Asthma, asthma control and risk of ischemic stroke:The HUNT study

Background: Asthma, a chronic inflammatory airway disease, shares common pathophysiological mechanisms with ischemic stroke. The aim of the study is to assess the association between asthma, levels of asthma control and ischemic stroke risk in men and women and by smoking habits. Methods: This prospective population-based cohort study utilized data on 58 712 adults from HUNT Study in Norway free from stroke. Self-reported asthma was categorized as ever asthma, non-active asthma and active asthma (i.e., being on asthma medication within 12 months of the baseline). Asthma control was defined ac-cording to the Global Initiative for Asthma questionnaire and was categorized into controlled and not controlled asthma. Stroke was ascertained by linking HUNT data with Nord-Trøndelag hospital records and the Norwegian Patient Registry. Results: During a mean follow-up of 17.3 �5.3 years, 2619 participants (4.5%) had a first stroke. Not controlled asthma was associated with a modest increased risk of stroke (adjusted HR 1.34, 95%CI 1.03–1.73). Subgroup analyses revealed that the respective association was stronger among those with history of smoking (HR 1.48, 95%CI 1.10–2.00) and males (HR 1.55, 95%CI 1.12–2.16) while absent in non-smokers (HR 1.02, 95%CI 0.61–1.70) and females (HR 1.05, 95%CI 0.69–1.60). Likewise, active asthma was associated with similar increased stroke risk among smokers and males and absent in non-smokers and females. Conclusions: Symptomatic and active asthma was associated with a modest increased relative risk for ischemic stroke in smokers and males. Future studies should clarify the difference in risks and mechanisms between different phenotypes of asthma

Genetic Associations and Architecture of Asthma-COPD Overlap

BACKGROUND: Some people have characteristics of both asthma and COPD (asthma-COPD overlap), and evidence suggests they experience worse outcomes than those with either condition alone. RESEARCH QUESTION: What is the genetic architecture of asthma-COPD overlap, and do the determinants of risk for asthma-COPD overlap differ from those for COPD or asthma? STUDY DESIGN AND METHODS: We conducted a genome-wide association study in 8,068 asthma-COPD overlap case subjects and 40,360 control subjects without asthma or COPD of European ancestry in UK Biobank (stage 1). We followed up promising signals (P < 5 x 10(-6)) that remained associated in analyses comparing (1) asthma-COPD overlap vs asthma-only control subjects, and (2) asthma-COPD overlap vs COPD-only control subjects. These variants were analyzed in 12 independent cohorts (stage 2). RESULTS: We selected 31 independent variants for further investigation in stage 2, and discovered eight novel signals (P < 5 x 10(-8)) for asthma-COPD overlap (meta-analysis of stage 1 and 2 studies). These signals suggest a spectrum of shared genetic influences, some predominantly influencing asthma (FAM105A, GLB1, PHB, TSLP), others predominantly influencing fixed airflow obstruction (IL17RD, C5orf56, HLA-DQB1). One intergenic signal on chromosome 5 had not been previously associated with asthma, COPD, or lung function. Subgroup analyses suggested that associations at these eight signals were not driven by smoking or age at asthma diagnosis, and in phenome-wide scans, eosinophil counts, atopy, and asthma traits were prominent. INTERPRETATION: We identified eight signals for asthma-COPD overlap, which may represent loci that predispose to type 2 inflammation, and serious long-term consequences of asthma.Peer reviewe

Genetic Associations and Architecture of Asthma-COPD Overlap

BackgroundSome people have characteristics of both asthma and COPD (asthma-COPD overlap), and evidence suggests they experience worse outcomes than those with either condition alone.Research QuestionWhat is the genetic architecture of asthma-COPD overlap, and do the determinants of risk for asthma-COPD overlap differ from those for COPD or asthma?Study Design and MethodsWe conducted a genome-wide association study in 8,068 asthma-COPD overlap case subjects and 40,360 control subjects without asthma or COPD of European ancestry in UK Biobank (stage 1). We followed up promising signals (P –6) that remained associated in analyses comparing (1) asthma-COPD overlap vs asthma-only control subjects, and (2) asthma-COPD overlap vs COPD-only control subjects. These variants were analyzed in 12 independent cohorts (stage 2).ResultsWe selected 31 independent variants for further investigation in stage 2, and discovered eight novel signals (P –8) for asthma-COPD overlap (meta-analysis of stage 1 and 2 studies). These signals suggest a spectrum of shared genetic influences, some predominantly influencing asthma (FAM105A, GLB1, PHB, TSLP), others predominantly influencing fixed airflow obstruction (IL17RD, C5orf56, HLA-DQB1). One intergenic signal on chromosome 5 had not been previously associated with asthma, COPD, or lung function. Subgroup analyses suggested that associations at these eight signals were not driven by smoking or age at asthma diagnosis, and in phenome-wide scans, eosinophil counts, atopy, and asthma traits were prominent.InterpretationWe identified eight signals for asthma-COPD overlap, which may represent loci that predispose to type 2 inflammation, and serious long-term consequences of asthma.</p

Asthma, asthma control and risk of ischemic stroke: The HUNT study

Background: Asthma, a chronic inflammatory airway disease, shares common pathophysiological mechanisms with ischemic stroke. The aim of the study is to assess the association between asthma, levels of asthma control and ischemic stroke risk in men and women and by smoking habits. Methods: This prospective population-based cohort study utilized data on 58 712 adults from HUNT Study in Norway free from stroke. Self-reported asthma was categorized as ever asthma, non-active asthma and active asthma (i.e., being on asthma medication within 12 months of the baseline). Asthma control was defined ac-cording to the Global Initiative for Asthma questionnaire and was categorized into controlled and not controlled asthma. Stroke was ascertained by linking HUNT data with Nord-Trøndelag hospital records and the Norwegian Patient Registry. Results: During a mean follow-up of 17.3 �5.3 years, 2619 participants (4.5%) had a first stroke. Not controlled asthma was associated with a modest increased risk of stroke (adjusted HR 1.34, 95%CI 1.03–1.73). Subgroup analyses revealed that the respective association was stronger among those with history of smoking (HR 1.48, 95%CI 1.10–2.00) and males (HR 1.55, 95%CI 1.12–2.16) while absent in non-smokers (HR 1.02, 95%CI 0.61–1.70) and females (HR 1.05, 95%CI 0.69–1.60). Likewise, active asthma was associated with similar increased stroke risk among smokers and males and absent in non-smokers and females. Conclusions: Symptomatic and active asthma was associated with a modest increased relative risk for ischemic stroke in smokers and males. Future studies should clarify the difference in risks and mechanisms between different phenotypes of asthma

Joint Association of Low Vitamin D and Vitamin K Status with Blood Pressure and Hypertension

Low Vitamin D and K status are both associated with an increased cardiovascular risk. New evidence from experimental studies on bone health suggest an interaction between Vitamin D and K; however, a joint association with vascular health outcomes is largely unknown. To prospectively investigate whether the combination of low Vitamin D and K status is associated with higher systolic and diastolic blood pressure in 402 participants and with incident hypertension in 231 participants free of hypertension at baseline. We used data from a subsample of the Longitudinal Aging Study Amsterdam, a population-based cohort of Dutch participants aged 55 to 65 years. Vitamin D and K status were assessed by 25-hydroxyVitamin D and dp-ucMGP (dephosphorylated uncarboxylated matrix gla protein) concentrations (high dp-ucMGP is indicative for low Vitamin K status) in stored samples from 2002 to 2003. Vitamin D and K status were categorized into 25-hydroxyVitamin D <50/≥50 mmol/L and median dp-ucMGP <323/≥323 pmol/L. During a median follow-up of 6.4 years, 62% of the participants (n=143) developed hypertension. The combination of low Vitamin D and K status was associated with increased systolic 4.8 mm Hg (95% confidence interval, 0.1-9.5) and diastolic 3.1 mm Hg (95% confidence interval, 0.5-5.7) blood pressure compared with high Vitamin D and K status (P for interaction =0.013 for systolic blood pressure and 0.068 for diastolic blood pressure). A similar trend was seen for incident hypertension: hazard ratio=1.62 (95% confidence interval, 0.96-2.73) for the low Vitamin D and K group. The combination of low Vitamin D and K status was associated with increased blood pressure and a trend for greater hypertension risk

Associations of asthma and asthma control with atrial fibrillation risk: Results from the Nord-Trøndelag health study (HUNT)

Importance Asthma, a chronic inflammatory airway disease, and atrial fibrillation (AF) share several common pathophysiological mechanisms. Research on the association between asthma and atrial fibrillation is lacking, and to our knowledge, no previous studies have assessed the dose-response association between levels of asthma control and AF. Objective To assess the association between asthma, levels of asthma control, and AF. Design, Setting, and Participants This prospective population cohort analyzed data on adults from a second and third iteration of the survey-based Nord-Trøndelag Health Study (HUNT) in Norway. All included participants were free from AF at baseline. Atrial fibrillation was ascertained by linking HUNT data with hospital records from the 2 hospitals in Nord-Trøndelag County. Data analysis was completed from May 2017 to November 2017. Exposures Self-reported asthma was categorized into 3 groups: those who had ever had asthma, those who self-report being diagnosed with asthma, and those who had active asthma. Asthma control was defined according to Global Initiative for Asthma guidelines and was categorized into controlled, partly controlled, and uncontrolled cases. Main Outcomes and Measures Atrial fibrillation. Results A total of 54 567 adults were included (of whom 28 821 [52.8%] were women). Of these, 5961 participants (10.9%) reported ever having asthma, 3934 participants (7.2%) reported being diagnosed with asthma, and 2485 participants (4.6%) reported having active asthma. During a mean (SD) follow-up of 15.4 (5.8) years, 2071 participants (3.8%) developed AF. Participants with physician-diagnosed asthma had an estimated 38% higher risk of developing AF (adjusted hazard ratio, 1.38 [95% CI, 1.18-1.61]) compared with participants without asthma. There was a dose-response association between levels of asthma control and risk of AF with the highest risk for AF in participants with uncontrolled asthma (adjusted hazard ratio, 1.74 [95% CI, 1.26–2.42]; P for trend < .001). Conclusions and Relevance Asthma and lack of asthma control were associated with moderately increased risks of AF in a dose-response manner. Further studies are needed to explore the underlying mechanisms and clarify causal pathways between asthma and AF

Genetic Associations and Architecture of Asthma-COPD Overlap

Background Some people have characteristics of both asthma and COPD (asthma-COPD overlap), and evidence suggests they experience worse outcomes than those with either condition alone. Research Question What is the genetic architecture of asthma-COPD overlap, and do the determinants of risk for asthma-COPD overlap differ from those for COPD or asthma? Study Design and Methods We conducted a genome-wide association study in 8,068 asthma-COPD overlap case subjects and 40,360 control subjects without asthma or COPD of European ancestry in UK Biobank (stage 1). We followed up promising signals (P Results We selected 31 independent variants for further investigation in stage 2, and discovered eight novel signals (P Interpretation We identified eight signals for asthma-COPD overlap, which may represent loci that predispose to type 2 inflammation, and serious long-term consequences of asthma.</p