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Original Research: Diffuse Lung Disease |

Risk Factors for Cardiovascular Disease in People With Idiopathic Pulmonary FibrosisRisk Factors in Idiopathic Pulmonary Fibrosis: A Population-Based Study FREE TO VIEW

William Dalleywater, BMBS; Helen A. Powell, PhD; Richard B. Hubbard, MD; Vidya Navaratnam, PhD
Author and Funding Information

From the Division of Epidemiology and Public Health (Drs Dalleywater, Powell, Hubbard, and Navaratnam) and the Respiratory Research Unit (Drs Powell, Hubbard, and Navaratnam), University of Nottingham, Nottingham, England.

CORRESPONDENCE TO: Vidya Navaratnam, PhD, Division of Epidemiology and Public Health/Respiratory Research Unit, University of Nottingham, Clinical Sciences Building, Nottingham City Hospital, Hucknall Rd, Nottingham, NG5 1PB, England; e-mail: vidya.navaratnam@nottingham.ac.uk


FUNDING/SUPPORT: Dr Hubbard is the British Lung Foundation/GlaxoSmithKline professor of respiratory epidemiology. Dr Powell is funded by the National Institute for Health Research (NIHR) through the Nottingham Respiratory Research Unit. Dr Navaratnam is an NIHR-funded Academic Clinical Fellow.

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians. See online for more details.


Chest. 2015;147(1):150-156. doi:10.1378/chest.14-0041
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Published online

OBJECTIVE:  People with idiopathic pulmonary fibrosis (IPF) have been shown to be at an increased risk for cardiovascular (CV) disease, but reasons for this are unknown. The aim of this study was to compare the prevalence of common CV risk factors in people with IPF and the general population and establish the incidence of ischemic heart disease (IHD) and stroke after the diagnosis of IPF, controlling for these risk factors.

METHODS:  We used data from a large, UK primary care database to identify incident cases of IPF and matched general-population control subjects. We compared the prevalence of risk factors for CV disease and prescription of CV medications in people with IPF (before diagnosis) with control subjects from the general population and assessed the incidence of IHD and stroke in people with IPF (after diagnosis) compared with control subjects.

RESULTS:  We identified 3,211 cases of IPF and 12,307 control subjects. Patients with IPF were more likely to have a record of hypertension (OR, 1.31; 95% CI, 1.19-1.44), and diabetes (OR, 1.20; 95% CI, 1.07-1.34) compared with control subjects; they were also more likely to have been prescribed several CV drugs. The rate of first-time IHD events was more than twice as high in patients than control subjects (rate ratio, 2.32; 95% CI, 1.85-2.93; P < .001), but the incidence of stroke was only marginally higher (P = .09). Rate ratios for IHD and stroke were not altered substantially after adjusting for CV risk factors.

CONCLUSIONS:  Several CV risk factors were more prevalent in people with IPF; however, this did not account for the increased rate of IHD in this group of patients.

Figures in this Article

Idiopathic pulmonary fibrosis (IPF) is a chronic fibrotic lung disease with few treatment options. The most common cause of morbidity and mortality in people with this condition is progression of fibrosis leading to respiratory failure, but several studies have identified an increased risk of acquiring comorbidities, which contribute to the disease burden.1,2

Cardiovascular diseases (CVDs) such as ischemic heart disease (IHD) and cerebrovascular disease constitute an important group of comorbid conditions affecting those with IPF.14 In a cohort of people referred for lung transplantation, Nathan and colleagues5 found significant coronary artery disease to be increased in people with IPF compared with people with COPD, with worse outcomes for those with both IPF and coronary artery disease. Using UK longitudinal electronic health records, we have demonstrated that people with IPF have an increased risk for CVD even before the IPF diagnosis is made.3

The reason behind this increase in CVD seen in IPF is unknown. It has been suggested that certain risk factors for CVD, such as diabetes mellitus, are more prevalent in those with IPF.68 A study by Reed and colleagues8 found a greater prevalence of hyperlipidemia, hypertension, and higher BMI among people with IPF compared with people with COPD. Studies looking at the rates of cigarette smoking among those with IPF are discordant, with some showing a small increase in rates of smoking9 and others finding no difference from the general population.10 The prevalence of cardiovascular (CV) risk factors in people with IPF has yet to be explored in a large epidemiologic study.

The aim of this study was to compare the prevalence of CV risk factors and prescriptions for drugs commonly used to manage CVD in people with IPF to the general population. We also aimed to establish the incidence of IHD and stroke after the diagnosis of IPF, controlling for the presence of CV risk factors and prescriptions for CV drugs.

Data Source

We used The Health Improvement Network (THIN), a UK longitudinal database of electronic primary care records containing information recorded in routine clinical care, from face-to-face consultations, and following communication from secondary care.11 Anonymized patient-level data include demographic information, medical diagnoses (coded using Read codes), and prescriptions. The version of THIN used for this study included information from 511 practices entered up to September 2011.

Study Population

We identified individuals with a new diagnosis of IPF made after January 1, 2000 (e-Appendix 1). Patients were included if their first diagnosis of IPF was recorded at least 12 months after registration with the practice and if they were at least 40 years old when first diagnosed. This definition was used to capture incident cases of IPF and improve diagnostic specificity. We excluded people with coexisting diagnoses of connective tissue disease (e-Appendix 2) or a record of extrinsic allergic alveolitis, sarcoidosis, pneumoconiosis, or asbestosis (e-Appendix 3) in addition to IPF, because it was not clear which diagnosis was correct.

For each incident case of IPF, we randomly selected up to four general-population control subjects, matched for age, sex, and general practice. Each case was assigned an index date that corresponded to their first diagnosis of IPF; matched control subjects were assigned the same date as the corresponding case patient. All patients and control subjects had at least 12 months of computerized records prior to their index date.

Exposures and Outcomes

We extracted data on diagnoses of IHD, ischemic and hemorrhagic stroke, hypertension, diabetes, hypercholesterolemia, and prescriptions for CV and diabetic medications, as well as smoking habit (current smoker, exsmoker, never smoker) using the data recorded closest to the index date, and BMI.

Statistical Analysis

We conducted a case-control study to compare the prevalence of risk factors for CVD and prescription of CV medications in people with IPF with control subjects from the general population. Conditional logistic regression was used to compare the odds of these exposures, prior to the index date, in patients and control subjects. We looked for evidence of effect modification by age and sex.

We performed a cohort study to investigate whether incidence of IHD or stroke was increased after diagnosis of IPF. For these analyses, we excluded people who had diagnoses of IHD or stroke prior to the index date. All individuals were assigned a start date, which was their index date, and a stop date, which was the first of either date of the outcome, date of death, or last date of data collection. Crude incidence rates of IHD and stroke were calculated. Cox regression, stratifying for the matching factors, was used to estimate rate ratios (RRs) for first-time IHD and stroke events in cases compared with control subjects. We looked for evidence of confounding by CV risk factors and prescriptions. Multiplicative interaction terms were applied to test for interactions between IPF and age, sex, or diabetes. Proportional hazards assumption was confirmed using graphical methods and scaled Schoenfeld residuals.

Likelihood ratio tests were used for all hypothesis testing. Statistical analyses were conducted using Stata version 12 (StataCorp LP). With 3,211 incident cases of IPF and 12,307 matched control subjects, we had > 90% power to detect an OR ≥ 1.5 for exposures affecting 5% of control subjects or to detect an OR ≥ 1.3 for exposures affecting 10% of control subjects.

There were 3,211 incident cases of IPF and 12,307 matched, general-population control subjects. Most of the patients were men (63.9%), and mean age at diagnosis was 75.7 years (SD, 9.8). Both patients and control subjects had a median of 9.8 years (interquartile range [IQR], 5.6-13.7) of computerized records prior to the index date.

Case-Control Study

Patients with IPF were 31% more likely to have a record of hypertension (OR, 1.31; 95% CI, 1.19-1.44; P < .001), and 20% more likely to have a record of diabetes mellitus prior to receiving a diagnosis of IPF compared with control subjects (OR, 1.20; 95% CI, 1.07-1.34; P < .001). We also found that patients were more than twice as likely to be exsmokers before the diagnosis of IPF was made compared with control subjects (Table 1). Patients with IPF were more likely to have been prescribed antianginals, angiotensin-converting enzyme inhibitors or angiotensin II receptor antagonists, digoxin, antiplatelets, and lipid-lowering medication compared with control subjects (Table 2). There was no evidence of effect modification by age or sex on any of these risk factors.

Table Graphic Jump Location
TABLE 1 ]  ORs for Risk Factors for Cardiovascular Disease Comparing Incident Cases of Idiopathic Pulmonary Fibrosis and Matched Subjects From the General Population
a 

P values are from the likelihood ratio test.

Table Graphic Jump Location
TABLE 2 ]  ORs for Prescribed Cardiovascular Medication Comparing Incident Cases of Idiopathic Pulmonary Fibrosis and Matched Control Subjects From the General Population

ACE = angiotensin-converting enzyme.

a 

P values are the likelihood ratio test.

Cohort Study

Median follow-up time after the index date was 1.7 years (IQR, 0.6-3.6 years) in patients with IPF and 3.3 years (IQR, 1.5-5.8 years) for control subjects. During this time, 135 patients and 474 control subjects had a first-time IHD event. The rate of first-time IHD events was more than two times higher in patients with IPF compared with control subjects (RR, 2.32; 95% CI, 1.85-2.93; P < .001) (Fig 1, Table 3). The incidence rate of stroke during the follow-up period was 11.3 per 1,000 person-years (95% CI, 9.2-14.0) in patients with IPF and 10.3 per 1,000 person-years (95% CI, 9.5-11.3) in the control subjects (Table 3).

Figure Jump LinkFigure 1 –  Cumulative incidence of ischemic heart disease in incident cases of IPF and general population control subjects. IPF = idiopathic pulmonary fibrosis.Grahic Jump Location
Table Graphic Jump Location
TABLE 3 ]  Incidence Rates and Rate Ratios for Ischemic Heart Disease and Stroke, Comparing Incident Cases of Idiopathic Pulmonary Fibrosis and Matched Control Subjects From the General Population
a 

Per 1,000 person-y.

b 

Rate ratios are adjusted for matching variables.

c 

P values are from the likelihood ratio test.

The RRs for IHD and stroke were not altered substantially after adjusting for the CVD risk factors listed in Table 1 or prescription of CV drugs listed in Table 2. There was no evidence of a statistical interaction between IPF and age or sex in any of our findings. Despite there being weak evidence that the effect of IPF on first-time IHD events was modified by diabetes (P = .21), the stratum-specific IHD RRs for IPF with and without diabetes were 3.34 (95% CI, 1.79-6.22) and 2.13 (95% CI, 1.64-2.77), respectively.

Of the study population, 13% (2,053 individuals) was lost to follow-up; this was similar in patients and control subjects (12.9% vs 13.3%; P = .57, χ2 test). A higher proportion of individuals who were lost to follow-up did not have any CV risk factors and were not prescribed antianginals, antiplatelets, or lipid-lowering drugs. There was no evidence that the proportional hazards assumptions in our final models for IHD (P = .31) or stroke (P = .49) were not met.

In this large population-based study, we found that people with IPF were more likely to have a recorded diagnosis of hypertension and diabetes mellitus before the diagnosis of IPF was made compared with the general population. People with IPF were also more likely to be prescribed antianginals, antiplatelets, and lipid-lowering medication compared with general-population control subjects. Individuals with IPF had twice the rate of first-time IHD events after their diagnosis compared with the general population, after adjusting for CV risk factors and prescription of CV drugs. There also was weak evidence that the incidence rate of strokes was higher in people with IPF.

The main strength of this study is the large number of individuals included in the study population and the long period of time over which the data were collected. This has enabled us to investigate in detail individual risk factors for CVD and prescription of commonly used CV drugs and to explore the possibility of confounding and effect modification. Studies of this nature and magnitude are difficult to conduct in a clinical setting. Our cohort study was restricted to individuals who had never had a previous IHD event or stroke, as the risk of subsequent CV events are likely to be different from the first. As our study is population based, the incident cases included are likely to capture individuals across the disease spectrum and avoid selection bias that can occur in studies conducted in tertiary referral centers. Furthermore, the use of electronic medical records limits the possibility of recall or observer bias.

The main limitation of our study is the validity of diagnoses of IPF within the dataset. We have demonstrated that diagnoses of pulmonary fibrosis in electronic primary care are records are accurate.10 Furthermore, as IPF is usually diagnosed in secondary care, it seems unlikely that a record of this diagnosis will be found in primary care records without confirmation from secondary care. The age distribution of cases with IPF in this study is similar to other population-based cohorts of IPF,1216 providing reassurance of the validity of diagnosis of IPF in these data. In addition, a study by Fell and colleagues17 demonstrated that age is a strong predictor of IPF in patients with an atypical radiographic pattern of usual interstitial pneumonia, whereby individuals aged > 65 years had 89% specificity for confirming IPF on lung biopsy. In our dataset, 81% of cases were aged > 65 years, providing further evidence that most of our cases have usual interstitial pneumonia. In addition, the mortality rate for patients with IPF during the study period was 193.7 per 1,000 person-years (95% CI, 184.2-203.8) and the median survival was 3.5 years, both of which are similar to other population studies of IPF.1,12,16,18,19 There is also the possibility of misclassification of IHD, stroke, and/or CV risk factors; however, studies have also demonstrated the validity of recording medical diagnoses20,21 and prescription records22 in computerized, longitudinal general-practice databases.

The possibility of ascertainment bias in our cohort study needs to be acknowledged. Individuals with chronic diseases such as IPF are more likely than the general population to see their physician regularly, and this may explain why other illnesses are more likely to be investigated and diagnosed. This may have led to an overestimation in the association between IPF and the CV outcomes. However, our findings show a weak association between IPF and stroke, suggesting that any ascertainment bias, if present, is likely to be minimal. Another potential limitation of the study is that the general practices are self-selecting with regard to contributing to THIN. However, the population of individuals from general practices that do contribute to THIN are thought to be broadly representative of the UK population. Thirteen percent of the study population was lost to follow-up, a higher proportion of whom were people without CV risk factors or prescriptions for CV medication. This raises the possibility that people who were lost to follow-up may have had a lower rate of IHD or stroke than those who remained in the study. Another limitation that needs consideration is that the median duration of follow-up after the index date for patients with IPF was shorter compared with the control subjects (1.7 years vs 3.3 years), which may have resulted in an underestimation in the incidence of IHD among patients.

The findings from our study are consistent with previous studies that have demonstrated an association between IPF and CVD.1,35,23,24 A study by Panos and colleagues1 showed that IHD and heart failure were common causes of death among patients with IPF. In a cross-sectional study of 630 patients referred for lung transplantation evaluation, Kizer and colleagues23 found increased prevalence of angiographic coronary artery disease in patients with fibrotic lung disease compared with those with nonfibrotic lung diseases, after controlling for traditional risk factors (OR, 2.18; 95% CI, 1.46-11.9). This is similar to the findings of another study in lung transplantation candidates that found angiographic evidence of coronary artery disease was significantly more common in people with lung fibrosis compared with those with COPD despite the smoking prevalence in being much higher in people with COPD.24 A study of 73 patients with IPF and 56 patients with COPD found the prevalence of coronary artery disease was higher in those with IPF (65.8% vs 46.1%), with more severe disease also being more common in those with IPF.5 People with IPF who have severe coronary artery disease also appear to have worse outcomes.5

Using UK primary care data, we have found that people with IPF had an increased risk for acute coronary syndrome, angina, and prescription of CV drugs compared with the general population, even before the diagnosis of IPF was made.3 We also found that the risk for acute coronary syndrome increased threefold in people with IPF compared with the general population after the diagnosis of IPF was established (RR, 3.14; 95% CI, 2.02-4.87).3 Similar findings were reported from a hospital-based, case-control study that showed the prevalence of coronary artery disease was five times higher in patients with IPF (OR, 5.37; 95% CI, 1.52-19.00; P < .01).4

Despite the possibility of ascertainment bias, our findings suggest that IPF is an independent risk factor for IHD. This is consistent with the findings of other studies and suggests that simply targeting risk factors for CVD in people with IPF may not be sufficient to reduce the incidence of IHD. It is possible, however, that IPF and IHD share other etiologic risk factors. Studies have suggested that people with IPF have an increased tendency to have blood clots14,25,26 and have higher factor VIII levels than the general population.14 Previous studies have also demonstrated that elevated factor VIII levels are associated with an increased risk for coronary artery disease.27,28

In conclusion, we have found that people with IPF have increased prevalence of CV risk factors. People with IPF also have an increased risk for IHD that cannot be attributed to the increased prevalence of these risk factors alone. While treatment of these risk factors must be considered during routine care of people with IPF, further research into the biologic mechanism behind the increased risk is warranted.

Author contributions: V. N. had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. W. D. served as principal author. R. B. H. and V. N. contributed to the conception and design of the study; W. D, H. A. P., R. B. H., and V. N. contributed to the data analysis and interpretation; W. D. and V. N. contributed to drafting the manuscript; H. A. P. and R. B. H. contributed to revision of the manuscript; and W. D., H. A. P., R. B. H., and V. N. approved the final manuscript.

Financial/nonfinancial disclosures: The authors have reported to CHEST that no potential conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.

Role of sponsors: The sponsors had no role in the design of the study, the collection and analysis of the data, or the preparation of the manuscript.

Other contributions: The authors would like to thank Chris Smith, BSc, for extracting the dataset and Andrew Fogarty, MD, for his comments on the manuscript.

Additional information: The e-Appendixes can be found in the Supplemental Materials section of the online article.

CV

cardiovascular

CVD

cardiovascular disease

IHD

ischemic heart disease

IPF

idiopathic pulmonary fibrosis

IQR

interquartile range

RR

rate ratio

THIN

The Health Improvement Network

Panos RJ, Mortenson RL, Niccoli SA, King TE Jr. Clinical deterioration in patients with idiopathic pulmonary fibrosis: causes and assessment. Am J Med. 1990;88(4):396-404. [CrossRef] [PubMed]
 
Daniels CE, Yi ES, Ryu JH. Autopsy findings in 42 consecutive patients with idiopathic pulmonary fibrosis. Eur Respir J. 2008;32(1):170-174. [CrossRef] [PubMed]
 
Hubbard RB, Smith C, Le Jeune I, Gribbin J, Fogarty AW. The association between idiopathic pulmonary fibrosis and vascular disease: a population-based study. Am J Respir Crit Care Med. 2008;178(12):1257-1261. [CrossRef] [PubMed]
 
Ponnuswamy A, Manikandan R, Sabetpour A, Keeping IM, Finnerty JP. Association between ischaemic heart disease and interstitial lung disease: a case-control study. Respir Med. 2009;103(4):503-507. [CrossRef] [PubMed]
 
Nathan SD, Basavaraj A, Reichner C, et al. Prevalence and impact of coronary artery disease in idiopathic pulmonary fibrosis. Respir Med. 2010;104(7):1035-1041. [CrossRef] [PubMed]
 
Gribbin J, Hubbard R, Smith C. Role of diabetes mellitus and gastro-oesophageal reflux in the aetiology of idiopathic pulmonary fibrosis. Respir Med. 2009;103(6):927-931. [CrossRef] [PubMed]
 
Enomoto T, Usuki J, Azuma A, Nakagawa T, Kudoh S. Diabetes mellitus may increase risk for idiopathic pulmonary fibrosis. Chest. 2003;123(6):2007-2011. [CrossRef] [PubMed]
 
Reed RM, Eberlein M, Girgis RE, et al. Coronary artery disease is under-diagnosed and under-treated in advanced lung disease. Am J Med. 2012;125:1228 e1213-1228 e1222. [CrossRef]
 
Harris JM, Johnston ID, Rudd R, Taylor AJ, Cullinan P. Cryptogenic fibrosing alveolitis and lung cancer: the BTS study. Thorax. 2010;65(1):70-76. [CrossRef] [PubMed]
 
Hubbard R, Venn A, Lewis S, Britton J. Lung cancer and cryptogenic fibrosing alveolitis. A population-based cohort study. Am J Respir Crit Care Med. 2000;161(1):5-8. [CrossRef] [PubMed]
 
The Health Improvement Network. CSD Health Research website. http://www.thin-uk.com. Accessed January 2, 2012.
 
Mapel DW, Hunt WC, Utton R, Baumgartner KB, Samet JM, Coultas DB. Idiopathic pulmonary fibrosis: survival in population based and hospital based cohorts. Thorax. 1998;53(6):469-476. [CrossRef] [PubMed]
 
Navaratnam V, Fleming KM, West J, et al. The rising incidence of idiopathic pulmonary fibrosis in the UK. Thorax. 2011;66(6):462-467. [CrossRef] [PubMed]
 
Navaratnam VFA, McKeever T, Thompson N, et al. Is an increased tendency to clot a risk factor for developing idiopathic pulmonary fibrosis. Thorax. 2012;67(suppl 2):A48. [CrossRef]
 
King TE Jr, Tooze JA, Schwarz MI, Brown KR, Cherniack RM. Predicting survival in idiopathic pulmonary fibrosis: scoring system and survival model. Am J Respir Crit Care Med. 2001;164(7):1171-1181. [CrossRef] [PubMed]
 
Hubbard R, Johnston I, Britton J. Survival in patients with cryptogenic fibrosing alveolitis: a population-based cohort study. Chest. 1998;113(2):396-400. [CrossRef] [PubMed]
 
Fell CD, Martinez FJ, Liu LX, et al. Clinical predictors of a diagnosis of idiopathic pulmonary fibrosis. Am J Respir Crit Care Med. 2010;181(8):832-837. [CrossRef] [PubMed]
 
Gribbin J, Hubbard RB, Le Jeune I, Smith CJ, West J, Tata LJ. Incidence and mortality of idiopathic pulmonary fibrosis and sarcoidosis in the UK. Thorax. 2006;61(11):980-985. [CrossRef] [PubMed]
 
Fernández Pérez ER, Daniels CE, Schroeder DR, et al. Incidence, prevalence, and clinical course of idiopathic pulmonary fibrosis: a population-based study. Chest. 2010;137(1):129-137. [CrossRef] [PubMed]
 
Hansell A, Hollowell J, Nichols T, McNiece R, Strachan D. Use of the General Practice Research Database (GPRD) for respiratory epidemiology: a comparison with the 4th Morbidity Survey in General Practice (MSGP4). Thorax. 1999;54(5):413-419. [CrossRef] [PubMed]
 
Herrett E, Thomas SL, Schoonen WM, Smeeth L, Hall AJ. Validation and validity of diagnoses in the General Practice Research Database: a systematic review. Br J Clin Pharmacol. 2010;69(1):4-14. [CrossRef] [PubMed]
 
Hollowell J. The General Practice Research Database: quality of morbidity data. Popul Trends. 1997;;(87):36-40.
 
Kizer JR, Zisman DA, Blumenthal NP, et al. Association between pulmonary fibrosis and coronary artery disease. Arch Intern Med. 2004;164(5):551-556. [CrossRef] [PubMed]
 
Izbicki G, Ben-Dor I, Shitrit D, et al. The prevalence of coronary artery disease in end-stage pulmonary disease: is pulmonary fibrosis a risk factor? Respir Med. 2009;103(9):1346-1349. [CrossRef] [PubMed]
 
Sode BF, Dahl M, Nielsen SF, Nordestgaard BG. Venous thromboembolism and risk of idiopathic interstitial pneumonia: a nationwide study. Am J Respir Crit Care Med. 2010;181(10):1085-1092. [CrossRef] [PubMed]
 
Sprunger DB, Olson AL, Huie TJ, et al. Pulmonary fibrosis is associated with an elevated risk of thromboembolic disease. Eur Respir J. 2012;39(1):125-132. [CrossRef] [PubMed]
 
Meade TW, Cooper JA, Stirling Y, Howarth DJ, Ruddock V, Miller GJ. Factor VIII, ABO blood group and the incidence of ischaemic heart disease. Br J Haematol. 1994;88(3):601-607. [CrossRef] [PubMed]
 
Meade TW, Stirling Y, Thompson SG, et al. An international and interregional comparison of haemostatic variables in the study of ischaemic heart disease. Report of a working group. Int J Epidemiol. 1986;15(3):331-336. [CrossRef] [PubMed]
 

Figures

Figure Jump LinkFigure 1 –  Cumulative incidence of ischemic heart disease in incident cases of IPF and general population control subjects. IPF = idiopathic pulmonary fibrosis.Grahic Jump Location

Tables

Table Graphic Jump Location
TABLE 1 ]  ORs for Risk Factors for Cardiovascular Disease Comparing Incident Cases of Idiopathic Pulmonary Fibrosis and Matched Subjects From the General Population
a 

P values are from the likelihood ratio test.

Table Graphic Jump Location
TABLE 2 ]  ORs for Prescribed Cardiovascular Medication Comparing Incident Cases of Idiopathic Pulmonary Fibrosis and Matched Control Subjects From the General Population

ACE = angiotensin-converting enzyme.

a 

P values are the likelihood ratio test.

Table Graphic Jump Location
TABLE 3 ]  Incidence Rates and Rate Ratios for Ischemic Heart Disease and Stroke, Comparing Incident Cases of Idiopathic Pulmonary Fibrosis and Matched Control Subjects From the General Population
a 

Per 1,000 person-y.

b 

Rate ratios are adjusted for matching variables.

c 

P values are from the likelihood ratio test.

References

Panos RJ, Mortenson RL, Niccoli SA, King TE Jr. Clinical deterioration in patients with idiopathic pulmonary fibrosis: causes and assessment. Am J Med. 1990;88(4):396-404. [CrossRef] [PubMed]
 
Daniels CE, Yi ES, Ryu JH. Autopsy findings in 42 consecutive patients with idiopathic pulmonary fibrosis. Eur Respir J. 2008;32(1):170-174. [CrossRef] [PubMed]
 
Hubbard RB, Smith C, Le Jeune I, Gribbin J, Fogarty AW. The association between idiopathic pulmonary fibrosis and vascular disease: a population-based study. Am J Respir Crit Care Med. 2008;178(12):1257-1261. [CrossRef] [PubMed]
 
Ponnuswamy A, Manikandan R, Sabetpour A, Keeping IM, Finnerty JP. Association between ischaemic heart disease and interstitial lung disease: a case-control study. Respir Med. 2009;103(4):503-507. [CrossRef] [PubMed]
 
Nathan SD, Basavaraj A, Reichner C, et al. Prevalence and impact of coronary artery disease in idiopathic pulmonary fibrosis. Respir Med. 2010;104(7):1035-1041. [CrossRef] [PubMed]
 
Gribbin J, Hubbard R, Smith C. Role of diabetes mellitus and gastro-oesophageal reflux in the aetiology of idiopathic pulmonary fibrosis. Respir Med. 2009;103(6):927-931. [CrossRef] [PubMed]
 
Enomoto T, Usuki J, Azuma A, Nakagawa T, Kudoh S. Diabetes mellitus may increase risk for idiopathic pulmonary fibrosis. Chest. 2003;123(6):2007-2011. [CrossRef] [PubMed]
 
Reed RM, Eberlein M, Girgis RE, et al. Coronary artery disease is under-diagnosed and under-treated in advanced lung disease. Am J Med. 2012;125:1228 e1213-1228 e1222. [CrossRef]
 
Harris JM, Johnston ID, Rudd R, Taylor AJ, Cullinan P. Cryptogenic fibrosing alveolitis and lung cancer: the BTS study. Thorax. 2010;65(1):70-76. [CrossRef] [PubMed]
 
Hubbard R, Venn A, Lewis S, Britton J. Lung cancer and cryptogenic fibrosing alveolitis. A population-based cohort study. Am J Respir Crit Care Med. 2000;161(1):5-8. [CrossRef] [PubMed]
 
The Health Improvement Network. CSD Health Research website. http://www.thin-uk.com. Accessed January 2, 2012.
 
Mapel DW, Hunt WC, Utton R, Baumgartner KB, Samet JM, Coultas DB. Idiopathic pulmonary fibrosis: survival in population based and hospital based cohorts. Thorax. 1998;53(6):469-476. [CrossRef] [PubMed]
 
Navaratnam V, Fleming KM, West J, et al. The rising incidence of idiopathic pulmonary fibrosis in the UK. Thorax. 2011;66(6):462-467. [CrossRef] [PubMed]
 
Navaratnam VFA, McKeever T, Thompson N, et al. Is an increased tendency to clot a risk factor for developing idiopathic pulmonary fibrosis. Thorax. 2012;67(suppl 2):A48. [CrossRef]
 
King TE Jr, Tooze JA, Schwarz MI, Brown KR, Cherniack RM. Predicting survival in idiopathic pulmonary fibrosis: scoring system and survival model. Am J Respir Crit Care Med. 2001;164(7):1171-1181. [CrossRef] [PubMed]
 
Hubbard R, Johnston I, Britton J. Survival in patients with cryptogenic fibrosing alveolitis: a population-based cohort study. Chest. 1998;113(2):396-400. [CrossRef] [PubMed]
 
Fell CD, Martinez FJ, Liu LX, et al. Clinical predictors of a diagnosis of idiopathic pulmonary fibrosis. Am J Respir Crit Care Med. 2010;181(8):832-837. [CrossRef] [PubMed]
 
Gribbin J, Hubbard RB, Le Jeune I, Smith CJ, West J, Tata LJ. Incidence and mortality of idiopathic pulmonary fibrosis and sarcoidosis in the UK. Thorax. 2006;61(11):980-985. [CrossRef] [PubMed]
 
Fernández Pérez ER, Daniels CE, Schroeder DR, et al. Incidence, prevalence, and clinical course of idiopathic pulmonary fibrosis: a population-based study. Chest. 2010;137(1):129-137. [CrossRef] [PubMed]
 
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