Background: Studies have shown that chronic obstructive pulmonary disease (COPD) exacerbation events are related to future events; however, previous literature typically reports frequent vs infrequent exacerbations per patient-year and no studies have investigated increasing number of severe exacerbations in relation to COPD outcomes. Objective: To investigate the association between baseline frequency and severity of exacerbations and subsequent mortality and exacerbation risk in a COPD cohort. Methods: Clinical Practice Research Datalink (CPRD) Aurum and Hospital Episode Statistics data were used to identify patients registered at general practices in the UK, who had a diagnosis of COPD, were over the age of 40 years, were smokers or ex-smokers and had data recorded from 2004 onwards. Frequency and severity of exacerbations in the baseline year were identified as moderate exacerbations (general practice events) and severe exacerbations (hospitalised events). Patients were categorised as having: none, 1 moderate only, 2 moderate only, 3+ moderate only, 1 severe (and any moderate), 2 severe (and any moderate), and 3+ severe (and any moderate exacerbations). Poisson regression was used to investigate the association between baseline exacerbation frequency/severity and exacerbation events and mortality over follow-up. Results: Overall, 340,515 COPD patients were included. Patients had higher rates of future exacerbations with increasing frequency and severity of baseline exacerbations compared to no baseline exacerbations. Adjusted incidence rate ratios (IRR) for patients with 1, 2, and 3+ moderate exacerbations compared to 0 exacerbations were 1.70 (95% CI 1.66-1.74), 2.31 (95% CI 2.24-2.37), and 3.52 (95% CI 3.43-3.62), respectively. Patients with increased frequency of baseline exacerbations were more likely to die from all-cause, COPD-related, and cardiovascular-related mortality in a graduated fashion. Conclusion:Increasing number and severity of exacerbations were associated with increasing risk of subsequent exacerbations, allcause mortality and COPD-related mortality. Even a single moderate event increases the risk of future events, illustrating that every exacerbation counts.
Accelerated lung function decline has been associated with increased risk of cardiovascular disease (CVD) in a general population, but little is known about this association in chronic obstructive pulmonary disease (COPD). We investigated the association between accelerated lung function decline and CVD outcomes and mortality in a primary care COPD population.COPD patients without a history of CVD were identified in the Clinical Practice Research Datalink (CPRD-GOLD) primary care dataset (n=36 282). Accelerated FEV1 decline was defined using the fastest quartile of the COPD population's decline. Cox regression assessed the association between baseline accelerated FEV1 decline and a composite CVD outcome over follow-up (myocardial infarction, ischaemic stroke, heart failure, atrial fibrillation, coronary artery disease, and CVD mortality). The model was adjusted for age, gender, smoking status, BMI, history of asthma, hypertension, diabetes, statin use, mMRC dyspnoea, exacerbation frequency, and baseline FEV1 percent predicted.6110 (16.8%) COPD patients had a CVD event during follow-up; median length of follow-up was 3.6 years [IQR 1.7–6.1]). Median rate of FEV1 decline was –19.4 mL·year−1 (IQR, –40.5 to 1.9); 9095 (25%) patients had accelerated FEV1 decline (>–40.5 mL·year−1), 27 287 (75%) did not (≤ –40.5 mL·year−1). Risk of CVD and mortality was similar between patients with and without accelerated FEV1 decline (HRadj 0.98 [95%CI, 0.90–1.06]). Corresponding risk estimates were 0.99 (95%CI 0.83–1.20) for heart failure, 0.89 (95%CI 0.70–1.12) for myocardial infarction, 1.01 (95%CI 0.82–1.23) for stroke, 0.97 (95%CI 0.81–1.15) for atrial fibrillation, 1.02 (95%CI 0.87–1.19) for coronary artery disease, and 0.94 (95%CI 0.71–1.25) for CVD mortality. Rather, risk of CVD was associated with mMRC score ≥2 and ≥2 exacerbations in the year prior.CVD outcomes and mortality were associated with exacerbation frequency and severity and increased mMRC dyspnoea but not with accelerated FEV1 decline.
Aims/hypothesisDiabetes is associated with an increased risk of dementia. We estimated the potential impact of trends in diabetes prevalence upon mortality and the future burden of dementia and disability in England and Wales.MethodsWe used a probabilistic multi-state, open cohort Markov model to integrate observed trends in diabetes, cardiovascular disease and dementia to forecast the occurrence of disability and dementia up to the year 2060. Model input data were taken from the English Longitudinal Study of Ageing, Office for National Statistics vital data and published effect estimates for health-state transition probabilities. The baseline scenario corresponded to recent trends in obesity: a 26% increase in the number of people with diabetes by 2060. This scenario was evaluated against three alternative projected trends in diabetes: increases of 49%, 20% and 7%.ResultsOur results suggest that changes in the trend in diabetes prevalence will lead to changes in mortality and incidence of dementia and disability, which will become visible after 10–15 years. If the relative prevalence of diabetes increases 49% by 2060, expected additional deaths would be approximately 255,000 (95% uncertainty interval [UI] 236,000–272,200), with 85,900 (71,500–101,600) cumulative additional cases of dementia and 104,900 (85,900–125,400) additional cases of disability. With a smaller relative increase in diabetes prevalence (7% increase by 2060), we estimated 222,200 (205,700–237,300) fewer deaths, and 77,000 (64,300–90,800) and 93,300 (76,700–111,400) fewer additional cases of dementia and disability, respectively, than the baseline case of a 26% increase in diabetes.Conclusions/interpretationReducing the burden of diabetes could result in substantial reductions in the incidence of dementia and disability over the medium to long term.Electronic supplementary materialThe online version of this article (10.1007/s00125-019-05015-4) contains peer-reviewed but unedited supplementary supplementary material, which is available to authorised users.
Background: Estimates for lung function decline in chronic obstructive pulmonary disease (COPD) have differed by study setting and have not been described in a UK primary care population. Purpose: To describe rates of FEV 1 and FVC decline in COPD and investigate characteristics associated with accelerated decline. Patients and Methods: Current/ex-smoking COPD patients (35 years+) who had at least 2 FEV 1 or FVC measurements ≥6 months apart were included using Clinical Practice Research Datalink. Patients were followed up for a maximum of 13 years. Accelerated rate of lung function decline was defined as the fastest quartile of decline using mixed linear regression, and association with baseline characteristics was investigated using logistic regression. Results: A total of 72,683 and 50,649 COPD patients had at least 2 FEV 1 or FVC measurements, respectively. Median rates of FEV 1 and FVC changes or decline were −18.1mL/year (IQR: −31.6 to −6.0) and −22.7mL/year (IQR: −39.9 to −6.7), respectively. Older age, high socioeconomic status, being underweight, high mMRC dyspnoea and frequent AECOPD or severe AECOPD were associated with an accelerated rate of FEV 1 and FVC decline. Current smoking, mild airflow obstruction and inhaled corticosteroid treatment were additionally associated with accelerated FEV 1 decline whilst women, sputum production and severe airflow obstruction were associated with accelerated FVC decline. Conclusion: Rate of FEV 1 and FVC decline was similar and showed similar heterogeneity. Whilst FEV 1 and FVC shared associations with baseline characteristics, a few differences highlighted the importance of both lung function measures in COPD progression. We identified important characteristics that should be monitored for disease progression.
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