Abstract P377: Oral Estrogen Hormone Therapy Use after Incident Venous Thrombosis and the Risk of Recurrence

Circulation ◽  
2014 ◽  
Vol 129 (suppl_1) ◽  
Author(s):  
Laura B Harrington ◽  
Kerri L Wiggins ◽  
Marc Blondon ◽  
James S Floyd ◽  
Joshua C Bis ◽  
...  

Background: Oral estrogen hormone therapy (HT) is associated with a 2-fold increased risk of incident venous thrombosis (VT). Patterns of HT use following an incident VT and the association between HT use and recurrence are poorly characterized. Objectives: We aimed: (1) to characterize the use of oral estrogen HT in the 5 months following a first VT event; and (2) to evaluate whether the use of HT following an incident VT is associated with VT recurrence. Methods: In Group Health Cooperative (GHC), an integrated health care system, we identified an inception cohort of women aged 40-89 who experienced an incident VT from 2002 to 2010 (n=1,121). Using medical record review, we followed participants for VT recurrence, defined by physician diagnosis >2 weeks after the incident VT with clinical and/or imaging evidence of a new or expanded clot. HT use at 80% compliance was defined using GHC computerized pharmacy data. Characterization of HT use was restricted to women who survived for ≥5 months. Cox proportional hazards models were used to evaluate the association between time-varying current HT use and risk of recurrent VT, adjusting for race, baseline age, BMI, idiopathic incident VT, diabetes status, and the following time-varying covariates: cancer, CVD, and current anticoagulation use. In primary analyses, time was defined as days since incident event and censoring occurred at last follow-up or death. To evaluate the influence of possible HT misclassification soon after the incident event, we conducted 2 sensitivity analyses in which women entered the risk set after 30 and 60 days post-incident VT. Additional secondary Cox analyses were restricted to current HT users at the time of incident VT. Results: Of women who survived ≥5 months post-incident VT (n=993), 12% used oral estrogen HT at time of the incident event (n=123); among these, 90 (73%) discontinued use whereas 33 (27%) continued to fill ≥1 HT prescription within the next 5 months. Compared with users who stopped HT, persistent users were on average older (70 vs. 65 years), had a lower BMI (29 vs. 32 kg/m 2 ), and were less likely to have experienced an incident PE as part of their first VT event (27% vs. 61%). Over an average follow-up of 3.4 years, we identified 164 recurrent VTs among 1,121 women. We found no evidence of an association between HT use after incident VT and VT recurrence risk, adjusted for confounders (HR=0.73; 95% CI: 0.26-1.99; p=0.53); no evidence of an association was found in sensitivity or secondary analyses. Conclusions: In this population of GHC enrollees, over one-quarter of oral estrogen HT users at VT incidence continued use and filled subsequent HT prescriptions in the 5 months following the incident event. We found no evidence of an association between post-event HT use and the risk of VT recurrence, however, the number of HT users in our population was small.

2019 ◽  
Vol 188 (8) ◽  
pp. 1484-1492 ◽  
Author(s):  
Stella Koutros ◽  
Jay H Lubin ◽  
Barry I Graubard ◽  
Aaron Blair ◽  
Patricia A Stewart ◽  
...  

Abstract We extended the mortality follow-up of a cohort of 25,460 workers employed at 8 acrylonitrile (AN)-producing facilities in the United States by 21 years. Using 8,124 deaths and 1,023,922 person-years of follow-up, we evaluated the relationship between occupational AN exposure and death. Standardized mortality ratios (SMRs) based on deaths through December 31, 2011, were calculated. Work histories and monitoring data were used to develop quantitative estimates of AN exposure. Hazard ratios were estimated by Cox proportional hazards regression. All-cause mortality and death from total cancer were less than expected compared with the US population. We observed an excess of death due to mesothelioma (SMR = 2.24, 95% confidence interval (CI): 1.39, 3.42); no other SMRs were elevated overall. Cox regression analyses revealed an elevated risk of lung and bronchial cancer (n = 808 deaths; for >12.1 ppm-year vs. unexposed, hazard ratio (HR) = 1.43, 95% CI: 1.13, 1.81; P for trend = 0.05), lagged 10 years, that was robust in sensitivity analyses adjusted for smoking and co-exposures including asbestos. Death resulting from bladder cancer (for >2.56 ppm vs. unexposed, lagged 10-year HR = 2.96, 95% CI: 1.38, 6.34; P for trend = 0.02) and pneumonitis (for >3.12 ppm-year vs. unexposed, HR = 4.73, 95% CI: 1.42, 15.76; P for trend = 0.007) was also associated with AN exposure. We provide additional evidence of an association between AN exposure and lung cancer, as well as possible increased risk for death due to bladder cancer and pneumonitis.


Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 1626-1626
Author(s):  
Mary Cushman ◽  
Ellen O’Meara ◽  
Aaron R. Folsom ◽  
Susan R. Heckbert ◽  
Neil Zakai ◽  
...  

Abstract Background: Obesity is associated with an increased risk of venous thrombosis (VT), however little is known about which components of obesity are important. Proposed hypotheses include an association of adipocyte products with hemostatic imbalance, increased body or leg size impairing venous return, increased inflammation, and differences in venous vessel walls in obese persons. We studied the associations of measures of body size and composition with risk of VT in the LITE study. Methods: The LITE is a prospective study evaluating VT risk factors in 21,680 participants aged 45–100, in the Atherosclerosis Risk in Communities (ARIC) study and the Cardiovascular Health Study (CHS). Baseline body size measures were obtained using standardized methods and bioelectric impedance was used to calculate fat and fat-free mass in CHS participants. 729 participants reporting prebaseline VT or baseline warfarin use were excluded. VT events during 12.6 years of follow up were validated by medical record review and classified as idiopathic or secondary. Body size measures were evaluated as risk factors using Cox proportional hazards models, adjusting for age, sex, race and diabetes status. Results: There were 451 VT events during follow-up (1.8 per 1000 person-years); 182 were idiopathic, 315 were deep vein thrombosis (DVT) and 136 pulmonary embolus (PE) +/− DVT. All body size measures were associated with increased risk of VT (table), with height having the weakest association. Those with severe obesity (body-mass index above 40 kg/m2) were at the highest risk, with a nearly 3-fold increased risk compared to those of normal weight. Both fat and fat-free mass were risk factors. Conclusion: In this prospective study, multiple measures of body size, and measures of body composition including fat and non-fat components, were risk factors for VT. Findings suggest a multicausal pathogenesis for obesity-related thrombosis. Further study is required to determine reasons for the association of body size and composition with VT. Relative Risk of VT by Body Size Categories (Quartiles (Q) Except when Noted; lowest quartile is the reference group) Q1 Q2 Q3 Q4 * P <0.05; ** categories are <25, 25–20, 30–40, >40 kg/m2 Body-mass index** 1.0 (reference) 1.3* 2.1* 2.9* Weight 1.0 (ref) 1.2 1.5* 2.5* Height 1.0 (ref) 1.1 1.2 1.4* Waist-hip ratio 1.0 (ref) 1.3 1.5* 1.6* Waist Circumference 1.0 (ref) 1.2 1.3 2.1* Hip Circumference 1.0 (ref) 1.3* 1.5* 2.2* Calf Circumference 1.0 (ref) 1.3 2.0* 2.3* Fat-Free Mass 1.0 (ref) 1.2 1.4 1.9* Fat Mass 1.0 (ref) 1.1 0.8 1.7*


2016 ◽  
Vol 34 (2_suppl) ◽  
pp. 92-92
Author(s):  
Antonio Finelli ◽  
Narhari Timilshina ◽  
Maria Komisarenko ◽  
Robert Sowerby ◽  
Robert James Hamilton ◽  
...  

92 Background: The role of 5α-reductase inhibitors (5-ARIs) in prostatic diseases remains controversial because of an FDA black box label. We have previously published on the impact of 5-ARIs in men managed with active surveillance (AS), demonstrating their protective effect against progression. However, the long-term safety of 5-ARIs in the setting of AS has never been described, thus we sought to assess this. Methods: This is a single-institution, prospectively maintained, retrospective cohort study comparing men taking a 5-ARI versus no 5-ARI while on AS for PCa. Pathologic progression was evaluated and defined as Gleason score > 6, maximum core involvement > 50%, or more than 3 cores positive on a follow-up prostate biopsy. Time dependent covariate analysis to account for time on AS but not on 5-ARI was conducted to diminish the likelihood of overestimating the benefit. To account for differences in prostate volume at baseline between 5-ARI and non-5-ARI groups sensitivity analyses were performed, restricting men in the non-5-ARI group to those with larger glands (volume > 40 ml). Kaplan-Meier analyses were conducted along with multivariable Cox proportional hazard regression modeling for predictors of pathologic progression. Results: The original cohort of 288 men on AS were analyzed. The median follow-up was 61.2 months (IQR: 29.8-95.24) with 124 men (43%) experiencing pathologic progression and 119 men (41.3%) abandoning AS. Men taking a 5-ARI experienced a lower rate of pathologic progression (24.3% vs 49.1%; p < 0.001) and were less likely to abandon AS (25.7% vs 46.3%; p = 0.002). On multivariable Cox proportional hazards analysis, lack of 5-ARI use was most strongly associated with pathologic progression (HR: 2.56; 95% confidence interval, 1.32-5.02). Sensitivity analyses done to account for gland size demonstrated that lack of 5-ARI use was still predictive of progression (HR: 2.76; CI, 1.45–5.25; p = 0.002). Importantly, 5-ARI use was not associated with increased risk of high-grade prostate cancer. Conclusions: 5-ARIs were associated with a significantly lower rate of pathologic progression and abandonment of AS in men with median follow-up of 5 years.


Author(s):  
Yuko Yamaguchi ◽  
Marta Zampino ◽  
Toshiko Tanaka ◽  
Stefania Bandinelli ◽  
Yusuke Osawa ◽  
...  

Abstract Background Anemia is common in older adults and associated with greater morbidity and mortality. The causes of anemia in older adults have not been completely characterized. Although elevated circulating growth and differentiation factor 15 (GDF-15) has been associated with anemia in older adults, it is not known whether elevated GDF-15 predicts the development of anemia. Methods We examined the relationship between plasma GDF-15 concentrations at baseline in 708 non-anemic adults, aged 60 years and older, with incident anemia during 15 years of follow-up among participants in the Invecchiare in Chianti (InCHIANTI) Study. Results During follow-up, 179 (25.3%) participants developed anemia. The proportion of participants who developed anemia from the lowest to highest quartile of plasma GDF-15 was 12.9%, 20.1%, 21.2%, and 45.8%, respectively. Adults in the highest quartile of plasma GDF-15 had an increased risk of developing anemia (Hazards Ratio 1.15, 95% Confidence Interval 1.09, 1.21, P&lt;.0001) compared to those in the lower three quartiles in a multivariable Cox proportional hazards model adjusting for age, sex, serum iron, soluble transferrin receptor, ferritin, vitamin B12, congestive heart failure, diabetes mellitus, and cancer. Conclusions Circulating GDF-15 is an independent predictor for the development of anemia in older adults.


2021 ◽  
Vol 10 (7) ◽  
pp. 1514
Author(s):  
Hilde Espnes ◽  
Jocasta Ball ◽  
Maja-Lisa Løchen ◽  
Tom Wilsgaard ◽  
Inger Njølstad ◽  
...  

The aim of this study was to explore sex-specific associations between systolic blood pressure (SBP), hypertension, and the risk of incident atrial fibrillation (AF) subtypes, including paroxysmal, persistent, and permanent AF, in a general population. A total of 13,137 women and 11,667 men who participated in the fourth survey of the Tromsø Study (1994–1995) were followed up for incident AF until the end of 2016. Cox proportional hazards regression analysis was conducted using fractional polynomials for SBP to provide sex- and AF-subtype-specific hazard ratios (HRs) for SBP. An SBP of 120 mmHg was used as the reference. Models were adjusted for other cardiovascular risk factors. Over a mean follow-up of 17.6 ± 6.6 years, incident AF occurred in 914 (7.0%) women (501 with paroxysmal/persistent AF and 413 with permanent AF) and 1104 (9.5%) men (606 with paroxysmal/persistent AF and 498 with permanent AF). In women, an SBP of 180 mmHg was associated with an HR of 2.10 (95% confidence interval [CI] 1.60–2.76) for paroxysmal/persistent AF and an HR of 1.80 (95% CI 1.33–2.44) for permanent AF. In men, an SBP of 180 mmHg was associated with an HR of 1.90 (95% CI 1.46–2.46) for paroxysmal/persistent AF, while there was no association with the risk of permanent AF. In conclusion, increasing SBP was associated with an increased risk of both paroxysmal/persistent AF and permanent AF in women, but only paroxysmal/persistent AF in men. Our findings highlight the importance of sex-specific risk stratification and optimizing blood pressure management for the prevention of AF subtypes in clinical practice.


2021 ◽  
Author(s):  
C R Langton ◽  
B W Whitcomb ◽  
A C Purdue-Smithe ◽  
L L Sievert ◽  
S E Hankinson ◽  
...  

Abstract STUDY QUESTION What is the association of oral contraceptives (OCs) and tubal ligation (TL) with early natural menopause? SUMMARY ANSWER We did not observe an association of OC use with risk of early natural menopause; however, TL was associated with a modestly higher risk. WHAT IS KNOWN ALREADY OCs manipulate hormone levels, prevent ovulation, and may modify the rate of follicular atresia, while TL may disrupt the blood supply to the ovaries. These mechanisms may be associated with risk of early menopause, a condition associated with increased risk of cardiovascular disease and other adverse health outcomes. STUDY DESIGN, SIZE, DURATION We examined the association of OC use and TL with natural menopause before the age of 45 years in a population-based study within the prospective Nurses’ Health Study II (NHSII) cohort. Participants were followed from 1989 to 2017 and response rates were 85-90% for each cycle. PARTICIPANTS/MATERIALS, SETTING, METHODS Participants included 106 633 NHSII members who were premenopausal and aged 25-42 years at baseline. Use, duration and type of OC, and TL were measured at baseline and every 2 years. Menopause status and age were assessed every 2 years. Follow-up continued until early menopause, age 45 years, hysterectomy, oophorectomy, death, cancer diagnosis, or loss to follow-up. We used Cox proportional hazards models to estimate hazard ratios (HRs) and 95% CIs adjusted for lifestyle, dietary, and reproductive factors. MAIN RESULTS AND THE ROLE OF CHANCE Over 1.6 million person-years, 2579 members of the analytic cohort experienced early natural menopause. In multivariable models, the duration, timing, and type of OC use were not associated with risk of early menopause. For example, compared with women who never used OCs, those reporting 120+ months of OC use had an HR for early menopause of 1.01 (95% CI, 0.87-1.17; P for trend=0.71). TL was associated with increased risk of early menopause (HR = 1.17, 95% CI, 1.06-1.28). LIMITATIONS, REASONS FOR CAUTION Our study population is homogenous with respect to race and ethnicity. Additional evaluation of these relations in more diverse populations is important. WIDER IMPLICATIONS OF THE FINDINGS To our knowledge, this is the largest study examining the association of OC use and TL with early natural menopause to date. While TL was associated with a modest higher risk of early menopause, our findings do not support any material hazard or benefit for the use of OCs. STUDY FUNDING/COMPETING INTEREST(S) The study was sponsored by UO1CA176726 and R01HD078517 from the National Institutes of Health and Department of Health and Human Services. The work was supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development. The authors have no competing interests to report. TRIAL REGISTRATION NUMBER N/A


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Woncheol Lee ◽  
Yoosoo Chang ◽  
Hocheol Shin ◽  
Seungho Ryu

AbstractWe examined the associations of smoking status and urinary cotinine levels, an objective measure of smoking, with the development of new-onset HL. This cohort study was performed in 293,991 Korean adults free of HL who underwent a comprehensive screening examination and were followed for up to 8.8 years. HL was defined as a pure-tone average of thresholds at 0.5, 1.0, and 2.0 kHz ≥ 25 dB in both ears. During a median follow-up of 4.9 years, 2286 participants developed new-onset bilateral HL. Self-reported smoking status was associated with an increased risk of new-onset bilateral HL. Multivariable-adjusted HRs (95% CIs) for incident HL comparing former smokers and current smokers to never-smokers were 1.14 (1.004–1.30) and 1.40 (1.21–1.61), respectively. Number of cigarettes, pack-years, and urinary cotinine levels were consistently associated with incident HL. These associations were similarly observed when introducing changes in smoking status, urinary cotinine, and other confounders during follow-up as time-varying covariates. In this large cohort of young and middle-aged men and women, smoking status based on both self-report and urinary cotinine level were independently associated with an increased incidence of bilateral HL. Our findings indicate smoking is an independent risk factor for HL.


Hypertension ◽  
2014 ◽  
Vol 64 (suppl_1) ◽  
Author(s):  
Stefanie Lip

Objective: It is unclear whether new onset diabetes (NOD) is a separate entity associated with excess risk in hypertensive patients. Methods: We studied 15111 hypertensive patients with up to 40 year follow-up at the Glasgow BP Clinic database. Diabetes status was defined based on hospital admissions for any diabetes related diagnosis or prescription of anti-diabetic drugs or diabetes monitoring materials. The date at first hospital encounter either for prescription or admission was considered as the onset of diabetes. NOD was classified into early and late (diagnosis <10yrs or >10years from first clinic visit). Cause-specific outcome analysis was performed using multivariate-adjusted Cox proportional hazards (Cox-PH) models. In order to address any potential competing risk introduced due to the long follow-up period, an additional composite end point of all-cause mortality+NOD was analysed. Results: There were 2521(17%) patients with DM, of whom 2061(14%) had NOD. The incidence rate of NOD was 9.2 per 1000 person-years. Prevalence of early NOD was 898 (6%) and late NOD 1163 (8%). The total time at risk was 239,952 person-years with a median survival time of 28.04 years (IQR: 16.24-39.95). There were 5225 deaths (52% from cardiovascular causes) during the follow-up period. Independent predictors of new-onset diabetes in order of decreasing significance were baseline glucose, BMI, age, alanine transaminase, alkaline phosphatase, gamma glutamyl transpeptidase and bilirubin. Of these age, glucose, BMI and alkaline phosphatase remained top predictors for the composite outcome of NOD+all-cause death. The mortality risk was the highest in those with prevalent DM (HR=1.5[95%CI=1.2;1.9]) and lowest in those with late NOD (0.79[0.68;0.92]). Early NOD and non-diabetic subjects had similar risks. Conclusions: Indices of liver function tests predict the risk of NOD and mortality in addition to BMI and baseline glucose. The risk posed by NOD is related to duration of diabetes primarily indicating the importance of efforts to delay onset of NOD.


Circulation ◽  
2017 ◽  
Vol 135 (suppl_1) ◽  
Author(s):  
Matteo Fabbri ◽  
Kathleen Yost ◽  
Lila Finney Rutten ◽  
Sheila Manemann ◽  
Susan Weston ◽  
...  

Background: Growing evidence documents the association between low health literacy and poorer health outcomes. However, less is known about the relationship between health literacy and outcomes among patients with heart failure (HF). We examined the association of health literacy with risk of hospitalization and mortality in patients with HF. Methods: Residents in an 11-county region in southeastern Minnesota with incident HF from 1/01/2013 to 3/31/2015 were identified using the International Classification of Diseases, Ninth Revision code 428 (n=3715) and prospectively surveyed to measure health literacy using established screening questions. A total of 1992 patients returned a survey (response rate 54%); 1779 patients with complete clinical data and adequate follow up were retained for analysis. Health literacy, measured as a composite on three 5-point scales, was categorized as adequate (≤ 10) or low (> 10). Cox proportional hazards regression and Andersen-Gill models were used to determine the association of health literacy with mortality and hospitalization. Results: Among 1779 patients (mean age 74, 53% male), 10% had low health literacy. After a mean follow-up of 8±4 months, 72 deaths and 600 hospitalizations occurred. Low health literacy was associated with increased mortality and hospitalizations (Figure). After adjusting for age, sex, comorbidity, education and marital status, the hazard ratio for death and hospitalization in patients with low health literacy was 2.84 (95% CI: 1.63, 4.96) and 1.43 (95% CI: 1.04, 1.96) respectively, compared to patients with adequate health literacy. Conclusions: Low health literacy is associated with increased risk of hospitalization and death among patients with HF. Health literacy is critical to the self-management demands of living with heart failure. Evaluation of health literacy in the clinical setting may guide inventions to target patients with low literacy.


Author(s):  
Ma Cherrysse Ulsa ◽  
Xi Zheng ◽  
Peng Li ◽  
Arlen Gaba ◽  
Patricia M Wong ◽  
...  

Abstract Background Delirium is a distressing neurocognitive disorder recently linked to sleep disturbances. However, the longitudinal relationship between sleep and delirium remains unclear. This study assessed the associations of poor sleep burden, and its trajectory, with delirium risk during hospitalization. Methods 321,818 participants from the UK Biobank (mean age 58±8y[SD]; range 37-74y) reported (2006-2010) sleep traits (sleep duration, excessive daytime sleepiness, insomnia-type complaints, napping, and chronotype–a closely-related circadian measure for sleep timing), aggregated into a sleep burden score (0-9). New-onset delirium (n=4,775) was obtained from hospitalization records during 12y median follow-up. 42,291 (mean age 64±8; range 44-83y) had repeat sleep assessment on average 8y after their first. Results In the baseline cohort, Cox proportional hazards models showed that moderate (aggregate scores=4-5) and severe (scores=6-9) poor sleep burden groups were 18% (hazard ratio 1.18 [95% confidence interval 1.08-1.28], p&lt;0.001) and 57% (1.57 [1.38-1.80], p&lt;0.001), more likely to develop delirium respectively. The latter risk magnitude is equivalent to two additional cardiovascular risks. These findings appeared robust when restricted to postoperative delirium and after exclusion of underlying dementia. Higher sleep burden was also associated with delirium in the follow-up cohort. Worsening sleep burden (score increase ≥2 vs. no change) further increased the risk for delirium (1.79 [1.23-2.62], p=0.002) independent of their baseline sleep score and time-lag. The risk was highest in those under 65y at baseline (p for interaction &lt;0.001). Conclusion Poor sleep burden and worsening trajectory were associated with increased risk for delirium; promotion of sleep health may be important for those at higher risk.


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