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Introduction:Oxidative stress has been linked to many cardiovascular diseases (CVD) and suggested to be higher in women than in men. However, few community cohorts have explored these associations and most studies of oxidative stress are conducted in populations with advanced CVD. We measured urinary isoprostane levels, a standard measure of oxidative stress, in a relatively young and healthy cohort, hypothesizing that higher oxidative stress is associated with an adverse cardiometabolic profile and female sex.Methods:We studied 478 women and 265 men of similar age (Mean (SD): 52.2 (2.2) in women vs 52.1 (2.3) years in men; p = 0.45) in the CARDIA study (39% were non-White). Urinary 8-isoprostane and 2, 3-dinor-8-isoprostane were measured using gas-chromatography-mass spectrometry and their sum indexed to urinary creatinine (IsoPs) was used for analysis. Multivariable adjusted linear regression models were used to evaluate the cross-sectional associations of sex and other CVD risk factors with log transformed IsoPs.Results:Unadjusted IsoPs levels were significantly higher in women compared to men (25.5 [17.9-41.1] vs 19.7 [13.9-30.9] ?g/g creatinine; p<0.001). In the multivariable adjusted model, female sex, current smoking, and higher values of body mass index (BMI), HDL cholesterol, triglycerides and eGFR were associated with higher IsoPs and Black race was associated with lower IsoPs levels (Table).Conclusions:Women, smokers, and those with higher BMI and serum triglycerides have elevated oxidative stress, which may contribute to increased risk for CVD. The observed positive relationship of HDL cholesterol with IsoP may be because HDL is the main lipoprotein carrier of IsoPs in the blood and involved in ?freeing? (hydrolysis of) esterified IsoPs from tissue cells. The significance of lower levels of IsoPs in blacks and the positive association with eGFR warrants further investigation.

Introduction:Menopause is associated with an adverse cardiovascular disease (CVD) risk factor profile, and elevated oxidative stress from loss of estrogen may contribute. However, the extent of difference in oxidative stress between pre- and post-menopausal women is not well characterized. We hypothesize that urinary isoprostane levels, a standard measure of oxidative stress, are higher in women who have undergone natural menopause compared to premenopausal women of similar age.Methods:We studied 279 post- and 199 pre-menopausal women from the CARDIA study. Urinary 8-isoprostane and 2, 3-dinor-8-isoprostane were measured by gas-chromatography-mass spectrometry and their sum indexed to urinary creatinine (IsoPs) was used for analysis. Multivariable linear regression was used to evaluate cross-sectional associations between menopausal status and log transformed IsoPs. Models were progressively adjusted: 1) age, race, study center 2) + smoking status, cumulative pack years 3) + BMI, systolic blood pressure, total and HDL cholesterol, triglycerides, diabetes, medication use for hypertension or cholesterol 4) + exercise and education.Results:Mean age (SD) was 52.9 (1.9) years for post- and 51.2 (2.2) years for pre-menopausal women (p <0.001). Antihypertensive (25% vs 17%, p = 0.04) and cholesterol lowering medication use (17% vs 9%, p = 0.01) were more common in postmenopausal women who had a trend towards more smokers (16% vs 11%, p = 0.15). Before adjustment, IsoPs levels were higher in post- compared to pre-menopausal women (Median [IQR]: 26.1 [18.2 to 45.6] vs 24.0 [16.9 to 37.3] ?g/g creatinine; p =0.04). Menopause was associated with 18% higher IsoPs (p = 0.02) in the minimally adjusted model. Adjustment for tobacco use attenuated the association (14%, p = 0.07) and inclusion of CVD risk factors led to additional attenuation (11%, p= 0.15). Adjustment for exercise and education had no substantial effect (10%, p = 0.16).Conclusion:Postmenopausal women had higher oxidative stress than premenopausal women, which may contribute to higher risk of CVD. This association was confounded by smoking and partially attenuated by other CVD risk factors, however the nature of associations between IsoPs and CVD risk factors warrants further investigation.

Introduction:People living with HIV (HIV+) may be at greater risk for sudden arrhythmic death than HIV-uninfected (HIV-) individuals. HIV-associated abnormal cardiac repolarization may contribute. We investigated whether HIV serostatus is associated with ventricular repolarization lability with QT Variability Index (QTVI), calculated as a log measure of QT interval variance normalized by heart rate (HR) variance.Methods:We studied 1120 men from the Multicenter AIDS Cohort Study (MACS), a cohort of HIV+ and HIV- men, who underwent ambulatory ECG using a wearable device with accelerometry functionality. An automated template-matching algorithm was used to analyze ECG recordings (median [IQR]: 78.3 [66.3-83.0] hours/person). Concurrent accelerometry data identified periods of recumbency. Average QTVI during periods of upright posture and recumbency were modeled in linear mixed-effects models controlling for demographics, cardiac risk factors, HIV-related and inflammatory biomarkers.Results:Mean (SD) age was 60.1 (11.9) years for HIV- and 54.3 (11.3) years for HIV+ participants, 83% of whom had undetectable (<20 copies/ml) viral load. HIV+ men had higher adjusted QTVI compared to HIV- men, especially in men with detectable viral load (Table). Analysis of QTVI components showed lower HR variability in HIV+ men with either detectable or undetectable viral load compared with HIV- men, and higher QT variability only in HIV+ men with detectable viral load compared to HIV- men. Higher levels of CRP, IL-6, ICAM-1, sCD163, and soluble TNF-? receptor2 were associated with higher QTVI and partially attenuated the association with HIV.Conclusions:HIV+ men have greater QTVI compared to HIV- men, especially in the setting of viremia and heightened inflammation. QTVI differences in HIV+ men suggest repolarization lability which may increase susceptibility to ventricular arrhythmias. Lower HR variability suggests a component of autonomic dysfunction.