Publications by authors named "Stephanie E Chiuve"

90 Publications

Integrating real-world data and modeling to project changes in femoral neck bone mineral density and fracture risk in premenopausal women.

Clin Transl Sci 2021 Mar 1. Epub 2021 Mar 1.

Clinical Pharmacology and Pharmacometrics, AbbVie, North Chicago, Illinois, USA.

Decline of bone mineral density (BMD) during menopause is related to increased risk of fractures in postmenopausal women, however, this relationship in premenopausal women has not been established. To quantify this relationship, real-world data (RWD) from the National Health and Nutrition Examination Survey (NHANES), and longitudinal data from the elagolix phase III clinical trials were modeled across a wide age range, and covariates were evaluated. The natural changes in femoral neck BMD (FN-BMD) were well-described by a bi-exponential relationship with first-order BMD formation (k ) and resorption (k ) rate constants. Body mass index (BMI) and race (i.e., Black) were significant predictors indicating that patients with high BMI or Black race experience a relatively lower BMD loss. Simulations suggest that untreated premenopausal women with uterine fibroids (UFs) from elagolix phase III clinical trials (median age 43 years [minimum 25-maximum 53]) lose 0.6% FN-BMD each year up to menopausal age. For clinical relevance, the epidemiological FRAX model was informed by the simulation results to predict the 10-year risk of major osteoporotic fracture (MOF). Premenopausal women with UFs, who received placebo only in the elagolix phase III trials, have a projected FN-BMD of 0.975 g/cm at menopause, associated with a 10-year risk of MOF of 2.3%. Integration of modeling, RWD, and clinical trials data provides a quantitative framework for projecting long-term postmenopausal risk of fractures, based on natural history of BMD changes in premenopausal women. This framework enables quantitative evaluation of the future risk of MOF for women receiving medical therapies (i.e., GnRH modulators) that adversely affect BMD.
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http://dx.doi.org/10.1111/cts.13006DOI Listing
March 2021

Chronic opioid use and complication risks in women with endometriosis: A cohort study in US administrative claims.

Pharmacoepidemiol Drug Saf 2021 Jun 16;30(6):787-796. Epub 2021 Mar 16.

Science Department, Aetion, Inc., New York, New York, USA.

Background: Women with endometriosis are prescribed opioids for pain relief but may be vulnerable to chronic opioid use given their comorbidity profile.

Methods: A cohort study was conducted in the Clinformatics™ DataMart database between 2006 and 2017 comparing women aged 18-50 years with endometriosis (N = 36 373) to those without (N = 2 172 936) in terms of risk of chronic opioid use, opioid dependence diagnosis, and opioid overdose. Chronic opioid use was defined as ≥120 days' supply dispensed or ≥10 fills of an opioid during any 365-day interval. Among women with endometriosis, we evaluated factors associated with higher risk of chronic opioid use and quantified the risk of complications associated with the use of opioids.

Results: Women with endometriosis were at greater risk for chronic opioid use (OR: 3.76; 95%CI: 3.57-3.96), dependence (OR: 2.73, 95%CI: 2.38-3.13) and overdose (OR: 4.34, 95%CI: 3.06-6.15) compared to women without. Chronic users displayed dose escalation and increase in days supplied over time, as well as co-prescribing with benzodiazepines and sedatives. Approximately 34% of chronic users developed constipation, 20% experienced falls, and 8% reported dizziness. Among endometriosis patients, women in younger age groups, those with other comorbidities associated with pain symptoms, as well as those with depression or anxiety were at a higher risk of developing chronic opioid use.

Conclusions: Women with endometriosis had a four times greater risk of chronic opioid use compared to women without. Multimorbidity among these patients was associated with the elevated risk of chronic opioid use and should be taken into account during treatment selection.
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http://dx.doi.org/10.1002/pds.5209DOI Listing
June 2021

Improving Heart Disease Risk Through Quality-Focused Diet Logging: Pre-Post Study of a Diet Quality Tracking App.

JMIR Mhealth Uhealth 2020 12 23;8(12):e21733. Epub 2020 Dec 23.

College of Computing and Informatics, Drexel University, Philadelphia, PA, United States.

Background: Diet-tracking mobile apps have gained increased interest from both academic and clinical fields. However, quantity-focused diet tracking (eg, calorie counting) can be time-consuming and tedious, leading to unsustained adoption. Diet quality-focusing on high-quality dietary patterns rather than quantifying diet into calories-has shown effectiveness in improving heart disease risk. The Healthy Heart Score (HHS) predicts 20-year cardiovascular risks based on the consumption of foods from quality-focused food categories, rather than detailed serving sizes. No studies have examined how mobile health (mHealth) apps focusing on diet quality can bring promising results in health outcomes and ease of adoption.

Objective: This study aims to design a mobile app to support the HHS-informed quality-focused dietary approach by enabling users to log simplified diet quality and view its real-time impact on future heart disease risks. Users were asked to log food categories that are the main predictors of the HHS. We measured the app's feasibility and efficacy in improving individuals' clinical and behavioral factors that affect future heart disease risks and app use.

Methods: We recruited 38 participants who were overweight or obese with high heart disease risk and who used the app for 5 weeks and measured weight, blood sugar, blood pressure, HHS, and diet score (DS)-the measurement for diet quality-at baseline and week 5 of the intervention.

Results: Most participants (30/38, 79%) used the app every week and showed significant improvements in DS (baseline: mean 1.31, SD 1.14; week 5: mean 2.36, SD 2.48; 2-tailed t test t=-2.85; P=.008) and HHS (baseline: mean 22.94, SD 18.86; week 4: mean 22.15, SD 18.58; t=2.41; P=.02) at week 5, although only 10 participants (10/38, 26%) checked their HHS risk scores more than once. Other outcomes, including weight, blood sugar, and blood pressure, did not show significant changes.

Conclusions: Our study showed that our logging tool significantly improved dietary choices. Participants were not interested in seeing the HHS and perceived logging diet categories irrelevant to improving the HHS as important. We discuss the complexities of addressing health risks and quantity- versus quality-based health monitoring and incorporating secondary behavior change goals that matter to users when designing mHealth apps.
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http://dx.doi.org/10.2196/21733DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7787891PMC
December 2020

Estimating the Effect of Elagolix Treatment for Endometriosis on Postmenopausal Bone Outcomes: A Model Bridging Phase III Trials to an Older Real-World Population.

JBMR Plus 2020 Dec 7;4(12):e10401. Epub 2020 Nov 7.

Mercy Health Osteoporosis and Bone Health Services Cincinnati OH USA.

Elagolix, a gonadotrophin-releasing hormone antagonist, is used in premenopausal women with endometriosis. There is a risk of bone loss with elagolix, but the long-term effects of BMD loss later in life cannot be directly assessed and has not been quantified. To address this gap in knowledge, this study indirectly estimated the impact of elagolix on postmenopausal fracture risk. BMD change in premenopausal women with endometriosis treated with elagolix was modeled from the phase III program data (elagolix group) and used to simulate treatment effects on (fracture risk assessment tool estimated) 10-year risks of hip and major osteoporotic fracture in women ages 50 to 79 years from the 2005-2010 National Health and Nutrition Examination Survey (NHANES; = 2303). Change in the proportion of women reaching risk-based antiosteoporotic treatment thresholds was also estimated. For elagolix versus NHANES, median 10-year risk of major osteoporotic fracture was 4.73% versus 4.70% in women ages 50 to 59 years, 7.03% versus 6.97% in women ages 60 to 69 years, and 10.83% versus 10.68% in women ages 70 to 79 years. Median 10-year risk of hip fracture in these same groups was 0.19% versus 0.18% for women ages 50 to 59 years, 0.51% versus 0.49% for women 60 to 69 years, and 2.22% versus 2.14% for women 70 to 79 years. The proportion of women reaching risk-based antiosteoporotic treatment thresholds caused by elagolix 150 mg daily for 12 months was 0.36% higher at age 50 to 59 years, 0.23% at age 60 to 69 years, and 1.79% at age 70 to 79 years. The number needed to harm was 643 for one additional hip fracture and 454 for one additional major osteoporotic fracture. Results were similar for elagolix 200 mg twice a day for 3 months. In the modeled scenarios, elagolix had minimal impact on long-term risk of fracture and reaching risk-based treatment thresholds. © 2020 The Authors. published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research © 2020 The Authors. published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.
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http://dx.doi.org/10.1002/jbm4.10401DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7745882PMC
December 2020

Depression, Anxiety, and Self-Directed Violence in Women With Endometriosis: A Retrospective Matched-Cohort Study.

Am J Epidemiol 2021 05;190(5):843-852

The purpose of this study was to compare the incidence of mental health outcomes in women in the United States with and without documented endometriosis. In a retrospective matched-cohort study using administrative health claims data from Optum's Clinformatics DataMart from May 1, 2000, through March 31, 2019, women aged 18-50 years with endometriosis (n = 72,677), identified by International Classification of Disease diagnosis codes (revisions 9 or 10), were matched 1:2 on age and calendar time to women without endometriosis (n = 147,251), with a median follow-up of 529 days (interquartile range, 195, 1,164). The rate per 1,000 person-years of anxiety, depression, and self-directed violence among women with endometriosis was 57.1, 47.7, and 0.9, respectively. Comparing women with endometriosis to those without, the adjusted hazard ratios and 95% confidence intervals were 1.38 (1.34, 1.42) for anxiety, 1.48 (1.44, 1.53) for depression, and 2.03 (1.60, 2.58) for self-directed violence. The association with depression was stronger among women younger than 35 years (P for heterogeneity < 0.01). Risk factors for incident depression, anxiety, and self-directed violence among women with endometriosis included endometriosis-related pain symptoms and prevalence of other chronic conditions associated with pain. The identification of risk factors for mental health conditions among women with endometriosis may improve patient-centered disease management.
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http://dx.doi.org/10.1093/aje/kwaa249DOI Listing
May 2021

Habitual Fish Consumption, n-3 Fatty Acids, and Nuclear Magnetic Resonance Lipoprotein Subfractions in Women.

J Am Heart Assoc 2020 03 27;9(5):e014963. Epub 2020 Feb 27.

Division of Preventive Medicine Center for Lipid Metabolomics Brigham and Women's Hospital Harvard Medical School Boston MA.

Background Supplementation with omega-3 (n-3) fatty acid or dietary fish may protect against atherosclerosis, but the potential mechanisms are unclear. Prior studies found modest triglyceride-lowering effects and slight increases in LDL (low-density lipoprotein) cholesterol. Limited evidence has examined n-3 effects on more detailed lipoprotein biomarkers. Methods and Results We conducted a study of 26 034 healthy women who reported information on fish and n-3 intake from a 131-item food-frequency questionnaire. We measured plasma lipids, apolipoproteins, and nuclear magnetic resonance spectroscopy lipoproteins and examined their associations with dietary intake of fish, total n-3, and the n-3 subtypes (eicosapentaenoic, docosahexaenoic, and α-linolenic acids). Top- versus bottom-quintile intake of fish and n-3 were significantly associated with lower triglyceride and large VLDL (very-low-density lipoprotein) particles. Fish intake, but not total n-3, was positively associated with total cholesterol, LDL cholesterol, apolipoprotein B, and larger LDL size, but only α-linolenic acid was associated with lower LDL cholesterol. Total n-3, docosahexaenoic acid, and α-linolenic acid intake were also positively associated with larger HDL (high-density lipoprotein) size and large HDL particles. High eicosapentaenoic acid intake was significantly associated with only a decreased level of VLDL particle concentration and VLDL triglyceride content. The n-3 fatty acids had some similarities but also differed in their associations with prospective cardiovascular disease risk patterns. Conclusions Higher consumption of fish and n-3 fatty acids were associated with multiple measures of lipoproteins that were mostly consistent with cardiovascular prevention, with differences noted for high intake of eicosapentaenoic acid versus docosahexaenoic acid and α-linolenic acid that were apparent with more detailed lipoprotein phenotyping. These hypothesis-generating findings warrant further study in clinical trials. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT00000479.
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http://dx.doi.org/10.1161/JAHA.119.014963DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7335538PMC
March 2020

Association Between a 20-Year Cardiovascular Disease Risk Score Based on Modifiable Lifestyles and Total and Cause-Specific Mortality Among US Men and Women.

J Am Heart Assoc 2018 11;7(21):e010052

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

Background The previously validated Healthy Heart Score effectively predicted the 20-year risk of cardiovascular disease (CVD). We examine whether the Healthy Heart Score may extend to an association with total and cause-specific mortality. Methods and results The prospective cohort study investigated 58 319 women (mean age 50.2 years) in the Nurses' Health Study (1984-2010) and 29 854 in men (mean age 52.7 years) in the Health Professionals' Follow-up Study (1986-2010) free of cancer and CVD at baseline. The Healthy Heart Score included baseline current smoking; high body mass index; low physical activity; no or excessive alcohol intake; low intake of fruits and vegetables, cereal fiber, or nuts; and high intake of sugar-sweetened beverages or red/processed meats. There were 19 122 total deaths. Compared with participants in the first quintile of the Healthy Heart Score (lowest CVD risk), participants in the fifth quintile (highest CVD risk) had a pooled hazard ratio of 2.26 (95% confidence interval [CI], 1.53-3.33) for total mortality; 2.85 (95 % CI, 1.92-4.23) for CVD mortality, and 2.14 (95% CI, 1.56-2.95) for cancer mortality. Participants in the fifth versus the first quintile also had significantly greater risk of death due to coronary heart disease (3.37; 95% CI, 2.16-5.25), stroke (1.75; 95% CI, 1.02-2.99), lung cancer (6.04; 95% CI, 2.78-13.13), breast cancer (1.45; 95% CI, 1.14-1.86), and colon cancer (1.51; 95% CI, 1.18-1.93). Conclusions The Healthy Heart Score, composed of 9 self-reported, modifiable lifestyle predictors of CVD, is a potentially useful tool for the counseling of healthy lifestyles that was strongly associated with greater risk of all-cause, CVD, and cancer mortality.
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http://dx.doi.org/10.1161/JAHA.118.010052DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6404201PMC
November 2018

Homocysteine, B Vitamins, MTHFR Genotype, and Incident Age-related Macular Degeneration.

Ophthalmol Retina 2018 May;2(5):508-510

Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston.

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http://dx.doi.org/10.1016/j.oret.2017.10.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6022858PMC
May 2018

Seafood Long-Chain n-3 Polyunsaturated Fatty Acids and Cardiovascular Disease: A Science Advisory From the American Heart Association.

Circulation 2018 07 17;138(1):e35-e47. Epub 2018 May 17.

Since the 2002 American Heart Association scientific statement "Fish Consumption, Fish Oil, Omega-3 Fatty Acids, and Cardiovascular Disease," evidence from observational and experimental studies and from randomized controlled trials continues to emerge to further substantiate the beneficial effects of seafood long-chain n-3 polyunsaturated fatty acids and cardiovascular disease. A recent American Heart Association science advisory addressed the specific effect of n-3 polyunsaturated fatty acid supplementation on clinical cardiovascular events. This American Heart Association science advisory extends that review and offers further support to include n-3 polyunsaturated fatty acids from seafood consumption. Several potential mechanisms have been investigated, including antiarrhythmic, anti-inflammatory, hematologic, and endothelial, although for most, longer-term dietary trials of seafood are warranted to substantiate the benefit of seafood as a replacement for other important sources of macronutrients. The present science advisory reviews this evidence and makes a suggestion in the context of the and in consideration of other constituents of seafood and the impact on sustainability. We conclude that 1 to 2 seafood meals per week be included to reduce the risk of congestive heart failure, coronary heart disease, ischemic stroke, and sudden cardiac death, especially when seafood replaces the intake of less healthy foods.
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http://dx.doi.org/10.1161/CIR.0000000000000574DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6903778PMC
July 2018

Prospective study of plasma homocysteine, its dietary determinants, and risk of age-related macular degeneration in men.

Ophthalmic Epidemiol 2018 02 16;25(1):79-88. Epub 2017 Oct 16.

a The Division of Preventive Medicine , Department of Medicine, Brigham and Women's Hospital, Harvard Medical School , Boston , MA, USA.

Purpose: Cross-sectional and case-control studies generally support a direct association between elevated plasma homocysteine and age-related macular degeneration (AMD), but data from prospective studies are limited. We examined the prospective relation of plasma homocysteine level, its dietary determinants, and risk of AMD in a large cohort of apparently healthy male physicians.

Methods: During a mean follow-up of 11.2 years, we identified 146 incident cases of visually significant AMD (responsible for a reduction of visual acuity to 20/30 or worse), and 146 controls matched for age, smoking status, and time of blood draw. We measured concentration of homocysteine in blood samples collected at baseline using an enzymatic assay. and we assessed dietary intake of B vitamins and related compounds betaine and choline with a food frequency questionnaire administered at baseline.

Results: AMD was not associated with plasma level of homocysteine; the multivariable-adjusted odds ratio (OR) of AMD comparing the highest and lowest quartile of homocysteine was 1.09 (95% confidence interval [95% CI]: 0.52-2.31; p for trend = 0.99). However, AMD was inversely associated with quartile of intake of total folate (OR: 0.55; 95% CI: 0.24-1.23; p for trend = 0.08), vitamin B from food (OR: 0.39; 95% CI: 0.17-0.88; p for trend = 0.01), and betaine (OR: 0.53; 95% CI: 0.22-1.27; p for trend = 0.048).

Conclusions: These prospective data from a cohort of apparently healthy men do not support a major role for homocysteine in AMD occurrence, but do suggest a possible beneficial role for higher intake of several nutrients involved in homocysteine metabolism.
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http://dx.doi.org/10.1080/09286586.2017.1362009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6204217PMC
February 2018

Healthful and Unhealthful Plant-Based Diets and the Risk of Coronary Heart Disease in U.S. Adults.

J Am Coll Cardiol 2017 Jul;70(4):411-422

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

Background: Plant-based diets are recommended for coronary heart disease (CHD) prevention. However, not all plant foods are necessarily beneficial for health.

Objectives: This study sought to examine associations between plant-based diet indices and CHD incidence.

Methods: We included 73,710 women in NHS (Nurses' Health Study) (1984 to 2012), 92,329 women in NHS2 (1991 to 2013), and 43,259 men in Health Professionals Follow-up Study (1986 to 2012), free of chronic diseases at baseline. We created an overall plant-based diet index (PDI) from repeated semiquantitative food-frequency questionnaire data, by assigning positive scores to plant foods and reverse scores to animal foods. We also created a healthful plant-based diet index (hPDI) where healthy plant foods (whole grains, fruits/vegetables, nuts/legumes, oils, tea/coffee) received positive scores, whereas less-healthy plant foods (juices/sweetened beverages, refined grains, potatoes/fries, sweets) and animal foods received reverse scores. To create an unhealthful PDI (uPDI), we gave positive scores to less-healthy plant foods and reverse scores to animal and healthy plant foods.

Results: Over 4,833,042 person-years of follow-up, we documented 8,631 incident CHD cases. In pooled multivariable analysis, higher adherence to PDI was independently inversely associated with CHD (hazard ratio [HR] comparing extreme deciles: 0.92; 95% confidence interval [CI]: 0.83 to 1.01; p trend = 0.003). This inverse association was stronger for hDPI (HR: 0.75; 95% CI: 0.68 to 0.83; p trend <0.001). Conversely, uPDI was positively associated with CHD (HR: 1.32; 95% CI: 1.20 to 1.46; p trend <0.001).

Conclusions: Higher intake of a plant-based diet index rich in healthier plant foods is associated with substantially lower CHD risk, whereas a plant-based diet index that emphasizes less-healthy plant foods is associated with higher CHD risk.
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http://dx.doi.org/10.1016/j.jacc.2017.05.047DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5555375PMC
July 2017

Meal Timing and Frequency: Implications for Cardiovascular Disease Prevention: A Scientific Statement From the American Heart Association.

Circulation 2017 Feb 30;135(9):e96-e121. Epub 2017 Jan 30.

Eating patterns are increasingly varied. Typical breakfast, lunch, and dinner meals are difficult to distinguish because skipping meals and snacking have become more prevalent. Such eating styles can have various effects on cardiometabolic health markers, namely obesity, lipid profile, insulin resistance, and blood pressure. In this statement, we review the cardiometabolic health effects of specific eating patterns: skipping breakfast, intermittent fasting, meal frequency (number of daily eating occasions), and timing of eating occasions. Furthermore, we propose definitions for meals, snacks, and eating occasions for use in research. Finally, data suggest that irregular eating patterns appear less favorable for achieving a healthy cardiometabolic profile. Intentional eating with mindful attention to the timing and frequency of eating occasions could lead to healthier lifestyle and cardiometabolic risk factor management.
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http://dx.doi.org/10.1161/CIR.0000000000000476DOI Listing
February 2017

Adolescent Diet Quality and Cardiovascular Disease Risk Factors and Incident Cardiovascular Disease in Middle-Aged Women.

J Am Heart Assoc 2016 12 20;5(12). Epub 2016 Dec 20.

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

Background: Primary prevention of cardiovascular disease (CVD) focuses on treatment of risk factors, including hypercholesterolemia, hypertension, and type 2 diabetes mellitus. We investigated whether a healthy diet in adolescence prevents development of clinical risk factors or incidence of CVD in adulthood.

Methods And Results: We examined the time to the first development of ≥1 clinical risk factor (hypercholesterolemia, hypertension, or type 2 diabetes mellitus) or CVD in relation to a high school Alternative Healthy Eating Index (HS-AHEI) within the Nurses' Health Study II. Among those who completed a food frequency questionnaire about their high school diet and adult diet (mean age 42 years), 27 406 women free of clinical risk factors and 42 112 women free of CVD in 1998 were followed to June 2011. Hazard ratios (HRs) and 95% CIs were adjusted for potential confounders in high school and adulthood. We documented 11 542 first diagnoses of clinical risk factors and 423 CVD events. The HS-AHEI was associated with a lower rate of risk factors (HR highest versus lowest quintiles 0.82; 95% CI, 0.77-0.87 [P trend <0.001]), was inversely associated with risk of developing ≥1 clinical risk factor in women with a low, medium, and high AHEI score during adulthood (HR high HS-AHEI/high adult AHEI versus low/low 0.79 [95% CI, 0.74-0.85]), but was not statistically significantly associated with incident CVD.

Conclusions: A healthy diet during adolescence is associated with lower risk of developing CVD risk factors. As diet tracks throughout life, and adult diet prevents CVD, healthy dietary habits that begin early are important for primordial prevention of CVD.
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http://dx.doi.org/10.1161/JAHA.116.003583DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5210420PMC
December 2016

Plasma Levels of Fatty Acid-Binding Protein 4, Retinol-Binding Protein 4, High-Molecular-Weight Adiponectin, and Cardiovascular Mortality Among Men With Type 2 Diabetes: A 22-Year Prospective Study.

Arterioscler Thromb Vasc Biol 2016 11 8;36(11):2259-2267. Epub 2016 Sep 8.

From the Department of Nutrition (G.L., M.D., S.E.C., E.B.R., P.W.F., F.B.H., Q.S.) and Department of Epidemiology (E.B.R., F.B.H.), Harvard T.H. Chan School of Public Health, Boston, MA; Division of Preventive Medicine (S.E.C.) and Channing Division of Network Medicine (E.B.R., F.B.H., Q.S.), Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA; Department of Clinical Sciences, Genetic and Molecular Epidemiology Unit, Lund University, Sweden (P.W.F.); Skåne University Hospital Malmö, Sweden (P.W.F.); Department of Public Health and Clinical Medicine, Faculty of Medicine, Umeå University, Sweden (P.W.F.); Division of General Internal Medicine, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston (J.B.M.); and Program in Medical and Population Genetics, Broad Institute, Cambridge, MA (J.B.M.).

Objective: To examine select adipokines, including fatty acid-binding protein 4, retinol-binding protein 4, and high-molecular-weight (HMW) adiponectin in relation to cardiovascular disease (CVD) mortality among patients with type 2 diabetes mellitus.

Approach And Results: Plasma levels of fatty acid-binding protein 4, retinol-binding protein 4, and HMW adiponectin were measured in 950 men with type 2 diabetes mellitus in the Health Professionals Follow-up Study. After an average of 22 years of follow-up (1993-2015), 580 deaths occurred, of whom 220 died of CVD. After multivariate adjustment for covariates, higher levels of fatty acid-binding protein 4 were significantly associated with a higher CVD mortality: comparing extreme tertiles, the hazard ratio and 95% confidence interval of CVD mortality was 1.78 (1.22-2.59; P trend=0.001). A positive association was also observed for HMW adiponectin: the hazard ratio (95% confidence interval) was 2.07 (1.42-3.06; P trend=0.0002), comparing extreme tertiles, whereas higher retinol-binding protein 4 levels were nonsignificantly associated with a decreased CVD mortality with an hazard ratio (95% confidence interval) of 0.73 (0.50-1.07; P trend=0.09). A Mendelian randomization analysis suggested that the causal relationships of HMW adiponectin and retinol-binding protein 4 would be directionally opposite to those observed based on the biomarkers, although none of the Mendelian randomization associations achieved statistical significance.

Conclusions: These data suggest that higher levels of fatty acid-binding protein 4 and HMW adiponectin are associated with elevated CVD mortality among men with type 2 diabetes mellitus. Biological mechanisms underlying these observations deserve elucidation, but the associations of HMW adiponectin may partially reflect altered adipose tissue functionality among patients with type 2 diabetes mellitus.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5083188PMC
http://dx.doi.org/10.1161/ATVBAHA.116.308320DOI Listing
November 2016

Hemoglobin A levels and risk of sudden cardiac death: A nested case-control study.

Heart Rhythm 2017 01 31;14(1):72-78. Epub 2016 Aug 31.

Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts; Center for Arrhythmia Prevention, Brigham and Women's Hospital, Boston, Massachusetts; Division of Preventive Medicine, Brigham and Women's Hospital, Boston, Massachusetts; Cardiovascular Division, Brigham and Women's Hospital, Boston, Massachusetts. Electronic address:

Background: Sudden cardiac death (SCD) is often the first manifestation of cardiovascular disease (CVD), and preventive strategies within this broad population are lacking. Patients with diabetes represent a high-risk subgroup, but few data exist regarding whether measures of glycemia mediate risk and/or add to SCD risk stratification.

Objective: The purpose of this study was to examine the association between hemoglobin A (HbA) and SCD.

Methods: We performed a case-control analysis among individuals enrolled in 6 prospective cohort studies. HbA levels were determined for 482 cases of SCD and 914 matched controls. Conditional logistic regression with fixed effects meta-analysis was used for analysis.

Results: In multivariable models, HbA levels were linearly associated with SCD risk over follow-up of 11.3 years (P <.001). Each 1% increment in HbA was associated with a hazard ratio (HR) of 1.32 (95% confidence interval [CI] 1.16-1.50). The magnitude of the association was greater in subjects without vs those with known CVD [HR per 1% increment 1.64 (95% CI 1.31-2.06) vs 1.15 (95% CI 0.99-1.33), P interaction = .009]. In models simultaneously controlling for diabetes status and HbA, the association between HbA and SCD remained significant (HR 1.29, 95% CI 1.07-1.55, P = .01), whereas the association between diabetes and SCD was attenuated (relative risk 1.21, 95% CI 0.64-2.27, P = .56).

Conclusion: In these prospective cohorts, HbA levels associated with SCD risk, particularly among those without known CVD, even after controlling for diabetes status. These data support the hypothesis that hyperglycemia mediates SCD risk among patients with diabetes.
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http://dx.doi.org/10.1016/j.hrthm.2016.08.044DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5754013PMC
January 2017

Association of Specific Dietary Fats With Total and Cause-Specific Mortality.

JAMA Intern Med 2016 08;176(8):1134-45

Department of Nutrition, Harvard T. H. Chan School of Public Health, Boston, Massachusetts3Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, Massachusetts4Channing Division for Network Medicine, Brigham and Women's Hospital a.

Importance: Previous studies have shown distinct associations between specific dietary fat and cardiovascular disease. However, evidence on specific dietary fat and mortality remains limited and inconsistent.

Objective: To examine the associations of specific dietary fats with total and cause-specific mortality in 2 large ongoing cohort studies.

Design, Setting, And Participants: This cohort study investigated 83 349 women from the Nurses' Health Study (July 1, 1980, to June 30, 2012) and 42 884 men from the Health Professionals Follow-up Study (February 1, 1986, to January 31, 2012) who were free of cardiovascular disease, cancer, and types 1 and 2 diabetes at baseline. Dietary fat intake was assessed at baseline and updated every 2 to 4 years. Information on mortality was obtained from systematic searches of the vital records of states and the National Death Index, supplemented by reports from family members or postal authorities. Data were analyzed from September 18, 2014, to March 27, 2016.

Main Outcomes And Measures: Total and cause-specific mortality.

Results: During 3 439 954 person-years of follow-up, 33 304 deaths were documented. After adjustment for known and suspected risk factors, dietary total fat compared with total carbohydrates was inversely associated with total mortality (hazard ratio [HR] comparing extreme quintiles, 0.84; 95% CI, 0.81-0.88; P < .001 for trend). The HRs of total mortality comparing extreme quintiles of specific dietary fats were 1.08 (95% CI, 1.03-1.14) for saturated fat, 0.81 (95% CI, 0.78-0.84) for polyunsaturated fatty acid (PUFA), 0.89 (95% CI, 0.84-0.94) for monounsaturated fatty acid (MUFA), and 1.13 (95% CI, 1.07-1.18) for trans-fat (P < .001 for trend for all). Replacing 5% of energy from saturated fats with equivalent energy from PUFA and MUFA was associated with estimated reductions in total mortality of 27% (HR, 0.73; 95% CI, 0.70-0.77) and 13% (HR, 0.87; 95% CI, 0.82-0.93), respectively. The HR for total mortality comparing extreme quintiles of ω-6 PUFA intake was 0.85 (95% CI, 0.81-0.89; P < .001 for trend). Intake of ω-6 PUFA, especially linoleic acid, was inversely associated with mortality owing to most major causes, whereas marine ω-3 PUFA intake was associated with a modestly lower total mortality (HR comparing extreme quintiles, 0.96; 95% CI, 0.93-1.00; P = .002 for trend).

Conclusions And Relevance: Different types of dietary fats have divergent associations with total and cause-specific mortality. These findings support current dietary recommendations to replace saturated fat and trans-fat with unsaturated fats.
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http://dx.doi.org/10.1001/jamainternmed.2016.2417DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5123772PMC
August 2016

ω-3 Polyunsaturated Fatty Acid Biomarkers and Coronary Heart Disease: Pooling Project of 19 Cohort Studies.

JAMA Intern Med 2016 08;176(8):1155-66

Department of Odontology, Umeå University, Umeå, Sweden.

Importance: The role of ω-3 polyunsaturated fatty acids for primary prevention of coronary heart disease (CHD) remains controversial. Most prior longitudinal studies evaluated self-reported consumption rather than biomarkers.

Objective: To evaluate biomarkers of seafood-derived eicosapentaenoic acid (EPA; 20:5ω-3), docosapentaenoic acid (DPA; 22:5ω-3), and docosahexaenoic acid (DHA; 22:6ω-3) and plant-derived α-linolenic acid (ALA; 18:3ω-3) for incident CHD.

Data Sources: A global consortium of 19 studies identified by November 2014.

Study Selection: Available prospective (cohort, nested case-control) or retrospective studies with circulating or tissue ω-3 biomarkers and ascertained CHD.

Data Extraction And Synthesis: Each study conducted standardized, individual-level analysis using harmonized models, exposures, outcomes, and covariates. Findings were centrally pooled using random-effects meta-analysis. Heterogeneity was examined by age, sex, race, diabetes, statins, aspirin, ω-6 levels, and FADS desaturase genes.

Main Outcomes And Measures: Incident total CHD, fatal CHD, and nonfatal myocardial infarction (MI).

Results: The 19 studies comprised 16 countries, 45 637 unique individuals, and 7973 total CHD, 2781 fatal CHD, and 7157 nonfatal MI events, with ω-3 measures in total plasma, phospholipids, cholesterol esters, and adipose tissue. Median age at baseline was 59 years (range, 18-97 years), and 28 660 (62.8%) were male. In continuous (per 1-SD increase) multivariable-adjusted analyses, the ω-3 biomarkers ALA, DPA, and DHA were associated with a lower risk of fatal CHD, with relative risks (RRs) of 0.91 (95% CI, 0.84-0.98) for ALA, 0.90 (95% CI, 0.85-0.96) for DPA, and 0.90 (95% CI, 0.84-0.96) for DHA. Although DPA was associated with a lower risk of total CHD (RR, 0.94; 95% CI, 0.90-0.99), ALA (RR, 1.00; 95% CI, 0.95-1.05), EPA (RR, 0.94; 95% CI, 0.87-1.02), and DHA (RR, 0.95; 95% CI, 0.91-1.00) were not. Significant associations with nonfatal MI were not evident. Associations appeared generally stronger in phospholipids and total plasma. Restricted cubic splines did not identify evidence of nonlinearity in dose responses.

Conclusions And Relevance: On the basis of available studies of free-living populations globally, biomarker concentrations of seafood and plant-derived ω-3 fatty acids are associated with a modestly lower incidence of fatal CHD.
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http://dx.doi.org/10.1001/jamainternmed.2016.2925DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5183535PMC
August 2016

Plant-Based Dietary Patterns and Incidence of Type 2 Diabetes in US Men and Women: Results from Three Prospective Cohort Studies.

PLoS Med 2016 06 14;13(6):e1002039. Epub 2016 Jun 14.

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

Background: Plant-based diets have been recommended to reduce the risk of type 2 diabetes (T2D). However, not all plant foods are necessarily beneficial. We examined the association of an overall plant-based diet and hypothesized healthful and unhealthful versions of a plant-based diet with T2D incidence in three prospective cohort studies in the US.

Methods And Findings: We included 69,949 women from the Nurses' Health Study (1984-2012), 90,239 women from the Nurses' Health Study 2 (1991-2011), and 40,539 men from the Health Professionals Follow-Up Study (1986-2010), free of chronic diseases at baseline. Dietary data were collected every 2-4 y using a semi-quantitative food frequency questionnaire. Using these data, we created an overall plant-based diet index (PDI), where plant foods received positive scores, while animal foods (animal fats, dairy, eggs, fish/seafood, poultry/red meat, miscellaneous animal-based foods) received reverse scores. We also created a healthful plant-based diet index (hPDI), where healthy plant foods (whole grains, fruits, vegetables, nuts, legumes, vegetable oils, tea/coffee) received positive scores, while less healthy plant foods (fruit juices, sweetened beverages, refined grains, potatoes, sweets/desserts) and animal foods received reverse scores. Lastly, we created an unhealthful plant-based diet index (uPDI) by assigning positive scores to less healthy plant foods and reverse scores to healthy plant foods and animal foods. We documented 16,162 incident T2D cases during 4,102,369 person-years of follow-up. In pooled multivariable-adjusted analysis, both PDI and hPDI were inversely associated with T2D (PDI: hazard ratio [HR] for extreme deciles 0.51, 95% CI 0.47-0.55, p trend < 0.001; hPDI: HR for extreme deciles 0.55, 95% CI 0.51-0.59, p trend < 0.001). The association of T2D with PDI was considerably attenuated when we additionally adjusted for body mass index (BMI) categories (HR 0.80, 95% CI 0.74-0.87, p trend < 0.001), while that with hPDI remained largely unchanged (HR 0.66, 95% CI 0.61-0.72, p trend < 0.001). uPDI was positively associated with T2D even after BMI adjustment (HR for extreme deciles 1.16, 95% CI 1.08-1.25, p trend < 0.001). Limitations of the study include self-reported diet assessment, with the possibility of measurement error, and the potential for residual or unmeasured confounding given the observational nature of the study design.

Conclusions: Our study suggests that plant-based diets, especially when rich in high-quality plant foods, are associated with substantially lower risk of developing T2D. This supports current recommendations to shift to diets rich in healthy plant foods, with lower intake of less healthy plant and animal foods.
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http://dx.doi.org/10.1371/journal.pmed.1002039DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4907448PMC
June 2016

Greater Adherence to the Alternative Healthy Eating Index Is Associated with Lower Incidence of Physical Function Impairment in the Nurses' Health Study.

J Nutr 2016 07 11;146(7):1341-7. Epub 2016 May 11.

Channing Division of Network Medicine and Departments of Epidemiology and.

Background: Physical function is integral to healthy aging, in particular as a core component of mobility and independent living in older adults, and is a strong predictor of mortality. Limited research has examined the role of diet, which may be an important strategy to prevent or delay a decline in physical function with aging.

Objective: We prospectively examined the association between the Alternative Healthy Eating Index-2010 (AHEI-2010), a measure of diet quality, with incident impairment in physical function among 54,762 women from the Nurses' Health Study.

Methods: Physical function was measured by the Medical Outcomes Short Form-36 (SF-36) physical function scale and was administered every 4 y from 1992 to 2008. Cumulative average diet was assessed using food frequency questionnaires, administered approximately every 4 y. We used multivariable Cox proportional hazards models to estimate the HRs of incident impairment of physical function.

Results: Participants in higher quintiles of the AHEI-2010, indicating a healthier diet, were less likely to have incident physical impairment than were participants in lower quintiles (P-trend < 0.001). The multivariable-adjusted HR of physical impairment for those in the top compared with those in the bottom quintile of the AHEI-2010 was 0.87 (95% CI: 0.84, 0.90). For individual AHEI-2010 components, higher intake of vegetables (P-trend = 0.003) and fruits (P-trend = 0.02); lower intake of sugar-sweetened beverages (P-trend < 0.001), trans fats (P-trend = 0.03), and sodium (P-trend < 0.001); and moderate alcohol intake (P-trend < 0.001) were each significantly associated with reduced rates of incident physical impairment. Among top contributors to the food components of the AHEI-2010, the strongest relations were found for increased intake of oranges, orange juice, apples and pears, romaine or leaf lettuce, and walnuts. However, associations with each component and with specific foods were generally weaker than the overall score, indicating that overall diet pattern is more important than individual parts.

Conclusions: In this large cohort of older women, a healthier diet was associated with a lower risk of developing impairments in physical function.
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http://dx.doi.org/10.3945/jn.115.227900DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4926850PMC
July 2016

Association Between a Healthy Heart Score and the Development of Clinical Cardiovascular Risk Factors Among Women: Potential Role for Primordial Prevention.

Circ Cardiovasc Qual Outcomes 2016 Feb;9(2 Suppl 1):S77-85

From the Departments of Nutrition (M.S.-P., J.M., F.B.H., E.B.R., W.C.W., S.E.C.) and Epidemiology (F.B.H., E.B.R., W.C.W., A.H.E., S.E.C.), Harvard T.H. Chan School of Public Health, Boston, MA; Channing Division of Network Medicine (F.B.H., E.B.R., W.C.W., A.H.E.) and Division of Preventive Medicine, Department of Medicine (S.E.C.), Brigham and Women's Hospital and Harvard Medical School, Boston, MA; and Department of Epidemiology and Biostatistics, School of Public Health, Indiana University, Bloomington (A.K.C.).

Background: The prevailing efforts for cardiovascular disease (CVD) prevention focused on treatment of common CVD risk factors rather than primordial prevention of risk factors through health behaviors. The previously validated Healthy Heart Score effectively predicted the 20-year risk of CVD in midadulthood; however, it is unknown whether this risk score is associated with clinically relevant CVD risk factors.

Methods And Results: We analyzed the association between the Healthy Heart Score and the incidence of clinical CVD risk factors, including diabetes mellitus, hypertension, and hypercholesterolemia among 69 505 US women in the Nurses' Health Study II (NHSII; 1991-2011). The Healthy Heart Score estimates the 20-year CVD risk based on 9 lifestyle factors; thus, a higher score reflected a higher predictive CVD risk. During 20 years, we documented 3275 incident cases of diabetes mellitus, 17 420 of hypertension, and 24 385 of hypercholesterolemia. Women with higher predicted CVD risk based on the Healthy Heart Score (highest quintile versus lowest quintile) had significantly greater risk of each clinical risk factor individually (hazard ratios: 18.1 [95% confidence interval, 14.4-22.7] for diabetes mellitus, 5.10 [4.66-5.57] for hypertension, and 2.57 [2.40-2.75] for hypercholesterolemia). The hazard ratio for developing the high-CVD profile was 52.5 (33.6-82.1). These associations were most pronounced among women who were younger, were nonsmokers, or had optimal weight.

Conclusions: An absolute 20-year risk of CVD, estimated by the Healthy Heart Score, was strongly associated with the development of CVD clinically relevant risk factors. This risk score may serve as the first step for CVD risk assessment in primordial prevention.
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http://dx.doi.org/10.1161/CIRCOUTCOMES.115.002372DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4772164PMC
February 2016

Adiposity throughout adulthood and risk of sudden cardiac death in women.

JACC Clin Electrophysiol 2015 Dec;1(6):520-528

Center for Arrhythmia Prevention, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA; The Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA; The Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA.

Background: Sudden cardiac death (SCD) is often the first manifestation of coronary heart disease (CHD) among women. Data regarding BMI and risk of SCD are limited and conflicting.

Objectives: We examined the association of BMI repeatedly measured over 32 years and BMI during early and mid-adulthood with risk of SCD in the Nurses' Health Study.

Methods: We prospectively followed 72,484 women free of chronic disease from 1980-2012. We ascertained adult height, current weight, and weight at age 18 at baseline and updated weight biennially. The primary endpoint was SCD (n=445).

Results: When updated biennially, higher BMI was associated with greater SCD risk after adjusting for confounders (p, linear trend: <0.001). Compared to a BMI of 21.0-22.9, the multivariate RR (95%CI) of SCD was 1.46 (1.05, 2.04) for BMI 25.0-29.9, 1.46 (1.00, 2.13) for BMI 30.0-34.9 and 2.18 (1.44, 3.28) for BMI ≥35.0. Among women with a BMI ≥35.0, SCD remained elevated even after adjustment for interim development of CHD and other mediators (RR: 1.72; 95%CI: 1.13, 2.60). In contrast, the association between BMI and fatal CHD risk was completely attenuated after adjustment for mediators. The magnitude of the association between BMI and SCD was greater when BMI was assessed at baseline or at age 18, at which time SCD risk remained significantly elevated at BMI≥30 after adjustment for mediators.

Conclusions: Higher BMI was associated with greater risk of SCD, particularly when assessed earlier in adulthood. Strategies to maintain a healthy weight throughout adulthood may minimize SCD incidence.
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http://dx.doi.org/10.1016/j.jacep.2015.07.011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4725590PMC
December 2015

Validation of a risk prediction tool for coronary heart disease in middle-aged women.

BMC Womens Health 2015 Nov 10;15:101. Epub 2015 Nov 10.

Alvin J. Siteman Cancer Center and Department of Surgery, Washington University School of Medicine, St. Louis, Missouri, USA.

Background: Health risk appraisal tools may be useful for identifying individuals who would benefit from lifestyle changes and increased surveillance. We evaluated the validity of the Your Disease Risk tool (YDR) for estimating relative risk of coronary heart disease (CHD) among middle-aged women.

Methods: We included 55,802 women in the Nurses' Health Study who completed a mailed questionnaire about risk factors in 1994 and had no history of heart disease at that time. Participants were followed through 2004 for the occurrence of CHD. We estimated each woman's 10-year relative risk of CHD using YDR, and we compared the estimated YDR relative risk category (ranging from "very much below average" to "very much above average") to the observed relative risk for each category using logistic regression. We also examined the discriminatory accuracy of YDR using concordance statistics (c-statistics).

Results: There were 1165 CHD events during the 10-year follow-up period. Compared to the "about average" category, the observed age-adjusted relative risk was 0.43 (95 % confidence interval: 0.33, 0.56) for the "very much below average" category and 2.48 (95 % confidence interval: 1.68, 3.67) for the "very much above average" category. The age-adjusted c-statistic for the model including the YDR relative risk category was 0.71 (95 % confidence interval: 0.69, 0.72). The model performed better in younger than older women.

Conclusion: The YDR tool appears to have moderate validity for estimating 10-year relative risk of CHD in this population of middle-aged women. Further research should aim to improve the tool's performance and to examine its validity in other populations.
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http://dx.doi.org/10.1186/s12905-015-0250-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4640388PMC
November 2015

Improvements In US Diet Helped Reduce Disease Burden And Lower Premature Deaths, 1999-2012; Overall Diet Remains Poor.

Health Aff (Millwood) 2015 Nov;34(11):1916-22

Walter C. Willett is a professor in the Departments of Nutrition and Epidemiology at the Harvard T.H. Chan School of Public Health and the Channing Division of Network Medicine, Department of Medicine, at the Brigham and Women's Hospital and Harvard Medical School.

Evaluation of time trends in dietary quality and their relation to disease burden provides essential feedback for policy making. We used an index titled the Alternate Healthy Eating Index 2010 to evaluate trends in dietary quality among 33,885 US adults. From 1999 to 2012 the index increased from 39.9 to 48.2 (perfect score = 110). Gaps in performance on the index across socioeconomic groups persisted or widened. Using data relating index scores to health outcomes in two large cohorts, we estimated that the improvements in dietary quality from 1999 to 2012 prevented 1.1 million premature deaths. Also, this improvement in diet quality resulted in 8.6 percent fewer cardiovascular disease cases, 1.3 percent fewer cancer cases, and 12.6 percent fewer type 2 diabetes cases. Although the steady improvement in dietary quality likely accounted for substantial reductions in disease burden from 1999 to 2012, overall dietary quality in the United States remains poor. Policy initiatives are needed to ensure further improvements.
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http://dx.doi.org/10.1377/hlthaff.2015.0640DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4783149PMC
November 2015

Optimal Lifestyle Components in Young Adulthood Are Associated With Maintaining the Ideal Cardiovascular Health Profile Into Middle Age.

J Am Heart Assoc 2015 Oct 29;4(11). Epub 2015 Oct 29.

Department of Preventive Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL (H.N., N.B.A., D.M.L.J.).

Background: Middle-aged adults with ideal blood pressure, cholesterol, and glucose levels exhibit substantially lower cardiovascular mortality than those with unfavorable levels. Four healthy lifestyle components-optimal body weight, diet, physical activity, and not smoking-are recommended for cardiovascular health (CVH). This study quantified associations between combinations of healthy lifestyle components measured in young adulthood and loss of the ideal CVH profile into middle age.

Methods And Results: Analyses included 2164 young adults in the Coronary Artery Risk Development in Young Adults study with the ideal CVH profile (defined as untreated blood pressure <120/80 mm Hg, total cholesterol <200 mg/dL, fasting blood glucose <100 mg/dL, and absence of cardiovascular disease) at baseline. Cox proportional hazards regression models estimated hazard ratios for loss of the ideal CVH profile over 25 years according to 4 individual and 16 combinations of optimal healthy lifestyle components measured in young adulthood: body mass index, physical activity, nonsmoking status, and diet quality. Models were adjusted for age, sex, race, education, study center, and baseline blood pressure, cholesterol, and glucose. Eighty percent (n=1737) of participants lost the ideal CVH profile by middle age; loss was greatest for young adults with no optimal healthy lifestyle components at baseline. Relative to young adults with no optimal healthy lifestyle components, those with all 4 were less likely to lose the ideal CVH profile (hazard ratio 0.59, 95% CI 0.44-0.80). Combinations that included optimal body mass index and nonsmoking status were each associated with lower risk.

Conclusions: Optimal body mass index and not smoking in young adulthood were protective against loss of the ideal CVH profile through middle age. Importance of diet and physical activity may be included through their effects on healthy weight.
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http://dx.doi.org/10.1161/JAHA.115.002048DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4845225PMC
October 2015

The Risk of Coronary Heart Disease Associated With Glycosylated Hemoglobin of 6.5% or Greater Is Pronounced in the Haptoglobin 2-2 Genotype.

J Am Coll Cardiol 2015 Oct;66(16):1791-1799

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

Background: Research targeting glycosylated hemoglobin A1c (HbA1c) to <6.5% to prevent coronary heart disease (CHD) events has conflicting results. We previously observed the haptoglobin (Hp) Hp2-2 genotype is associated with a ∼10-fold increased CHD risk among individuals with HbA1c ≥6.5%, and thus might be useful in identifying those at high risk of CHD who would benefit from maintaining HbA1c <6.5%.

Objectives: This study sought to model whether HbA1c ≥ 6.5% in the Hp2-2 genotype is associated with CHD in a prospective case-control study nested within the Health Professionals Follow-Up Study (HPFS).

Methods: HbA1c concentration and Hp genotype were determined for 695 incident cases of CHD from 1994 to 2010 and matched control participants. Logistic regression models calculated relative risk (RR) and 95% CI, for the first and second halves of follow-up, adjusting for confounding variables. A dataset from the Nurses' Health Study served as a replication cohort.

Results: The prevalence of the Hp2-2 genotype in HPFS was 39%. Compared with HbA1c <6.5%, the RR of CHD for HbA1c ≥6.5% for the Hp2-2 genotype over full follow-up was 3.07 (95% CI: 1.37 to 6.86) to 3.88 (95% CI: 1.31 to 11.52) during the first half of follow-up and 2.16 (95% CI: 0.61 to 7.61) in the second half. The corresponding RRs for the Hp1-1 + Hp2-1 genotypes were: full follow-up, 2.19 (95% CI: 1.14 to 4.24); first half, 1.60 (95% CI: 0.73 to 3.53); and second half, 4.72 (95% CI: 1.26 to 17.65).

Conclusions: In 2 independent cohorts, the risk of CHD associated with HbA1c ≥6.5% is pronounced in the Hp2-2 genotype, particularly in early cases. The Hp2-2 genotype may identify individuals at greatest CHD risk from hyperglycemia.
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http://dx.doi.org/10.1016/j.jacc.2015.07.076DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4616252PMC
October 2015

Saturated Fats Compared With Unsaturated Fats and Sources of Carbohydrates in Relation to Risk of Coronary Heart Disease: A Prospective Cohort Study.

J Am Coll Cardiol 2015 Oct;66(14):1538-1548

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

Background: The associations between dietary saturated fats and the risk of coronary heart disease (CHD) remain controversial, but few studies have compared saturated with unsaturated fats and sources of carbohydrates in relation to CHD risk.

Objectives: This study sought to investigate associations of saturated fats compared with unsaturated fats and different sources of carbohydrates in relation to CHD risk.

Methods: We followed 84,628 women (Nurses' Health Study, 1980 to 2010), and 42,908 men (Health Professionals Follow-up Study, 1986 to 2010) who were free of diabetes, cardiovascular disease, and cancer at baseline. Diet was assessed by a semiquantitative food frequency questionnaire every 4 years.

Results: During 24 to 30 years of follow-up, we documented 7,667 incident cases of CHD. Higher intakes of polyunsaturated fatty acids (PUFAs) and carbohydrates from whole grains were significantly associated with a lower risk of CHD comparing the highest with lowest quintile for PUFAs (hazard ratio [HR]: 0.80, 95% confidence interval [CI]: 0.73 to 0.88; p trend <0.0001) and for carbohydrates from whole grains (HR: 0.90, 95% CI: 0.83 to 0.98; p trend = 0.003). In contrast, carbohydrates from refined starches/added sugars were positively associated with a risk of CHD (HR: 1.10, 95% CI: 1.00 to 1.21; p trend = 0.04). Replacing 5% of energy intake from saturated fats with equivalent energy intake from PUFAs, monounsaturated fatty acids, or carbohydrates from whole grains was associated with a 25%, 15%, and 9% lower risk of CHD, respectively (PUFAs, HR: 0.75, 95% CI: 0.67 to 0.84; p < 0.0001; monounsaturated fatty acids, HR: 0.85, 95% CI: 0.74 to 0.97; p = 0.02; carbohydrates from whole grains, HR: 0.91, 95% CI: 0.85 to 0.98; p = 0.01). Replacing saturated fats with carbohydrates from refined starches/added sugars was not significantly associated with CHD risk (p > 0.10).

Conclusions: Our findings indicate that unsaturated fats, especially PUFAs, and/or high-quality carbohydrates can be used to replace saturated fats to reduce CHD risk.
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http://dx.doi.org/10.1016/j.jacc.2015.07.055DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4593072PMC
October 2015

Birth weight and later life adherence to unhealthy lifestyles in predicting type 2 diabetes: prospective cohort study.

BMJ 2015 Jul 21;351:h3672. Epub 2015 Jul 21.

Department of Nutrition, Harvard T H Chan School of Public Health, 665 Huntington Avenue, Boston, MA 02115, USA Department of Epidemiology, Harvard T H Chan School of Public Health, Boston Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston

Objectives: To prospectively assess the joint association of birth weight and established lifestyle risk factors in adulthood with incident type 2 diabetes and to quantitatively decompose the attributing effects to birth weight only, to adulthood lifestyle only, and to their interaction.

Design: Prospective cohort study.

Setting: Health Professionals Follow-up Study (1986-2010), Nurses' Health Study (1980-2010), and Nurses' Health Study II (1991-2011).

Participants: 149,794 men and women without diabetes, cardiovascular disease, or cancer at baseline.

Main Outcome Measure: Incident cases of type 2 diabetes, identified through self report and validated by a supplementary questionnaire. Unhealthy lifestyle was defined on the basis of body mass index, smoking, physical activity, alcohol consumption, and the alternate healthy eating index.

Results: During 20-30 years of follow-up, 11,709 new cases of type 2 diabetes were documented. The multivariate adjusted relative risk of type 2 diabetes was 1.45 (95% confidence interval 1.32 to 1.59) per kg lower birth weight and 2.10 (1.71 to 2.58) per unhealthy lifestyle factor. The relative risk of type 2 diabetes associated with a combination of per kg lower birth weight and per unhealthy lifestyle factor was 2.86 (2.26 to 3.63), which was more than the addition of the risk associated with each individual factor, indicating a significant interaction on an additive scale (P for interaction < 0.001). The attributable proportions of joint effect were 22% (95% confidence interval 18.3% to 26.4%) to lower birth weight alone, 59% (57.1% to 61.5%) to unhealthy lifestyle alone, and 18% (13.9% to 21.3%) to their interaction.

Conclusion: Most cases of type 2 diabetes could be prevented by the adoption of a healthier lifestyle, but simultaneous improvement of both prenatal and postnatal factors could further prevent additional cases.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4510778PMC
http://dx.doi.org/10.1136/bmj.h3672DOI Listing
July 2015

Response to Letters Regarding Article, "Dietary Linoleic Acid and Risk of Coronary Heart Disease: A Systematic Review and Meta-Analysis of Prospective Cohort Studies".

Circulation 2015 Jul;132(3):e23-4

Department of Nutrition, Harvard School of Public Health, Boston, MAChanning Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MADepartment of Epidemiology, Harvard School of Public Health, Boston, MA.

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http://dx.doi.org/10.1161/CIRCULATIONAHA.115.015526DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4590780PMC
July 2015