JoAnn Manson

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Verified

JoAnn verified their affiliation via an institutional email.

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• MD, DrPH
• Professor and Chief at Harvard University

Clonal hematopoiesis of indeterminate potential (CHIP) is associated with increased mortality and malignancy risk, yet the determinants of clonal expansion remain poorly understood. We performed sequencing at >4,000x depth of coverage for CHIP mutations in 6,976 postmenopausal women from the Women's Health Initiative at two timepoints: the WHI base...

Poor dietary habits are a major contributor to chronic disease burden, yet nutrition counseling remains underutilized in primary care settings despite proven effectiveness. This article presents a novel adaptation of the 5 A’s framework (Assess, Advise, Agree, Assist, Arrange) titled ‘The 5 A’s Approach to Promoting Nutrition Counseling in Primary...

Large, randomized trials testing omega-3 polyunsaturated fatty acid (ω-3 PUFA) supplementation to reduce cardiovascular events have reported contradictory results. Interpretation of these trials is challenging, because different dosages and formulations of ω-3 PUFA were tested. Furthermore, the exact mechanisms for the reduction in cardiovascular e...

Purpose Social determinants of health (SDOH) may impact cardiovascular (CV) risk in women with and without breast cancer (BC). Methods In 153,401 participants without prevalent CV disease from the Women’s Health initiative (WHI), we assessed key SDOH factors: geographic region, rurality, insurance status, and household income. Multivariable Cox pr...

Background Little is known about the longitudinal trajectories of novel neurodegenerative biomarkers including neurofilament light (NfL), tau, and glial fibrillary acidic protein (GFAP). Objectives We aimed to investigate the short- and long-term natural history of these biomarkers measured longitudinally among healthy adults. Methods In this coh...

Background The association of metformin with mortality has been mixed, and no prior study has determined whether metformin initiation is associated with exceptional longevity, defined as survival to ages 90 and older. Methods We performed a new-user, active comparator cohort study using the target trial emulation framework among the Women’s Health...

BACKGROUND Mortality due to ischemic heart disease (IHD) has declined in countries with high socioeconomic development. Whether these declines extend to other settings, and whether socioeconomic development influences IHD mortality among men and women differently, is unknown. METHODS We obtained annual data on sex-specific IHD mortality rates for...

Aims/hypothesis Findings from RCTs and observational studies indicate a positive association between statin use and risk of type 2 diabetes. Mendelian randomisation studies provide evidence to support that the effect is causal. However, little is known about the long-term effects, and data on different types of statins remain limited. Methods We a...

M.S. LeBoff: Stock Owner; Self; Johnson &Johnson, Amgen Inc. S.H. Chou: None. D.M. Ratnarajah: None. N.R. Cook: None. F. Giulianini: None. J.E. Buring: None. J.E. Manson: None. D.I. Chasman: None. An estimated 37% of U.S. adults aged ≥60 use vitamin D supplements.1 In an ancillary study to the VITamin D and OmegA-3 TriaL (VITAL) we recently reporte...

Background Metabolically unhealthy obesity (MUO), marked by high visceral adiposity and unhealthy glycemic traits, is a risk factor for colorectal cancer (CRC) and adenoma (CRA). However, the underlying mechanisms of MUO are not fully understood. We sought to characterize inflammatory proteomic signatures of MUO and their associations with incident...

Background Wearable devices provide an opportunity to remotely collect objective data on a patient’s physical activity (PA) and sleep patterns, blood pressure (BP), blood glucose, and other health-related metrics. To date, the prevalence of use and role of wearable devices in older adults diagnosed with cancer remains unclear. We sought to evaluate...

Introduction Experimental studies have shown anti-carcinogenic properties of vitamin D, but meta-analyses of randomized trials of vitamin D supplementation show reduction in cancer mortality but not cancer incidence. This study evaluated the effects of randomized moderate-dose vitamin D3 supplementation on mammographic features associated with brea...

Importance: Pre-pandemic physical activity (PA) levels may be associated with a lower risk of experiencing depressive symptoms in the context of psychosocial resilience during a global crisis. Objective: To investigate the association between self-reported pre-pandemic PA levels and the risk of experiencing depressive symptoms during the beginning...

Observational and experimental evidence suggests that vitamin D plays a role in type 2 diabetes (T2D). However, prior randomized supplementation trials are limited to high-risk patients with prediabetes. Here we aim to evaluate whether vitamin D supplementation reduces risk of T2D in a general population of older US adults. The study design is an a...

Background Emerging evidence suggests a role of psychological well-being in the development of cardiovascular disease (CVD), but supportive data remain limited. This study assessed the prospective associations between life satisfaction and incident CVD, as well as the relative importance of life satisfaction compared to traditional risk factors. M...

Background: Exposure to certain chemicals in disinfectants has been associated with vascular dysfunction in toxicological studies, but the association between disinfectant exposure and clinical cardiovascular disease (CVD) remains unclear. Objective: To evaluate the association between occupational exposure to disinfectants and subsequent risk of C...

Importance Abnormalities of choroidal blood flow in the eye are associated with occurrence of age-related macular degeneration (AMD). Cocoa flavanols show beneficial effects on vascular risk factors in small and short-term trials and may help reduce AMD risk. Objective To examine whether daily supplementation with cocoa extract, a source of flavan...

Background: Obesity is a risk factor for CVD incidence and mortality. Accumulating evidence implicates viscerally located adiposity may be particularly relevant for the progression of cardiovascular risk factors, with chronic inflammation as a plausible causal pathway. However, prior research has lacked precise phenotyping to characterize the relat...

Introduction: Previous studies identified a possible association between indoor radon concentrations and increased risk of stroke; however, the underlying biological mechanisms are unclear. We therefore investigated the associations between indoor radon concentrations and leukocyte and platelet counts to explore inflammation and thrombosis as poten...

Introduction: Although some trials have reported that multivitamin-multimineral (MVM) supplements reduce age-related chronic conditions such as cancer, cataracts, and cognitive decline among older adults, whether MVM slows the aging process remains unknown. Hypothesis: We hypothesized that a daily MVM could reduce biological aging measured by DNA m...

Introduction: Epigenetic (DNA methylation) clocks have been derived as hallmarks of biological age based on their ability to predict chronological age or aging-related phenotypes. However, studies comprehensively examining the associations between epigenetic age acceleration and premature mortality in nationally representative U.S. populations are...

Background: This study aimed to estimate the association between cardiovascular disease (CVD) risk and incident fracture in postmenopausal women. Methods: The study included data from women without a history of CVD enrolled in the Women’s Health Initiative, who had available CVD biomarker information at baseline necessary to compute a 10-year overa...

Background: Plant-based diets are recommended to lower the risk of type 2 diabetes (T2D) and coronary heart disease (CHD). Proteomic responses to plant-based diets may reveal biological pathways underlying the associations between plant-based diets and cardiometabolic disease risk. Hypothesis: Proteomic profiles reflecting adherence and biological...

Backgrounds: Cocoa flavanols have potential blood pressure (BP)-lowering effects in shorter-term, smaller-scale randomized clinical trials (RCTs), but its effect on incident hypertension has not been examined in a large-scale RCT. The COcoa Supplement and Multivitamin Outcomes Study (COSMOS) evaluated whether longer-term cocoa extract supplementati...

Introduction: The portfolio diet, a cholesterol-lowering plant-based diet, is recommended for lowering low-density lipoprotein cholesterol (LDL-C), however, less is known about its long-term impact on cardiometabolic disease. Objective metabolic response to diet using metabolomics can provide additional insight into how diet affects disease risk. O...

Diet quality is a key modifiable risk factor for cardiovascular health. Racial and ethnic disparities in diet quality have been well-documented. However, few studies test how geographical context affects these associations in older women. Furthermore, these inequities have been reported to be unevenly distributed across different geographic regions...

Introduction: Light is the strongest zeitgeber (time cue) for the human central circadian clock, and its effects on health may vary depending on the time of day by either strengthening or dampening circadian rhythms. However, the relations between various light exposures and human health remain largely unknown, partly due to the lack of available m...

Introduction: Higher coffee consumption has been consistently associated with lower type 2 diabetes (T2D) risk but the underlying mechanisms are largely unknown. Our prior study showed higher coffee intake was associated with improved post-load glucose clarence and insulin sensitivity, and lower visceral adiposity. Hypothesis: We hypothesized that...

Background: Radon is an emerging risk factor for stroke, but its relationship with common forms of coronary heart disease (CHD) is unclear. Methods: We studied the radon-myocardial infarction (MI) association among US women without a history of MI or coronary revascularization at the 1993-1998 screening visit of the Women’s Health Initiative Clinic...

Background: Extending the healthspan – years of lived without disease – is a public health priority. Healthy diets have been linked to lower chronic disease risk, but the underlying mechanisms are largely unknown. We have previously identified plasma multi-metabolite signatures that measure intakes and metabolic responses to different dietary patte...

Importance Alzheimer disease (AD) predominates in females at almost twice the rate relative to males. Mounting evidence in adults without AD indicates that females exhibit higher tau deposition than age-matched males, particularly in the setting of elevated β-amyloid (Aβ), but the evidence for sex differences in tau accumulation rates is inconclusi...

Importance Research investigating weight loss and mortality risk often fails to differentiate between intentional and unintentional weight loss and typically uses body mass index (BMI) as the measure of excess body weight. Objective To evaluate associations between weight loss and waist circumference (WC) reduction and mortality, considering weigh...

Importance For younger postmenopausal women, clinical guidelines recommend using osteoporosis risk prediction tools to identify candidates with low bone mineral density (BMD). However, the performance of these tools is not well quantified. Objective To examine the performance of Osteoporosis Risk Assessment Instrument (ORAI) and Osteoporosis Index...

Background Differences in dietary protein have been associated with stroke risk, with possible heterogeneity in associations by stroke type or food sources of protein. Objectives We examined the associations of individual dietary amino acids, as the constituents of dietary protein, with risks of ischemic, hemorrhagic, and total stroke. Methods We...

OBJECTIVE To assess the long-term changes in cardiovascular biomarkers during the WHI (Women's Health Initiative) hormone therapy (HT) clinical trials of conjugated equine estrogens (CEE) alone and CEE plus medroxyprogesterone acetate (MPA). METHODS HT trial participants from the CEE alone (n=1,188, 0.625 mg/d CEE or placebo) and the CEE+MPA (n=1,...

Randomized controlled trials in nutrition (RCTN) face unique challenges, including the considerable influence of the background diet and the challenge of assuring intervention adherence by participants. The impact of these factors on the outcome of RCTNs has been difficult to quantify, but nutritional biomarkers represent a valuable tool to address...

Background Studies have shown an association of chronic kidney disease with heart failure (HF); however, this association has not been adequately examined in postmenopausal women, who are at heightened risk of both chronic kidney disease and HF. Additionally, association with HF subtypes is not well characterized. Methods and Results Incident HF w...

Polygenic risk scores (PRS) hold prognostic value for identifying individuals at higher risk of type 2 diabetes (T2D). However, further characterization is needed to understand the generalizability of T2D PRS in diverse populations across various contexts. We characterized a multi-ancestry T2D PRS among 244,637 cases and 637,891 controls across eig...

Osteoporosis is a major public health problem among older adults. Forty percent of older U.S. adults take multivitamin/multimineral (MVM) supplementation. The effects of MVM supplementation on fractures is unclear. Preclinical and observational studies suggest that MVM and flavanols may have beneficial effects on bone. We conducted an ancillary stu...

Background Genome‐wide association studies have identified several hundred susceptibility single nucleotide variants for coronary artery disease (CAD). Despite single nucleotide variant‐based genome‐wide association studies improving our understanding of the genetics of CAD, the contribution of structural variants (SVs) to the risk of CAD remains l...

Recent advancements in machine learning (ML) for analyzing heterogeneous treatment effects (HTE) are gaining prominence within the medical and epidemiological communities, offering potential breakthroughs in the realm of precision medicine by enabling the prediction of individual responses to treatments. This paper introduces the methodological fra...

Large-scale whole-genome sequencing (WGS) studies have improved our understanding of the contributions of coding and noncoding rare variants to complex human traits. Leveraging association effect sizes across multiple traits in WGS rare variant association analysis can improve statistical power over single-trait analysis, and also detect pleiotropi...

Introduction: Migraines are a known risk factor for stroke among reproductive-aged women, though the relation of migraines to stroke risk among postmenopausal women remains unclear. We assessed the association between a history of diagnosed migraine and incident stroke among postmenopausal women and investigated age differences in the association....

Objective Although dysregulated inflammation has been postulated as a biological mechanism associated with post-acute sequelae of severe acute respiratory coronavirus 2 (SARS-CoV-2) infection (PASC) and shown to be a correlate and an outcome of PASC, it is unclear whether inflammatory markers can prospectively predict PASC risk. We examined the ass...

Background/Objectives: While previous study results have suggested an elevated risk of type 2 diabetes with potato consumption, limited and inconsistent results are available on the association of potato consumption with the risk of cardiovascular disease (CVD) and hypertension (HTN). We assessed the associations of (i) total potato consumption wit...

Background Obesity, classified by body mass index (BMI), is associated with higher postmenopausal breast cancer (BCa) risk. Yet, the associations between abdominal visceral (VAT) and subcutaneous adipose tissue (SAT) with BCa are unclear. Methods We assessed BCa associations with abdominal VAT and SAT in a prospective cohort of postmenopausal wome...

Background The importance of integrating physical and psychosocial factors in assessing frailty -health outcomes has been increasingly acknowledged, while the related evidence is lacking. We sought to investigate the associations of joint physical-psychosocial frailty with risk of premature mortality and evaluate the relative importance of individu...

Clonal hematopoiesis of indeterminate potential (CHIP) is associated with increased mortality and malignancy risk, yet the determinants of clonal expansion remain poorly understood. We performed sequencing at >4,000x depth of coverage for CHIP mutations in 6,986 postmenopausal women from the Women's Health Initiative at two timepoints approximately...

Background Older women have a higher prevalence of Alzheimer’s disease relative to comparably aged men. Although the biological mechanisms driving this sex difference remain elusive, emerging data suggest that longevity, APOEε4, inflammation, and blood glucose levels may play roles. Our objective was to examine the associations of APOEε4, high sens...

Background There is an urgent need to identify novel, accessible and affordable strategies to prevent cognitive decline and progression in the Alzheimer disease and related dementias (ADRD) continuum. Vitamin D3 and marine omega‐3 fatty acids (omega‐3s) supplements show promise for cognitive protection, with potential variations in their effects by...

Background and Aims To identify the patterns of coffee drinking timing in the US population and evaluate their associations with all-cause and cause-specific mortality. Methods This study included 40 725 adults from the National Health and Nutrition Examination Survey 1999–2018 who had complete information on dietary data and 1463 adults from the...

Objective: To assess the association of systolic and diastolic blood pressure (SBP and DBP) in recently menopausal women with white matter hyperintensity (WMH) volume later in life and determine whether short-term menopausal hormone therapy (mHT) modifies these associations. Methods: Kronos Early Estrogen Prevention Study (KEEPS) was a multicent...

Background Epidemiological studies have been inconsistent regarding an association between proton pump inhibitor (PPI) use and risk of primary cardiovascular disease (CVD) events. Methods We studied 85,189 postmenopausal women (mean age 63 years at baseline) without known CVD at enrollment into the Women's Health Initiative Observational Study (19...

Importance Classification of persons with long COVID (LC) or post–COVID-19 condition must encompass the complexity and heterogeneity of the condition. Iterative refinement of the classification index for research is needed to incorporate newly available data as the field rapidly evolves. Objective To update the 2023 research index for adults with...

The relationship between mitochondrial DNA (mtDNA) heteroplasmy and nuclear DNA (nDNA) methylation (CpGs) remains to be studied. We conducted an epigenome-wide association analysis of heteroplasmy burden scores across 10,986 participants (mean age 77, 63% women, and 54% non-White races/ethnicities) from seven population-based observational cohorts....

Objective To prospectively investigate the associations between dark, milk, and total chocolate consumption and risk of type 2 diabetes (T2D) in three US cohorts. Design Prospective cohort studies. Setting Nurses’ Health Study (NHS; 1986-2018), Nurses’ Health Study II (NHSII; 1991-2021), and Health Professionals Follow-Up Study (HPFS; 1986-2020)....

Aims/hypothesis Vitamin D insufficiency is associated with an elevated risk of type 2 diabetes, but evidence from randomised trials on the benefits of vitamin D supplementation is limited, especially for average-risk populations. The Finnish Vitamin D Trial (FIND) investigated the effects of vitamin D3 supplementation at two different doses on the...

Background Findings from Kronos Early Estrogen Prevention Study (KEEPS)-Cog trial suggested no cognitive benefit or harm after 48 months of menopausal hormone therapy (mHT) initiated within 3 years of final menstrual period. To clarify the long-term effects of mHT initiated in early postmenopause, the observational KEEPS Continuation Study reevalua...

Backgrounds: Randomized controlled trials (RCTs) have demonstrated benefits of marine omega-3 polyunsaturated fatty acids (omega-3 FA) supplementation for the prevention of coronary heart disease (CHD). However, it has not been clear which individuals would benefit the most from the supplementation. We sought to predict the individual treatment eff...

Introduction: Women with breast cancer (BC) are at increased risk for cardiovascular disease (CVD). Currently, there is no standardized approach to assess CVD risk in women with BC, despite recommendations for risk assessment. We estimated and compared the performance of established ASCVD risk scores (Framingham Risk Score [FRS], Atherosclerotic Ca...

Background: Recent animal studies connect high sodium intake to the gut-immune axis and highlight the gut microbiome as a potential therapeutic target to counteract salt-sensitive conditions and hypertension. However, the relationship between sodium intake on the gut-immune axis in humans is largely unknown. We previously showed that dietary sodium...

Background: Psychological stress affects cardiovascular (CV) health via multiple physiological and behavioral pathways. Few studies have assessed whether psychological stress impacts heart failure (HF) incidence. A prior large cohort study identified unique associations between perceived stress and HF subtype, but these associations were confounded...

Background Dysglycemia and insulin resistance increase type 2 diabetes (T2D) and cardiovascular disease (CVD) risk, yet associations with specific glucose-insulin homeostatic biomarkers have been inconsistent. Vitamin D and marine omega-3 fatty acids (n-3 FA) may improve insulin resistance. We sought to examine the association between baseline leve...

Background Obesity, defined by body mass index (BMI) alone, is a metabolically heterogeneous disorder with distinct cardiovascular manifestations across individuals. This study aimed to investigate the associations of a proteomic signature of BMI with risk of major subtypes of cardiovascular disease (CVD). Methods A total of 40 089 participants fr...

Whole genome sequences (WGS) enable discovery of rare variants which may contribute to missing heritability of coronary artery disease (CAD). To measure their contribution, we apply the GREML-LDMS-I approach to WGS of 4949 cases and 17,494 controls of European ancestry from the NHLBI TOPMed program. We estimate CAD heritability at 34.3% assuming a...

Disclosure: D.K. Tobias: None. A. Pradhan: None. E. Duran: None. C. Li: None. Y. Song: None. J. Buring: None. N. Cook: None. S. Mora: None. J.E. Manson: None. Background: Observational and experimental evidence suggest a role for vitamin D in the prevention of type 2 diabetes (T2D). However, prior randomized trials in high-risk populations of vitam...

Disclosure: S.H. Chou: None. S.L. Booth: None. D. Ratnarajah: None. N. Cook: None. G. Kotler: None. X. Fu: None. J. Buring: None. J.E. Manson: None. M.S. LeBoff: None. Vitamin D and vitamin K have interdependent roles in bone metabolism. We recently reported that, in the VITamin D and OmegA-3 TriaL (VITAL), daily supplemental vitamin D (2000 IU/d)...

Disclosure: F. Galbiati: None. J. Kang: None. D.J. Cote: None. J.E. Manson: None. U.B. Kaiser: None. Background: High prolactin (PRL) levels inhibit gonadotropin-releasing hormone (GnRH), causing hypogonadism. GnRH release is regulated by neurokinin B (NKB) and kisspeptin. NKB antagonists are used in treatment of menopausal hot flashes and vasomoto...

Disclosure: E.R. Uddenberg: None. N. Safwan: None. G. Cook-Wiens: None. O. Obrutu: None. M. Saadedine: None. M.D. Hurtado: None. S. Faubion: None. M.D. Pisarska: None. S.L. Berga: None. J.E. Manson: None. C.N. Bairey Merz: None. C.L. Shufelt: None. Background: Functional hypothalamic amenorrhea (FHA) occurs in women of reproductive age and is a com...

Disclosure: E.R. Uddenberg: None. N. Safwan: None. G. Cook-Wiens: None. O. Obrutu: None. M. Saadedine: None. M.D. Hurtado: None. S. Faubion: None. M.D. Pisarska: None. S.L. Berga: None. J.E. Manson: None. C.N. Bairey Merz: None. C.L. Shufelt: None. Background: Functional hypothalamic amenorrhea (FHA) occurs in women of reproductive age and is a com...

Background Women who reach menarche and menopause at earlier ages have been shown to be at increased risk for numerous conditions including cardiovascular disease, cancer, depression, and obesity; however, risk factors for earlier ages of menarche and menopause are not fully understood. Therefore, we aimed to perform a retrospective investigation o...

The effect of a healthy low-carbohydrate diet (HLCD) and time-restricted eating (TRE), alone or in combination, on body weight and gut microbiome beyond caloric restriction remains unclear. In this 12-week two-by-two factorial randomized trial with a 28-week follow-up among 96 participants with overweight or obesity, isocaloric-restricted feeding y...

Healthy dietary patterns have been linked to a decreased risk of chronic diseases. However, it remains uncertain whether proteomic signatures can reflect proteome response to healthy diet patterns, and whether these proteomic signatures are associated with health outcomes. Using data from the UK Biobank including Olink plasma proteins, we identifie...

Coronary heart disease (CHD) is one of the leading causes of mortality and morbidity in the United States. Accurate time-to-event CHD prediction models with high-dimensional DNA methylation and clinical features may assist with early prediction and intervention strategies. We developed a state-of-the-art deep learning autoencoder survival analysis...

Background: A 2021 meta-analysis of 37 randomised controlled trials (RCTs) of vitamin D supplementation for prevention of acute respiratory infections (ARI) revealed a statistically significant protective effect of the intervention (odds ratio [OR] 0.92, 95% confidence interval [CI] 0.86 to 0.99). Since then, 6 eligible RCTs have completed, includi...

Midlife vascular risk factors influence later cognitive decline and Alzheimer's disease (AD). The decrease in serum estradiol levels during menopause has been associated with cognitive impairment and increased vascular risk, such as high blood pressure (BP), which independently contributes to cognitive dysfunction and AD. We describe the extent to...

Aims Circulating dimethylguanidino valeric acid (DMGV) was identified as a novel metabolite related to cardiorespiratory fitness and cardiometabolic abnormalities. Circulating DMGV levels are subjective to dietary modulation; however, studies on its associations with intakes of coronary heart disease (CHD)–related foods/nutrients are limited. We in...