JoAnn E Manson's research while affiliated with Harvard University and other places
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Publications (707)
OBJECTIVE
Observational studies have indicated that cocoa flavanol supplementation may be a promising strategy for type 2 diabetes (T2D) prevention. We aimed to directly evaluate its clinical efficacy in a large randomized clinical trial (RCT).
RESEARCH DESIGN AND METHOD
The Cocoa Supplement and Multivitamin Outcomes Study (COMSOS) was a 2 × 2 fac...
Background: Higher consumption of Mediterranean diet (MED) intake has been associated with reduced risk of all-cause mortality but limited data are available examining long-term outcomes in women or the underlying molecular mechanisms of this inverse association in human populations. We aimed to investigate the association of MED intake with long-t...
This study aimed to investigate whether n−3 fatty acid supplementation reduced cardiovascular disease (CVD) events in a novel analysis using hierarchical composite CVD outcomes based on win ratio in the VITamin D and OmegA-3 TriaL (VITAL). This was a secondary analysis of our VITAL randomized trial, which assessed the effects of marine n−3 fatty ac...
OBJECTIVE
Clonal hematopoiesis of indeterminate potential (CHIP) is an aging-related accumulation of somatic mutations in hematopoietic stem cells, leading to clonal expansion. CHIP presence has been implicated in atherosclerotic coronary heart disease (CHD) and all-cause mortality, but its association with incident type 2 diabetes (T2D) is unknown...
Background: Social isolation and loneliness pose significant public health challenges globally. The objective of this study is to investigate the association between social isolation, loneliness, and the risk of type 2 diabetes mellitus (T2DM).
Methods: 423,503 UK adults from the UK Biobank (UKB) and 13,800 Chinese adults from the China Health and...
Importance
Although premenstrual disorders (PMDs) end at menopause, it is unclear whether they are associated with the timing and symptom severity of menopause.
Objective
To prospectively examine whether women with PMDs have increased risks of early menopause and menopause-related vasomotor symptoms (VMS).
Design, Setting, and Participants
This p...
Background:
Associations of weight changes and intentionality of weight loss with longevity are not well described.
Methods:
Using longitudinal data from the Women's Health Initiative (N = 54 437; 61-81 years), we examined associations of weight changes and intentionality of weight loss with survival to ages 90, 95, and 100. Weight was measured...
Background:
Circulating adiponectin and leptin have been associated with risk of pancreatic cancer. However, the relationship between long-term exposure to these adipokines in the prediagnostic period with patient survival has not been investigated.
Methods:
Adipokine levels were measured in prospectively collected samples from 472 pancreatic ca...
Most women worldwide experience menopausal symptoms during the menopause transition or postmenopause. Vasomotor symptoms are most pronounced during the first four to seven years but can persist for more than a decade, and genitourinary symptoms tend to be progressive. Although the hallmark symptoms are hot flashes, night sweats, disrupted sleep, an...
Background:
Sickle cell trait affects ∼ 8% of African American individuals, along with many other individuals with ancestry from malaria-endemic regions worldwide. While traditionally considered a benign condition, recent evidence suggests sickle cell trait is associated with lower eGFR and higher risk of kidney diseases, including end-stage kidne...
Objective:
The menopausal transition results in a progressive decrease in circulating estrogen levels. Experimental evidence in rodents has indicated that estrogen depletion leads to a reduction of energy expenditure and physical activity. It is unclear whether treatment with estrogen therapy increases physical activity level in postmenopausal wom...
Background:
Chronic psychological distress is associated with increased risk of cardiovascular disease (CVD) and investigators have posited inflammatory factors may be centrally involved in these relationships. However, mechanistic evidence and molecular underpinnings of these processes remain unclear, and data are particularly sparse among women....
Background:
Premature menopause is a risk factor for accelerated cardiovascular aging, but underlying mechanisms remain incompletely understood. This study investigated the role of leukocyte telomere length (LTL), a marker of cellular aging and genomic instability, in the association of premature menopause with cardiovascular disease.
Methods:
P...
Background:
Multimorbidity, defined as the presence of two or more chronic health conditions, is increasingly common among older adults. The combination of lifestyle characteristics such as diet quality, smoking status, alcohol intake, physical activity, sleep duration, and body fat as assessed by body mass index (BMI) or waist circumference, and...
Background:
Evidence is uncertain about the association between serum 25-hydroxyvitamin D (25(OH)D) concentration and health outcomes in people with type 2 diabetes.
Objective:
We aimed to assess the association between vitamin D status and all-cause mortality and cardiovascular disease in people with type 2 diabetes.
Methods:
We did a systema...
Introduction:
Whether apolipoprotein E's (APOE's) involvement in lipid metabolism contributes to Alzheimer's disease (AD) risk remains unknown.
Methods:
Incident probable dementia and cognitive impairment (probable dementia+mild cognitive impairment) were analyzed in relation to baseline serum lipids (total, low-density lipoprotein [LDL], high-d...
Background & aims:
Systematic reviews, meta-analyses and Mendelian randomization studies suggest that cardiometabolic diseases may be associated with COVID-19 risk and prognosis, with evidence implicating insulin resistance (IR) as a common biological mechanism. As driving factors for IR, we examined body mass index (BMI) and waist circumference (...
Objective: To test vitamin D3 and omega-3 fatty acids (omega-3s) for late-life depression prevention under the National Academy of Medicine framework for indicated (targeting subthreshold depression) and selective (targeting presence of high-risk factors) prevention. Methods: The VITamin D and OmegA-3 TriaL (VITAL) is a 2 × 2 factorial trial of vit...
Unlabelled:
There is limited research examining aircraft noise and cardiovascular disease (CVD) risk. The objective of this study was to investigate associations of aircraft noise with CVD among two US cohorts, the Nurses' Health Study (NHS) and Nurses' Health Study II (NHSII).
Methods:
Between 1994 and 2014, we followed 57,306 NHS and 60,058 NH...
Background
Epigenetic age acceleration (AgeAccel) indicates faster biological aging relative to chronological age and has been independently associated with several age‐related outcomes. However, the cross‐sectional and longitudinal associations of AgeAccel with global cognitive function is understudied.
Method
We therefore studied 734 women (mean...
Background:
A substantial observational literature relating specific fatty acid classes to chronic disease risk may be limited by its reliance on self-reported dietary data.
Objectives:
We aimed to develop biomarkers for saturated (SFA), monounsaturated (MFA) and polyunsaturated (PFA) fatty acid densities, and to study their associations with ca...
Understanding the role of both menopausal hormone therapy (MHT) along with non-hormonal options for the treatment of vasomotor symptoms, sleep disruption, and genitourinary symptoms after menopause is critical to the health of women during middle and later life. Recent updates to the evidence for the treatment of menopausal symptoms pertaining to b...
Background:
Maintenance of cognitive abilities is of critical importance to older adults, yet only a few effective strategies to slow down the cognitive decline currently exist. Multivitamin supplementation is used to promote general health; however, it is unclear whether it favorably affects cognition in older age.
Objectives:
To examine the ef...
Background:
The Women's Health Initiative (WHI) randomized, controlled Dietary Modification (DM) trial of a low-fat dietary pattern suggested intervention benefits related to breast cancer, coronary heart disease (CHD), and diabetes. Here we use WHI observational data for the further insight into the chronic disease implications of adopting this t...
Objective
To investigate the intake of specific types of beverages in relation to mortality and cardiovascular disease (CVD) outcomes among adults with type 2 diabetes.
Design
Prospective cohort study.
Setting
Health professionals in the United States.
Participants
15 486 men and women with a diagnosis of type 2 diabetes at baseline and during f...
Objective:
To identify whether sex disparities in leisure-time physical activity (LTPA) vary across population subgroups.
Participants and methods:
We used data from the Behavioral Risk Factor Surveillance System (BRFSS) spanning 2011 to 2021. We examined subgroups by age, race/ethnicity, income, employment, education, marital status, body mass...
Importance:
Postmenopausal females represent around 70% of all individuals with Alzheimer disease. Previous literature shows elevated levels of tau in cognitively unimpaired postmenopausal females compared with age-matched males, particularly in the setting of high β-amyloid (Aβ). The biological mechanisms associated with higher tau deposition in...
Background:
The association of total energy expenditure with all-cause mortality is uncertain, as is the dependence of this association on age.
Objective:
To examine the association between total energy expenditure and all-cause mortality, and its age interaction, in a Women's Health Initiative (WHI) cohort of postmenopausal U.S. females (1992-p...
To evaluate the effect of vitamin D3 supplementation on cancer mortality in the general population and on prognosis in cancer patients, a systematic review and meta-analysis of randomised, placebo-controlled trials (RCTs) and individual patient data (IPD) was conducted. Overall, 14 RCTs with a total of 104,727 participants (2,015 cancer deaths) wer...
Background: Average life expectancy has increased substantially in recent decades in most developed countries; however, a sizable proportion of the increased life expectancy is spent in suboptimal health.
Hypothesis: We investigated whether levels of cardiovascular health (CVH), estimated by the American Heart Association’s newly released Life’s Es...
Introduction: The link between gestational diabetes mellitus (GDM) and long-term risk of type 2 diabetes (T2D) and cardiovascular disease (CVD) is well established; however, risk factors underlying the progression of disease remain uncertain.
Hypothesis: Female reproductive factors including ages at menarche, menopause, and first birth, number of l...
Background: The COcoa Supplement and Multivitamin Outcomes Study (COSMOS) is a recently completed randomized, double-blind, placebo-controlled, 2x2 factorial trial of a multivitamin and cocoa extract supplement (containing 500 mg/d flavanols) in 21,442 older adults. In view of favorable effects of multivitamins on cognition and promising signals fo...
Objective:
We examined the relationship between ultra-processed food (UPF) intake and type 2 diabetes (T2D) risk among 3 large U.S. cohorts, conducted a meta-analysis of prospective cohort studies, and assessed meta-evidence quality.
Research design and methods:
We included 71,871 women from the Nurses' Health Study, 87,918 women from the Nurses...
Introduction: Adverse pregnancy outcomes (APOs) have been linked with maternal mortality, higher risk of metabolic and cardiovascular diseases, and adverse neonatal outcomes. The World Health Organization recommends the adoption of a healthy lifestyle (maintaining a normal BMI, not smoking, regular exercise, healthy diet, avoiding harmful alcohol i...
Introduction: Recent evidence suggests that dietary proteins modulate the microbial composition and metabolite production to influence host physiology. Gut-microbiota-related metabolites, such as trimethylamine N-oxide (TMAO) and its precursors, phenylacetylglutamine (PAGln) and p-tolyl (cresol) sulfate, have been recently implicated as atherogenic...
Introduction: There is limited evidence on the association between long-term consumption of ultra-processed foods (UPF) and the risk of type 2 diabetes (T2D), among the U.S population. The overall strength of this association has also not been established.
Hypothesis: Higher intake of UPF is associated with a higher risk of T2D in U.S. adults. The...
Background:
Few studies have examined accelerometer-measured physical activity and incident breast cancer (BC). Thus, this study examined associations between accelerometer-measured vector magnitude counts per 15 seconds (VM/15s) and average daily minutes of light physical activity (LPA), moderate-to-vigorous PA (MVPA), and total PA (TPA) and BC r...
Few studies have demonstrated reproducible gene–diet interactions (GDIs) impacting metabolic disease risk factors, likely due in part to measurement error in dietary intake estimation and insufficient capture of rare genetic variation. We aimed to identify GDIs across the genetic frequency spectrum impacting the macronutrient–glycemia relationship...
Background:
The role of sex hormone-binding globulin (SHBG) levels in clinical risk stratification and intervention for coronary heart disease (CHD) remains uncertain. We aimed to examine whether circulating levels of SHBG are predictive of CHD risk in men and women.
Methods:
We investigated the association between SHBG and the risk of incident...
Background:
Obesity is a leading risk factor for chronic diseases, potentially related to excess abdominal adiposity. Phthalates are environmental chemicals that have been suggested to act as obesogens, driving obesity risk. For the associations between phthalates and adiposity, prior studies have focused primarily on body mass index. We hypothesi...
Low circulating vitamin D levels are more prevalent in Black than White individuals. We analyzed the Women's Health Initiative (WHI) calcium plus vitamin D (CaD) randomized clinical trial extended follow‐up data to evaluate associations between calcium plus vitamin D supplementation and incident cancer, cardiovascular disease (CVD), and cause‐speci...
This study sought to examine the association between DNA methylation and body mass index (BMI) and the potential of BMI-associated cytosine-phosphate-guanine (CpG) sites to provide information about metabolic health. We pooled summary statistics from six trans-ethnic epigenome-wide association studies (EWASs) of BMI representing nine cohorts (n = 1...
Importance:
The current Dietary Guidelines for Americans recommend multiple healthy eating patterns. However, few studies have examined the associations of adherence to different dietary patterns with long-term risk of total and cause-specific mortality.
Objective:
To examine the associations of dietary scores for 4 healthy eating patterns with...
Background:
The VITAL study was a nationwide, randomized, double-blind, placebo-controlled, 2 × 2 factorial trial of vitamin D3 (2000 IU/day) and marine n-3 FAs (1 g/day) supplements. We recently reported that vitamin D supplementation with or without omega 3 fatty acids reduced autoimmune disease by 22% in the VITAL study.
Objective:
To investi...
Background:
Chocolate contains both potentially harmful components (ie, stearic acid and added sugar) and beneficial components (ie, phenolics and flavonoids). Despite its popularity, the long-term health effects of chocolate consumption remain unclear.
Objective:
The aim of this study was to examine the association of chocolate consumption with...
Importance
Statin-associated muscle symptoms (SAMS) are common and may lead to discontinuation of indicated statin therapy. Observational studies suggest that vitamin D therapy is associated with reduced statin intolerance, but no randomized studies have been reported.
Objective
To test whether vitamin D supplementation was associated with prevent...
To date, the VITamin D and OmegA-3 TriaL (VITAL) is the only large-scale randomized trial of marine omega-3 fatty acid (n-3 FA) supplementation for cardiovascular disease (CVD) prevention in a general population unselected for elevated cardiovascular risk. We review the findings of VITAL, as well as results from recent secondary prevention trials a...
Introduction: Phenylacetylglutamine (PAGln) has been recently discovered as a gut-microbiota-related metabolite, and circulating PAGln may be related to risks of cardiometabolic abnormalities. Gut microbiota-related dietary intakes and high-protein foods may affect circulating PAGln levels.
Hypothesis: We assessed whether circulating PAGln levels m...
Introduction: Circulating dimethylguanidino valeric acid (DMGV) has been related to visceral adiposity and unhealthy obesogenic lifestyle factors, and recently emerged as an early marker of cardiovascular disease.
Hypothesis: We tested whether circulating DMGV was associated with the risk of coronary heart disease (CHD) among women. We also investi...
Background
Low heart rate variability (HRV), a measure of autonomic imbalance, is associated with increased risk of coronary heart disease (CHD) and heart failure (HF). However, its relationship with HF subtypes; heart failure with preserved ejection fraction (HFpEF) and heart failure with reduced ejection fraction (HFrEF) has not been studied prio...
Background
Breastfeeding has been associated with a reduced maternal long-term risk of chronic diseases, but its association with mortality is poorly known.
Methods
We included 166,708 female United States (US) nurses from the Nurses’ Health Study (1986-2016) and the Nurses’ Health Study II (1989-2019) who experienced at least one pregnancy lastin...
Objective:
The aim of this study was to examine the association between common menopausal symptoms (MS) and long-term cardiovascular disease (CVD) and all-cause mortality.
Methods:
In an observational cohort of 80,278 postmenopausal women with no known CVD at baseline from the Women's Health Initiative, we assessed individual MS severity (mild v...
Statins are highly effective medications that reduce risk of atherosclerotic cardiovascular disease, but are very commonly discontinued by patients because of muscle symptoms. The risk factors for statin-associated muscle symptoms (SAMS) are not well understood, so in this study we examined the predictors of SAMS in a well-studied cohort of patient...
Background
Asymptomatic atrial fibrillation (AF) is associated with an increased risk of stroke. The yield of serial electrocardiographic (ECG) screening for AF is unknown.
Objectives
The aim of this study was to determine the frequency of AF detected by serial, 7-day ECG patch screenings in older women identified as having an elevated risk of AF...
Objectives
To examine associations of pituitary-ovarian hormone levels with cognition before and after different formulations of hormone therapy (HT) or placebo independent of treatment group.
Methods
Recently menopausal, healthy women were randomized to 0.45 mg/day oral conjugated equine estrogens (o-CEE, n = 109), 50 μg/day transdermal 17β (tE2,...
Background:
Epigenetic age acceleration (EAA), a measure of accelerated biological aging, has been associated with increased risk of several age-related chronic conditions. This is the first study to prospectively examine the relationship between EAA and both multimorbidity count and a weighted multimorbidity score among long-lived postmenopausal...
Objective:
To evaluate vitamin D supplementation for preventing or treating overactive bladder (OAB) and urinary incontinence (UI) in men.
Methods:
Ancillary study of men aged ≥55 years in the VITamin D and OmegA-3 TriaL (VITAL). Randomized treatments included: vitamin D3 (cholecalciferol), marine omega-3 fatty acids, or matching placebo. Struct...
Introduction:
Dietary supplements are touted for cognitive protection, but supporting evidence is mixed. COSMOS-Mind tested whether daily administration of cocoa extract (containing 500 mg/day flavanols) versus placebo and a commercial multivitamin-mineral (MVM) versus placebo improved cognition in older women and men.
Methods:
COSMOS-Mind, a la...
Importance:
Women have a lower incidence of atrial fibrillation (AF) compared with men in several studies, but it is unclear whether this sex difference is independent of sex differences in prevalent cardiovascular disease (CVD), body size, and other risk factors.
Objective:
To examine sex differences in AF incidence and whether AF risk factors...
Background
Prior studies examined associations between Healthy Eating Index (HEI) and chronic disease risk based on self-reported diet without measurement error correction.
Objectives
Our objective was to test associations between biomarker-calibration of food frequency questionnaire (FFQ)-derived HEI-2010 with incident cardiovascular disease (CVD...
The goal of this study was to examine associations between accelerometer-measured physical activity (PA) and sedentary time (ST) with mortality by a genetic risk score (GRS) for longevity. Among 5,446 women, (mean [ SD ]: age, 78.2 [6.6] years), 1,022 deaths were observed during 33,350 person-years of follow-up. Using multivariable Cox proportional...
Cardiovascular disease (CVD) remains a major health threat in women. While traditional CVD risk factors such as hypertension, hyperlipidemia, diabetes, and smoking have been recognized for over 50 years, optimal control of these risk factors remains a major challenge. Unique sex-specific risk factors such as adverse pregnancy outcomes, premature me...
Background
Weight at birth has been associated with the development of various adult diseases, but its association with mortality remains unclear.
Methods
We included 22,389 men from the Health Professionals Follow-up Study (1994-2018) and 162,231 women from the Nurses’ Health Study (1992-2018) and the Nurses’ Health Study II (1991-2019). The haza...
This JAMA Insights Clinical Update discusses updated recommendations on the use of aspirin for primary prevention of atherosclerotic cardiovascular disease in women and stresses the importance of shared clinical decision-making.
BACKGROUND
To clarify the mechanisms underlying physical activity (PA)-related cardioprotection, we examined the association of PA with plasma bioactive lipids (BALs) and cardiovascular disease (CVD) events. We additionally performed genome-wide associations.
METHODS
PA-bioactive lipid associations were examined in VITAL (VITamin D and OmegA-3 Tri...
Adiposity has been associated with several health conditions as well as timing of menopause. Prior epidemiologic studies on the association of adiposity and anti-Müllerian hormone (AMH) have been inconsistent. We evaluated the relations of anthropometric measures with AMH at two time periods in a subset of premenopausal participants in the Nurses'...
Background
Low birth weight has been associated with a greater risk of cardiovascular disease (CVD). However, the interaction between low birth weight and adult lifestyle factors on the risk of CVD remains unclear.
Methods
We included 20,169 men from the Health Professionals Follow-up Study (HPFS, 1986–2016), 52,380 women from the Nurses’ Health St...
The WHI (Women’s Health Initiative) enrolled 161,808 racially and ethnically diverse postmenopausal women, ages 50-79 years, from 1993 to 1998 at 40 clinical centers across the United States. In its clinical trial component, WHI evaluated 3 randomized interventions (menopausal hormone therapy; diet modification; and calcium/vitamin D supplementatio...
Introduction
Both osteoporosis and cardiovascular disease (CVD) increase in women after menopause. Estrogen deficiency is thought to be an underlying mechanism for both these conditions.
Methods
Healthy menopausal women (n = 374, age 42–58 years) underwent cardiac CT scans over four years as participants in the Kronos Early Estrogen Prevention Stu...
Aims/hypothesis
Plant-based diets, especially when rich in healthy plant foods, have been associated with a lower risk of type 2 diabetes. However, whether plasma metabolite profiles related to plant-based diets reflect this association was unknown. The aim of this study was to identify the plasma metabolite profiles related to plant-based diets, a...
Interval breast cancer refers to cancer diagnosed after a negative screening mammogram and before the next scheduled screening mammogram. Interval breast cancer has worse prognosis than screening-detected cancer. Body mass index (BMI) influences the accuracy of mammography and overall postmenopausal breast cancer risk, yet how is obesity associated...
Background:
Although effective in reducing the risk of type 2 diabetes (T2D), in-person lifestyle modification programs have been underutilized. To minimize barriers related to convenience and accessibility, recent research has focused on developing virtual or remote interventions that may have comparable or greater efficacy in promoting lifestyle...
In a multi-stage analysis of 52,436 individuals aged 17-90 across diverse cohorts and biobanks, we train, test, and evaluate a polygenic risk score (PRS) for hypertension risk and progression. The PRS is trained using genome-wide association studies (GWAS) for systolic, diastolic blood pressure, and hypertension, respectively. For each trait, PRS i...
Background
Recommended systolic blood pressure (SBP) targets often do not consider the relationship of low diastolic blood pressure (DBP) levels with cardiovascular disease (CVD) and all-cause mortality risk, which is especially relevant for older people with concurrent comorbidities.
We examined the relationship of DBP levels to CVD and all-cause...
Background
Both genetic and lifestyle factors contribute to the risk of type 2 diabetes, but the extent to which there is a synergistic effect of the 2 factors is unclear. The aim of this study was to examine the joint associations of genetic risk and diet quality with incident type 2 diabetes.
Methods and findings
We analyzed data from 35,759 men...
A relatively high healthy lifestyle index (HLI) score, representing a healthy diet, participation in moderate to vigorous physical exercise, no smoking, low to no alcohol intake, and a normal body mass index, has been associated with a reduced risk of invasive breast cancer. However, no study has shown an association between the HLI and the risk of...
Objective: The aim of this study was to test the individual and combined benefit of vitamin D, omega-3, and a simple home strength exercise program on the risk of any invasive cancer.
Design: The DO-HEALTH trial is a three-year, multicenter, 2 × 2 × 2 factorial design double-blind, randomized-controlled trial to test the individual and combined ben...
Background
Epidemiologic studies on the relationship between avocado intake and long‐term cardiovascular disease (CVD) risk are lacking.
Methods and Results
This study included 68 786 women from the NHS (Nurses’ Health Study) and 41 701 men from the HPFS (Health Professionals Follow‐up Study; 1986–2016) who were free of cancer, coronary heart dise...
Background and aim
Iron deficiency is associated with increased morbidity and mortality in older adults. However, data on its prevalence and incidence among older adults is limited. The aim of this study was to investigate the prevalence and incidence of iron deficiency in European community-dwelling older adults aged ≥ 70 years.
Methods
Secondary...
Background
Studies of diet and chronic disease include a recent important focus on dietary patterns. Patterns are typically defined by listing dietary variables, and by totaling scores that reflect whether consumption is encouraged or discouraged for listed variables. However, precision may be improved by including total energy consumption among th...
Background:
Circulating branched-chain amino acids (BCAAs; isoleucine, leucine, and valine) are strongly associated with higher risk of incident type 2 diabetes (T2D); however determinants of elevated fasting levels are largely unknown.
Objective:
We aimed to characterize the modifiable lifestyle factors related to plasma BCAAs.
Methods:
We pe...
Background
Cocoa extract and multivitamins have been proposed to reduce the risk of cardiovascular disease (CVD) and cancer, respectively. However, few randomized clinical trials have tested their long-term effects on these outcomes.
Methods
The COcoa Supplement and Multivitamin Outcomes Study (COSMOS) is a randomized, double-blind, placebo-control...
Introduction: The relationship between artificially sweetened beverage (ASB) intake and type 2 diabetes (T2D) risk remains inconclusive. Few studies have evaluated whether circulating metabolites that reflect ASB consumption may unveil potential mechanisms underlying the association between ASB consumption and T2D risk.
Hypothesis: We hypothesized...
