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Aim: Evaluate if cardiovascular (CV) risk factors increase at a greater rate during the prediabetes (preDM) stage rather than the diabetes (DM) stage by sex. Methods: We pooled data from the Atherosclerosis Risk in Communities Study and the Multi-Ethnic Study of Atherosclerosis. The CV risk outcome was the metabolic syndrome (MetS) severity z-score derived from components of waist circumference, HDL, triglycerides, SBP, and fasting glucose accounting for the weight of each component. The score was calculated for participants at visits 1 to 4 (3-year interval between visits) . We used linear mixed regressions to model the MetS z-score over time in men and women by levels of glucose (normal Results: Men and women had a greater rate of change in MetS severity during the preDM than the DM stage. Women had a significantly greater increase of MetS severity than men during the preDM stage, while men had a significantly greater increase in the DM stage than women. Conclusion: A more rapid increase in MetS severity occurred in preDM than in DM. Women exhibited a faster increase in MetS severity compared to men during the preDM stage. Greater attention should be given to CV risk in women with preDM. Disclosure Y.Yoshida: None. Z.Chen: n/a. R.L.Baudier: None. M.Krousel-wood: None. A.H.Anderson: None. V.Fonseca: Consultant; Abbott, Asahi Kasei Corporation, Bayer AG, Novo Nordisk, Sanofi, Research Support; Fractyl Health, Inc., Jaguar Gene Therapy, Stock/Shareholder; Abbott, Amgen Inc., BRAVO4Health, Mellitus Health. F.Mauvais-jarvis: Consultant; Mithra Pharmaceutical. Funding NIH K12HD043451

OBJECTIVE Early menopause may be associated with higher cardiovascular disease (CVD) risk. Type 2 diabetes mellitus (T2DM), coupled with early menopause, may result in even greater CVD risk in women. We examined CVD risk in women with early compared with normal-age menopause, with and without T2DM overall, and by race/ethnicity. RESEARCH DESIGN AND METHODS We pooled data from the Atherosclerosis Risk in Communities study, the Multi-Ethnic Study of Atherosclerosis, and the Jackson Heart Study. We included women with data on menopausal status, menopausal age, and T2DM, excluding pre- or perimenopausal women and those with prevalent CVD. Outcomes included incident coronary heart disease (CHD), stroke, heart failure (HF), and atherosclerotic cardiovascular disease (ASCVD) (CHD or stroke). We estimated the risk associated with early ( RESULTS We included 9,374 postmenopausal women for a median follow-up of 15 years. We observed 1,068 CHD, 659 stroke, 1,412 HF, and 1,567 ASCVD events. T2DM significantly modified the effect of early menopause on CVD risk. Adjusted hazard ratios for early menopause and the outcomes were greater in women with T2DM versus those without (CHD 1.15 [95% CI 1.00, 1.33] vs. 1.09 [1.03, 1.15]; stroke 1.21 [1.04, 1.40] vs. 1.10 [1.04, 1.16]; ASCVD 1.29 [1.09, 1.51] vs. 1.10 [1.04, 1.17]; HF 1.18 [1.00, 1.39] vs. 1.09 [1.03, 1.16]). The modifying effect of T2DM on the association between early menopause and ASCVD was only statistically significant in Black compared with White women. CONCLUSIONS Early menopause was associated with an increased risk for CVD in postmenopausal women. T2DM may further augment the risk, particularly in Black women.

Background: Early menopause may be associated with higher cardiovascular disease (CVD) risk due to the early cessation of estrogens protection. The presence of diabetes (DM) coupled with early menopause may result in even greater CVD risk in postmenopausal women. We compared CVD risk in women with early vs. normal age menopause with and without DM. Methods: We pooled data from the Atherosclerosis Risk in Communities Study, the Multi-Ethnic Study of Atherosclerosis, and the Jackson Heart Study. Women with data on menopausal status, age at menopause and DM (yes/no) were included. We excluded pre- or peri-menopausal women, those with hysterectomy/oophorectomy or prevalent CVD. Outcomes were incident coronary heart disease (CHD), ischemic or hemorrhagic stroke, heart failure (HF), and a composite CVD outcome (CHD, stroke or HF). Cox models examined the risk associated with early ( Results: During a median follow-up of 15 yrs for 5964 postmenopausal women, 684 CHD, 434 stroke, 962 HF and 1535 CVD events occurred. In adjusted models, women with early menopause had elevated risk of CHD (Hazard ratio 1.12, 95% CI 1.03-1.22), stroke (1.09, 1.01-1.18) and HF (1.09, 1.00-1.19) compared to those with normal age menopause. DM was a significant effect modifier to the relationship between early menopause and CHD, stroke or CVD (P for interaction ≤0.05). HRs for early menopause and the outcomes were greater in diabetic than nondiabetic women (CHD 1.34, 1.02-1.78 vs. 1.10, 1.00-1.20; stroke 1.26, 0.98-1.61 vs. 1.07, 0.98-1.16; CVD 1.41, 1.01-1.95 vs. 1.04, 0.94-1.14). Conclusion: Early menopause increases risk for CVD in postmenopausal women; DM places this group at even higher CVD risk. Attention to CVD risk monitoring and management in women with early menopause, with and without diabetes, should be considered. Disclosure Y. Yoshida: None. Z. Chen: None. R. L. Baudier: None. M. Krousel-wood: None. A. H. Anderson: None. V. Fonseca: Consultant; Self; Abbott Diabetes, Asahi Kasei Corporation, Bayer Inc., Boehringer Ingelheim Pharmaceuticals, Inc., Intarcia Therapeutics, Inc., Novo Nordisk, Pfizer Inc., Sanofi-Aventis, Stock/Shareholder; Self; Amgen Inc., Bravo4health, Mellitus Health. F. Mauvais-jarvis: None. Funding National Institutes of Health (K12HD043451)

U.S. veterans have a high prevalence of post-traumatic stress disorder (PTSD), for which no effective psychotropic medications are indicated. Nearly 25% of veterans have diabetes, for which metformin is a first line treatment. Although metformin is associated with improved neurodegenerative outcomes, there is no evidence on the association between metformin and PTSD-related symptom relief. This study aimed to examine whether metformin was associated with a clinically meaningful reduction in PTSD symptoms (≥20 points reduction PTSD checklist for DSM-5 {PCL-5}) score)) among veterans with PTSD using data from Veterans Health Administration. The metformin cohort was defined as first metformin use after a recorded PTSD diagnosis with a PCL-5 score ≥33 (i.e., clinical cut-score). The control cohort (never used metformin) was selected by propensity score 1:1 matching on the likelihood of initiating metformin with the covariates of age, gender, race, durations of PTSD, diabetes, and depression, and baseline CCI, PCL-5, and PHQ-9 scores. Multivariable Cox proportional regression was used to assess the association between metformin exposure and improvement in the PCL-5 scores. A total of 7950 veterans (mean age: 51.9 ± 13.6 years, male: 85%, white: 61.4%, African American: 28.8%) with confirmed PTSD were comparable on the baseline demographics and medical conditions between metformin and control PSM-matched cohorts with a median follow-up 1.2 years in both cohorts. The baseline PCL-5 score was 56.2±11.6 and 56.5±11.7 in metformin and control cohort, respectively. The metformin-treated cohort was more likely to have a clinically meaningful reduction in PTSD symptoms (adjusted hazard ratio (aHR): 1.31, 95%CI: 1.16-1.48), compared the control cohort. Furthermore, patients on metformin ≥2 years were 22% more likely to reduce PTSD symptoms (aHR: 1.22, 95%CI: 1.04-1.43), compared with metformin exposure Disclosure S. Liu: None. A.M. Raines: None. Y. Yoshida: None. W. Tang: None. J.I. Constans: None. V. Fonseca: Consultant; Self; Abbott, Asahi Kasei Corporation, AstraZeneca, Bayer Inc., Novo Nordisk Inc., Sanofi. Research Support; Self; Boehringer Ingelheim Pharmaceuticals, Inc. Stock/Shareholder; Self; Amgen, Bravo4health. L. Shi: None.