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19, SE 0.06, P=0.002) was associated with worse left ventricular (LV) global longitudinal strain (GLS). Additionally, higher Y15 ICAM-1 (β-coefficient per 1-SD higher 0.18, SE 0.06, P=0.004) and its increase from Y7 to Y15 (β-coefficient per 1-SD higher 0.16, SE 0.07, P=0.03) were also independently associated with worse LV GLS. E-selectin and ICAM-1 partially mediated the associations between higher BMI and black race with worse GLS. Neither E-selectin nor ICAM-1 were associated with measures of LV diastolic function after multivariable adjustment. CONCLUSION Circulating levels of E-selectin and ICAM-1 and increases in ICAM-1 over the course of young adulthood are associated with worse indices of LV systolic function in midlife. These findings suggest associations of endothelial activation with subclinical HFpEF. BACKGROUND The Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) trial compared atorvastatin with placebo in 4,731 participants with recent stroke or transient ischemic attack and no known coronary heart disease. Atorvastatin reduced the first occurrence of stroke and the first occurrence of a composite of vascular events. OBJECTIVES This post hoc analysis assessed the occurrence of all (first and subsequent) vascular events and the effect of atorvastatin to reduce these events by vascular territory (cerebrovascular, coronary, or peripheral) in SPARCL. METHODS Treatment effects on total adjudicated vascular events, overall and by vascular territory, were summarized by marginal proportional hazards models. Vascular event rates were estimated for each treatment group with cumulative incidence functions. RESULTS The placebo group had an estimated 41.2 first and 62.7 total vascular events per 100 participants over six years. There were 164 fewer first and 390 fewer total vascular events in the atorvastatin group (total events hazard ratio 0.68, 95% confidence interval 0.60 to 0.77). The total events reduction included 177 fewer cerebrovascular, 170 fewer coronary, and 43 fewer peripheral events. Over six years, an estimated 20 vascular events per 100 participants were avoided with atorvastatin treatment. CONCLUSIONS In participants with recent stroke or transient ischemic attack, the total number of vascular events prevented with atorvastatin was more than twice the number of first events prevented. Total event reduction provides a comprehensive metric to capture the totality of atorvastatin clinical efficacy in reducing disease burden after stroke or transient ischemic attack. BACKGROUND In the COAPT trial, transcatheter mitral valve repair (TMVr) with the MitraClip rapidly improved health status and reduced the long-term risks of death and heart failure (HF) hospitalization in patients with HF and severe secondary mitral regurgitation (SMR) who remained symptomatic despite maximally-tolerated guideline directed medical therapy (GDMT). OBJECTIVE To examine if early health status changes were associated with long-term clinical outcomes in the COAPT population. Selleckchem BI-3802 METHODS We evaluated the association between change in health status (KCCQ-OS) from baseline to 1 month and the composite rate of death or HF hospitalization between 1 month and 2 years in the COAPT trial and tested whether treatment (TMVr or GDMT alone) modified this association. RESULTS Among 551 patients with HF and severe SMR who were alive at 1 month, those randomized to TMVr were more likely than GDMT alone to achieve a ≥10-point improvement in KCCQ-OS from baseline to 1 month (TMVr 58%, GDMT alone 26%). Early improvement in KCCQ-OS was inversely associated with the risk of death or HF hospitalization between 1 month and 2 years (p less then 0.001). When analyzed as a continuous variable, a 10-point increase in KCCQ-OS was associated with a 14% lower risk of death or HF hospitalization (HR 0.86, 95% CI 0.81-0.92, p less then 0.001), with no significant interaction with treatment group (pinteraction=0.17). After adjusting for demographic and clinical factors, the association between change in KCCQ-OS and outcomes was strengthened (HR 0.79, 95% CI 0.73-0.86, p less then 0.001). CONCLUSION In patients with HF and severe SMR, a short-term change in disease-specific health status was strongly associated with the subsequent long-term risk of death or HF hospitalization. These findings reinforce the prognostic utility of serial KCCQ-OS assessments to identify patients at risk for poor long-term clinical outcomes in this population. Plasma fatty acids have been reported to be dysregulated in mild cognitive impairment (MCI) and Alzheimer's disease (AD), though outcomes are not always consistent, and subject numbers often small. Our aim was to use a meta-analysis and systematic review approach to identify if plasma fatty acid dysregulation would be observed in case control studies of AD and MCI. Six databases were searched for studies reporting quantified levels of fatty acids in MCI and/or AD individuals, relative to cognitively normal controls. Docosahexaenoic (DHA) and vaccenic acids were significantly lower and higher respectively in MCI relative to controls. Total fatty acids were 27.2% lower in AD relative to controls, and this was reflected almost uniformly in all specific fatty acids in AD. Changes to plasma/serum fatty acids were identified in both MCI and AD relative to age and gender matched controls. Differences were greatest in AD, in both total number of fatty acids significantly altered, and the degree of change. Docosahexaenoic acid was lower in both MCI and AD, suggesting that it may be a driver of pathology. The marked increase in adolescent reward-seeking behavior has important implications for adaptive and maladaptive development. Reward-seeking is linked to increased testosterone and increased neural responses to reward cues. How acute testosterone changes modulate neural reward systems remains unclear. Based on previous work, adolescents, particularly males, showing an increase in endogenous testosterone reactivity were hypothesized to show increased neural response to reward in ventromedial prefrontal cortex, ventral striatum, and posterior cingulate cortex. Sixty-one healthy adolescents aged 10-13 (38 female, mean age = 12.01 [SD = 1.00]) completed a reward-cue processing task during fMRI. Saliva samples to be assayed for testosterone were collected immediately before and after scanning. Acute testosterone changes were not associated with variation in behavioral performance. Within ventromedial prefrontal and posterior cingulate cortices, increased acute testosterone change was associated with reduced discrimination between rewarded and un-rewarded trials.