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      Is having asthma associated with an increased risk of dying from cardiovascular disease? A prospective cohort study of 446 346 Taiwanese adults

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          Abstract

          Objectives

          A significant proportion of cardiovascular disease (CVD) cannot be explained by well-known risk factors such as high cholesterol, hypertension and diabetes. One potential novel risk factor for CVD is asthma. We aimed to investigate the association between asthma and mortality due to CVD.

          Design

          Prospective cohort study.

          Setting

          A large health check-up programme from 1994 to 2011 in Taipei, Taiwan.

          Participants

          446 346 Taiwanese adults. Each participant answered questions regarding asthma history (yes/no) and current daily use of asthma medications (yes/no). Active asthma was defined as those using current daily medications for asthma.

          Outcomes

          The participants were followed for mortality from CVD, coronary heart disease (CHD) and stroke obtained through linkage to the cause-of-death register until 31 December 2011.

          Results

          We found an increased risk of dying from CVD in individuals with active asthma (adjusted HR (aHR) 1.32, 95% CI 1.08 to 1.62). The risk of death from CHD or stroke was increased in a similar manner (aHR 1.16, 95% CI 0.78 to 1.73 and aHR 1.23, 95% CI 0.86 to 1.74, respectively) although the HR estimates were less precise than that of CVD. For deaths from CVD, CHD and stroke, we found stronger associations with active asthma than non-active asthma, and for CVD and stroke stronger associations in men than women.

          Conclusion

          Our study suggests that asthma, particularly active asthma, may be associated with adverse cardiovascular consequences.

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          Most cited references28

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          C-Reactive protein, a sensitive marker of inflammation, predicts future risk of coronary heart disease in initially healthy middle-aged men: results from the MONICA (Monitoring Trends and Determinants in Cardiovascular Disease) Augsburg Cohort Study, 1984 to 1992.

          Inflammatory reactions in coronary plaques play an important role in the pathogenesis of acute atherothrombotic events; inflammation elsewhere is also associated with both atherogenesis generally and its thrombotic complications. Recent studies indicate that systemic markers of inflammation can identify subjects at high risk of coronary events. We used a sensitive immunoradiometric assay to examine the association of serum C-reactive protein (CRP) with the incidence of first major coronary heart disease (CHD) event in 936 men 45 to 64 years of age. The subjects, who were sampled at random from the general population, participated in the first MONICA Augsburg survey (1984 to 1985) and were followed for 8 years. There was a positive and statistically significant unadjusted relationship, which was linear on the log-hazards scale, between CRP values and the incidence of CHD events (n=53). The hazard rate ratio (HRR) of CHD events associated with a 1-SD increase in log-CRP level was 1.67 (95% CI, 1.29 to 2. 17). After adjustment for age, the HRR was 1.60 (95% CI, 1.23 to 2. 08). Adjusting further for smoking behavior, the only variable selected from a variety of potential confounders by a forward stepping process with a 5% change in the relative risk of CRP as the selection criterion, yielded an HRR of 1.50 (95% CI, 1.14 to 1.97). These results confirm the prognostic relevance of CRP, a sensitive systemic marker of inflammation, to the risk of CHD in a large, randomly selected cohort of initially healthy middle-aged men. They suggest that low-grade inflammation is involved in pathogenesis of atherosclerosis, especially its thrombo-occlusive complications.
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            Gender differences in airway behaviour over the human life span.

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              Severe exacerbations and decline in lung function in asthma.

              To evaluate the association between asthma exacerbations and the decline in lung function, as well as the potential effects of an inhaled corticosteroid, budesonide, on exacerbation-related decline in patients with asthma. To determine whether severe asthma exacerbations are associated with a persistent decline in lung function. The START (inhaled steroid treatment as regular therapy in early asthma) study was a 3-year, randomized, double-blind study of 7,165 patients (5-66 yr) with persistent asthma for less than 2 years, to determine whether early intervention with low-dose inhaled budesonide prevents severe asthma-related events (exacerbations requiring hospitalization or emergency treatment) and decline in lung function. There were 315 patients who experienced at least one severe asthma exacerbation, of which 305 were analyzable, 190 in the placebo group and 115 in the budesonide group. In the placebo group, the change in post-bronchodilator FEV(1) % predicted from baseline to the end of the study, in patients who did or did not experience a severe exacerbation was -6.44% and -2.43%, respectively (P < 0.001). A significant difference was seen in both children and in adults, but not in adolescents. In the budesonide group, the change in the post-bronchodilator FEV(1) % predicted in patients who did or did not experience a severe exacerbation was -2.48% and -1.72%, respectively (P = 0.57). The difference in magnitude of reduction afforded by budesonide, in patients who experienced at least one severe asthma-related event compared with those who did not, was statistically significant (P = 0.042). Severe asthma exacerbations are associated with a more rapid decline in lung function. Treatment with low doses of inhaled corticosteroid is associated with an attenuation of the decline.
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                Author and article information

                Journal
                BMJ Open
                BMJ Open
                bmjopen
                bmjopen
                BMJ Open
                BMJ Publishing Group (BMA House, Tavistock Square, London, WC1H 9JR )
                2044-6055
                2018
                31 May 2018
                : 8
                : 5
                : e019992
                Affiliations
                [1 ] departmentDepartment of Public Health and Nursing , Norwegian University of Science and Technology , Trondheim, Norway
                [2 ] departmentInstitute of Epidemiology and Preventive Medicine , College of Public Health, National Taiwan University , Taipei City, Taiwan
                [3 ] China Medical University Hospital , Taichung, Taiwan
                [4 ] departmentInstitute of Population Health Sciences , National Health Research Institutes , Miaoli County, Taiwan
                [5 ] departmentInstitute of Health Behaviors and Community Sciences , College of Public Health, National Taiwan University , Taipei City, Taiwan
                [6 ] departmentDepartment of Thoracic and Occupational Medicine , St. Olavs Hospital , Trondheim, Norway
                [7 ] departmentK.G. Jebsen Center for Genetic Epidemiology, Department of Public Health and Nursing , Norwegian University of Science and Technology , Trondheim, Norway
                [8 ] departmentMRC Integrative Epidemiology Unit , University of Bristol , Bristol, UK
                Author notes
                [Correspondence to ] Dr Chi Pang Wen; cwengood@ 123456nhri.org.tw and Dr Shu-Sen Chang; shusenchang@ 123456ntu.edu.tw
                Article
                bmjopen-2017-019992
                10.1136/bmjopen-2017-019992
                5988076
                29858410
                2bc8ad65-9653-459f-939b-107824938bd6
                © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

                This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/

                History
                : 06 October 2017
                : 12 March 2018
                : 19 April 2018
                Funding
                Funded by: the Liaison Committee between the Central Norway Regional Health Authority and the Norwegian University of Science and Technology;
                Categories
                Epidemiology
                Research
                1506
                1692
                Custom metadata
                unlocked

                Medicine
                asthma,cardiology,epidemiology
                Medicine
                asthma, cardiology, epidemiology

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