| 1. |
- Ahrén, Jonatan, et al.
(författare)
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A hypothesis - generating Swedish extended national cross-sectional family study of multimorbidity severity and venous thromboembolism
- 2023
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Ingår i: BMJ Open. - 2044-6055. ; 13:6, s. 1-8
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: Venous thromboembolism (VTE) is a common worldwide disease. The burden of multimorbidity, that is, two or more chronic diseases, has increased. Whether multimorbidity is associated with VTE risk remains to be studied. Our aim was to determine any association between multimorbidity and VTE and any possible shared familial susceptibility.DESIGN: A nationwide extended cross-sectional hypothesis - generating family study between 1997 and 2015.SETTING: The Swedish Multigeneration Register, the National Patient Register, the Total Population Register and the Swedish cause of death register were linked.PARTICIPANTS: 2 694 442 unique individuals were analysed for VTE and multimorbidity.MAIN OUTCOMES AND MEASURES: Multimorbidity was determined by a counting method using 45 non-communicable diseases. Multimorbidity was defined by the occurrence of ≥2 diseases. A multimorbidity score was constructed defined by 0, 1, 2, 3, 4 or 5 or more diseases.RESULTS: Sixteen percent (n=440 742) of the study population was multimorbid. Of the multimorbid patients, 58% were females. There was an association between multimorbidity and VTE. The adjusted odds ratio (OR) for VTE in individuals with multimorbidity (2 ≥ diagnoses) was 3.16 (95% CI: 3.06 to 3.27) compared with individuals without multimorbidity. There was an association between number of diseases and VTE. The adjusted OR was 1.94 (95% CI: 1.86 to 2.02) for one disease, 2.93 (95% CI: 2.80 to 3.08) for two diseases, 4.07 (95% CI: 3.85 to 4.31) for three diseases, 5.46 (95% CI: 5.10 to 5.85) for four diseases and 9.08 (95% CI: 8.56 to 9.64) for 5 ≥ diseases. The association between multimorbidity and VTE was stronger in males OR 3.45 (3.29 to 3.62) than in females OR 2.91 (2.77 to 3.04). There were significant but mostly weak familial associations between multimorbidity in relatives and VTE.CONCLUSIONS: Increasing multimorbidity exhibits a strong and increasing association with VTE. Familial associations suggest a weak shared familial susceptibility. The association between multimorbidity and VTE suggests that future cohort studies where multimorbidity is used to predict VTE might be worthwhile.
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| 2. |
- Andell, Pontus, et al.
(författare)
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Neighborhood socioeconomic status and aortic stenosis : A Swedish study based on nationwide registries and an echocardiographic screening cohort
- 2020
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Ingår i: International Journal of Cardiology. - : Elsevier BV. - 0167-5273 .- 1874-1754. ; 318, s. 153-159
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Tidskriftsartikel (refereegranskat)abstract
- Background: Aortic stenosis (AS) is the most common valvular heart disease in developed countries, confers high mortality in advanced cases, but can effectively be reversed using endovascular or open-heart surgery. We evaluated the association between AS and neighborhood socioeconomic status (NSES). Methods: We used Swedish population-based nationwide registers and an echocardiography screening cohort during the study period 1997–2014. NSES was determined by an established neighborhood deprivation index composed of education, income, unemployment, and receipt of social welfare. Multilevel adjusted logistic regression models determined the association between NSES and incident AS (according to ICD-10 diagnostic codes). Results: The study population of men and women (n=6,641,905) was divided into individuals living in high (n = 1,608,815 [24%]), moderate (n = 3,857,367 [58%]) and low (n = 1,175,723 [18%]) SES neighborhoods. There were 63,227 AS cases in total. Low NSES (versus high) was associated with a slightly increased risk of AS (OR 1.06 [95% CI 1.03–1.08]) in the nationwide study population. In the echocardiography screening cohort (n = 1586), the association between low NSES and AS was markedly stronger (OR: 2.73 [1.05–7.12]). There were more previously undiagnosed AS cases in low compared to high SES neighborhoods (3.1% versus 1.0%). Conclusions: In this nationwide Swedish register study, low NSES was associated with a slightly increased risk of incident AS. However, the association was markedly stronger in the echocardiography screening cohort, which revealed an almost three-fold increase of AS among individuals living in low SES neighborhoods, possibly indicating an underdiagnosis of AS among these individuals.
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| 3. |
- Andersson, Therese, 1983-
(författare)
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Acute Pulmonary Embolism : not just an acute condition after all
- 2022
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: Acute pulmonary embolism (PE) is the third most common cardiovascular disease following myocardial infarction and stroke. Despite diagnostic improvements, the diagnosis of PE is still associated with many difficulties, as the symptoms of an acute PE are nonspecific. Even though an acute PE is associated with a high short-term mortality, less attention has been given to long-term mortality. In addition, the clinical course following an acute PE may be accompanied by substantial morbidity, and one feared complication is chronic thromboembolic pulmonary hypertension (CTEPH), a progressive pulmonary vasculopathy. In addition to CTEPH, increasing evidence suggests that a large proportion of patients report persistent functional impairment several years after an acute PE. Recently, the term chronic thromboembolic pulmonary disease (CTEPD) has been proposed for those with remaining symptoms and signs of residual thrombotic material in the pulmonary arteries. Methods and Results: A nation-wide Swedish cohort of all patients (n= 5793) diagnosed with an acute PE in 2005 was identified. The incidence of PE was 0.6/1000 person-years, and during a 4-year follow-up, the mortality was more than doubled compared with an age- and sex-matched control group. We found that the acute PE associated with multiple comorbidities, and with cardiovascular diseases in particular. All surviving patients in 2007 (n=3510) were invited to answer a questionnaire regarding dyspnea and related comorbidities. We demonstrated a substantially higher prevalence of both exertional dyspnea (53.0% vs. 17.3%) and wake-up dyspnea (12% vs. 1.7%) in patients compared to controls from the Northern Sweden MONICA study. Furthermore, PE associated independently with dyspnea in a multivariable analysis. Through a manual review of approximately 10 % of the patient’s medical records, a positive predictive value of 79% was found for the PE diagnosis. Post-PE patients with remaining dyspnea and/or previously known risk factors for CTEPH development were referred for blood sampling and levels of N-terminal (NT)-prohormone (pro) brain-type natriuretic peptide (BNP) were determined. Thereafter, they were referred to their local hospital for a pulmonary ventilation/perfusion (V/Q) scintigraphy and echocardiography. Approximately 45% of the V/Q-scans showed perfusion defects and 27 % of echocardiographies showed signs of pulmonary hypertension. In total, 24 cases of CTEPH were identified, resulting in a prevalence of 0.4 % (95 % confidence interval 0.2 %–0.6 %). Conclusion: An acute PE is a serious event, associated with decreased survival, multiple comorbidities, frequent dyspnea, and pathological investigational findings. The term CTEPD seems reasonable as it captures that this is a disease of the pulmonary vasculature, and that pharmacological and surgical interventions used for CTEPH may be useful. Regardless, proper follow-up after acute PE is essential for timely identification of patients in need of appropriate investigations and care.
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| 4. |
- Azzouz, Mehjar, 1999, et al.
(författare)
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Air pollution and biomarkers of cardiovascular disease and inflammation in the Malmo Diet and Cancer cohort
- 2022
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Ingår i: Environmental Health. - : Springer Science and Business Media LLC. - 1476-069X. ; 21:1
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Tidskriftsartikel (refereegranskat)abstract
- Introduction Air pollution is associated with increased risk of cardiovascular disease, possibly through chronic systemic inflammation that promotes the progression of atherosclerosis and the risk of cardiovascular events. This study aimed to investigate the associations between air pollution and established biomarkers of inflammation and cardiovascular disease. Methods The Cardiovascular Subcohort of the Malmo Diet and Cancer cohort includes 6103 participants from the general population of Malmo, Sweden. The participants were recruited 1991-1994. Annual mean residential exposure to particulate matter < 2.5 and < 10 mu m (PM2.5 and PM10), and nitrogen oxides (NOx) at year of recruitment were assigned from dispersion models. Blood samples collected at recruitment, including blood cell counts, and biomarkers (lymphocyte- and neutrophil counts, C-reactive protein (CRP), soluble urokinase-type plasminogen activator receptor (suPAR), lipoprotein-associated phospholipase A(2) (Lp-PLA(2)), ceruloplasmin, orosomucoid, haptoglobin, complement-C3, and alpha-1-antitrypsin) were analyzed. Multiple linear regression models were used to investigate the cross-sectional associations between air pollutants and biomarkers. Results The mean annual exposure levels in the cohort were only slightly or moderately above the new WHO guidelines of 5 mu g/m(3) PM2.5 (10.5 mu g/m(3) PM2.5). Residential PM2.5 exposure was associated with increased levels of ceruloplasmin, orosomucoid, C3, alpha-1-antitrypsin, haptoglobin, Lp-PLA(2) and the neutrophil-lymphocyte ratio. Ceruloplasmin, orosomucoid, C3 and alpha-1-antitrypsin were also positively associated with PM10. There were no associations between air pollutants and suPAR, leukocyte counts or CRP. The associations between particles and biomarkers were still significant after removing outliers and adjustment for CRP levels. The associations were more prominent in smokers. Conclusion Long-term residential exposure to moderate levels of particulate air pollution was associated with several biomarkers of inflammation and cardiovascular disease. This supports inflammation as a mechanism behind the association between air pollution and cardiovascular disease.
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| 5. |
- Azzouz, Mehjar, 1999, et al.
(författare)
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Long-term ambient air pollution and venous thromboembolism in a population-based Swedish cohort.
- 2023
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Ingår i: Environmental pollution (Barking, Essex : 1987). - : Elsevier. - 1873-6424 .- 0269-7491. ; 331:Pt 1
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Tidskriftsartikel (refereegranskat)abstract
- Air pollution is a major contributor to the global burden of disease and has been linked to several diseases and conditions, including cardiovascular disease. The biological mechanisms are related to inflammation and increased coagulability, factors that play an important role in the pathogenesis of venous thromboembolism (VTE, i.e., deep vein thrombosis or pulmonary embolism). This study investigates if long-term exposure to air pollution is associated with increased VTE incidence. The study followed 29408 participants from the Malmö Diet and Cancer (MDC) cohort, which consists of adults aged 44-74 recruited in Malmö, Sweden between 1991 and 1996. For each participant, annual mean residential exposures to particulate matter <2.5μg (PM2.5) and <10μg (PM10), nitrogen oxides (NOx) and black carbon (BC) from 1990 up to 2016 were calculated. Associations with VTE were analysed using Cox proportional hazard models for air pollution in the year of the VTE event (lag0) and the mean of the prior 1-10 years (lag1-10). Annual air pollution exposures for the full follow-up period had the following means: 10.8μg/m3 for PM2.5, 15.8μg/m3 for PM10, 27.7μg/m3 for NOx, and 0.96μg/m3 for BC. The mean follow-up period was 19.5 years, with 1418 incident VTE events recorded during this period. Exposure to lag1-10 PM2.5 was associated with an increased risk of VTE (HR 1.17 (95%CI 1.01-1.37)) per interquartile range (IQR) of 1.2μg/m3 increase in PM2.5 exposure. No significant associations were found between other pollutants or lag0 PM2.5 and incident VTE. When VTE was divided into specific diagnoses, associations with lag1-10 PM2.5 exposure were similarly positive for deep vein thrombosis but not for pulmonary embolism. Results persisted in sensitivity analyses and in multi-pollutant models. Long-term exposure to moderate concentrations of ambient PM2.5 was associated with increased risks of VTE in the general population in Sweden.
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| 6. |
- Berntsson, John, et al.
(författare)
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Risk of Stroke in Patients With Atrial Fibrillation Is Associated With Stroke in Siblings : A Nationwide Study
- 2020
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Ingår i: Journal of the American Heart Association. - 2047-9980. ; 9:3, s. 014132-014132
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Tidskriftsartikel (refereegranskat)abstract
- Background: It remains unclear whether heritable factors can contribute to risk stratification for ischemic stroke in patients with atrial fibrillation (AF). We examined whether having a sibling with ischemic stroke was associated with increased risk of ischemic stroke and mortality in patients with AF. Methods and Results: In this nationwide study of the Swedish population, patients with AF and their siblings were identified from the Swedish patient registers and the Swedish MGR (Multi-Generation Register). Ischemic stroke events were retrieved from the Swedish patient registers and CDR (Cause of Death Register). Risk of ischemic stroke was compared between patients with AF with and without a sibling affected by ischemic stroke, AF, or both ischemic stroke and AF. The total study population comprised 113 988 subjects (mean age, 60±12 years) diagnosed with AF between 1989 and 2012. In total, 11 709 of them were diagnosed with a first ischemic stroke and 20 097 died during a mean follow-up time of 5.5 years for ischemic stroke and 5.9 years for mortality. After adjustment for covariates having a sibling with ischemic stroke, or both ischemic stroke and AF, was associated with increased risk of ischemic stroke (hazard ratio, 1.31; 95% CI, 1.23-1.40 or hazard ratio, 1.36; 95% CI, 1.24-1.49, respectively). Furthermore, ischemic stroke in a sibling was associated with all-cause mortality (hazard ratio, 1.09; 95% CI, 1.05-1.14). In contrast, the risk of stroke was only marginally increased for patients with AF with a spouse affected by ischemic stroke. Conclusions: Having a sibling affected by ischemic stroke confers an increased risk of ischemic stroke and death independently of traditional risk factors in patients with AF.
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| 7. |
- Brink, Annie, et al.
(författare)
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Sex-Specific Risk Factors for Deep Venous Thrombosis and Pulmonary Embolism in a Population-Based Historical Cohort Study of Middle-Aged and Older Individuals
- 2023
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Ingår i: Journal of the American Heart Association. - 2047-9980. ; 12:5, s. 1-13
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Whether sex-specific differences exist for risk factors for pulmonary embolism (PE) and deep venous thrombosis (DVT), with the exception of pregnancy and estrogen therapy, has been sparsely studied. We aimed to study whether sex-specific differences of risk factors exist for noncancer-related DVT and PE in middle-aged and older individuals without cardiovascular history or previous diagnosis in a population-based historical (retrospective) cohort. METHODS AND RESULTS: Potential venous thromboembolism (VTE) risk factors were registered at baseline in 15 807 women and 9996 men aged 44 to 74 years, who participated in the Malmö Diet and Cancer study (1991–1996). We excluded subjects with a previous history of VTE, cancer, a diagnosis of cardiovascular disease, or a diagnosis of cancer-associated VTE during follow-up. Patients were followed up from baseline until the first event of PE or DVT, death, or December 31, 2018. During the follow-up period, 365 (2.3%) women and 168 (1.7%) men were affected by first DVT, and 309 (2.0%) women and 154 (1.5%) men were affected by first PE. In the multivariable Cox regression models, the anthropometric obesity markers of weight, body mass index, waist and hip circumference, fat percentage, and muscle weight were in a dose-dependent way associated with DVT and PE among women but not men. In an analysis that included patients with cardiovascular disease and cancer-related VTE, the results were similar for women. For men, several obesity measures became significantly associated with PE or DVT but were weaker than in women, especially for DVT. CONCLUSIONS: Anthropometric obesity measures are more important risk factors for both DVT and PE among women than men, especially for individuals without cardiovascular history or previous diagnosis or cancer-related VTE.
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| 8. |
- Calling, Susanna, et al.
(författare)
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Lung function, respiratory symptoms and incident venous thromboembolism during a 44-year follow-up
- 2023
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Ingår i: Thrombosis Update. - Oxford : Elsevier. - 2666-5727. ; 12
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Tidskriftsartikel (refereegranskat)abstract
- Background: Chronic obstructive pulmonary disease (COPD) and infections are risk factors for venous thromboembolism (VTE), but the reasons behind the associations are not fully known. Few studies have investigated whether lung function and respiratory symptoms in individuals without COPD are associated with VTE. Objectives: To study the incidence of VTE in individuals without COPD and other major VTE risk factors, in relation to baseline lung function and respiratory symptoms, through a 44-year follow-up prospective cohort study. Methods: As part of a health screening program, a total of 20,253 men and 7361 women underwent a baseline examination from 1974 to 1992, including a spirometry test and a self-administered questionnaire about respiratory symptoms, e.g., chronic bronchitis, cough, phlegm, and dyspnoea. Lung function was assessed through quartiles of forced expiratory volume in 1 s/forced vital capacity (FEV1/FVC). Through linkage with national registers, all individuals were followed for incidence of VTE. Results: Respiratory symptoms (cough and dyspnoea) at baseline were associated with an increased risk of incident VTE in women after adjustments for age, height, BMI, smoking status, varicose veins, and FEV1/FVC. The adjusted hazard ratio in relation to chronic bronchitis was 1.57 (95% confidence interval 1.17–2.11). Poor lung function was not associated with an increased risk of VTE after adjustments for potential confounders. Conclusion: Women with respiratory symptoms of cough and dyspnoea without COPD have an increased risk of VTE, independent of lung function and major VTE risk factors. Further studies are needed to confirm the association and to study the clinical applicability of the results. © 2023 The Authors
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| 9. |
- Fedorowski, Artur, et al.
(författare)
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Familial Associations of Complete Atrioventricular Block : A National Family Study in Sweden
- 2023
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Ingår i: Circulation. Genomic and precision medicine. - 2574-8300. ; 16:2
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Complete atrioventricular block (CAVB) is a major reason for implantation of permanent pacemakers, but knowledge of CAVB inheritance is sparse. This nationwide study aimed to determine the occurrence of CAVB in first-, second-, and third-degree relatives (full siblings, half-siblings, and cousins).METHODS: The Swedish multigeneration register was linked to the Swedish nationwide patient register for the period 1997 to 2012. All Swedish full sibling, half-sibling, and cousin pairs born to Swedish parents between 1932 and 2012 were included. Competing risks and time-to-event, subdistributional hazard ratios (SHRs) according to Fine and Gray and hazard ratios using Cox proportional hazards model were estimated using robust SEs and considering the relatedness of relatives (full siblings, half-siblings, cousins). Additionally, odds ratios (ORs) for CAVB were calculated for traditional cardiovascular comorbidities.RESULTS: The study population (n=6 113 761) consisted of 5 382 928 full siblings, 1 266 391 half-siblings, and 3 750 913 cousins. In total, 6442 (0.11%) unique individuals were diagnosed with CAVB. Of these, 4200 (65.2%) were males. SHRs for CAVB were 2.91 for full siblings (95% CI, 2.43-3.49), 1.51 for half-siblings (0.56-4.10), and 3.54 for cousins (1.73-7.26) of affected individuals. Age-stratified analysis showed higher risk in young individuals born from 1947 to 1986: SHR, 5.30 (3.78-7.43) for full siblings, SHR, 3.30 (1.06-10.31) for half-siblings, and SHR, 3.15 (1.39-7.17) for cousins. Similar familial HRs according to Cox proportional hazard model and ORs were obtained without any major differences. Apart from familial relationship, CAVB was associated with hypertension (OR, 1.83), diabetes (OR, 1.41), coronary heart disease (OR, 2.08), heart failure (OR, 5.01), and structural heart disease (OR, 4.59).CONCLUSIONS: Risk of CAVB among relatives of affected individuals depends on relationship degree, being strongest in young siblings. The familial association extending to third-degree relatives indicates presence of genetic components in the cause of CAVB.
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| 10. |
- Fedorowski, Artur, et al.
(författare)
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Risk Factors for Syncope Associated With Multigenerational Relatives With a History of Syncope
- 2021
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Ingår i: JAMA Network Open. - : American Medical Association (AMA). - 2574-3805. ; 4:3
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Tidskriftsartikel (refereegranskat)abstract
- Importance: Reflex syncope is the major cause of transient loss of consciousness, which affects one-third of the population, but effective treatment for individuals with severe syncope is lacking. Better understanding of reflex syncope predisposition may offer new therapeutic solutions.Objectives: To determine the familial risk of syncope in first-, second-, and third-degree relatives of affected individuals and to explore the role of genes and family environment in reflex syncope.Design, Setting, and Participants: In this national population-based family cohort study, the Swedish multigeneration register was linked to 3 Swedish nationwide registers: hospital discharge, outpatient care, and primary care registers for the period from 1997 to 2015. Sibling pairs born to Swedish parents between 1948 and 2005 were included. Linkage was also made to half-siblings and cousins. Data analysis was performed from June to October 2020.Exposures: Register-based syncope diagnosis among relatives: pairs of twins, siblings, half-siblings, and cousins.Main Outcomes and Measures: Odds ratios for syncope were calculated for relatives (twins, siblings, half-siblings, and cousins) of individuals who had syncope compared with relatives of individuals without syncope for reference. Sensitivity analysis excluding families with definite nonreflex syncope diagnosis was performed.Results: Among the study population of 2 694 442 participants, 1 381 453 (51.3%) were male, and the median (interquartile range) age was 32 (22-43) years. The study population consisted of 24 020 twins, 1 546 108 siblings, 264 244 half-siblings, and 1 044 546 cousins. In total, 61 861 (2.30%) unique individuals were diagnosed with syncope. Sixty-two percent (38 226) of the syncope-positive individuals were female. The odds ratio (OR) for syncope was 2.39 (95% CI, 1.61-3.53) for twins, 1.81 (95% CI, 1.71-1.91) for siblings, 1.28 (95% CI, 1.20-1.37) for half-siblings, and 1.13 (95% CI, 1.10-1.17) for cousins of individuals with syncope. The OR was highest among male twins at 5.03 (95% CI, 2.57-9.85). The proportion of syncope-positive individuals was consistently higher in women vs men, regardless of degree of relationship (twins: 346 [2.88%] vs 193 [1.61%]; siblings: 22 111 [2.92%] vs 13 419 [1.70%], half-siblings: 4148 [3.44%] vs 2425 [1.93%], cousins: 14 498 [2.87%] vs 9246 [1.72%]). Exclusion of nonreflex syncope diagnoses did not change syncope risk in affected families.Conclusions and Relevance: In this Swedish national population-based study, the risk of syncope among relatives of affected individuals was associated with the relationship degree and was strongest in twins and siblings, which suggests that there are genetic components of reflex syncope. Women were more likely to experience syncope independently of family relationship. A better understanding of genetic predisposition to reflex syncope may offer new therapeutic options in severely affected individuals.
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