| 1. |
- Ahmad, Abrar, et al.
(författare)
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Association between TLR9 rs5743836 polymorphism and risk of recurrent venous thromboembolism
- 2017
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Ingår i: Journal of Thrombosis and Thrombolysis. - : Springer Science and Business Media LLC. - 1573-742X .- 0929-5305. ; 44:1, s. 130-138
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Tidskriftsartikel (refereegranskat)abstract
- Recent gene knockout studies on mice have shown the role of toll-like receptor 9 (TLR9) in resolution of venous thromboembolism (VTE) through sterile inflammation. However, the role of a putative functional TLR9 polymorphism (rs5743836) in risk assessment of VTE recurrence remains unknown. The aim of our study was to investigate the TLR9 rs5743836 polymorphism in VTE patients and its association with the risk of VTE recurrence. We analyzed TLR9 rs5743836 polymorphism in Malmö thrombophilia study patients; a prospective follow-up study of 1465 VTE patients by Taqman PCR. From a total of 1465 VTE patients, those who had VTE before inclusion and those who died or had VTE recurrence during anticoagulant treatment were excluded (n = 415). Cox regression analyses were performed on the remaining 1050 VTE patients, including 126 (12.5%) patients that had recurrent VTE during follow-up period. TLR9 polymorphism was significantly associated with higher risk of VTE recurrence in female patients (HR 3.46, 95% CI 1.06-11.33) independent of acquired risk factors for VTE, family history, risk of thrombophilia and deep vein thrombosis (DVT) location. Similarly, in unprovoked VTE patients, TLR9 polymorphism was significantly associated with higher risk of VTE recurrence in female patients (HR 5.94, 95% CI 1.25-28.13) after adjusting for family history, risk of thrombophilia and DVT location. No association between TLR9 polymorphism and risk of VTE recurrence was found in male patients. Our results suggest that TLR9 rs5743836 polymorphism is an independent risk factor for VTE recurrence in female patients but not in males.
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| 2. |
- Ahmad, Abrar, et al.
(författare)
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Risk prediction of recurrent venous thromboembolism : a multiple genetic risk model
- 2019
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Ingår i: Journal of Thrombosis and Thrombolysis. - : Springer Science and Business Media LLC. - 0929-5305 .- 1573-742X. ; 47:2, s. 216-226
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Tidskriftsartikel (refereegranskat)abstract
- A single genetic biomarker is unable to accurately predict the risk for venous thromboembolism (VTE) recurrence. We aimed to: (a) develop a multiple single nucleotide polymorphisms (SNPs) model to predict the risk of VTE recurrence and (b) validate a previously described genetic risk score (GRS) and compare its performance with the model developed in this study. Twenty-two SNPs, including established and putative SNPs associated with VTE risk, were genotyped in the Malmö thrombophilia study cohort (MATS; n = 1465, follow-up ~ 10 years) by using TaqMan PCR. Out of 22-SNPs, 12 had an association with the risk of VTE recurrence and were included for calculating GRSs. The risk of VTE recurrence was calculated by stratifying patients according to number of risk alleles. In 12-SNP GRS, patients with ≥ 7 risk alleles were associated with higher risk of VTE recurrence compared to patients having ≤ 6 risk alleles. In a simplified model (8-SNP GRS), the discriminative power of 8-SNP GRS was similar to that of 12-SNP GRS based on post-test probabilities (PP). Furthermore, 8-SNP GRS further improved the risk prediction of VTE recurrence in unprovoked VTE and male patients (PP% = 15.4 vs 8.3, 17.1 vs 7.2 and 19.0 vs 7.1 for high risk groups vs low risk groups in whole population, males and unprovoked VTE patients respectively). In addition, we also validated previously described 5-SNP GRS in our cohort and found that the 8-SNP GRS performed better than the 5-SNP GRS in terms of higher PP. Our results show that a multiple SNP GRS consisting of 8-SNPs may be an effective model for prediction of VTE recurrence, particularly in unprovoked VTE and male patients.
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| 3. |
- Ahmad, Abrar, et al.
(författare)
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Thrombomodulin gene c.1418C>T polymorphism and risk of recurrent venous thromboembolism.
- 2016
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Ingår i: Journal of Thrombosis and Thrombolysis. - : Springer Science and Business Media LLC. - 1573-742X .- 0929-5305. ; 42:1, s. 135-141
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Tidskriftsartikel (refereegranskat)abstract
- Thrombomodulin gene (THBD) is a critical cofactor in protein C anticoagulant system. THBD c.1418C>T polymorphism is reported to be associated with higher risk of primary venous thromboembolism (VTE) but its role in VTE recurrence is unknown. The aim of this study was to investigate the role of THBD polymorphism in VTE recurrence. THBD c.1418C>T polymorphism was genotyped by using Taqman polymerase chain reaction in a prospective population based study of 1465 consecutive objectively verified VTE patients. Uni- and multivariate Cox regression were performed for the risk assessment of VTE recurrence. Patients who had VTE before inclusion or had recurrence or died during anticoagulant treatment were excluded. Among the remaining (N = 1046) patients, 126 (12.05 %) had VTE recurrence during the follow up period (from 1998 to 2008). THBD polymorphism was not significantly associated with risk of VTE recurrence in the univariate [Hazard ratio (HR) 1.11, 95 % confidence interval (CI) 0.78-1.59, p = 0.55] as well as the multivariate analysis adjusted for age, sex and thrombophilia (HR 1.11, 95 % CI 0.78-1.59, p = 0.54). Similarly, in unprovoked first VTE (n = 614), no association was observed between THBD polymorphism and risk of VTE recurrence (HR 1.22 and 95 % CI 0.78-1.89, p = 0.38). In this prospective study, our results do not suggest a predictive role for THBD c.1418C>T polymorphism in VTE recurrence.
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| 4. |
- Memon, Ashfaque, et al.
(författare)
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Transforming growth factor (TGF)-β levels and unprovoked recurrent venous thromboembolism.
- 2014
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Ingår i: Journal of Thrombosis and Thrombolysis. - : Springer Science and Business Media LLC. - 1573-742X .- 0929-5305. ; 38:3, s. 348-354
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Tidskriftsartikel (refereegranskat)abstract
- Prediction of recurrence in patients with unprovoked venous thromboembolism (VTE) remains a challenge. Studies of atherosclerosis suggest a protective role of transforming growth factor (TGF)-β. However, the role of TGF-β has not been studied in VTE. The aim of this study was to investigate TGF-β as a predictive marker of recurrent VTE in patients with a first episode of unprovoked VTE. Patients in the Malmö Thrombophilia Study (MATS) were followed after the discontinuation of anticoagulant treatment until the diagnosis of recurrent VTE or the end of the study in December 2008 (mean ± SD 38.5 months ± 27). Among patients with a first episode of unprovoked VTE, we identified 42 patients with recurrent VTE during the follow-up period. Two age- and sex-matched control subjects without recurrent VTE were selected for each patient (n = 84). Plasma levels of the three isoforms of TGF-β (TGF-β1, TGF-β2 and TGF-β3) were quantified simultaneously by TGF-β 3-plex immunoassay. Compared to controls, plasma levels of TGF-β1 and TGF-β2 were significantly lower in patients with recurrent VTE (p < 0.05), whereas no difference was found for TGF-β3. In a multivariate Cox regression analyses, adjusted for inherited thrombophilia, age, sex and BMI, low levels of TGF-β1 [hazard ratio (HR) = 2.2, 95 % confidence interval (CI) 1.1-4.3; p = 0.02] and TGF-β2 (HR = 2.4, 95 % CI 1.2-4.7; p = 0.01) were independently associated with a higher risk of recurrent VTE. We propose TGF-β1 and TGF-β2 as potential predictive markers for recurrence in patients with unprovoked VTE.
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| 5. |
- Nymberg, Peter, et al.
(författare)
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Mitochondria-DNA copy-number and incident venous thromboembolism among middle-aged women : a population-based cohort study
- 2021
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Ingår i: Journal of Thrombosis and Thrombolysis. - : Springer Science and Business Media LLC. - 1573-742X .- 0929-5305. ; 52:1, s. 148-157
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Tidskriftsartikel (refereegranskat)abstract
- Venous thromboembolism (VTE) is the third most common cardiovascular disease. Low amount of mitochondrial DNA copy number (mtDNA-CN) has been associated with arterial cardiovascular disease (CVD) and reflects mitochondrial dysfunctions. However, whether mtDNA-CN is associated with VTE has not been determined. To examine the association between mtDNA-CN and incident VTE among middle-aged women. 6917 women aged 50-64 years, followed for 20 years in the Women's Health In the Lund Area (WHILA) study. DNA samples for mtDNA quantification were available from 2521 women. Quantification of mtDNA-CN was performed using a well-optimized droplet digital PCR method. After exclusions of women with anticoagulant treatment, women living in nursing homes, and women who were diagnosed with cancer, stroke, VTE, or coronary heart disease at baseline, a cohort of 2117 women remained for analysis. Cox regression was used to analyze the relationship between mtDNA-CN and time to VTE (hazard ratio = HR). In total, 87 women were diagnosed with VTE during follow-up, corresponding to an incidence rate of 2.8 per 1000 person-years. Neither crude nor adjusted HR for mtDNA-CN were significantly associated with incident VTE. A sensitivity analysis with inclusion of excluded women did not change the results. MtDNA-CN was not significantly associated with VTE. The present study suggests that mtDNA-CN, reflecting mitochondrial dysfunction, should not be considered a biomarker that plays a major role for developing VTE. However, due to limited study size we may not exclude minor associations.
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| 6. |
- Nymberg, Peter, et al.
(författare)
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Self-rated health and venous thromboembolism among middle-aged women : a population-based cohort study
- 2020
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Ingår i: Journal of Thrombosis and Thrombolysis. - : Springer Science and Business Media LLC. - 0929-5305 .- 1573-742X. ; 49:3, s. 344-351
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Tidskriftsartikel (refereegranskat)abstract
- Venous thromboembolism (VTE) is one of the most common types of cardiovascular diseases (CVDs) and is associated with increased mortality-risk. Poor-self rated health (SHR) has been associated with elevated inflammatory markers and CVDs. However, little is known about as a predictor of incident VTE. To examine the association between self-rated health, lifestyle and incident VTE among middle-aged women. 6917 women aged 50–64 years, followed for 20 years in the Women’s Health In the Lund Area (WHILA) study. After exclusion of those who medicated with anticoagulants, were living in nursing homes or suffered from cancer, stroke, VTE or CHD before baseline, a cohort of 5626 women remained. Cox regression was used to analyse the relationship between self-rated health and time to VTE, censored for any of the previous mentioned diseases during follow-up. Data were collected by questionnaires, physical examinations and Swedish registers. In total, 220 women were affected by VTE corresponding to an incidence rate of 3.9 per 1000 person-years. Adjustment for self-rated health did not significantly predict incident VTE, and neither did any of the lifestyle-related habits (e.g. physical activity and dietary habits including alcohol consumption), besides smoking. This study supports previous results with varicose veins and waist circumference as strong predictors of VTE. Poor self-rated health does not seem to be a valid predictor of VTE. Among lifestyle-related parameters, smoking was significantly associated with risk of VTE. We could also confirm the effect of the other already known risk factors.
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| 7. |
- Sundquist, Kristina, et al.
(författare)
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Polymorphisms in PARK2 and MRPL37 are associated with higher risk of recurrent venous thromboembolism in a sex-specific manner
- 2018
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Ingår i: Journal of Thrombosis and Thrombolysis. - : Springer Science and Business Media LLC. - 0929-5305 .- 1573-742X. ; 46:2, s. 154-165
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Tidskriftsartikel (refereegranskat)abstract
- Recent studies indicate that mitochondrial DNA (mtDNA) dysfunction is a biomarker of oxidative stress and can predict the risk of cardiovascular diseases (CVDs). Genetic variants in PARK2 (rs4708928) and MRPL37 (rs10888838) genes have been shown to be associated with altered levels of mtDNA in a sex-specific manner. However, the role of these genetic variants in risk assessment of recurrent venous thromboembolism (VTE) is unknown. We investigated the role of these polymorphisms in VTE recurrence in patients from the Malmö thrombophilia study (MATS, n = 1465), followed for ~ 10 years. Genotyping was performed by TaqMan polymerase chain reaction. Female patients with PARK2 polymorphism had significantly higher risk of VTE recurrence (Hazard ratio [HR] = 2.39, 95% confidence interval [CI] 1.09–5.24) and male patients with MRPL37 polymorphism had a significantly higher risk of VTE recurrence (HR = 1.79, 95% CI 1.01–3.17) on multivariate Cox regression analysis. Combined analysis of these polymorphism with factor V Leiden (FVL) showed that female patients with both, FVL and PARK2 polymorphism had even higher risk of VTE recurrence (HR = 4.49, 95% CI 1.58–12.75) compared to FVL or PARK2 polymorphism alone or both wild-type (reference). Similarly, male patients with both FVL and MRPL37 polymorphism had significantly higher risk of VTE recurrence (HR = 2.97, 95% CI 1.45–6.08) compared to those with FVL or MRPL37 polymorphisms alone or the reference group. Polymorphisms in nuclear genome regulating mtDNA together with FVL may be promising biomarkers for predicting VTE recurrence in a sex specific manner. The abstract should be followed by 3-4 bullet points that highlight the major findings. The final bullet point should address future research.
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| 8. |
- Zöller, Bengt, et al.
(författare)
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Alcohol use disorders are associated with venous thromboembolism.
- 2015
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Ingår i: Journal of Thrombosis and Thrombolysis. - : Springer Science and Business Media LLC. - 1573-742X .- 0929-5305. ; 40:2, s. 167-173
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Tidskriftsartikel (refereegranskat)abstract
- Moderate alcohol consumption has been suggested to protect against venous thromboembolism (VTE). However, it is not known how alcohol abuse and its associated somatic complications affect the risk of VTE. The present study determined the risk of pulmonary embolism (PE) and deep vein thrombosis (DVT) of the lower extremities in patients with alcohol use disorders (AUDs) in Sweden. All inpatients with AUDs in 2002-2010 without a previous VTE event (72,024 patients) were matched to five controls without AUD and followed until the end of follow-up (December 31, 2010), death, emigration or a VTE event. Cox regression was used to determine adjusted hazard ratios (HRs) for VTE. AUD patients were further divided into those without alcohol-related somatic complications (AUD-) and those with alcohol-related somatic complications (AUD+, i.e., encephalopathy, epilepsy, polyneuropathy, myopathy, cardiomyopathy, gastritis, liver disease, acute pancreatitis, and chronic pancreatitis). The adjusted HR for VTE was significantly increased for both AUD- (HR 1.70, 95 % CI 1.55-1.87) and AUD+ (HR 1.73, 95 % CI 1.37-2.19) patients. The risk of DVT was increased in both AUD+ and AUD- patients (HR 1.62, 95 % CI 1.45-1.83 and HR 1.99, 95 % CI 1.53-2.59, respectively). However, the risk of PE was only significantly increased in AUD- patients (HR 1.87, 95 % 1.59-1.20) and not in AUD+ patients (HR 1.16, 95 % 0.70-1.91). In conclusion, the present study shows that AUD increases the risk of VTE, even in the absence of alcohol-related somatic complications. Our findings suggest that severe alcohol abuse increases the risk of VTE.
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| 9. |
- Zöller, Bengt, et al.
(författare)
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Family history of venous thromboembolism and mortality after venous thromboembolism : a Swedish population-based cohort study
- 2017
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Ingår i: Journal of Thrombosis and Thrombolysis. - : Springer Science and Business Media LLC. - 0929-5305 .- 1573-742X. ; 43:4, s. 469-475
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Tidskriftsartikel (refereegranskat)abstract
- Studies on whether family history (FH) of venous thromboembolism (VTE) affects long-term mortality after VTE are missing. The aim of this study was to determine whether FH of VTE affects long-term mortality after a first episode of VTE. Using Swedish medical databases, we conducted a 30-year nationwide cohort study of 49,159 adult Swedish born patients included in the multi-generation register (born 1932 or later) with a first-time VTE (1981–2010). Using Cox regression, we assessed mortality Hazard ratios (HRs) with 95% confidence intervals (CIs). Totally 10,093 (20.5%) patients with VTE had a first-degree FH of VTE (parent/sibling). Patients without FH of VTE had significantly more VTE provoking risk factors and comorbidities than those with FH. The mortality HR the first 10-years after first time VTE was decreased for those with FH of VTE compared to for those without FH: crude HR 0.807, 95% CI 0.771–0.845 and adjusted HR 0.864, 95% CI 0.826–0.905. After 10-years of follow-up there was no significant effect of FH of VTE on mortality: crude HR = 1.018, 95% CI 0.905–1.145 and adjusted HR = 0.995, 95% CI 0.884–1.119. Cancer-associated mortality was more common in those without FH the first 10 years (56.9 vs. 53.4%, p = 0.002). After 10 years there were no difference in cancer-associated mortality (4.9 vs. 5.6%, p = 0.604). The results suggest that patients with FH of VTE have lower thrombotic threshold and need less provoking factors and comorbidities. They have also slightly lower total and cancer mortality the first 10 years after VTE.
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| 10. |
- Zöller, Bengt, et al.
(författare)
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Neighborhood deprivation and hospitalization for venous thromboembolism in Sweden.
- 2012
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Ingår i: Journal of Thrombosis and Thrombolysis. - : Springer Science and Business Media LLC. - 1573-742X .- 0929-5305. ; 34:3, s. 374-382
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Tidskriftsartikel (refereegranskat)abstract
- Arterial cardiovascular disease and neighborhood deprivation are associated. However, no study has determined whether neighborhood deprivation is associated with venous thromboembolism (VTE). We aimed to determine whether there is an association between neighborhood deprivation and hospitalization for VTE, and whether effects vary across sociodemographic groups. The entire Swedish population aged 25-74 was followed from January 1, 2000 until hospitalization for VTE, death, emigration, or the end of the study period (December 31, 2008). Data were analyzed by multilevel logistic regression, with individual-level characteristics (age, marital status, family income, educational attainment, immigration status, urban/rural status, mobility, and comorbidity) at the first level and level of neighborhood deprivation at the second level. Neighborhood deprivation was significantly associated with VTE hospitalization rate in both men (OR = 1.09) and women (OR = 1.38). In the full model, which took account of individual-level socioeconomic characteristics and comorbidities, the odds of VTE remained significant only in women (OR = 1.12, 95 % CI 1.06-1.20) in the most deprived neighborhoods. Neighborhood characteristics affect odds of hospitalization for VTE, particularly in women. Thus, neighborhood deprivation is a common risk factor for both arterial cardiovascular disease and VTE. This study adds to knowledge of the negative effects of neighborhood deprivation on cardiovascular health.
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