Study (NHS; 1980-2016) and 93,915 women from the NHSII (1991-2017). Incident breast cancer cases (n = 11,943) were confirmed with medical records, and subtypes were determined by tissue microarray data and pathology reports. Information on diet and breast cancer risk factors was repeatedly ascertained in follow-up questionnaires. A DRRD score was derived with 9 factors: lower glycemic index of diet; lower intakes of trans fat, sugar-sweetened beverages/fruit juices, and red/processed meat; higher intakes of cereal fiber, coffee, nuts, and whole fruits; and a higher ratio of polyunsaturated to saturated fat (score range: 9-45). Multivariable-adjusted hazard ratios (MVHRs) and 95% CIs were calculated with Cox proportional hazards models.

Results: Being in the highest compared with the lowest DRRD adherence quintile was associated with a modestly lower breast cancer risk (MVHRQ5vsQ1: 0.89; 95% CI: 0.84, 0.95; P-trend = 0.0002); this was attenuated after adjusting for weight change since age 18 y (MVHRQ5vsQ1: 0.92; 95% CI: 0.87, 0.98; P-trend = 0.01). The inverse association was strongest among women with current BMI < 25 kg/m2 (MVHRQ5vsQ1: 0.89; 95% CI: 0.81, 0.98; P-trend = 0.004; P-interaction = 0.04). Among tumor molecular subtypes, the strongest inverse association was observed with basal-type tumors (MVHRQ5vsQ1: 0.67; 95% CI: 0.45, 1.01; P-trend = 0.04).

Conclusions: Greater DRRD-adherence was associated with lower breast cancer risk, likely mediated by less weight gain with a DRRD; however, independently of weight change, DRRD-adherence was modestly associated with lower breast cancer risk, particularly among lean women.
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http://dx.doi.org/10.1093/ajcn/nqaa268DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7727476PMC
December 2020

Red blood cell membrane trans fatty acid levels and risk of non-Hodgkin lymphoma: a prospective nested case-control study.

Am J Clin Nutr 2020 12;112(6):1576-1583

Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.

Background: Trans fatty acid (TFA) intake persists in much of the world, posing ongoing threats to public health that warrant further elucidation. Published evidence suggests a positive association of self-reported TFA intake with non-Hodgkin lymphoma (NHL) risk.

Objectives: To confirm those reports, we conducted a prospective study of prediagnosis RBC membrane TFA levels and risk of NHL and common NHL histologic subtypes.

Methods: We conducted a nested case-control study in Nurses' Health Study and Health Professionals Follow-Up Study participants with archived RBC specimens and no history of cancer at blood draw (1989-1090 and 1994-1995, respectively). We confirmed 583 incident NHL cases (332 women and 251 men) and individually matched 583 controls on cohort (sex), age, race, and blood draw date/time. We analyzed RBC membrane TFA using GLC (in 2013-2014) and expressed individual TFA levels as a percentage of total fatty acids. We used unconditional logistic regression adjusted for the matching factors to estimate ORs and 95% CIs for overall NHL risk per 1 SD increase in TFA level and assessed histologic subtype-specific associations with multivariable polytomous logistic regression.

Results: Total and individual TFA levels were not associated with risk of all NHL or most subtypes. We observed a positive association of total TFA levels with diffuse large B cell lymphoma (DLBCL) risk [n = 98 cases; OR (95% CI) per 1 SD increase: 1.30 (1.05, 1.61); P = 0.015], driven by trans 18:1n-9(ω-9)/elaidic acid [OR (95% CI): 1.34 (1.08, 1.66); P = 0.007], trans 18:1n-7/vaccenic acid [OR (95% CI): 1.28 (1.04, 1.58); P = 0.023], and trans 18:2n-6t,t [OR (95% CI): 1.26 (1.01, 1.57); P = 0.037].

Conclusions: Our findings extended evidence for TFA intake and DLBCL risk but not for other NHL subtypes. Reduced TFA consumption through dietary choices or health policy measures may support prevention of DLBCL, an aggressive NHL subtype.
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http://dx.doi.org/10.1093/ajcn/nqaa251DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7727472PMC
December 2020

The associations between major dietary patterns and risk of periodontitis.

J Clin Periodontol 2021 Jan 9;48(1):2-13. Epub 2020 Nov 9.

Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, MA, USA.

Aim: To prospectively investigate the associations between major dietary patterns and incidence of periodontitis.

Methods: We included 34,940 men from the Health Professionals Follow-Up Study, free of periodontal disease and major illnesses at baseline. Detailed medical and dental history was collected through biennial mailed questionnaires, and dietary information was provided through quadrennial food frequency questionnaires. Using principal component analysis, we identified two major dietary patterns ("prudent" and "Western"). We used Cox proportional hazard models to examine the associations between the two dietary patterns and self-reported incidence of periodontitis over a 24-year follow-up period. We investigated each pattern separately.

Results: There was no overall association between Western or prudent dietary patterns and periodontitis. Among obese, however, the Western dietary pattern was significantly associated with incident periodontitis. The hazard ratio for those in the highest quintile of Western diet versus those in the lowest (reference) was 1.83 (95% confidence interval: 1.21-2.76).

Conclusions: There was no overall association between Western or prudent dietary patterns and periodontitis; however, in subgroups analysis, the Western diet was significantly associated with higher periodontitis risk only among obese men, a finding that requires replication and biological explication.
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http://dx.doi.org/10.1111/jcpe.13380DOI Listing
January 2021

Calculating Sensitivity, Specificity, and Predictive Values for Correlated Eye Data.

Invest Ophthalmol Vis Sci 2020 09;61(11):29

Division of Preventive Medicine and the Channing Lab, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts, United States.

Purpose: To describe and demonstrate appropriate statistical approaches for estimating sensitivity, specificity, predictive values and their 95% confidence intervals (95% CI) for correlated eye data.

Methods: We described generalized estimating equations (GEE) and cluster bootstrap to account for inter-eye correlation and applied them for analyzing the data from a clinical study of telemedicine for the detection of retinopathy of prematurity (ROP).

Results: Among 100 infants (200 eyes) selected for analysis, 20 infants had referral-warranted ROP (RW-ROP) in both eyes and 9 infants with RW-ROP only in one eye based on clinical eye examination. In the per-eye analysis that included both eyes of an infant, the image evaluation for RW-ROP had sensitivity of 83.7% and specificity of 86.8%. The 95% CI's from the naïve approach that ignored the inter-eye correlation were narrower than those of the GEE approach and cluster bootstrap for both sensitivity (width of 95% CI: 22.4% vs. 23.2% vs. 23.9%) and specificity (11.4% vs. 12.5% vs. 11.6%). The 95% CIs for sensitivity and specificity calculated from left eyes and right eyes separately were wider (35.2% and 30.8% respectively for sensitivity, 25.4% and 17.3% respectively for specificity).

Conclusions: When an ocular test is performed in both eyes of some or all of the study subjects, the statistical analyses are best performed at the eye-level and account for the inter-eye correlation by using either the GEE or cluster bootstrap. Ignoring the inter-eye correlation results in 95% CIs that are inappropriately narrow and analyzing data from two eyes separately are not efficient.
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http://dx.doi.org/10.1167/iovs.61.11.29DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7500131PMC
September 2020

Brief Preoperative Screening for Frailty and Cognitive Impairment Predicts Delirium after Spine Surgery.

Anesthesiology 2020 12;133(6):1184-1191

Background: Frailty and cognitive impairment are associated with postoperative delirium, but are rarely assessed preoperatively. The study was designed to test the hypothesis that preoperative screening for frailty or cognitive impairment identifies patients at risk for postoperative delirium (primary outcome).

Methods: In this prospective cohort study, the authors administered frailty and cognitive screening instruments to 229 patients greater than or equal to 70 yr old presenting for elective spine surgery. Screening for frailty (five-item FRAIL scale [measuring fatigue, resistance, ambulation, illness, and weight loss]) and cognition (Mini-Cog, Animal Verbal Fluency) were performed at the time of the preoperative evaluation. Demographic data, perioperative variables, and postoperative outcomes were gathered. Delirium was the primary outcome detected by either the Confusion Assessment Method, assessed daily from postoperative day 1 to 3 or until discharge, if patient was discharged sooner, or comprehensive chart review. Secondary outcomes were all other-cause complications, discharge not to home, and hospital length of stay.

Results: The cohort was 75 [73 to 79 yr] years of age, 124 of 219 (57%) were male. Many scored positive for prefrailty (117 of 218; 54%), frailty (53 of 218; 24%), and cognitive impairment (50 to 82 of 219; 23 to 37%). Fifty-five patients (25%) developed delirium postoperatively. On multivariable analysis, frailty (scores 3 to 5 [odds ratio, 6.6; 95% CI, 1.96 to 21.9; P = 0.002]) versus robust (score 0) on the FRAIL scale, lower animal fluency scores (odds ratio, 1.08; 95% CI, 1.01 to 1.51; P = 0.036) for each point decrease in the number of animals named, and more invasive surgical procedures (odds ratio, 2.69; 95% CI, 1.31 to 5.50; P = 0.007) versus less invasive procedures were associated with postoperative delirium.

Conclusions: Screening for frailty and cognitive impairment preoperatively using the FRAIL scale and the Animal Verbal Fluency test in older elective spine surgery patients identifies those at high risk for the development of postoperative delirium.

Editor’s Perspective:
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http://dx.doi.org/10.1097/ALN.0000000000003523DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7657972PMC
December 2020

Personal use of permanent hair dyes and cancer risk and mortality in US women: prospective cohort study.

BMJ 2020 09 2;370:m2942. Epub 2020 Sep 2.

Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA

Objective: To evaluate the associations between personal use of permanent hair dyes and cancer risk and mortality.

Design: Prospective cohort study.

Setting And Participants: 117 200 women enrolled in the Nurses' Health Study, an ongoing prospective cohort study of female nurses in the United States. The women were free of cancer at baseline, reported information on personal use of permanent hair dyes, and were followed for 36 years.

Exposure: Status, duration, frequency, and integral use (cumulative dose calculated from duration and frequency) of permanent hair dyes. Age at first use and time since first use of permanent hair dyes.

Main Outcome Measures: Associations of personal use of permanent hair dyes with risk of overall cancer and specific cancers, and cancer related death. Age and multivariable adjusted hazard ratios and 95% confidence intervals were estimated by using Cox proportional hazard models.

Results: Ever users of permanent hair dyes had no significant increases in risk of solid cancers (n=20 805, excluding non-melanoma skin cancers; hazard ratio 0.98, 95% confidence interval 0.96 to 1.01) or hematopoietic cancers overall (n=1807; 1.00, 0.91 to 1.10) compared with non-users. Additionally, ever users did not have an increased risk of most specific cancers (cutaneous squamous cell carcinoma, bladder cancer, melanoma, estrogen receptor positive breast cancer, progesterone receptor positive breast cancer, hormone receptor positive breast cancer, brain cancer, colorectal cancer, kidney cancer, lung cancer, and most of the major subclasses and histological subtypes of hematopoietic cancer) or cancer related death (n=4860; 0.96, 0.91 to 1.02). Basal cell carcinoma risk was slightly increased for ever users (n=22 560; 1.05, 1.02 to 1.08). Cumulative dose was positively associated with risk of estrogen receptor negative breast cancer, progesterone receptor negative breast cancer, hormone receptor negative breast cancer, and ovarian cancer. An increased risk of Hodgkin lymphoma was observed only for women with naturally dark hair (based on 70 women, 24 with dark hair), and a higher risk of basal cell carcinoma was observed for women with naturally light hair.

Conclusion: No positive association was found between personal use of permanent hair dye and risk of most cancers and cancer related mortality. The increased risk of basal cell carcinoma, breast cancer (estrogen receptor negative, progesterone receptor negative, hormone receptor negative) and ovarian cancer, and the mixed findings in analyses stratified by natural hair color warrant further investigation.
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http://dx.doi.org/10.1136/bmj.m2942DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7463170PMC
September 2020

Growth and Clinical Outcomes of Very Low-Birth-Weight Infants Receiving Acidified vs Nonacidified Liquid Human Milk Fortifiers.

Nutr Clin Pract 2020 Aug 25. Epub 2020 Aug 25.

Department of Pediatric Newborn Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA.

Background: Liquid human milk fortifiers are used commonly in neonatal intensive care. Use of an acidified HMF (A-HMF) is associated with transient metabolic acidosis, but whether growth outcomes differ between infants fed A-HMF vs nonacidified HMF (NA-HMF) remains unknown.

Methods: Retrospective cohort study of 255 infants born at <33 weeks' gestation and ≤1500 g who were receiving ≥75% fortified human milk on day of life 14, in a level III neonatal intensive care unit (NICU) from May 2015 to December 2018. Infants born before October 2017 (n = 165) received A-HMF, whereas infants born after October 2017 (n = 90) received NA-HMF. We used logistic regression to estimate odds of metabolic acidosis (serum bicarbonate <16 mEq/L in the first 21 days of life) in infants receiving A-HMF vs NA-HMF and linear mixed models to compare the mean size at discharge (weight, length, head z-scores) by HMF type. We adjusted models for confounders and accounted for the nonindependence of multiple births.

Results: Median gestational age was 28.7 weeks (range, 22.6-32.9) and birth weight 1.1 kg (range, 0.4-1.5). Infants receiving A-HMF had higher adjusted odds of metabolic acidosis than infants receiving NA-HMF (adjusted odds ratio, 2.7; 95% CI, 1.2-6.2). There were no differences between groups in size z-scores at discharge.

Conclusions: In human-milkfed, very-low-birthweight infants, fortification with liquid A-HMF may contribute to metabolic acidosis in the first month of life, but this practice does not appear to impair growth through NICU discharge, compared with fortification with NA-HMF.
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http://dx.doi.org/10.1002/ncp.10569DOI Listing
August 2020

Prepregnancy adherence to dietary recommendations for the prevention of cardiovascular disease in relation to risk of hypertensive disorders of pregnancy.

Am J Clin Nutr 2020 12;112(6):1429-1437

Department of Nutrition, Harvard TH Chan School of Public Health, Boston, MA, USA.

Background: It is unclear whether adherence to diet recommendations for the prevention of cardiovascular disease (CVD) in the general population is also related to the risk of hypertensive disorders of pregnancy, including pre-eclampsia and gestational hypertension (GHTN).

Objectives: The aim was to evaluate the relation of prepregnancy adherence to the American Heart Association (AHA) diet recommendations and the Dietary Approaches to Stop Hypertension (DASH) with the risk of pre-eclampsia and GHTN.

Methods: Between 1991 and 2009, we prospectively followed 16,892 singleton pregnancies among 11,535 women who participated in the Nurses' Health Study II. Prepregnancy diet was assessed every 4 y, from which we calculated dietary pattern scores from the DASH diet (8 components) and the diet recommendations from the AHA 2020 Strategic Impact Goals (primary score: 5 components; secondary score: primary score plus 3 components). Pregnancy outcomes were self-reported, and we estimated the RR (95% CI) of pre-eclampsia and GHTN with log-binomial regression using generalized estimating equations to account for repeat pregnancies and adjusting for potential confounders.

Results: Women had a mean (SD) age of 34.4 (34.0) y at pregnancy. Pre-eclampsia was reported in 495 (2.9%) pregnancies and GHTN in 561 (3.3%) pregnancies. The RR (95% CI) of pre-eclampsia for women in the highest quintile of the DASH was 0.65 (0.48, 0.87) compared with women in the lowest score quintile. A similar inverse trend was observed for the AHA primary (0.74; 95% CI: 0.55, 1.00) and secondary (0.81; 95% CI: 0.61, 1.07) scores comparing women in the highest versus the lowest score quintile. Neither the DASH nor the AHA scores were related to GHTN.

Conclusions: Women with higher adherence to dietary recommendations for the prevention of CVD in the general population had a lower risk of pre-eclampsia-a common pregnancy complication related to higher CVD risk among women-than women with lower adherence to these recommendations.
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http://dx.doi.org/10.1093/ajcn/nqaa214DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7727486PMC
December 2020

Interplay Between Statins, Cav1 (Caveolin-1), and Aldosterone.

Hypertension 2020 09 3;76(3):962-967. Epub 2020 Aug 3.

From the Division of Endocrinology, Diabetes and Hypertension, Brigham and Women's Hospital (A.V.H., R.M.E., G.RM., L.H.P., J.S.W., G.H.W., G.K.A.), Harvard Medical School, Boston, MA.

Statin use is associated with lower aldosterone levels. We hypothesized that caveolin-1 may be important for the uptake of statins into the adrenal gland and would affect statin's aldosterone-lowering effects. The aim of this study was to test whether the caveolin-1 risk allele (rs926198) would affect aldosterone levels associated with statin use. The Hypertensive Pathotype database includes healthy and hypertensive individuals who have undergone assessment of adrenal hormones. Individuals were studied off antihypertensive medications but were maintained on statins if prescribed by their personal physician. Adrenal hormones were measured at baseline and after 1 hour of angiotensin II stimulation on both high- and low-sodium diets. A mixed-model repeated-measures analysis was employed with a priori selected covariates of age, sex, body mass index, and protocol (low versus high sodium, baseline versus angiotensin II stimulated aldosterone). A total of 250 individuals were included in the study; 31 individuals were taking statins (12.4%) and 219 were not. Among statin users, carrying a caveolin-1 risk allele resulted in a 25% (95% CI, 1-43.2) lower aldosterone level (=0.04). However, among nonstatin users, carrying a caveolin-1 risk allele resulted in no significant effect on aldosterone levels (=0.38). Additionally, the interaction between caveolin-1 risk allele and statin use on aldosterone levels was significant (=0.03). These findings suggest caveolin-1 risk allele carrying individuals are likely to receive the most benefit from statin's aldosterone-lowering properties; however, due to the observational nature of this study, these findings need further investigation.
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http://dx.doi.org/10.1161/HYPERTENSIONAHA.120.14777DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7418929PMC
September 2020

Tutorial on Biostatistics: Longitudinal Analysis of Correlated Continuous Eye Data.

Ophthalmic Epidemiol 2021 Feb 2;28(1):3-20. Epub 2020 Aug 2.

Division of Preventive Medicine and the Channing Lab, Department of Medicine, Brigham and Women's Hospital , Boston, Massachusetts, USA.

Purpose: To describe and demonstrate methods for analyzing longitudinal correlated eye data with a continuous outcome measure.

Methods: We described fixed effects, mixed effects and generalized estimating equations (GEE) models, applied them to data from the Complications of Age-Related Macular Degeneration Prevention Trial (CAPT) and the Age-Related Eye Disease Study (AREDS). In CAPT (N = 1052), we assessed the effect of eye-specific laser treatment on change in visual acuity (VA). In the AREDS study, we evaluated effects of systemic supplement treatment among 1463 participants with AMD category 3.

Results: In CAPT, the inter-eye correlations (0.33 to 0.53) and longitudinal correlations (0.31 to 0.88) varied. There was a small treatment effect on VA change (approximately one letter) at 24 months for all three models ( = .009 to 0.02). Model fit was better with the mixed effects model than the fixed effects model ( < .001). In AREDS, there was no significant treatment effect in all models ( > .55). Current smokers had a significantly greater VA decline than non-current smokers in the fixed effects model ( = .04) and the mixed effects model with random intercept ( = .0003), but marginally significant in the mixed effects model with random intercept and slope ( = .08), and GEE models ( = .054 to 0.07). The model fit was better with the fixed effects model than the mixed effects model ( < .0001).

Conclusion: Longitudinal models using the eye as the unit of analysis can be implemented using available statistical software to account for both inter-eye and longitudinal correlations. Goodness-of-fit statistics may guide the selection of the most appropriate model.
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http://dx.doi.org/10.1080/09286586.2020.1786590DOI Listing
February 2021

Latency estimation for chronic disease risk: a damped exponential weighting model.

Eur J Epidemiol 2020 Sep 30;35(9):807-819. Epub 2020 Jul 30.

Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.

Identifying the susceptible period when environmental factors affect disease risk is essential for understanding disease etiology. Most existing epidemiologic studies use oversimplified summaries of time-dependent exposures such as baseline or most current exposure, or the cumulative average of exposure over available follow-up periods. In this paper, we introduce a damped exponential weighting model for estimating optimal exposure weights for different time intervals. This model can accommodate flexible patterns of weights and can be fit using standard software. We applied the model to assess the latency of BMI and alcohol for post-menopausal breast cancer based on 30-year exposure history in the Nurses' Health Study. We have also performed a simulation study to assess the validity of the proposed hypothesis testing and estimation procedures in realistic conditions. We found that the type I error is close to 0.05; the bias in our parameter estimates is low and the coverage probability of interval estimates is close to 0.95. For ER+/PR+ breast cancer we found that recent BMI was a more important predictor of risk than more distant BMI; for ER-/PR- breast cancer, no latency was found and risk was characterized by cumulative high levels of BMI over a long period of time. For alcohol intake, we saw a strong positive association with cumulative intake for ER+/PR+ breast cancer; no significant association was found for cumulative intake or for any latency measure of risk for ER-/PR- breast cancer. Our results underscore the value of an easy-to-implement approach to latency analysis of exposure profiles for chronic disease.
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http://dx.doi.org/10.1007/s10654-020-00658-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7530062PMC
September 2020

Dietary flavonoids and flavonoid-rich foods: validity and reproducibility of FFQ-derived intake estimates.

Public Health Nutr 2020 12 23;23(18):3295-3303. Epub 2020 Jul 23.

Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA.

Objective: To evaluate the validity and reproducibility of a 152-item semi-quantitative FFQ (SFFQ) for estimating flavonoid intakes.

Design: Over a 1-year period, participants completed two SFFQ and two weighed 7-d dietary records (7DDR). Flavonoid intakes from the SFFQ were estimated separately using Harvard (SFFQHarvard) and Phenol-Explorer (SFFQPE) food composition databases. 7DDR flavonoid intakes were derived using the Phenol-Explorer database (7DDRPE). Validity was assessed using Spearman's rank correlation coefficients deattenuated for random measurement error (rs), and reproducibility was assessed using rank intraclass correlation coefficients.

Setting: This validation study included primarily participants from two large observational cohort studies.

Participants: Six hundred forty-one men and 724 women.

Results: When compared with two 7DDRPE, the validity of total flavonoid intake assessed by SFFQPE was high for both men and women (rs = 0·77 and rs = 0·74, respectively). The rs for flavonoid subclasses ranged from 0·47 for flavones to 0·78 for anthocyanins in men and from 0·46 for flavonols to 0·77 for anthocyanins in women. We observed similarly moderate (0·4-0·7) to high (≥0·7) validity when using SFFQHarvard estimates, except for flavonesHarvard (rs = 0·25 for men and rs = 0·19 for women). The SFFQ demonstrated high reproducibility for total flavonoid and flavonoid subclass intake estimates when using either food composition database. The intraclass correlation coefficients ranged from 0·69 (flavonolsPE) to 0·80 (proanthocyanidinsPE) in men and from 0·67 (flavonolsPE) to 0·77 (flavan-3-ol monomersHarvard) in women.

Conclusions: SFFQ-derived intakes of total flavonoids and flavonoid subclasses (except for flavones) are valid and reproducible for both men and women.
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http://dx.doi.org/10.1017/S1368980020001627DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7736217PMC
December 2020

Intake of whole grain foods and risk of type 2 diabetes: results from three prospective cohort studies.

BMJ 2020 07 8;370:m2206. Epub 2020 Jul 8.

Department of Nutrition, Harvard TH Chan School of Public Health, 665 Huntington Avenue, Boston, MA 02115, USA

Objective: To examine the associations between the intake of total and individual whole grain foods and the risk of type 2 diabetes.

Design: Prospective cohort studies.

Setting: Nurses' Health Study (1984-2014), Nurses' Health Study II (1991-2017), and Health Professionals Follow-Up Study (1986-2016), United States.

Participants: 158 259 women and 36 525 men who did not have type 2 diabetes, cardiovascular disease, or cancer at baseline.

Main Outcome Measures: Self-reports of incident type 2 diabetes by participants identified through follow-up questionnaires and confirmed by a validated supplementary questionnaire.

Results: During 4 618 796 person years of follow-up, 18 629 participants with type 2 diabetes were identified. Total whole grain consumption was categorized into five equal groups of servings a day for the three cohorts. After adjusting for lifestyle and dietary risk factors for diabetes, participants in the highest category for total whole grain consumption had a 29% (95% confidence interval 26% to 33%) lower rate of type 2 diabetes compared with those in the lowest category. For individual whole grain foods, pooled hazard ratios (95% confidence intervals) for type 2 diabetes in participants consuming one or more servings a day compared with those consuming less than one serving a month were 0.81 (0.77 to 0.86) for whole grain cold breakfast cereal, 0.79 (0.75 to 0.83) for dark bread, and 1.08 (1.00 to 1.17) for popcorn. For other individual whole grains with lower average intake levels, comparing consumption of two or more servings a week with less than one serving a month, the pooled hazard ratios (95% confidence intervals) were 0.79 (0.75 to 0.83) for oatmeal, 0.88 (0.82 to 0.94) for brown rice, 0.85 (0.80 to 0.90) for added bran, and 0.88 (0.78 to 0.98) for wheat germ. Spline regression showed a non-linear dose-response association between total whole grain intake and the risk of type 2 diabetes where the rate reduction slightly plateaued at more than two servings a day (P<0.001 for curvature). For whole grain cold breakfast cereal and dark bread, the rate reduction plateaued at about 0.5 servings a day. For consumption of popcorn, a J shaped association was found where the rate of type 2 diabetes was not significantly raised until consumption exceeded about one serving a day. The association between higher total whole grain intake and lower risk of type 2 diabetes was stronger in individuals who were lean than in those who were overweight or obese (P=0.003 for interaction), and the associations did not vary significantly across levels of physical activity, family history of diabetes, or smoking status.

Conclusion: Higher consumption of total whole grains and several commonly eaten whole grain foods, including whole grain breakfast cereal, oatmeal, dark bread, brown rice, added bran, and wheat germ, was significantly associated with a lower risk of type 2 diabetes. These findings provide further support for the current recommendations of increasing whole grain consumption as part of a healthy diet for the prevention of type 2 diabetes.
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http://dx.doi.org/10.1136/bmj.m2206DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7341349PMC
July 2020