International Journal of Cardiology 179 (2015) 312–314
Contents lists available at ScienceDirect
International Journal of Cardiology journal homepage: www.elsevier.com/locate/ijcard
Letter to the Editor
Elevated QRISK2 score in patients hospitalized for acute exacerbation of COPD versus stable COPD outpatients Elisa Pagliaroli a,⁎,1, Divya Mohan b,1, Vijay Padmanaban c, Paolo Palange a, Sarah Elkin c, Michael I. Polkey b a b c
Public Health and Infectious Diseases, Sapienza University, Rome, Italy Royal Brompton Hospital & Harefield NHS Foundation Trust, NIHR Respiratory Biomedical Research Unit, Imperial College, London, UK St Marys Hospital, Chest and Allergy, Imperial College, London, UK
a r t i c l e
i n f o
Article history: Received 16 October 2014 Accepted 5 November 2014 Available online 6 November 2014 Keywords: QRISK2 score Cardiovascular disease Acute exacerbation of COPD (AECOPD)
Sir, Cardiovascular diseases (CVD) are the second commonest cause of death in patients with chronic obstructive pulmonary disease (COPD) [1], and, conversely, impaired lung function represents an independent risk factor for CVD [2]. Myocardial ischemia is particularly frequent during an acute exacerbation of COPD (AECOPD), being present in approximately 1 in 12 patients hospitalized with AECOPD [3]. This occurs probably because atherosclerosis is related to inflammation, and several studies report an increase in inflammatory markers during AECOPD such as fibrinogen, leucocyte count, C reactive protein (CRP) and interleukin-6, which can contribute to thrombus formation [4–6]. Patel et al. reported an elevation of arterial stiffness during an episode AECOPD compared to stable condition, and higher values of aPWV in patients with the frequent exacerbation phenotype, suggesting that endothelium dysfunction might be implicated [7]. Unfortunately, there is a lack of a validated systematic approach for easily assessing and, consequently, managing cardiovascular risk in patients with COPD. The QRISK2 [8] score has been validated in the UK general population as a better tool than others such as the NICE Framingham score [9], (a modified US Framingham equation, adjusted for South Asian ethnicity and family history for cardiovascular disease). It includes interesting risk factors like social deprivation, rheumatoid ⁎ Corresponding author at: Department of Public Health and Infectious Diseases, Sapienza University, Viale dell'Università, 37, Rome, Italy. E-mail address: [email protected] (E. Pagliaroli). 1 These authors contributed equally to this work.
http://dx.doi.org/10.1016/j.ijcard.2014.11.065 0167-5273/© 2014 Elsevier Ireland Ltd. All rights reserved.
arthritis, atrial fibrillation, chronic renal failure and nine different ethnicities which elevate the accuracy to give a 10 year risk of fatal and non fatal cardiac and cerebral events. We wished to evaluate the QRISK2 score in patients with AECOPD versus stable COPD patients, and investigate the potential utility of QRISK2 in COPD. In particular our concern was that if the effects of COPD were too great, then we would not observe different Q-risk2 values between stable and acutely exacerbated patients. A literature review failed to find prior Q-risk 2 data in COPD patients. We therefore analyzed retrospectively clinically collected data from 169 patients admitted for AECOPD to an acute care London (UK) hospital between 2011 and 2014. Exacerbation was defined when this was the primary diagnosis in the discharge summary. We also obtained data from 61 COPD outpatients, clinically stable for at least 4 weeks prior to undergoing assessments, who were participating in another observational study with local ethical committee approval (REC 11/LO/ 1636) and patient's written consent. The hospitalized patients were further divided into two subgroups according to the presence (Group 1, n = 77) or the absence (Group 2, n = 92) of a previous recorded episode of myocardial infarction, angina, TIA, or stroke. Stable outpatient formed Group 3. Medical history, body mass index (BMI), lipid profile, blood pressure were recorded. Spirometry data from the last clinically stable period within 1 year were used. Shapiro–Wilks test was used to test for normality, and Kruksal– Wallis ANOVA and two-tailed Mann–Whitney test (Graphpad Prism v5.0 software) were used for comparisons between groups. Data are expressed as mean with standard deviation in parentheses. The hospitalized patients and stable outpatients were differed slightly but significantly in terms of age 72 (9) vs 70 (10) vs 66 (8) years, p = 0.0003, but not in terms of gender (68% vs 55% vs 67% male), BMI [25.2 (8.2) vs 23.5 (5.2) vs 24.7 (5.3) kg/m2], spirometry [FEV1%pred of 40.4 (19.1) vs 41.4 (15.6) vs 42.8 (19.3)] and total cholesterol/HDL ratio [3.58 (1.17) vs 3.52 (1.22) vs 3.43 (0.93)]; the majority of them were ex-smokers (69% vs 76% vs 84%). Exacerbators reported a higher number of previous vascular events versus stable outpatients: 41% vs 4% (p b 0.0001) had a history of myocardial infarction or angina, 6% versus 2% (p = 0.09) reported cerebrovascular events and 4% vs 0% reported both cerebro- and cardiovascular events (p = 0.4). Exacerbators also reported a higher number of comorbidities than stable outpatients: 17% vs 14% vs 3% (p b 0.001) respectively in Groups 1, 2 and 3 for atrial fibrillation; 27% vs 9% vs 2%
E. Pagliaroli et al. / International Journal of Cardiology 179 (2015) 312–314
313
Table 1 Baseline demographics of the three Groups. Values expressed as mean (standard deviation).
No. of patients Age (years) Male Caucasian or not spec. Ex smokers FEV1%predicted Body Mass Index (kg/m2) Cholesterol/HDL ratio Systolic blood. pres. (mm Hg) Atrial fibrillation Chronic renal failure Type 2 diabetes Previous myocardial infarction/angina Previous transient ischaemic attack/stroke Previous cerebro- & cardiovascular diseases
Group 1
Group 2
Group 3
Exacerbators with CVD
Exacerbators without CVD
Outpatients
77 (46%) 72 (9) 68% 94% 69% 40.4 (19.1) 25.2 (8.2) 3.58 (1.17) 129 (18) 17% 9% 27% 41% 6% 4%
92 (64%) 70 (10) 55% 90% 76% 41.4 (15.6) 23.5 (5.2) 3.52 (1.22) 129 (16) 14% 1% 9% – – –
61 66 (8) 67% 93% 84% 42.8 (19.3) 24.7 (5.3) 3.43 (0.93) 136 (16) 3% 0 2% 4% 2% 0
(p b 0.0001) for type 2 diabetes; and 9% vs 1% vs 0% (p = 0.004) for chronic renal failure. Systolic blood pressure was significantly different between groups [129 (18) vs 129 (16) vs 136 (16) mm Hg, p = 0.047], although we noted that 56% of the all patients with AECOPD were prescribed one or more anti-hypertensive drug compared with only 30% of the stable cohort (p b 0.001) (Table 1). The relative risk according to the QRISK2 score, as defined as the Absolute Risk (AR)/Theoretical Risk (TR = risk of a normal age-matched person) ratio, was significantly higher in the hospitalized (groups 1 and 2) versus the stable group: 1.87 (1.5) vs 1.24 (0.43) vs 1.12 (0.49); p b 0.0001. Moreover, the AR among Groups 1, 2 and 3 was significantly different [37 (14)% vs 26 (13)% vs19 (12)%; p b 0.0001], with stable outpatients having a lower AR than even hospitalized exacerbators without a history of cardiovascular event (Fig. 1). TR between the three groups also differed significantly [25 (11)% vs 23 (11)% vs 18 (10)%; p = 0.0013]. This considerable difference in risk is biologically plausible because hospitalized patients reported a greater number of comorbidities, including hypertension and type 2 diabetes, which are known to predispose to
P value
– 0.0003 0.19 0.5 0.1 0.9 0.4 0.8 0.047 b0.001 0.004 b0.0001 b0.0001 0.09 0.4
cardiovascular diseases. However, ischemic events in our cohort appeared particularly high in comparison with other reported data [10], which might be explained by the type and severity of patients admitted to hospital in current practice while milder patients are managed in community settings. Our study has limitations in that the hospitalized cohort was studied retrospectively, whereas the stable one prospectively, and the former was slightly older than the latter. Our cohort of exacerbators reported more prior ischemic events than stable outpatients: since they also had higher QRISK-2 scores, the data suggest that QRISK-2 retains discriminant ability despite the presence of COPD. In conclusion, we suggest that the QRISK-2 score could be a useful and simple tool in clinical practice to help identify COPD patients in whom further evaluation may be justified. Conflict of interest The authors report no relationships that could be construed as a conflict of interest. Acknowledgement This work was supported by the NIHR Respiratory Biomedical Research Unit at the Royal Brompton and Harefield NHS Foundation Trust and Imperial College who partly funded MIP's and DM's salary. DM was also partially supported by an award from the Technology Strategy Board. A grant provided by Sapienza University contributed equally to the study. References
Fig. 1. Absolute risk of cardiovascular event in next 10 years as measured via QRISK2 score. Group 1 consists of patients hospitalized for exacerbation of COPD with a prior history of cardiac events (n = 77), Group 2 contains patients hospitalized for exacerbation of COPD without a history of prior cardiac events (n = 92) and Group 3 consists of stable outpatients with COPD (n = 61).
[1] S. Sidney, M. Sorel, C.P. Quesenberry Jr., C. DeLuise, S. Lanes, M.D. Eisner, COPD and incident cardiovascular disease hospitalizations and mortality: Kaiser Permanente Medical Care Program, Chest 128 (4) (2005) 2068–2075. [2] D.D. Sin, L.L. Wu, S.F.P. Man, The relationship between reduced lung function and cardiovascular mortality, Chest 127 (2005) 1952–1959. [3] D.A. McAllister, J.D. Maclay, N.L. Millis, A. Leitch, P. Reid, R. Carruthers, et al., Diagnosis of myocardial infarction following hospitalization for exacerbation of COPD, Eur. Respir. J. 39 (5) (2012) 1097–1103. [4] S. Van Eaden, J. Leipsic, S.F.P. Man, D.D. Sin, The relationship between lung inflammation and cardiovascular disease, Am. J. Respir. Crit. Care Med. 186 (1) (2012) 11–16. [5] M. Roca, A. Verduri, L. Corbetta, E. Clini, L.M. Fabbri, B. Beghè, Mechanism of acute exacerbation of respiratory symptoms in chronic obstructive pulmonary disease, Eur. J. Clin. Investig. 43 (5) (2013) 510–521. [6] G.C. Donaldson, J.R. Hurst, C.J. Smith, R.B. Hubbard, J.A. Wedzicha, Increased risk of myocardial infarction and stroke following exacerbation of COPD, Chest 137 (5) (2010) 1091–1097.
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E. Pagliaroli et al. / International Journal of Cardiology 179 (2015) 312–314
[7] A.R. Patel, B.S. Kowlessar, G.C. Donaldson, et al., Cardiovascular risk, myocardial injury, and exacerbation of chronic obstructive pulmonary disease, Am. J. Respir. Crit. Care Med. 188 (9) (2013) 1091–1099. [8] J. Hippisley-Cox, C. Coupland, Y. Vinogradova, et al., Predicting cardiovascular risk in England and Wales: prospective derivation and validation of QRISK2, Br. Med. J. 336 (7659) (2008) 1475–1482.
[9] G.S. Collins, D.G. Altman, An independent and external validation of QRISK2 cardiovascular disease risk score: a prospective open cohort study, Br. Med. J. 340 (2010) c2442. [10] S. Roversi, P. Roversi, G. Spadafora, R. Rossi, L. Fabbri, Coronary artery disease concomitant with chronic obstructive pulmonary disease, Eur. J. Clin. Investig. 44 (1) (2014) 93–102.
Contents lists available at ScienceDirect
International Journal of Cardiology journal homepage: www.elsevier.com/locate/ijcard
Letter to the Editor
Elevated QRISK2 score in patients hospitalized for acute exacerbation of COPD versus stable COPD outpatients Elisa Pagliaroli a,⁎,1, Divya Mohan b,1, Vijay Padmanaban c, Paolo Palange a, Sarah Elkin c, Michael I. Polkey b a b c
Public Health and Infectious Diseases, Sapienza University, Rome, Italy Royal Brompton Hospital & Harefield NHS Foundation Trust, NIHR Respiratory Biomedical Research Unit, Imperial College, London, UK St Marys Hospital, Chest and Allergy, Imperial College, London, UK
a r t i c l e
i n f o
Article history: Received 16 October 2014 Accepted 5 November 2014 Available online 6 November 2014 Keywords: QRISK2 score Cardiovascular disease Acute exacerbation of COPD (AECOPD)
Sir, Cardiovascular diseases (CVD) are the second commonest cause of death in patients with chronic obstructive pulmonary disease (COPD) [1], and, conversely, impaired lung function represents an independent risk factor for CVD [2]. Myocardial ischemia is particularly frequent during an acute exacerbation of COPD (AECOPD), being present in approximately 1 in 12 patients hospitalized with AECOPD [3]. This occurs probably because atherosclerosis is related to inflammation, and several studies report an increase in inflammatory markers during AECOPD such as fibrinogen, leucocyte count, C reactive protein (CRP) and interleukin-6, which can contribute to thrombus formation [4–6]. Patel et al. reported an elevation of arterial stiffness during an episode AECOPD compared to stable condition, and higher values of aPWV in patients with the frequent exacerbation phenotype, suggesting that endothelium dysfunction might be implicated [7]. Unfortunately, there is a lack of a validated systematic approach for easily assessing and, consequently, managing cardiovascular risk in patients with COPD. The QRISK2 [8] score has been validated in the UK general population as a better tool than others such as the NICE Framingham score [9], (a modified US Framingham equation, adjusted for South Asian ethnicity and family history for cardiovascular disease). It includes interesting risk factors like social deprivation, rheumatoid ⁎ Corresponding author at: Department of Public Health and Infectious Diseases, Sapienza University, Viale dell'Università, 37, Rome, Italy. E-mail address: [email protected] (E. Pagliaroli). 1 These authors contributed equally to this work.
http://dx.doi.org/10.1016/j.ijcard.2014.11.065 0167-5273/© 2014 Elsevier Ireland Ltd. All rights reserved.
arthritis, atrial fibrillation, chronic renal failure and nine different ethnicities which elevate the accuracy to give a 10 year risk of fatal and non fatal cardiac and cerebral events. We wished to evaluate the QRISK2 score in patients with AECOPD versus stable COPD patients, and investigate the potential utility of QRISK2 in COPD. In particular our concern was that if the effects of COPD were too great, then we would not observe different Q-risk2 values between stable and acutely exacerbated patients. A literature review failed to find prior Q-risk 2 data in COPD patients. We therefore analyzed retrospectively clinically collected data from 169 patients admitted for AECOPD to an acute care London (UK) hospital between 2011 and 2014. Exacerbation was defined when this was the primary diagnosis in the discharge summary. We also obtained data from 61 COPD outpatients, clinically stable for at least 4 weeks prior to undergoing assessments, who were participating in another observational study with local ethical committee approval (REC 11/LO/ 1636) and patient's written consent. The hospitalized patients were further divided into two subgroups according to the presence (Group 1, n = 77) or the absence (Group 2, n = 92) of a previous recorded episode of myocardial infarction, angina, TIA, or stroke. Stable outpatient formed Group 3. Medical history, body mass index (BMI), lipid profile, blood pressure were recorded. Spirometry data from the last clinically stable period within 1 year were used. Shapiro–Wilks test was used to test for normality, and Kruksal– Wallis ANOVA and two-tailed Mann–Whitney test (Graphpad Prism v5.0 software) were used for comparisons between groups. Data are expressed as mean with standard deviation in parentheses. The hospitalized patients and stable outpatients were differed slightly but significantly in terms of age 72 (9) vs 70 (10) vs 66 (8) years, p = 0.0003, but not in terms of gender (68% vs 55% vs 67% male), BMI [25.2 (8.2) vs 23.5 (5.2) vs 24.7 (5.3) kg/m2], spirometry [FEV1%pred of 40.4 (19.1) vs 41.4 (15.6) vs 42.8 (19.3)] and total cholesterol/HDL ratio [3.58 (1.17) vs 3.52 (1.22) vs 3.43 (0.93)]; the majority of them were ex-smokers (69% vs 76% vs 84%). Exacerbators reported a higher number of previous vascular events versus stable outpatients: 41% vs 4% (p b 0.0001) had a history of myocardial infarction or angina, 6% versus 2% (p = 0.09) reported cerebrovascular events and 4% vs 0% reported both cerebro- and cardiovascular events (p = 0.4). Exacerbators also reported a higher number of comorbidities than stable outpatients: 17% vs 14% vs 3% (p b 0.001) respectively in Groups 1, 2 and 3 for atrial fibrillation; 27% vs 9% vs 2%
E. Pagliaroli et al. / International Journal of Cardiology 179 (2015) 312–314
313
Table 1 Baseline demographics of the three Groups. Values expressed as mean (standard deviation).
No. of patients Age (years) Male Caucasian or not spec. Ex smokers FEV1%predicted Body Mass Index (kg/m2) Cholesterol/HDL ratio Systolic blood. pres. (mm Hg) Atrial fibrillation Chronic renal failure Type 2 diabetes Previous myocardial infarction/angina Previous transient ischaemic attack/stroke Previous cerebro- & cardiovascular diseases
Group 1
Group 2
Group 3
Exacerbators with CVD
Exacerbators without CVD
Outpatients
77 (46%) 72 (9) 68% 94% 69% 40.4 (19.1) 25.2 (8.2) 3.58 (1.17) 129 (18) 17% 9% 27% 41% 6% 4%
92 (64%) 70 (10) 55% 90% 76% 41.4 (15.6) 23.5 (5.2) 3.52 (1.22) 129 (16) 14% 1% 9% – – –
61 66 (8) 67% 93% 84% 42.8 (19.3) 24.7 (5.3) 3.43 (0.93) 136 (16) 3% 0 2% 4% 2% 0
(p b 0.0001) for type 2 diabetes; and 9% vs 1% vs 0% (p = 0.004) for chronic renal failure. Systolic blood pressure was significantly different between groups [129 (18) vs 129 (16) vs 136 (16) mm Hg, p = 0.047], although we noted that 56% of the all patients with AECOPD were prescribed one or more anti-hypertensive drug compared with only 30% of the stable cohort (p b 0.001) (Table 1). The relative risk according to the QRISK2 score, as defined as the Absolute Risk (AR)/Theoretical Risk (TR = risk of a normal age-matched person) ratio, was significantly higher in the hospitalized (groups 1 and 2) versus the stable group: 1.87 (1.5) vs 1.24 (0.43) vs 1.12 (0.49); p b 0.0001. Moreover, the AR among Groups 1, 2 and 3 was significantly different [37 (14)% vs 26 (13)% vs19 (12)%; p b 0.0001], with stable outpatients having a lower AR than even hospitalized exacerbators without a history of cardiovascular event (Fig. 1). TR between the three groups also differed significantly [25 (11)% vs 23 (11)% vs 18 (10)%; p = 0.0013]. This considerable difference in risk is biologically plausible because hospitalized patients reported a greater number of comorbidities, including hypertension and type 2 diabetes, which are known to predispose to
P value
– 0.0003 0.19 0.5 0.1 0.9 0.4 0.8 0.047 b0.001 0.004 b0.0001 b0.0001 0.09 0.4
cardiovascular diseases. However, ischemic events in our cohort appeared particularly high in comparison with other reported data [10], which might be explained by the type and severity of patients admitted to hospital in current practice while milder patients are managed in community settings. Our study has limitations in that the hospitalized cohort was studied retrospectively, whereas the stable one prospectively, and the former was slightly older than the latter. Our cohort of exacerbators reported more prior ischemic events than stable outpatients: since they also had higher QRISK-2 scores, the data suggest that QRISK-2 retains discriminant ability despite the presence of COPD. In conclusion, we suggest that the QRISK-2 score could be a useful and simple tool in clinical practice to help identify COPD patients in whom further evaluation may be justified. Conflict of interest The authors report no relationships that could be construed as a conflict of interest. Acknowledgement This work was supported by the NIHR Respiratory Biomedical Research Unit at the Royal Brompton and Harefield NHS Foundation Trust and Imperial College who partly funded MIP's and DM's salary. DM was also partially supported by an award from the Technology Strategy Board. A grant provided by Sapienza University contributed equally to the study. References
Fig. 1. Absolute risk of cardiovascular event in next 10 years as measured via QRISK2 score. Group 1 consists of patients hospitalized for exacerbation of COPD with a prior history of cardiac events (n = 77), Group 2 contains patients hospitalized for exacerbation of COPD without a history of prior cardiac events (n = 92) and Group 3 consists of stable outpatients with COPD (n = 61).
[1] S. Sidney, M. Sorel, C.P. Quesenberry Jr., C. DeLuise, S. Lanes, M.D. Eisner, COPD and incident cardiovascular disease hospitalizations and mortality: Kaiser Permanente Medical Care Program, Chest 128 (4) (2005) 2068–2075. [2] D.D. Sin, L.L. Wu, S.F.P. Man, The relationship between reduced lung function and cardiovascular mortality, Chest 127 (2005) 1952–1959. [3] D.A. McAllister, J.D. Maclay, N.L. Millis, A. Leitch, P. Reid, R. Carruthers, et al., Diagnosis of myocardial infarction following hospitalization for exacerbation of COPD, Eur. Respir. J. 39 (5) (2012) 1097–1103. [4] S. Van Eaden, J. Leipsic, S.F.P. Man, D.D. Sin, The relationship between lung inflammation and cardiovascular disease, Am. J. Respir. Crit. Care Med. 186 (1) (2012) 11–16. [5] M. Roca, A. Verduri, L. Corbetta, E. Clini, L.M. Fabbri, B. Beghè, Mechanism of acute exacerbation of respiratory symptoms in chronic obstructive pulmonary disease, Eur. J. Clin. Investig. 43 (5) (2013) 510–521. [6] G.C. Donaldson, J.R. Hurst, C.J. Smith, R.B. Hubbard, J.A. Wedzicha, Increased risk of myocardial infarction and stroke following exacerbation of COPD, Chest 137 (5) (2010) 1091–1097.
314
E. Pagliaroli et al. / International Journal of Cardiology 179 (2015) 312–314
[7] A.R. Patel, B.S. Kowlessar, G.C. Donaldson, et al., Cardiovascular risk, myocardial injury, and exacerbation of chronic obstructive pulmonary disease, Am. J. Respir. Crit. Care Med. 188 (9) (2013) 1091–1099. [8] J. Hippisley-Cox, C. Coupland, Y. Vinogradova, et al., Predicting cardiovascular risk in England and Wales: prospective derivation and validation of QRISK2, Br. Med. J. 336 (7659) (2008) 1475–1482.
[9] G.S. Collins, D.G. Altman, An independent and external validation of QRISK2 cardiovascular disease risk score: a prospective open cohort study, Br. Med. J. 340 (2010) c2442. [10] S. Roversi, P. Roversi, G. Spadafora, R. Rossi, L. Fabbri, Coronary artery disease concomitant with chronic obstructive pulmonary disease, Eur. J. Clin. Investig. 44 (1) (2014) 93–102.
