| 661. |
- Zöller, Bengt, et al.
(författare)
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A nationwide family study of venous thromboembolism and risk of arterial vascular disease
- 2016
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Ingår i: Heart. - : BMJ. - 1355-6037 .- 1468-201X. ; 102:16, s. 1315-1321
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: This nationwide study aimed to determine whether venous thromboembolism (VTE) shares familial susceptibility with aortic aneurysm (AA), peripheral artery disease (PAD) and arterial thrombosis and embolisation (ATE) in locations other than the heart and brain.METHODS: Nationwide Swedish family study. Data from the Swedish Multi-Generation Register for subjects aged 0-78 years old, covering the period 1964-2010, were linked to the Hospital Register. Familial risks (standardised incidence ratio, SIR) of AA, PAD and ATE were determined for individuals with a first-degree relative (parents/sibling) diagnosed with VTE. Separate analyses were done to determine risks for spouses.RESULTS: A total of 13 063 individuals had AA, 15 494 had PAD and 7325 had ATE. Fully adjusted familial risks for individuals with family history (parent/sibling) of VTE were 1.04 (95% CI 1.00 to 1.08)) for AA, 1.42 (1.35 to 1.49) for ATE and 1.08 (1.04 to 1.13) for PAD. The familial sibling risks were 1.07 (0.99 to 1.14) for AA, 1.61 (1.48 to 1.74) for ATE and 1.19 (1.11 to 1.26) for PAD. Among individuals younger than 50 years of age, the familial risks were: 1.13 (0.99 to 1.29) for AA, 1.76 (1.62 to 1.91) for ATE and 1.12 (1.03 to 1.21) for PAD. In spouses of patients with VTE, the SIRs were 1.21 (1.17 to 1.25) for AA, 1.19 (1.14 to 1.23) for ATE and 1.26 (1.21 to 1.30) for PAD.CONCLUSIONS: VTE shares only weak familial susceptibility with AA and PAD in the Swedish population. However, ATE partially shares a moderate familial susceptibility and possibly genetic factors with VTE. Moreover, familial non-genetic factors may contribute to the observed familial associations.
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| 662. |
- Zöller, Bengt, et al.
(författare)
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A sibling based design to quantify genetic and shared environmental effects of venous thromboembolism in Sweden
- 2017
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Ingår i: Thrombosis Research. - : Elsevier BV. - 0049-3848. ; 149, s. 82-87
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Few large studies have examined the heritability of venous thromboembolism (VTE). Moreover, twin studies have been suggested to overestimate heritability. The aim of the present study was to determine the heritability nationwide in the general Swedish population using full siblings and half-siblings. Methods: VTE was defined using the Swedish patient register. Full sibling (FS) and half-sibling (HS) pairs born 1950-1990 were obtained from the Swedish Multi-generation Register. A maximum of 5. years age difference was allowed. We also required that the individuals within the pair should reside in the same household for at least 8. years or not at all (0. years) before the youngest turned 16. Information about sibling pair residence within the same household, small residential area, and municipality was obtained from Statistics Sweden. We assumed three potential sources of liability to VTE: additive genetic (A), shared (or common/familial) environment (C), and unique environment (E) components. Results: Totally 881,206 FS pairs and 95,198 HS pairs were included. The full model predicted heritability for VTE with 47% for males and 40% for females. Environmental factors shared by siblings contributed to 0% of the variance in liability for both sexes, and unique environment (E) components accounted for 53% in males and 60% in females. Conclusion: The high heritability of VTE risk indicates that genetic susceptibility plays a substantial role for VTE in the Swedish general population. Overestimation of heritability from twin studies is not likely. The proportion of the variance attributable to shared familial environment factors is small. . Subject codes: Genetics, epidemiology, thrombosis, cardiovascular disease, embolism. .
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| 663. |
- Zöller, Bengt, et al.
(författare)
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Age- and gender-specific familial risks for venous thromboembolism: a nationwide epidemiological study based on hospitalizations in sweden.
- 2011
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Ingår i: Circulation. - 1524-4539. ; 124:9, s. 1012-1020
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Tidskriftsartikel (refereegranskat)abstract
- Background- This nationwide study sought to determine age- and gender-specific familial risks in siblings hospitalized for venous thromboembolism (VTE). Methods and Results- The Swedish Multigeneration Register on 0- to 75-year-old subjects was linked to the Hospital Discharge Register for the years 1987-2007. Standardized incidence ratios were calculated for individuals whose siblings were hospitalized for VTE compared with those whose siblings were not affected. Among a total of 45 362 hospitalized cases with VTE, 2393 affected siblings were identified, with a familial standardized incidence ratio of 2.45 (95% confidence interval [CI], 1.66 to 3.61). Gender-specific differences in incidence rates were observed. The familial risks were significantly increased from the age of 10 to 69 years, with a familial standardized incidence ratio of 4.77 (95% CI, 1.96 to 10.83) at ages 10 to 19 years, which decreased to 2.08 (95% CI, 1.35 to 3.20) at ages 60 to 69 years, although the absolute risk increased with age. The familial standardized incidence ratios for siblings with 2 and ≥3 affected probands were 51.87 (95% CI, 31.47 to 85.00) and 53.69 (95% CI, 25.59 to 108.50), respectively. Spouses had low familial risks (standardized incidence ratio=1.07; 95% CI, 1.04 to 1.10; observed spouse cases=3900). Conclusions- Familial factors, although influenced by age and gender, are important risk factors for VTE. The present study shows that VTE is aggregated in families and suggests that uncovering the sources of familial aggregation (genetic and nongenetic) may be worthwhile. Moreover, in a small fraction of siblings, the familial risk was very high, suggesting segregation of rare but strong genetic risk factors
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| 664. |
- Zöller, Bengt, et al.
(författare)
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Age-and sex-specific seasonal variation of venous thromboembolism in patients with and without family history: a nationwide family study in Sweden.
- 2013
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Ingår i: Thrombosis and Haemostasis. - 0340-6245. ; 110:6, s. 1164-1171
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Tidskriftsartikel (refereegranskat)abstract
- Seasonal variation in venous thromboembolism (VTE) risk in individuals with familial predisposition to VTE has not been explored. This nationwide study aimed to determine whether there are age- and sex-specific seasonal differences in risk of hospitalisation of VTE among individuals with and without a family history of VTE. The Swedish Multi-Generation Register was linked to Hospital Discharge Register data for the period 1964-2010. Seasonal variation in first VTE events in 1987-2010 for individuals with and without a family history of VTE (siblings or parents) was determined by several independent methods. Stratified analyses were performed according to age, sex, and VTE subtype (pulmonary embolism [PE] or deep venous thrombosis [DVT]). Seasonal variation in VTE incidence, mostly with a peak during the winter, was observed in both sexes in individuals with and without family history with overall peak-to-low ratios (PLRs) of 1.15 and 1.21, respectively. The peak day was December 25 and February 1 for those with and without a family history of VTE, respectively. Seasonal variation was strongest among individuals aged >50 years. Among individuals aged 0-25 years with a family history, the peak for VTE was in July (PLR = 1.20). Significant seasonal variation was observed for PE and DVT with the exception of DVT among those with a family history (PLR = 1.01). In conclusion, our data support the presence of a modest seasonal variation of VTE among individuals with and without a family history of VTE. However, young age and family history may modify and attenuate the effect of season on VTE.
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| 665. |
- 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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| 666. |
- Zöller, Bengt, et al.
(författare)
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Association of irritable bowel syndrome and venous thromboembolism
- 2018
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Ingår i: Scandinavian Journal of Gastroenterology. - : Informa UK Limited. - 1502-7708 .- 0036-5521. ; 53:7, s. 784-789
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Inflammatory bowel disease (IBD) is associated with venous thromboembolism (VTE). Whether functional gastrointestinal disorders, such as irritable bowel syndrome (IBS), are associated with VTE has not been determined. This nationwide study aimed to determine the risk of VTE in IBS outpatients in primary and specialist care.DESIGN: We performed two matched case-control studies. Cases (n = 90,502) were individuals in Sweden aged 18-80 years with a first hospital diagnosis of VTE between 2001 and 2010. Five controls (n = 452,510) from the Swedish Total Population Register were matched to each case for birth, sex, country of birth, and education level. Diagnosis of IBS was determined in the Swedish hospital outpatient register. This procedure was replicated for the primary care population. As the Primary Care data did not have nationwide coverage, we only included individuals that were registered in the Primary Care database. A total of 9766 cases of hospital diagnosed VTE individuals could be found in the Primary Care population and they were matched to 48,830 controls also from the Primary health care population. Conditional logistic regression was used to determine odds ratio (OR) for first VTE diagnosis. Results The adjusted OR for VTE when IBS was diagnosed in hospital outpatient care was 1.49 (95% confidence interval 1.33-1.67). The crude OR for VTE was 1.18 (0.94-1.48) when IBS was diagnosed in primary care.CONCLUSIONS: This is the first study describing an association between VTE and IBS. The results suggest that specialist treated IBS patients have increased risk of VTE.
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| 667. |
- Zöller, Bengt, et al.
(författare)
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Association of Short-Term Mortality of Venous Thromboembolism with Family History of Venous Thromboembolism and Charlson Comorbidity Index
- 2019
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Ingår i: Thrombosis and Haemostasis. - : Georg Thieme Verlag KG. - 0340-6245 .- 2567-689X. ; 119:1, s. 48-55
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Tidskriftsartikel (refereegranskat)abstract
- Studies on short-term prognosis of venous thromboembolism (VTE) that take family history of VTE and Charlson Comorbidity Index (CCI) into account are sparse. The aim was to investigate the importance of family history of VTE and CCI for short-term mortality after a first episode of VTE. Using Swedish medical databases, we conducted a 90-day nationwide cohort study of 41,700 Swedish born patients with a first-time VTE (July 2005-August 2012). Patients diagnosed with VTE and prescribed anticoagulant treatment were included. Mortality hazard ratios (HRs) with 95% confidence intervals (CIs) were determined with Cox regression. Patients with first-degree (sibling/parent) family history of VTE (n = 11,405, 27.4%) had significantly lower CCI than those without family history. Independent risk factors for 90-day mortality in the adjusted model were: female sex (HR = 1.19, 95% CI: 1.09-1.29), increasing age (HR = 1.02, 95% CI: 1.01-1.02 per year), pulmonary embolism (HR = 1.21, 95% CI: 1.11-1.32) or combined pulmonary embolism and deep venous thrombosis (HR = 1.60, 95% CI: 1.27-2.01) compared with deep venous thrombosis, CCI = 1 (HR = 2.93, 95% CI: 2.32-3.72), CCI = 2 (HR = 8.65, 95% CI: 7.16-10.46) or CCI = 3 (HR = 22.25, 95% CI: 18.73-26.44) compared with CCI = 0. Having one or two or more affected first-degree relatives with VTE was associated with lower mortality, HR = 0.83 (95% CI: 0.74-0.92) and HR = 0.65 (95% CI: 0.51-0.85), respectively. The mortality rate was 0.70% in patients with a CCI of zero. In receiver operating characteristic (ROC) analysis, the area under the ROC curve for CCI was 0.84 (0.83-0.95). Family history of VTE is associated with lower mortality while CCI is a strong predictor for short-term mortality in VTE. Co-morbidities are important for risk assessment of VTE.
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| 668. |
- Zöller, Bengt, et al.
(författare)
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Autoimmune diseases and venous thromboembolism : a review of the literature
- 2012
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Ingår i: American Journal of Cardiovascular Disease. - 2160-200X. ; 2:3, s. 171-183
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Tidskriftsartikel (refereegranskat)abstract
- Venous thromboembolism (VTE) is major health problem and is sometimes complicated by lethal pulmonary embolism (PE). Disturbances of the coagulation and anticoagulation systems are important risk factors for VTE. Comparative studies suggest that coagulation and innate immunity have a shared evolutionary origin. It is therefore unsurprising that the immune and coagulation systems are linked, with many molecular components being important for both systems. Systemic inflammation modulates thrombotic responses by suppressing fibrinolysis, upregulating procoagulant, and downregulating anticoagulants, and autoimmune disorders such as systemic lupus erythematosus (SLE), inflammatory bowel disease (IBD), and Behçet's syndrome have been linked to an increased risk of VTE. Recent reports have further shown that a majority of autoimmune and immune-mediated disorders are linked to an increased risk of venous thrombosis, PE, or VTE. For instance, a Swedish nationwide study found that the risk of PE was increased in the first year after hospitalization for 33 different autoimmune disorders. Especially high risks were noted for several autoimmune diseases such as immune thrombocytopenic purpura, polyarteritis nodosa, polymyositis/dermatomyositis, ulcerative colitis, and SLE. Another study from England, also based on hospitalization data, found that immune-mediated disorders were associated with an increased risk of VTE compared with other medical causes of hospitalization. Multiple mechanisms may operate and disease-specific factors, such as cardiolipin antibodies, have been identified. However, inflammation by itself appears to change the hemostatic balance in a thrombogenic direction. Recent epidemiological studies, together with previous experimental and clinical studies, indicate that autoimmune disorders should not only be viewed as inflammatory disorders, but also hypercoagulable disorders. Research to identify thrombotic risk factors, elucidate the mechanisms involved, and investigate prophylactic regiments is needed. The present review describes the epidemiological, clinical, and experimental evidence for the connection between VTE and autoimmune and immune-mediated disorders.
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| 669. |
- Zöller, Bengt, et al.
(författare)
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Body Height and Incident Risk of Venous Thromboembolism : A Cosibling Design
- 2017
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Ingår i: Circulation: Cardiovascular Genetics. - 1942-325X. ; 10:5
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Body height has been associated with an increased risk of venous thromboembolism (VTE), but the association can be confounded with shared familial factors (genetic/environmental). A cosibling design is useful for deeper understanding about the relationship between VTE and height.METHODS AND RESULTS: From Swedish national registry databases, we used a corelative design with full siblings alongside a general Swedish population sample. A cohort of male conscripts (n=1 610 870), born in 1951 to 1992 without previous VTE, was followed from enlistment (1969-2010) until 2012. Another cohort of first-time pregnant women (n=1 093 342) from the medical birth register, without previous VTE, was followed from first pregnancy (1982-2012) until 2012. Using the Multi-Generation Register, we identified all full-sibling pairs discordant for height. This cosibling design allowed for adjustment for familial factors (genetic/environmental). Compared with the tallest women (>185 cm) and men (>190 cm), there was a graded decreased risk by lower height for both men and women. The risk was lowest in women and men with the shortest stature (<155 and <160 cm, respectively): hazard ratios=0.31 (95% confidence interval, 0.22-0.42) and 0.35 (95% confidence interval, 0.22-0.55), respectively. There was a graded association also in the cosibling design comparing siblings with varying degree of discordance for height (reference was the taller sibling): ≥10 cm difference between brothers hazard ratios=0.69 (95% confidence interval, 0.61-0.78) and sisters hazard ratios=0.65 (95% confidence interval, 0.52-0.80), respectively.CONCLUSIONS: Height is an independent predictor of VTE. The use of sibling pairs reduces the likelihood that familial confounding explains the results. The findings are important for the understanding of the pathogenesis of VTE.
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| 670. |
- Zöller, Bengt, et al.
(författare)
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Cardiovascular fitness in young males and risk of unprovoked venous thromboembolism in adulthood
- 2017
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Ingår i: Annals of Medicine. - : Informa UK Limited. - 0785-3890 .- 1365-2060. ; 49:2, s. 176-184
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Tidskriftsartikel (refereegranskat)abstract
- Background: Whether high cardiovascular fitness is associated with reduced risk of venous thromboembolism (VTE) is unknown. The present study aims to determine whether high cardiovascular fitness reduces the risk of VTE. Methods: A Swedish cohort of male conscripts (n = 773,925) born in 1954–1970 with no history of previous VTE were followed from enlistment (1972–1990) until 2010. Data on cardiovascular fitness using a cycle ergonometric test (maximal aerobic workload in Watt [Wmax]) at conscription were linked with national hospital register data and the Multi-Generation Register. We identified all full-siblings and first-cousin pairs discordant for maximal aerobic workload. This co-relative design allows for adjustment for familial resemblance. Results: In total, 3005 (0.39%) males were affected by VTE. Cardiovascular fitness estimated with Wmax was not associated with VTE risk when adjusted for body mass index (BMI). However, cardiovascular fitness estimated with Wmax/kg and adjusted for BMI was associated with reduced risk for VTE (Hazard ratio (HR) 0.81, 95% confidence interval (CI) 0.78–0.85 per standard deviation compared with mean Wmax/kg). The association was weaker over time and also when examining discordant first cousins and full-sibling pairs. Conclusions: These results suggest that there is a relationship between cardiovascular fitness and weight that is important for future VTE risk.Key messagesWhether high cardiovascular fitness is associated with reduced risk of venous thromboembolism (VTE) is unknown.A Swedish cohort of male conscripts (n = 773,925) tested with a cycle ergometric test with no history of previous VTE were followed from enlistment (1972–1990) until 2010.Cardiovascular fitness estimated with Wmax/kg and adjusted for BMI was associated with reduced risk for VTE (HR 0.81, 95% CI 0.78–0.85).These results suggest that there is a relationship between cardiovascular fitness and weight that is important for future VTE risk.
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