| 661. |
- 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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| 662. |
- 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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| 663. |
- 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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| 664. |
- 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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| 665. |
- 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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| 666. |
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| 667. |
- Zöller, Bengt, et al.
(författare)
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Determination of age-specific and sex-specific familial risks for the different manifestations of venous thromboembolism: A nationwide family study in Sweden.
- 2011
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Ingår i: Thrombosis and Haemostasis. - 0340-6245. ; 106:1, s. 102-112
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Tidskriftsartikel (refereegranskat)abstract
- This nationwide study aimed to determine whether differences exist in age-specific and sex-specific familial risks for pulmonary embolism (PE), venous thrombosis of the lower limbs (VT) and other forms of venous thromboembolism (OVTE) among offspring, siblings and spouses of affected individuals. The Swedish Multi-Generation Register was linked to the Hospital Discharge Register data for the period 1987-2007. Standardised incidence ratios (SIRs) were calculated for individuals whose relatives were hospitalised for venous thromboembolism (VTE), as determined by the International Classification of Diseases (ICD), and those whose relatives were unaffected by VTE. The total number of hospitalised VTE patients was 45,362. All VTE patients were categorised as PE, VT or OVTE according to ICD at first hospitalisation. For example, the parental SIRs for PE, VT and OVTE in offspring at age 10-19 years were 2.89 (95% CI 1.48-5.06), 4.99 (95% CI 3.22-6.10) and 3.89 (95% CI 2.51-5.75), respectively. The low spousal risks of PE (1.08; 95% CI 1.02-1.13), VT (1.06; 95% CI 1.011.12) and OVTE (1.07; 95% CI 1.00-1.15) suggest the familial risks to be largely genetic. In both men and women, familial relative risks were increased for all the different manifestations of VTE with the exception of those older than 70 years. Familial history is a risk indicator in both sexes, and is potentially useful for clinical risk assessment for the different manifestations of VTE.
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| 668. |
- Zöller, Bengt, et al.
(författare)
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Epidemiology of Familial Aggregation of Venous Thromboembolism
- 2016
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Ingår i: Seminars in Thrombosis and Hemostasis. - : Georg Thieme Verlag KG. - 0094-6176 .- 1098-9064. ; 42:8, s. 821-832
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Forskningsöversikt (refereegranskat)abstract
- Familial aggregation (clustering) of venous thromboembolism (VTE) is the clustering of VTE within a family. Though several genes, such as antithrombin, protein C, protein S, factor V, and prothrombin are associated with the familial clustering of VTE, these loci only partially explain the familial aggregation of VTE. The epidemiology of the familial aggregation of VTE exhibits typical characteristics of complex traits. The family history of VTE in first-degree relatives is associated with a two to three times increased familial relative risk (FRR). The FRR of VTE is higher in younger individuals, increases with a number of affected relatives, decreases as the familial relationship becomes more distant, increases with severity (unprovoked), and exhibits slightly stronger male transmission (Carter effect). High FRR is observed in individuals with two or more affected siblings (FRR > 50). Because familial aggregation represents the sum of shared family environmental and genetic factors, one should not assume that evidence of familial aggregation implies genetic effects. However, studies in twins, extended families, adoptees, and spouses indicate a weak involvement of shared environmental factors to the familial aggregation of VTE. Moreover, familial aggregation of VTE fulfills the Hill's criteria for causation. In conclusion, familial aggregation of VTE signals a clinically relevant inherent predisposition for VTE.
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| 669. |
- Zöller, Bengt, et al.
(författare)
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Familial aggregation of multimorbidity in Sweden: national explorative family study
- 2023
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Ingår i: BMJ Medicine. - 2754-0413. ; 2:1, s. 1-13
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Tidskriftsartikel (refereegranskat)abstract
- Objectives To examine whether multimorbidity aggregates in families in Sweden.Design National explorative family study.Setting Swedish Multigeneration Register linked to the National Patient Register, 1997-2015. Multimorbidity was assessed with a modified counting method of 45 chronic non-communicable diseases according to ICD-10 (international classification of diseases, 10th revision) diagnoses.Participants 2 694 442 Swedish born individuals (48.73% women) who could be linked to their Swedish born first, second, and third degree relatives. Twins were defined as full siblings born on the same date.Main outcome measures Multimorbidity was defined as two or more non-communicable diseases. Familial associations for one, two, three, four, and five or more non-communicable diseases were assessed to examine risks depending on the number of non-communicable diseases. Familial adjusted odds ratios for multimorbidity were calculated for individuals with a diagnosis of multimorbidity compared with relatives of individuals unaffected by multimorbidity (reference). An initial principal component decomposition followed by a factor analysis with a principal factor method and an oblique promax rotation was used on the correlation matrix of tetrachoric correlations between 45 diagnoses in patients to identify disease clusters.Results The odds ratios for multimorbidity were 2.89 in twins (95% confidence interval 2.56 to 3.25), 1.81 in full siblings (1.78 to 1.84), 1.26 in half siblings (1.24 to 1.28), and 1.13 in cousins (1.12 to 1.14) of relatives with a diagnosis of multimorbidity. The odds ratios for multimorbidity increased with the number of diseases in relatives. For example, among twins, the odds ratios for multimorbidity were 1.73, 2.84, 4.09, 4.63, and 6.66 for an increasing number of diseases in relatives, from one to five or more, respectively. Odds ratios were highest at younger ages: in twins, the odds ratio was 3.22 for those aged ≤20 years, 3.14 for those aged 21-30 years, and 2.29 for those aged >30 years at the end of follow-up. Nine disease clusters (factor clusters 1-9) were identified, of which seven aggregated in families. The first three disease clusters in the principal component decomposition were cardiometabolic disease (factor 1), mental health disorders (factor 2), and disorders of the digestive system (factor 3). Odds ratios for multimorbidity in twins, siblings, half siblings, and cousins for the factor 1 cluster were 2.79 (95% confidence interval 0.97 to 8.06), 2.62 (2.39 to 2.88), 1.52 (1.34 to 1.73), and 1.31 (1.23 to 1.39), and for the factor 2 cluster, 5.79 (4.48 to 7.48) 3.24 (3.13 to 3.36), 1.51 (1.45 to 1.57), and 1.37 (1.341.40).Conclusions The results of this explorative family study indicated that multimorbidity aggregated in Swedish families. The findings suggest that map clusters of diseases should be used for the genetic study of common diseases to show new genetic patterns of non-communicable diseases.
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| 670. |
- Zöller, Bengt, et al.
(författare)
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Familial Mortality Risks in Patients with Ischemic Stroke : A Swedish Sibling Study
- 2022
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Ingår i: Stroke. - 0039-2499. ; 53:5, s. 1615-1623
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Tidskriftsartikel (refereegranskat)abstract
- Background: The influence of familial factors on the prognosis of ischemic stroke (IS) is unknown. This nationwide follow-up study evaluated familial mortality risks of IS among Swedish sibling pairs hospitalized for IS. Methods: We linked Swedish nationwide registers for the identification of 1380 Swedish born sibling pairs (2760 cases), where both siblings were hospitalized for first-time IS between 1991 and 2010. Median age was 62 years (range, 26-78 years). Sibling pairs with cancer were excluded. Familial hazard ratios (FHRs) for mortality after first IS hospitalization were determined with Cox regression. The influence of proband survival after IS was categorized as short sibling survival (<1, 2, 3, 4, or 5 years) or long sibling survival (≥1, 2, 3, 4, or 5 years) after IS. FHRs were adjusted for age at onset, sex, education, county, year of diagnosis, days of hospitalization, and comorbidities. Results: Short sibling survival (ie, <3 or <4 years) after IS was associated with an adjusted FHR of 1.29 (95% CI, 1.05-1.58) and 1.24 (95% CI, 1.02-1.51), respectively, for overall mortality after IS. Stratified analysis showed that short sibling survival (ie, <2 - <5 years) was stronger and significant only among younger individuals (<62 years) and males. Highest FHR for short sibling survival (ie, <4 years) was 1.42 (95% CI, 1.08-1.88) for younger individuals and 1.50 (95% CI, 1.21-1.87) for males. For young male subjects, FHR was 1.80 (95% CI, 1.33-2.46). In the adjusted model, mortality was also associated with sex, education, age at onset, year of diagnosis, days of hospitalization, coronary heart disease, diabetes, dementia, heart failure, obesity, alcoholism, and hyperlipidemia. Conclusions: Our results suggest that family history of short survival in siblings after IS is associated with mortality after IS for younger male subjects. Additional studies are needed to characterize possible genetic and nongenetic familial environmental causes of this association.
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