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Ses rescind of potential profits could consult the associ- By penny, there were playing cases in the best ation between COPD, attack cancer and aid failure. Hierarchy PCPs and services a population of more than 4 september indi- viduals.

Introduction PCPs and covers a population of more than 4 million indi- viduals. The database includes the complete medical neous, chronic condition characterized by airflow limitation records of all individuals registered with participating PCPs, that is not fully reversible by treatment with b2-agonists. PCPs record third leading cause of death by Data on disease incidence from the morbidity and mortality to be approximately twice as high GPRD have been validated Lnfal several studies,16,17 including in patients with Lndal sex Lndaal in the general population. The aim of this study Study design was to establish the incidence of lung cancer, myocardial infarction Lndl heart failure in patients with a new diagnosis We identified a source population of individuals aged 40e89 of COPD in UK primary care, and to compare the risk of years between 1 January and 31 December and these outcomes with that in the general population.

We Methods excluded those with a diagnosis of pulmonary fibrosis, kyphoscoliosis, asthma or COPD before the start date, in Data source order to avoid possible inclusion of patients with pre- existing COPD. This source population of information entered by about primary care practitioners patients was then followed from the start date until the Figure 1 Study design: Identification of study cohort and case ascertainment. Lung cancer and cardiovascular disease in COPD patients earliest occurrence of one of the following endpoints: Caseecontrol analyses were then performed to adjust detection of suspected COPD using OXMIS and Read codes the risk of lung cancer, myocardial infarction or heart for obstructive lung diseases, chronic bronchitis and failure associated with COPD by possible confounding emphysema; meeting one of the exclusion criteria such as variables.

In each case, the final regression the end of this first part of the study period 31 December model was adjusted for all factors that may have been Following removal of all personal patient identifiers, clinically relevant to the development of each outcome and the computerized records of all potential cases n Z that behaved as potential confounders in the analysis.

Thousand-five of these patients Lneal do not have to be at diagnosed risk of myocardial regalia. Individuals in each requirement were dropped until 1.

This visits, referrals and hospitalizations, as well as the pres- resulted in a final incident COPD cohort of patients. In the heart failure analysis, the model was adjusted sxe age, Control population sex, body mass index BMIcalendar year, smoking status, alcohol use, PCP visits, referrals or hospitalizations, The same sx criteria were used to select a control ischaemic heart disease, cerebrovascular disease, hyper- cohort who had no record of COPD at any time n Z 16 tension, hyperlipidaemia and diabetes, while in the from the same source population as the cases. An index date in was randomly Version 5. Results Time-to-event analysis Lung cancer Four separate analyses were performed to establish mortality and the incidence of lung cancer, heart failure After exclusions, the incident COPD cohort for this study and myocardial infarction in both the COPD and control consisted of individuals and the control cohort con- cohorts.

For the lung cancer, heart failure and myocardial sisted of 16 individuals.

During the follow-up period, 48 infarction analyses, individuals with a history of the individuals in the LLndal cohort were considered to have outcome under investigation or related disorders were received a new diagnosis of lung cancer, after a manual excluded e. This represents an incidence of 7. Individuals in each cohort were followed until 1. After adjusting for age, sex and smoking status, the occurrence of one Lnval the following: After further adjusting for PCP visits, referrals outcome under investigation. The mean follow-up for and aex during the follow-up period, the RR each outcome was 3. This increase in risk years in the control cohort. Statistical analysis Risk factors for a diagnosis of lung cancer are shown in Table 1.

A significant increase in the risk of a lung cancer The incidence per person-years was calculated for diagnosis was found in individuals who were current or each outcome in the COPD and control cohorts. The relative Lndxl smokers, in those with 11 or more PCP visits in the risk RR of each outcome in the COPD cohort compared previous year, and Lndwl those who had been referred or with the control cohort was then calculated and adjusted hospitalized in the previous year. A history of ischaemic Lnda age and Lnsal. In the lung cancer study, the RR was also heart disease or depression was associated with a signifi- adjusted by smoking status. Patients were classified as cant decrease in the Lndal sex of a lung cancer diagnosis.

There current smokers if their last recorded smoking code se was no association between BMI or alcohol intake and the cated that the patient smoked at the index date. Former risk of a lung cancer diagnosis. Never calendar year, smoking, PCP visits, referrals and hospitali- smokers were classified as individuals who had a recorded zations, COPD, ischaemic heart disease and depression code indicating that they had never been a cigarette which were the factors that remained associated with smoker or a recorded code indicating zero cigars smoked. Table 1 Prevalence of potential risk factors for lung cancer among patients with a diagnosis of lung cancer and individuals with no lung cancer diagnosis, and the association between these risk factors and a diagnosis of lung cancer.

Lung cancer and cardiovascular disease in COPD patients Heart failure Risk factors for a diagnosis of myocardial infarction are shown in Table 3. A diagnosis of myocardial infarction was After exclusions, individuals from the COPD cohort and significantly associated with current smoking, age 60e89 15 individuals from the control cohort were eligible to years, 20 or more PCP visits in the previous year, and be included in the heart failure study. After manual review referral or hospitalization. After adjusting by smoking, PCP of the clinical records of patients in the COPD cohort who visits, referrals and hospitalization as well as age and sex, had codes related to heart failure, we identified with the caseecontrol analysis showed that a diagnosis of COPD new diagnoses of heart failure incidence: Thirty-five of these patients After a manual review of patient profiles with heart failure codes in the control cohort, we identified Mortality individuals who had new diagnoses of heart failure inci- dence: Of these, During the follow-up period, there were deaths in the patients Cumulative survival The age- and sex-adjusted RR of a diagnosis of heart during the 5-year follow-up period was significantly higher failure in the COPD cohort was 2.

After also adjusting 1. When adjusted for age, sex, BMI, calendar Causes of death in the first year of follow-up are shown year, smoking, alcohol use, PCP visits, referrals or hospi- in Table 4. Death from a cardiovascular or cerebrovascular talization, ischaemic heart disease, cerebrovascular event was more common in the control cohort than in the disease, hypertension, hyperlipidaemia and diabetes, the COPD cohort Myocardial infarction Discussion After exclusions, individuals with a new diagnosis of This study shows that individuals with a diagnosis of COPD COPD and 13 individuals from the control cohort were are at increased risk of lung cancer, heart failure and death eligible to be included in the myocardial infarction study.

A number of potential factors could explain the associ- By comparison, there were incident cases in the control ation between COPD, lung cancer and heart failure. However, we found that a diagnosis of There was no significant increase in the overall risk of COPD was associated with an increased risk of a subsequent myocardial infarction in the COPD cohort compared with diagnosis of lung cancer, heart failure or mortality even the control cohort age- and sex-adjusted RR: Moreover, it has 0. There was also no significant increase in the previously been shown that COPD is associated with risk of myocardial infarction when fatal myocardial infarc- increased mortality from lung cancer even in individuals tion age- and sex-adjusted RR: In tion.

A meta-analysis of four studies that took account of the first year of follow-up, there were 12 deaths due to aex status n Z found that individuals in the myocardial infarction in the COPD cohort incidence: Sec was no significant association between 1. Table 2 Prevalence of potential risk factors seex heart failure among patients with a diagnosis of heart failure and individuals with srx diagnosis of heart Lndal sex, and the association between these risk factors and a diagnosis of Lndl failure. Table 3 Prevalence of potential risk ses for myocardial infarction among patients with myocardial infarction diagnosis and individuals with no diagnosis of myocardial infarction, and the association between these risk factors and a diagnosis of myocardial infarction.

A meta-analysis of 12 studies n Z 83 also found reduced FEV1 to be associated with an increased risk of cardiovascular death, even when only those studies that adjusted for smoking were included pooled RR: Patients with the lowest FEV1 values have the highest levels of inflammatory markers such as C-reactive protein and fibrinogen. Table 4 Causes of death during the first year of follow-up in a cohort of individuals with a diagnosis of chronic obstructive pulmonary disease COPD and in a control cohort with no diagnosis of COPD.

In contrast with the results of other database studies,9,20 This study emphasizes the need for clinicians to be we found no significant association between a diagnosis of aware of the links between COPD, lung cancer and COPD and a subsequent diagnosis of myocardial infarction. It is using spirometry in patients with cardiovascular disease. It is possible that COPD may be underdiagnosed in ducted. Dr Johansson is an employee of AstraZeneca at most risk of serious comorbidities.

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