Real-world comparison of bleeding risks among non-valvular atrial fibrillation patients prescribed apixaban, dabigatran, or rivaroxaban.

Limited real-world data are available regarding the comparative safety of non-vitamin K antagonist oral anticoagulants (NOACs). The objective of this retrospective claims observational cohort study was to compare the risk of bleeding among non-valvular atrial fibrillation (NVAF) patients prescribed apixaban, dabigatran, or rivaroxaban. NVAF patients aged ≥18 years with a 1-year baseline period were included if they were new initiators of NOACs or switched from warfarin to a NOAC. Cox proportional hazards modelling was used to estimate the adjusted hazard ratios of any bleeding, clinically relevant non-major (CRNM) bleeding, and major inpatient bleeding within 6 months of treatment initiation for rivaroxaban and dabigatran compared to apixaban. Among 60,227 eligible patients, 8,785 were prescribed apixaban, 20,963 dabigatran, and 30,529 rivaroxaban. Compared to dabigatran or rivaroxaban patients, apixaban patients were more likely to have greater proportions of baseline comorbidities and higher CHA2DS2-VASc and HAS-BLED scores. After adjusting for baseline clinical and demographic characteristics, patients prescribed rivaroxaban were more likely to experience any bleeding (HR: 1.35, 95% confidence interval [CI]: 1.26-1.45), CRNM bleeding (HR: 1.38, 95% CI: 1.27-1.49), and major inpatient bleeding (HR: 1.43, 95% CI: 1.17-1.74), compared to patients prescribed apixaban. Dabigatran patients had similar bleeding risks as apixaban patients. In conclusion, NVAF patients treated with rivaroxaban appeared to have an increased risk of any bleeding, CRNM bleeding, and major inpatient bleeding, compared to apixaban patients. There was no significant difference in any bleeding, CRNM bleeding, or inpatient major bleeding risks between patients treated with dabigatran and apixaban.

Ischemic Stroke in Nonvalvular Atrial Fibrillation at Warfarin Initiation: Assessment via a Large Insurance Database.

BACKGROUND AND PURPOSE: Stroke risk may increase shortly after warfarin initiation in nonvalvular atrial fibrillation patients. Because of the brief period and limited number of events, large samples are needed to study this effect. We compared 30-day rates of ischemic stroke between nonvalvular atrial fibrillation patients initiating warfarin to nonwarfarin comparators using an insurance claims database. METHODS: We identified nonvalvular atrial fibrillation patients via 1 inpatient/2 outpatient diagnosis claims from the MarketScan database, January 1, 2009, to December 31, 2010. We studied patients initiating warfarin using prescription claims and 1:1 matched 22 669 initiators to comparators based on age, sex, diagnosis date, and warfarin propensity score. Follow-up began on initiation date; patients were censored at discontinuation/switch of therapy, disenrollment, or end of the study. The median follow-up was 415 days. Cox regression was used to study differences in ischemic stroke risks between warfarin initiators and comparators while controlling for important prognostic factors. RESULTS: Warfarin initiators were generally similar to comparators in clinical features but had higher CHADS2 scores (1.26 versus 1.19). The first 30-day ischemic stroke rate was higher among warfarin initiators than comparators (1.47%/y (27/1836) versus 0.98%/y (18/1837); P=0.18) but lower subsequently (0.81%/y [134/16 543] versus 1.09%/y [406/37 248]; P=0.002). Multivariable regression confirmed a significant interaction between follow-up and warfarin use with the adjusted hazard ratios (95% confidence intervals) for warfarin/comparator as 1.46 (0.80-2.65) in the first 30 days and 0.70 (0.57-0.85) afterward. CONCLUSIONS: Warfarin effect was qualitatively different in the first 30 days after initiation than subsequently. This is consistent with a modest increase in stroke risk occurring briefly after starting warfarin.

Effect of Race and Ethnicity on Antihypertensive Medication Utilization Among Women in the United States: Study of Women's Health Across the Nation (SWAN).

BACKGROUND: Antihypertensive medication use may vary by race and ethnicity. Longitudinal antihypertensive medication use patterns are not well described in women. METHODS AND RESULTS: Participants from the Study of Women's Health Across the Nation (SWAN), a prospective cohort of women (n=3302, aged 42-52), who reported a diagnosis of hypertension or antihypertensive medication use at any annual visit were included. Antihypertensive medications were grouped by class and examined by race/ethnicity adjusting for potential confounders in logistic regression models. A total of 1707 (51.7%) women, mean age 50.6 years, reported hypertension or used antihypertensive medications at baseline or during follow-up (mean 9.1 years). Compared with whites, blacks were almost 3 times as likely to receive a calcium channel blocker (odds ratio, 2.92; 95% CI, 2.24-3.82) and twice as likely to receive a thiazide diuretic (odds ratio, 2.38; 95% CI, 1.93-2.94). Blacks also had a higher probability of reporting use of ≥2 antihypertensive medications (odds ratio, 1.95; 95% CI, 1.55-2.45) compared with whites. Use of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers and thiazide diuretics increased over time for all racial/ethnic groups. Contrary to our hypothesis, rates of ß-blocker usage did not decrease over time. CONCLUSIONS: Among this large cohort of multiethnic midlife women, use of antihypertensive medications increased over time, with angiotensin-converting enzyme inhibitors/angiotensin receptor blockers becoming the most commonly used antihypertensive medication, even for blacks. Thiazide diuretic utilization increased over time for all race/ethnic groups as did use of calcium channel blockers among blacks; both patterns are in line with guideline recommendations for the management of hypertension.

Duration of the menopausal transition is longer in women with young age at onset: the multiethnic Study of Women's Health Across the Nation.

OBJECTIVE: The menopausal transition (MT) is a critical period associated with physiologic changes that influence women's long-term health and longevity. Information is, however, limited regarding factors that influence age at the onset of the MT and its duration (ie, time from MT onset to the final menstrual period). METHODS: We analyzed data for 1,145 women from four sites of the Study of Women's Health Across the Nation who participated in the menstrual calendar substudy, had the start of the MT identified, and had no missing covariate information. Participants included from four racial/ethnic groups: African American, white, Chinese, and Japanese. Women completed daily menstrual calendars from 1996 to 2006 and questions on hormone therapy use monthly. Baseline measures included education, economic strain, and menstrual cycle characteristics. Annual measures included height, weight, and smoking status. Cox proportional hazards models were used to analyze the data. RESULTS: The adjusted median duration of the MT ranged from 4.37 years among the oldest age-at-onset quartile to 8.57 years among the youngest age-at-onset quartile (P < 0.001). Cigarette smoking was associated with an earlier onset (P < 0.001) and a shorter duration (P < 0.001). African American women had a longer duration (P = 0.012) than white women. Body mass index was associated with a later onset of the MT (P = 0.001) but not its duration. CONCLUSIONS: The duration of the MT was largely influenced by the age at which it began: earlier onset was associated with a longer transition. This finding provides a strong rationale for developing improved markers of the onset of the early MT.

Longitudinal analysis of changes in weight and waist circumference in relation to incident vasomotor symptoms: the Study of Women's Health Across the Nation (SWAN).

OBJECTIVE: Greater body mass index (BMI) and body fat are associated with vasomotor symptoms (VMS). Thus, weight loss may prevent VMS. We analyzed whether concurrent BMI or waist circumference and/or changes in weight or waist circumference predicted incident VMS and whether these relations differed by menopause stage or race/ethnicity. METHODS: Data from 10 follow-up visits for 1,546 participants in the Study of Women's Health Across the Nation who reported no VMS at baseline were modeled for time to first symptomatic visit in relation to concurrent BMI and waist circumference and change in weight and waist circumference during early and late menopause using discrete survival analyses, adjusting for covariates. RESULTS: Greater concurrent BMI and waist circumference were significantly related to greater any and frequent (≥6 d in the last 2 wk) incident VMS in early menopause and lower VMS risk in late menopause. Percentage weight change since baseline and since the prior visit was unrelated to incident any VMS in either menopause stage. Percentage weight change since baseline had a significant shallow U-shaped association with incident frequent VMS in early menopause (P = 0.02), a shallow inverse U-shape in late menopause (P = 0.02), and a significant interaction with menopause stage (P = 0.004) but not with race/ethnicity. Recent weight change was unassociated with incident VMS in either menopause stage. Results were similar for waist change. CONCLUSIONS: Concurrent BMI and waist circumference were positively related to incident VMS in early menopause and negatively related in late menopause. Maintaining healthy weight in early menopause may help prevent VMS.

Change in sexual functioning over the menopausal transition: results from the Study of Women's Health Across the Nation.

OBJECTIVE: The aim of the study was to identify whether there is a decline in sexual functioning related to the menopausal transition or to hysterectomy. METHODS: In a cohort of 1,390 women aged 42 to 52, with intact uterus and at least one ovary, not using hormone therapy, and pre- or early perimenopausal at baseline, we fit piecewise linear growth curves to 5,798 repeated measurements (seven visits spanning 14.5 y) of a sexual functioning score (range, 5-25) as a function of time relative to date of final menstrual period (FMP) or hysterectomy. RESULTS: Mean sexual functioning at baseline in women with a dateable FMP was 18.0 (SD, 3.4). There was no change in sexual function until 20 months before the FMP. From 20 months before until 1 year after the FMP, sexual function decreased by 0.35 annually (95% CI, -0.44 to -0.26) and continued to decline more than 1 year after the FMP, but at a slower rate (-0.13 annually, 95% CI, -0.17 to -0.10). The decline was smaller in African Americans and larger in Japanese than whites. Vaginal dryness, lubricant use, depressive symptoms, or anxiety did not explain decline in sexual function. Women who had a hysterectomy before the FMP did not show a decline in sexual function before hysterectomy, but scores declined afterward (0.21 annually, 95% CI, -0.28 to -0.14). CONCLUSIONS: Decline in sexual function became apparent 20 months before FMP and slowed 1 year after FMP through 5 years afterward. A decline in sexual function was observed immediately after hysterectomy and persisted for the 5 years of observation.

Characterizing the trajectories of vasomotor symptoms across the menopausal transition.

OBJECTIVE: The aim of the study was to investigate the heterogeneity of temporal patterns of vasomotor symptoms (VMS) over the menopausal transition and identify factors associated with these patterns in a diverse sample of women. METHODS: The Study of Women's Health Across the Nation is a multisite longitudinal study of women from five racial/ethnic groups transitioning through the menopause. The analytic sample included 1,455 women with nonsurgical menopause and a median follow-up of 15.4 years. Temporal patterns of VMS and associations with serum estradiol and follicle-stimulating hormone, race/ethnicity, body mass index, and demographic and psychosocial factors were examined using group-based trajectory modeling. RESULTS: Four distinct trajectories of VMS were found: onset early (11 years before the final menstrual period) with decline after menopause (early onset, 18.4%), onset near the final menstrual period with later decline (late onset, 29.0%), onset early with persistently high frequency (high, 25.6%), and persistently low frequency (low, 27.0%). Relative to women with persistently low frequency of VMS, women with persistently high and early onset VMS had a more adverse psychosocial and health profile. Black women were overrepresented in the late onset and high VMS subgroups relative to white women. Obese women were underrepresented in the late onset subgroup. In multivariable models, the pattern of estradiol over the menopause was significantly associated with the VMS trajectory. CONCLUSIONS: These data distinctly demonstrate heterogeneous patterns of menopausal symptoms that are associated with race/ethnicity, reproductive hormones, premenopause body mass index, and psychosocial characteristics. Early targeted intervention may have a meaningful impact on long-term VMS.

Trajectories of estradiol and follicle-stimulating hormone over the menopause transition and early markers of atherosclerosis after menopause.

AIM: The purpose of this study was to assess associations between distinct patterns of circulating estradiol (E2) and follicle-stimulating hormone (FSH) over the menopause transition (MT) and subclinical measures of atherosclerosis after menopause. METHODS AND RESULTS: Four temporal patterns of E2 decline (Low: low before and after final menstrual period (FMP); Medium: medium before and high after FMP; High-early decline: high prior to FMP and early decline thereafter; High-late decline: high prior to FMP and late decline thereafter) and three of FSH rise (Low, Medium, High) over 9.6 years across FMP were identified and linked to carotid intima-media-thickness (IMT), adventitial diameter (AD), and presence of carotid plaque (cPlaque) measured after menopause at the 12th annual visit (visit 12). Participants were 856 women (age at visit 12 = 59.5 ± 2.7 years) from the Study of Women's Health Across the Nation (SWAN), who never reported a stroke or a heart attack. In models adjusted for visit 12 or baseline cardiovascular disease (CVD) risk factors, odds of having any cPlaque were ∼43% lower among women with the High-early decline E2 trajectory compared to women with the Low E2 trajectory. In contrast, women with the Medium E2 trajectory had significantly higher IMT than those with the Low E2 trajectory adjusting for visit 12 CVD risk factors. Interestingly, adjusting for baseline CVD risk factors attenuated this association. The Low FSH group had lower IMT than the Medium and High FSH groups (p ≤ 0.05) in all models. CONCLUSION: During MT, women are subjected to hormonal alterations that could potentially increase their risk of developing CVD after menopause.

Varying patterns of brachial artery flow-mediated dilatation in women with polycystic ovary syndrome and controls: An application of the group-based trajectory modeling.

PURPOSE: To identify changing patterns of absolute change in brachial artery lumen diameter (LD) after reactive hyperemia in women with polycystic ovary syndrome (PCOS) and controls and to quantify the association of PCOS status and participants' factors with these patterns. METHODS: Brachial flow-mediated dilation was measured in 128 women with PCOS and 148 controls aged 30-60 years. Group-based trajectory modeling was used to investigate absolute change in LD every 30 seconds for 2 minutes after occluding cuff deflation. Multinomial logistic regression was used to identify factors associated with trajectories. RESULTS: Three patterns emerged, namely nondilators (42.2%), dilators (44.6%), and enhanced dilators (13.0%). The proportion of women with PCOS did not differ across groups. Independently of age and PCOS status, larger baseline LD (odds ratio; 95% confidence interval: 2.51; 1.29, 4.89) and lower insulin levels (0.70; 0.52, 0.93) were associated with nondilators rather than with dilators. Higher total cholesterol was associated with dilators in women with PCOS but with nondilators in controls. CONCLUSIONS: Trajectory modeling identified distinct patterns of change in LD and factors associated with the endothelial response. This method may be a useful tool to understand the brachial flow-mediated vasodilator response.

Ectopic adiposity is associated with autonomic risk factors and subclinical cardiovascular disease in young adults.

OBJECTIVE: To examine the relationship between ectopic adiposity and markers of cardiometabolic risk, autonomic control, and subclinical cardiovascular disease (CVD). METHODS: Cross-sectional analyses were performed in 324 subjects with overweight and obesity. Single-slice CT images were analyzed to calculate thigh muscle attenuation (MA), a measure of ectopic adiposity. Autonomic control was assessed using low-frequency to respiratory-frequency heart rate variability (LFa/RFa ratio). Carotid intima-media thickness (IMT) was a marker of subclinical CVD. RESULTS: Among overweight participants, those with low MA had lower HDL-c, higher LFa/RFa ratio, and subcutaneous thigh fat compared to high MA individuals despite no difference in visceral fat or insulin resistance. Significant associations were not observed in the class I obese group. In the class II obese group, those with high MA had higher triglycerides and insulin levels, yet there was no difference in visceral fat compared to the low MA group. Mean IMT was significantly higher in the low MA compared to the high MA overweight group (0.63 mm vs. 0.58 mm, P = 0.04) but was similar between the low and high MA class II obese groups. CONCLUSIONS: Excess ectopic adiposity in muscle tissue is associated with metabolic and autonomic risk factors and subclinical CVD, most notably in overweight individuals, independent of insulin resistance and visceral abdominal fat.

Nulliparity is associated with less healthy markers of subclinical cardiovascular disease in young women with overweight and obesity.

OBJECTIVE: Higher parity is associated with increased subclinical cardiovascular disease (CVD) in mid-life and older women and with increased CVD risk overall. The relationship between parity, subclinical CVD, and infertility in young women with overweight and obesity has been infrequently evaluated. METHODS: Reproductive histories were obtained in 191 (66%) young women with overweight and obesity (BMI 25-39.9 kg/m(2) ) participating in a weight loss trial. Baseline carotid intima-media thickness (IMT) and inter-adventitial diameter (IAD) were assessed via B-mode ultrasound. Linear regression was used to estimate the relationship between parity and carotid measures, adjusted for demographic, cardiovascular, and reproductive risk factors. RESULTS: Nulliparous women (n = 70, age 34.9 ± 7.1) had increased common carotid IAD (0.230 mm, SE 0.08, P = 0.003) and mean common carotid artery (CCA) IMT (0.031 mm, SE 0.01, P = 0.007) compared with parous women (n = 102, age 39.5 ± 4.9), persisting after adjustment for age, race, and CVD risk factors. No other reproductive factors were statistically significantly associated. CONCLUSIONS: Nulliparity is associated with markers of less healthy carotid arteries in a sample of disease-free 25- to 45-year-old women with overweight or obesity. This may represent a beneficial effect of pregnancy or indicate overall better health in women with overweight/obesity who are capable of childbearing.

Duration of menopausal vasomotor symptoms over the menopause transition.

IMPORTANCE: The expected duration of menopausal vasomotor symptoms (VMS) is important to women making decisions about possible treatments. OBJECTIVES: To determine total duration of frequent VMS (≥ 6 days in the previous 2 weeks) (hereafter total VMS duration) during the menopausal transition, to quantify how long frequent VMS persist after the final menstrual period (FMP) (hereafter post-FMP persistence), and to identify risk factors for longer total VMS duration and longer post-FMP persistence. DESIGN, SETTING, AND PARTICIPANTS: The Study of Women's Health Across the Nation (SWAN) is a multiracial/multiethnic observational study of the menopausal transition among 3302 women enrolled at 7 US sites. From February 1996 through April 2013, women completed a median of 13 visits. Analyses included 1449 women with frequent VMS. MAIN OUTCOMES AND MEASURES: Total VMS duration (in years) (hot flashes or night sweats) and post-FMP persistence (in years) into postmenopause. RESULTS: The median total VMS duration was 7.4 years. Among 881 women who experienced an observable FMP, the median post-FMP persistence was 4.5 years. Women who were premenopausal or early perimenopausal when they first reported frequent VMS had the longest total VMS duration (median, >11.8 years) and post-FMP persistence (median, 9.4 years). Women who were postmenopausal at the onset of VMS had the shortest total VMS duration (median, 3.4 years). Compared with women of other racial/ethnic groups, African American women reported the longest total VMS duration (median, 10.1 years). Additional factors related to longer duration of VMS (total VMS duration or post-FMP persistence) were younger age, lower educational level, greater perceived stress and symptom sensitivity, and higher depressive symptoms and anxiety at first report of VMS. CONCLUSIONS AND RELEVANCE: Frequent VMS lasted more than 7 years during the menopausal transition for more than half of the women and persisted for 4.5 years after the FMP. Individual characteristics (eg, being premenopausal and having greater negative affective factors when first experiencing VMS) were related to longer-lasting VMS. Health care professionals should counsel women to expect that frequent VMS could last more than 7 years, and they may last longer for African American women.

Trajectory clustering of estradiol and follicle-stimulating hormone during the menopausal transition among women in the Study of Women's Health across the Nation (SWAN).

CONTEXT: Variability in the pattern of change in estradiol (E2) and FSH levels over the menopause transition has not been well defined. OBJECTIVE: The current study aimed to determine whether different trajectories of E2 and FSH could be identified and whether race/ethnicity and body mass index were related to the different trajectories. DESIGN: The Study of Women's Health Across the Nation is a longitudinal observational study of the menopausal transition. SETTING: Women aged 42-52 yr from seven participating sites were recruited and underwent up to 11 annual visits. PARTICIPANTS: Postmenopausal women with 12 or more months of amenorrhea that was not due to hysterectomy/oophorectomy and who were not using hormone therapy before the final menstrual period participated in the study. MAIN OUTCOME MEASURES: Annual serum E2 and FSH levels anchored to final menstrual period were measured. RESULTS: Four distinct E2 trajectories and three distinct FSH trajectories were identified. The E2 trajectories were: slow decline (26.9%), flat (28.6%), rise/slow decline (13.1%), and rise/steep decline (31.5%). The FSH trajectories were: low (10.6%), medium (48.7%), and high (41.7%) rising patterns. Obesity increased the likelihood of a flat E2 and low FSH trajectory for all race/ethnic groups. Normal-weight Caucasian and African-American women tended to follow the rise/steep decline E2 and high FSH trajectories. Normal-weight Chinese/Japanese women tended to follow the slow decline E2 and the high/medium FSH trajectories. CONCLUSIONS: E2 and FSH trajectories over the menopausal transition are not uniform across the population of women. Race/ethnicity and body mass index affect the trajectory of both E2 and FSH change over the menopausal transition.

Do changes in sex steroid hormones precede or follow increases in body weight during the menopause transition? Results from the Study of Women's Health Across the Nation.

CONTEXT: Whether menopause-related changes in sex steroids account for midlife weight gain in women or whether weight drives changes in sex steroids remains unanswered. OBJECTIVE: The objective of the study was to characterize the potential reciprocal nature of the associations between sex hormones and their binding protein with waist circumference in midlife women. DESIGN, SETTING, AND PARTICIPANTS: The study included 1528 women (mean age 46 yr) with 9 yr of follow-up across the menopause transition from the observational Study of Women's Health Across the Nation. MAIN OUTCOME MEASURES: Waist circumference, SHBG, testosterone, FSH, and estradiol were measured. RESULTS: Current waist circumference predicted future SHBG, testosterone, and FSH but not vice versa. For each SD higher current waist circumference, at the subsequent visit SHBG was lower by 0.04-0.15 SD, testosterone was higher by 0.08-0.13 SD, and log(2) FSH was lower by 0.15-0.26 SD. Estradiol results were distinct from those above, changing direction across the menopause transition. Estradiol and waist circumference were negatively associated in early menopausal transition stages and positively associated in later transition stages (for each SD higher current waist circumference, future estradiol was lower by 0.15 SD in pre- and early perimenopause and higher by 0.38 SD in late peri- and postmenopause; P for interaction <0.001). In addition, they appeared to be reciprocal, with current waist circumference associated with future estradiol and current estradiol associated with future waist circumference. However, associations in the direction of current waist circumference predicting future estradiol levels were of considerably larger magnitude than the reverse. CONCLUSIONS: These Study of Women's Health Across the Nation data suggest that the predominant temporal sequence is that weight gain leads to changes in sex steroids rather than vice versa.

Breastfeeding and subsequent maternal visceral adiposity.

Women gain visceral fat during pregnancy. Studies examining the impact of breastfeeding on maternal body composition are inconclusive. We examined the extent to which breastfeeding was associated with visceral adiposity in a sample of US women. This was a cross-sectional analysis of 351 women aged 45-58 years, who were free of clinical cardiovascular disease and had not used oral contraceptives or hormone replacement therapy in the 3 months prior to enrollment in the Study of Women's Health Across the Nation (SWAN)-Heart Study (2001-2003). History of breastfeeding was self-reported. Computed tomography was used to assess abdominal adiposity. Among premenopausal/early-peri-menopausal mothers, those who never breastfed had 28% greater visceral adiposity (95% confidence interval (CI): 11-49, P = 0.001), 4.7% greater waist-hip ratio (95% CI: 1.9-7.4, P < 0.001), and 6.49 cm greater waist circumference (95% CI: 3.71-9.26, P < 0.001) than mothers who breastfed all of their children for ≥3 months in models adjusting for study site; age; parity; years since last birth; socioeconomic, lifestyle, and family history variables; early adult BMI; and current BMI. In comparison to women who were nulliparous, mothers who breastfed all of their children for ≥3 months had similar amounts of visceral fat (P > 0.05). In contrast, premenopausal/early-peri-menopausal mothers who had never breastfed had significantly greater visceral adiposity (42% (95% CI: 17-70), P < 0.001), waist circumference (6.15 cm (95% CI: 2.75-9.56), P < 0.001), and waist-hip ratio (3.7% (95% CI: 0.69-6.8), P = 0.02) than nulliparous women. No significant relationships were observed among late peri-menopausal/postmenopausal women. In conclusion, until menopause, mothers who did not breastfeed all of their children for ≥3 months exhibit significantly greater amounts of metabolically active visceral fat than mothers who had breastfed all of their children for ≥3 months.

Adherence and persistence with duloxetine and hospital utilization in patients with major depressive disorder.

The aim of this study was to examine the association between duloxetine adherence/persistence and hospital utilization. In a managed care claims database, 8521 patients with a major depressive disorder diagnosis were initiated on duloxetine in 2006. Patients had no active duloxetine prescription for 6 months before initiation and had continuous enrollment for 12 months preinitiation and postinitiation. Adherence was defined as medication possession ratio of 0.8 or more, and persistence was defined as the duration of therapy without exceeding a 30-day gap. Logistic regression and negative binominal regression were conducted. Overall, 55.8% of patients were adherent and the average duration of duloxetine therapy was 118.4 days within 6 months after initiation. Adherent patients had significantly lower rates of hospitalization (19.7 vs. 23.4%, P<0.0001) and emergency room visits (30.6 vs. 36.9%, P<0.0001) than nonadherent patients. Hospitalization and emergency room visits were significantly reduced with treatment persistence (P<0.0001). After adjustment for demographics, comorbidities, and prior hospitalization, adherence was associated with reduced hospitalization (odds ratio=0.86) and emergency room visits (odds ratio=0.80). Patients on duloxetine of more than 90 days, compared with less than 31 days, were 16% less likely to be hospitalized and 22% less likely to have emergency room visits. Duloxetine adherence and persistence appear to be associated with reduced hospital utilization in the 1-year follow-up period.

Lactation and maternal measures of subclinical cardiovascular disease.

OBJECTIVE: To examine the relationship between lactation and subclinical cardiovascular disease in a population free of clinical cardiovascular disease. METHODS: We conducted a cross-sectional analysis of 297 women who reported at least one live birth on enrollment in the Study of Women Across the Nation-Heart Study. Participants were mothers aged 45-58 years who were free of clinical cardiovascular disease. History of lactation was self-reported. Electron beam tomography was used to assess coronary and aortic calcification. B-mode ultrasonography was used to assess carotid adventitial diameter, intima-media thickness, and carotid plaque. Multivariable linear and logistic regression models were used to estimate whether lactation was independently associated with markers of subclinical cardiovascular disease. RESULTS: In unadjusted models, compared with mothers who had breastfed all of their children for at least 3 months, mothers who had not breastfed were more likely to have coronary artery calcification (17% compared with 32%), aortic calcification (17% compared with 39%), carotid plaque (10% compared with 18%), and larger carotid adventitial diameters (mean+/-standard deviation 6.63+/-0.59 compared with 6.87+/-0.60 mm). After adjusting for measures of socioeconomic status and lifestyle and family history variables, mothers who had not breastfed remained more likely to have aortic calcification (odds ratio [OR] 3.85, 95% confidence interval [CI] 1.47-10.00) and coronary artery calcification (OR 2.78, 95% CI 1.05-7.14) than mothers who had consistently breastfed. After further adjustment for body mass index and traditional risk factors for cardiovascular disease, mothers who had not breastfed remained more likely to have aortic calcification than mothers who had consistently breastfed (OR 5.26, 95% CI 1.47-20.00). CONCLUSION: Mothers who do not breastfeed their infants seem to be at increased risk of vascular changes associated with future cardiovascular disease. LEVEL OF EVIDENCE: II.