JoAnn E. Manson

Background: Body roundness index (BRI) is an anthropometric measure that combines waist circumference (WC) and height. It reflects central adiposity more accurately than the body mass index (BMI). Evidence linking BRI to long-term cancer risk, particularly in postmenopausal women, remains limited. Methods: We examined associations between BRI and incident site-specific cancers (n = 33,892) in 144,865 postmenopausal women 50 to 79 years of age at enrollment into the Women’s Health Initiative (WHI) and followed for a median of 17.9 years. BRI was assessed at baseline in all participants and at year 3 in 60% of participants. Cox proportional hazards models estimated associations between BRI and cancer incidence, adjusting for sociodemographic, reproductive, and lifestyle factors. Results: Higher BRI levels were associated with increased risks of kidney, endometrial, liver, esophageal, thyroid, colorectal, stomach, pancreatic, bladder, breast, and lung cancers and with non–Hodgkin lymphoma (NHL), particularly diffuse large B-cell lymphoma (DLBCL). Adjustment for BMI attenuated associations for endometrial, breast, and kidney cancers but strengthened those for liver, lung, and esophageal cancers. Results were consistent across sensitivity analyses and models incorporating repeated BRI measurements. Age-stratified (</≥ 63 years) models indicated stronger associations for kidney cancer among younger women and a significant positive association for melanoma among older women. Conclusions: Among postmenopausal women, higher BRI was associated with an increased risk of cancer at multiple sites independently of BMI. These findings support an important role for central adiposity in cancer risk beyond overall body size. Impact: In postmenopausal women, BRI may improve the estimation of site-specific cancer risk beyond BMI by capturing central adiposity.

Context: Body mass index (BMI) does not capture central adiposity, which may provide additional information for type 2 diabetes (T2D) risk stratification. Objective: To evaluate BMI-specific waist circumference (WC) categories in relation to incident T2D and assess their performance across independent cohorts. Methods: Prospective analyses included 133 620 Women's Health Initiative (WHI) participants free of T2D at baseline, randomly assigned to training (70%; n = 93 463) and test (30%; n = 40 157) samples. External validation included the Health and Retirement Study (HRS; n = 2885) and Healthy Aging in Neighborhoods of Diversity across the Life Span (HANDLS; n = 1037). Cox models estimated T2D risk across BMI and BMI-specific WC categories. Discrimination was assessed using Harrell's c-statistics. Results: In WHI, T2D risk increased progressively across BMI categories (adjusted hazard ratios [HRs], 1.51-3.30) and joint BMI–WC categories (HRs, 1.40-4.43). Within BMI strata, higher WC generally identified greater T2D risk. Associations were directionally consistent in HRS and HANDLS. Age modified associations, with stronger gradients at younger ages, whereas race and ethnicity interactions were not statistically significant. Model discrimination was modest (c-statistics approximately 0.60-0.75). Conclusion: Body mass index-specific WC categories refine adiposity-related T2D risk stratification beyond BMI alone but provide modest individual-level discrimination. Waist circumference may complement BMI in identifying women warranting more comprehensive metabolic risk assessment rather than serving as a stand-alone T2D prediction tool.

We address concerns regarding inter-individual differences in flavanol metabolism and biomarker levels and explain why they do not affect the conclusions of our study of the impact of background diet and adherence on the outcomes analysis of COSMOS.

BACKGROUND: Elevated 1-hour glucose levels during an oral glucose tolerance test strongly predict type 2 diabetes (T2D) and cardiovascular disease. We investigated whether the fasting blood metabolome predicting 1-hour glucose could be a target for improving β-cell function, long-term glycemic trajectories, and reducing the risks of T2D and coronary heart disease. We also investigated whether plasma microRNAs derived from key metabolic organs regulate changes in a metabolomic risk score (MRS) for predicting 1-hour glucose. METHODS: Untargeted blood metabolomics and a frequently sampled 75-g oral glucose tolerance test were performed in participants from the OmniCarb trial (n=162). In an independent weight-loss dietary intervention trial (POUNDS Lost [Preventing Overweight Using Novel Dietary Strategies]), temporal changes in MRS and plasma microRNAs measured by genome-wide sequencing were analyzed. In addition, associations of MRS at baseline and its 10-year changes with long-term risk of incident T2D and coronary heart disease were prospectively investigated in the NHS (Nurses’ Health Study). RESULTS: We created a fasting blood MRS for predicting 1-hour glucose (Pearson r =0.8) and found significant associations with half-day (diurnal) postprandial glucose excursions and insulin secretion after 5-week controlled feeding interventions varying in carbohydrate amount and glycemic index. In the POUNDS Lost trial, diet-induced changes in MRSs were related to 2-year trajectories of glucose metabolism; circulating microRNAs regulating cardiometabolic abnormalities were pivotal factors influencing these changes. In the NHS, women in the top 20% of MRS had a multivariate-adjusted relative risk of 3.80 (95% CI, 2.22–6.51) for T2D and 1.48 (95% CI, 1.04–2.12) for coronary heart disease compared with those in the lowest 20%. In addition, 10-year increases in plasma metabolites related to 1-hour glucose were linearly associated with a higher risk of T2D. CONCLUSIONS: Our findings indicate that fasting blood metabolomic signatures predicting elevated 1-hour glucose reflect disease pathophysiology and could be targets for preventing T2D and coronary heart disease.

BACKGROUND: Current dietary guidelines are largely based on evidence from the general population, and data on dietary patterns and survival after myocardial infarction (MI) remain limited. We evaluated post-MI adherence to multiple healthy dietary patterns, as well as changes in adherence from before to after MI diagnosis, in relation to mortality among MI survivors. METHODS: We included 3277 women from the Nurses’ Health Study and 2618 men from the Health Professionals Follow-Up Study who survived a nonfatal MI. The mean age at MI diagnosis was 68.2 (SD, 10.2) years. Diet was assessed using validated food frequency questionnaires and updated every 2 to 4 years. We calculated post-MI adherence scores for 8 healthy patterns: the Alternate Healthy Eating Index, the Healthy Eating Index-2015, the Alternate Mediterranean Diet Score, the Dietary Approaches to Stop Hypertension, the Healthful Plant-Based Diet Index, the reversed empirical dietary inflammatory pattern, the reversed empirical dietary index for hyperinsulinemia, and the reversed empirical dietary index for insulin resistance. The main outcome was total mortality, with cardiovascular disease mortality and recurrent nonfatal MI as secondary outcomes. RESULTS: During 15.7 years of follow-up after MI, 3858 deaths (65.4%) were documented, including 1639 cardiovascular disease deaths (42.5% of deaths). Comparing the highest with the lowest quintile, higher post-MI dietary scores were consistently associated with lower total mortality, with the hazard ratio of 0.67 (95% CI, 0.60–0.74) for Alternate Healthy Eating Index, 0.73 (95% CI, 0.65–0.81) for Healthy Eating Index-2015, 0.66 (95% CI, 0.59–0.75) for Alternate Mediterranean Diet Score, 0.77 (95% CI, 0.69–0.86) for Dietary Approaches to Stop Hypertension, 0.74 (95% CI, 0.66–0.83) for Healthful Plant-Based Diet Index, 0.77 (95% CI, 0.68–0.86) for reversed empirical dietary inflammatory pattern, 0.73 (95% CI, 0.65–0.83) for reversed empirical dietary index for insulin resistance, and 0.71 (95% CI, 0.64–0.80) for reversed empirical dietary index for hyperinsulinemia. Similar inverse associations were observed for cardiovascular disease mortality and recurrent nonfatal MI. Improved Alternate Healthy Eating Index adherence from before to after MI was associated with lower mortality (hazard ratio, 0.86 [95% CI, 0.76–0.97]), whereas decreased adherence to most patterns was associated with higher mortality. CONCLUSIONS: Among individuals who survived MI, adherence to post-MI dietary patterns emphasizing higher diet quality was associated with better long-term survival. These findings support dietary guidance focusing on overall diet quality for the secondary prevention of deaths among MI survivors.

BACKGROUND: Hypertensive disorders of pregnancy (HDP) affect over 10% of pregnancies worldwide, but their association with cardiovascular-kidney-metabolic (CKM) syndrome remains unexplored. METHODS: The present study included parous UK Biobank participants. The primary exposure was HDP history. CKM syndrome was categorized from stage 0 (no risk factors) to 4 (cardiovascular disease). Logistic regression tested the association of HDP history with CKM stage, adjusted for age, age ² , race, Townsend Deprivation Index, and smoking status. Cox models evaluated progression to stage 4, in addition, adjusting for baseline CKM stage. Replication analyses were performed in the Women Health Initiative, with CKM stage assessed at 2 study visits. RESULTS: Among 219 639 UK Biobank (mean age, 56.9 years) and 3591 Women Health Initiative participants (61.7 years at baseline, 78.1 years at the follow-up visit), 2836 (1.3%) and 304 (8.4%), respectively, had a history of HDP. In the UK Biobank, HDP history was significantly associated with higher CKM stage (adjusted odds ratio, 3.40 [95% CI, 3.12–3.71]; P P P <0.001). Replication in the Women Health Initiative produced consistent results. CONCLUSIONS: HDP history was associated with greater CKM stage and progression to advanced CKM syndrome, supporting its use as an early life predictor of adverse CKM trajectories.

BACKGROUND: Many women have suboptimal cardiovascular health (CVH), which declines during midlife. Few studies have characterized CVH across the menopausal transition or identified its sociodemographic and neighborhood determinants. METHODS: We analyzed a prospective cohort of women in eastern Massachusetts enrolled during pregnancy (1999–2002) and followed to midlife (2019–2024). Exposures included household income, education, race and ethnicity, and neighborhood Social Vulnerability Index (categorized from very low [<20th percentile] to very high [≥80th percentile]; higher categories=greater neighborhood vulnerability). Women self-reported their menopause status using questionnaires. Using Life’s Essential 8, we derived CVH scores (0–100 points; higher score=better CVH) at 3-, 8-, 13-, 18-, and 23-year follow-up visits. Linear spline mixed-effect models examined associations of sociodemographics and neighborhood Social Vulnerability Index with differences in CVH across different menopause stages (premenopause, perimenopause, and postmenopause). RESULTS: Among 1200 women (mean enrollment age, 32.1 years; 67.5% Non-Hispanic White), 15.4% had household incomes ≤$40 000/y, 8.8% had ≤high school education, and 17.4% resided in very high Social Vulnerability Index neighborhoods. After covariate adjustment, women with lower income, lower education, or identifying as Non-Hispanic Black exhibited lower CVH across follow-up. Independent of individual sociodemographics, continued residence in vulnerable neighborhoods over time was associated with lower CVH and unfavorable CVH trajectories across follow-up. For example, residence in very high (versus very low) Social Vulnerability Index neighborhoods from enrollment to 3-year follow-up corresponded to mean CVH differences of −6.7 (95% CI, −12.3 to −1.2) at 3-year, −9.8 (95% CI, −15.6 to −4.0) at 8-year, −8.9 (95% CI, −13.9 to −3.9) at 13-year, −6.7 (95% CI, −12.9 to −0.5) at 18-year, and −7.2 (95% CI, −12.5 to −1.9) at 23-year follow-up, and with faster CVH score decline during premenopause (−0.62 points/y; 95% CI, −1.22 to −0.02). CONCLUSIONS: Women from disadvantaged sociodemographic backgrounds or residing in vulnerable neighborhoods exhibit poorer CVH across the menopausal transition, highlighting opportunities to optimize long-term CVH and mitigate cardiovascular disease risk.