The risk of venous thromboembolism attributed to established prothrombotic genotypes

Author(s):  
Line Holted Evensen ◽  
Carl Arne Lochen Arnesen ◽  
Frits R. Rosendaal ◽  
Maiken Elvestad Gabrielsen ◽  
Ben Michael Brumpton ◽  
...  

Background: The proportion of venous thromboembolism (VTE) events that can be attributed to established prothrombotic genotypes has been scarcely investigated in the general population. We aimed to estimate the proportion of VTEs in the population that could be attributed to established prothrombotic genotypes using a population-based case-cohort. Methods: Cases with incident VTE (n=1,493) and a randomly sampled sub-cohort (n=13,069) were derived from the Tromsø Study (1994-2012) and the Nord-Trøndelag Health (HUNT) Study (1995-2008). DNA-samples were genotyped for 17 single nucleotide polymorphism (SNPs) associated with VTE. Hazard ratios with 95% confidence intervals (CIs) were estimated in Cox regression models. Population attributable fraction (PAF) with 95% bias-corrected CIs (based on 10,000 bootstrap samples) were estimated using a cumulative model where SNPs significantly associated with VTE were added one-by-one in ranked order of the individual PAFs. Results: Six SNPs were significantly associated with VTE (rs1799963 [Prothrombin], rs2066865 [FGG], rs6025 [FV Leiden], rs2289252 [F11], rs2036914 [F11] and rs8176719 [ABO]. The cumulative PAF for the six-SNP model was 45.3% (95% CI 19.7-71.6) for total VTE and 61.7% (95% CI 19.6-89.3) for unprovoked VTE. The PAF for prothrombotic genotypes was higher for DVT (52.9%) than for PE (33.8%), and higher for those aged <70 years (66.1%) than for those aged ≥70 years (24.9%). Conclusions: Our findings suggest that 45-62% of all VTE events in the population can be attributed to known prothrombotic genotypes. The PAF of established prothrombotic genotypes was higher in DVT than in PE, and higher in the young than in the elderly.

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Penelope Rampersad ◽  
Susan E Bronskill ◽  
Alice Chong ◽  
Peter C Austin ◽  
Jack V Tu ◽  
...  

Introduction: Frailty is commonly encountered in elderly patients with HF. However, the impact of both frailty and HF on outcomes in the population has not been delineated. There is a need for operationalizable definitions of frailty to explore variations in care among the elderly. Objective: To assess common indicators of frailty as predictors of mortality and rehospitalisation within 1 year in a population-based study of very elderly HF patients. Methods: Community-dwelling HF patients aged >75 yrs discharged from hospital or ED in Ontario, Canada, were studied using the Enhanced Feedback for Effective Cardiac Treatment and Emergency HF Mortality Risk Grade databases. Surrogates of frailty, including dementia, falls, incontinence, immobility, caregiver dependence, and abnormal weight loss, were identified from chart abstraction and linked hospitalization records. Survival analyses were performed using multiple Cox regression, for frail vs non-frail status and for each frailty component. Results: 9964 patients were identified (age 84±5 yrs). After adjustment for age, sex, vital signs, laboratory variables, and comorbidities, presence of any frailty indicator was associated with mortality: adjusted hazard ratio [HR] 1.18 (95%CI; 1.06-1.32, p=0.003). Frailty increased the risk of readmission and the association was more pronounced than for mortality (see Figure ): adjusted HR 1.29 (95%CI; 1.18-1.41, p<.001). Among the individual frailty components, significant predictors of mortality were: dementia (HR 1.49, 95%CI; 1.34-1.64, p<.001) and care provider dependency (HR 1.17, 95%CI; 1.01-1.36, p=0.038). In contrast, other frailty components increased the risk of readmission, specifically: falls (HR 1.17, 95%CI; 1.06-1.29, p=0.003) and incontinence (HR 1.64, 95%CI; 1.18-2.29, p=0.004). Conclusion: Frailty indicators derived from clinical and administrative data sources are associated with death and readmission in a very elderly HF cohort.


2021 ◽  
pp. 1-8
Author(s):  
Charles Kassardjian ◽  
Jessica Widdifield ◽  
J. Michael Paterson ◽  
Alexander Kopp ◽  
Chenthila Nagamuthu ◽  
...  

Background: Prednisone is a common treatment for myasthenia gravis (MG), and osteoporosis is a known potential risk of chronic prednisone therapy. Objective: Our aim was to evaluate the risk of serious fractures in a population-based cohort of MG patients. Methods: An inception cohort of patients with MG was identified from administrative health data in Ontario, Canada between April 1, 2002 and December 31, 2015. For each MG patient, we matched 4 general population comparators based on age, sex, and region of residence. Fractures were identified through emergency department and hospitalization data. Crude overall rates and sex-specific rates of fractures were calculated for the MG and comparator groups, as well as rates of specific fractures. Adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox regression. Results: Among 3,823 incident MG patients (followed for a mean of 5 years), 188 (4.9%) experienced a fracture compared with 741 (4.8%) fractures amongst 15,292 matched comparators. Crude fracture rates were not different between the MG cohort and matched comparators (8.71 vs. 7.98 per 1000 patient years), overall and in men and women separately. After controlling for multiple covariates, MG patients had a significantly lower risk of fracture than comparators (HR 0.74, 95% CI 0.63–0.88). Conclusions: In this large, population-based cohort of incident MG patients, MG patients were at lower risk of a major fracture than comparators. The reasons for this finding are unclear but may highlight the importance osteoporosis prevention.


2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Tsung-Kun Lin ◽  
Jing-Yang Huang ◽  
Lung-Fa Pan ◽  
Gwo-Ping Jong

Abstract Background Some observational studies have found a significant association between the use of statin and a reduced risk of dementia. However, the results of these studies are unclear in patients with rheumatoid arthritis (RA). This study is to determine the association between the use of statins and the incidence of dementia according to sex and age-related differences in patients with RA. Methods We conducted a nationwide retrospective cohort study using the Taiwan Health Insurance Review and Assessment Service database (2003–2016). The primary outcome assessed was the risk of dementia by estimating hazard ratios (HRs) and 95% confidence intervals (CIs). Multiple Cox regression was used to estimate the adjusted hazard ratio of new-onset dementia. Subgroup analysis was also conducted. Results Among the 264,036 eligible patients with RA aged > 40 years, statin users were compared with non-statin users by propensity score matching at a ratio of 1:1 (25,764 in each group). However, no association was found between the use of statins and the risk of new-onset dementia (NOD) in patients with RA (HR: 1.01; 95% CI: 0.97–1.06). The subgroup analysis identified the use of statin as having a protective effect against developing NOD in male and older patients. Conclusion No association was observed between the use of a statin and the risk of NOD in patients with RA, including patients of both genders and aged 40–60 years, but these parameters were affected by gender and age. The decreased risk of NOD in patients with RA was greater among older male patients. Use of a statin in older male (> 60 years) patients with RA may be needed in clinical practice to prevent dementia.


2021 ◽  
Vol 79 (4) ◽  
pp. 1601-1612
Author(s):  
Johan Frederik Håkonsen Arendt ◽  
Erzsébet Horváth-Puhó ◽  
Henrik Toft Sørensen ◽  
Ebba Nexø ◽  
Lars Pedersen ◽  
...  

Background: It is controversial whether B12 deficiency causes dementia or B12 treatment can prevent dementia. Objective: To assess associations between low plasma (P-)B12 levels, B12 treatment, and risk of Alzheimer’s disease (AD; primary outcome) and all-cause or vascular dementia (secondary outcomes). Methods: We conducted a population-based cohort study using Danish registry data to assess associations between low P-B12 levels, high-dose injection or oral B12 treatment, and risk of dementia (study period 2000–2013). The primary P-B12 cohort included patients with a first-time P-B12 measurement whose subsequent B12 treatment was recorded. The secondary B12 treatment cohort included patients with a first-time B12 prescription and P-B12 measurement within one year before this prescription. For both cohorts, patients with low P-B12 levels (<200 pmol/L) were propensity score-matched 1:1 with patients with normal levels (200–600 pmol/L). We used multivariable Cox regression to compute 0–15-year hazard ratios for dementia. Results: For low P-B12 and normal P-B12 level groups, we included 53,089 patients in the primary P-B12 cohort and 13,656 patients in the secondary B12 treatment cohort. In the P-B12 cohort, hazard ratios for AD centered around one, regardless of follow-up period or treatment during follow-up. In the B12 treatment cohort, risk of AD was unaffected by low pre-treatment P-B12 levels, follow-up period and type of B12 treatment. Findings were similar for all-cause and vascular dementia. Conclusion: We found no associatio1n between low P-B12 levels and dementia. Associations were unaffected by B12 treatment. Results do not support routine screening for B12 deficiency in patients with suspected dementia.


2014 ◽  
Vol 112 (08) ◽  
pp. 255-263 ◽  
Author(s):  
Alexander T. Cohen ◽  
Luke Bamber ◽  
Stephan Rietbrock ◽  
Carlos Martinez

SummaryContemporary data from population studies on the incidence and complications of venous thromboembolism (VTE) are limited. An observational cohort study was undertaken to estimate the incidence of first and recurrent VTE. The cohort was identified from all patients in the UK Clinical Practice Research Datalink (CPRD) with additional linked information on hospitalisation and cause of death. Between 2001 and 2011, patients with first VTE were identified and the subset without active cancer-related VTE observed for up to 10 years for recurrent VTE. The 10-year cumulative incidence rates (CIR) were derived with adjustment for mortality as a competing risk event. A total of 35,373 first VTE events (12,073 provoked, 16,708 unprovoked and 6592 active cancer-associated VTE) among 26.9 million person-years of observation were identified. The overall incidence rate (IR) of VTE was 131.5 (95% CI, 130.2–132.9) per 100,000 person-years and 107.0 (95% CI, 105.8–108.2) after excluding cancer-associated VTE. DVT was more common in the young and PE was more common in the elderly. VTE recurrence occurred in 3671 (CIR 25.2%). The IR for recurrence peaked in the first six months at around 11 per 100 person years. It levelled out after three years and then remained at around 2 per 100 person years from year 4–10 of follow-up. The IRs for recurrences were particularly high in young men. In conclusion, VTE is common and associated with high recurrence rates. Effort is required to prevent VTE and to reduce recurrences.


2021 ◽  
pp. 1-10
Author(s):  
Amanda V. Bakian ◽  
Danli Chen ◽  
Chong Zhang ◽  
Heidi A. Hanson ◽  
Anna R. Docherty ◽  
...  

Abstract Background The degree to which suicide risk aggregates in US families is unknown. The authors aimed to determine the familial risk of suicide in Utah, and tested whether familial risk varies based on the characteristics of the suicides and their relatives. Methods A population-based sample of 12 160 suicides from 1904 to 2014 were identified from the Utah Population Database and matched 1:5 to controls based on sex and age using at-risk sampling. All first through third- and fifth-degree relatives of suicide probands and controls were identified (N = 13 480 122). The familial risk of suicide was estimated based on hazard ratios (HR) from an unsupervised Cox regression model in a unified framework. Moderation by sex of the proband or relative and age of the proband at time of suicide (<25 v. ⩾25 years) was examined. Results Significantly elevated HRs were observed in first- (HR 3.45; 95% CI 3.12–3.82) through fifth-degree relatives (HR 1.07; 95% CI 1.02–1.12) of suicide probands. Among first-degree relatives of female suicide probands, the HR of suicide was 6.99 (95% CI 3.99–12.25) in mothers, 6.39 in sisters (95% CI 3.78–10.82), and 5.65 (95% CI 3.38–9.44) in daughters. The HR in first-degree relatives of suicide probands under 25 years at death was 4.29 (95% CI 3.49–5.26). Conclusions Elevated familial suicide risk in relatives of female and younger suicide probands suggests that there are unique risk groups to which prevention efforts should be directed – namely suicidal young adults and women with a strong family history of suicide.


2021 ◽  
Author(s):  
Tsung-Kun Lin ◽  
Jing-Yang Huang ◽  
Lung-Fa Pan ◽  
Gwo-Ping Jong

Abstract Background: Some observational studies have found a significant association between the use of statin and a reduced risk of dementia. However, the results of these studies are unclear in patients with rheumatoid arthritis (RA). This study is to determine the association between the use of statins and the incidence of dementia according to sex and age-related differences in patients with RA.Methods: We conducted a nationwide retrospective cohort study using the Taiwan Health Insurance Review and Assessment Service database (2003–2016). The primary outcome assessed was the risk of dementia by estimating hazard ratios (HRs) and 95% confidence intervals (CIs). Multiple Cox regression was used to estimate the adjusted hazard ratio of new-onset dementia. Subgroup analysis was also conducted.Results: Among the 264,036 eligible patients with RA aged > 40 years, statin users were compared with non-statin users by propensity score matching at a ratio of 1:1 (25,764 in each group). However, no association was found between the use of statins and the risk of new-onset dementia (NOD) in patients with RA (HR: 1.01; 95%CI: 0.97–1.06). The subgroup analysis identified the use of statin as having a protective effect against developing NOD in male and older patients.Conclusion: There is no association between the use of statin and the risk of NOD in patients with RA, but these parameters are influenced by gender and age. The decreased risk of NOD in patients with RA was greater among male and older patients. The use of statin in older male patients with RA for the prevention of dementia may be needed in clinical practice.


2020 ◽  
Vol 26 ◽  
pp. 107602962095491
Author(s):  
Olivia S. Costa ◽  
Jan Beyer-Westendorf ◽  
Veronica Ashton ◽  
Dejan Milentijevic ◽  
Kenneth Todd Moore ◽  
...  

African Americans (AAs) and obese individuals have increased thrombotic risk. This study evaluated the effectiveness and safety of rivaroxaban versus warfarin in obese, AAs with nonvalvular atrial fibrillation (NVAF) or venous thromboembolism (VTE). Optum® De-Identified Electronic Health Record (EHR) data was used to perform separate propensity-score matched analyses of adult, oral anticoagulant (OAC)-naïve AAs with NVAF or acute VTE, respectively; who had a body mass index≥30kg/m2 and ≥12-months EHR activity with ≥1-encounter before OAC initiation. Cox regression was performed and reported as hazard ratios (HRs) with 95% confidence intervals (CIs). For the NVAF analysis, 1,969 rivaroxaban- and 1,969 warfarin-users were matched. Rivaroxaban was not associated with a difference in stroke/systemic embolism versus warfarin (HR = 0.88, 95%CI = 0.60-1.28), but less major bleeding (HR = 0.68, 95%CI = 0.50-0.94) was observed. Among 683 rivaroxaban-users with VTE, 1:1 matched to warfarin-users, rivaroxaban did not alter recurrent VTE (HR = 1.36, 95%CI = 0.79-2.34) or major bleeding (HR = 0.80, 95%CI = 0.37-1.71) risk versus warfarin at 6-months (similar findings observed at 3- and 12-months). Rivaroxaban appeared to be associated with similar thrombotic, and similar or lower major bleeding risk versus warfarin in these obese, AA cohorts.


Cephalalgia ◽  
2013 ◽  
Vol 34 (5) ◽  
pp. 327-335 ◽  
Author(s):  
Knut Hagen ◽  
Eystein Stordal ◽  
Mattias Linde ◽  
Timothy J Steiner ◽  
John-Anker Zwart ◽  
...  

Background Headache has not been established as a risk factor for dementia. The aim of this study was to determine whether any headache was associated with subsequent development of vascular dementia (VaD), Alzheimer’s disease (AD) or other types of dementia. Methods This prospective population-based cohort study used baseline data from the Nord-Trøndelag Health Study (HUNT 2) performed during 1995–1997 and, from the same Norwegian county, a register of cases diagnosed with dementia during 1997–2010. Participants aged ≥20 years who responded to headache questions in HUNT 2 were categorized (headache free; with any headache; with migraine; with nonmigrainous headache). Hazard ratios (HRs) for later inclusion in the dementia register were estimated using Cox regression analysis. Results Of 51,383 participants providing headache data in HUNT 2, 378 appeared in the dementia register during the follow-up period. Compared to those who were headache free, participants with any headache had increased risk of VaD ( n = 63) (multivariate-adjusted HR = 2.3, 95% CI 1.4–3.8, p = 0.002) and of mixed dementia (VaD and AD ( n = 52)) (adjusted HR = 2.0, 95% CI 1.1–3.5, p = 0.018). There was no association between any headache and later development of AD ( n = 180). Conclusion In this prospective population-based cohort study, any headache was a risk factor for development of VaD.


2017 ◽  
Vol 17 (2) ◽  
pp. 411-422 ◽  
Author(s):  
Yi-Ting Kuo ◽  
Hou-Hsun Liao ◽  
Jen-Huai Chiang ◽  
Mei-Yao Wu ◽  
Bor-Chyuan Chen ◽  
...  

Background: Pancreatic cancer is a difficult-to-treat cancer with a late presentation and poor prognosis. Some patients seek traditional Chinese medicine (TCM) consultation. We aimed to investigate the benefits of complementary Chinese herbal medicine (CHM) among patients with pancreatic cancer in Taiwan. Methods: We included all patients with pancreatic cancer who were registered in the Taiwanese Registry for Catastrophic Illness Patients Database between 1997 and 2010. We used 1:1 frequency matching by age, sex, the initial diagnostic year of pancreatic cancer, and index year to enroll 386 CHM users and 386 non-CHM users. A Cox regression model was used to compare the hazard ratios (HRs) of the risk of mortality. The Kaplan-Meier curve was used to compare the difference in survival time. Results: According to the Cox hazard ratio model mutually adjusted for CHM use, age, sex, urbanization level, comorbidity, and treatments, we found that CHM users had a lower hazard ratio of mortality risk (adjusted HR = 0.67, 95% CI = 0.56-0.79). Those who received CHM therapy for more than 90 days had significantly lower hazard ratios of mortality risk than non-CHM users (90- to 180-day group: adjusted HR = 0.56, 95% CI = 0.42-0.75; >180-day group: HR = 0.33, 95% CI = 0.24-0.45). The survival probability was higher for patients in the CHM group. Bai-hua-she-she-cao (Herba Oldenlandiae; Hedyotis diffusa Spreng) and Xiang-sha-liu-jun-zi-tang (Costus and Chinese Amomum Combination) were the most commonly used single herb and Chinese herbal formula, respectively. Conclusions: Complementary Chinese herbal therapy might be associated with reduced mortality among patients with pancreatic cancer. Further prospective clinical trial is warranted.


Sign in / Sign up

Export Citation Format

Share Document