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Clinical and economic burden of patients diagnosed with COPD with comorbid cardiovascular disease

Open ArchivePublished:June 20, 2011DOI:https://doi.org/10.1016/j.rmed.2011.04.005

      Summary

      Background

      Cardiovascular disease (CVD) and chronic obstructive pulmonary disease (COPD) commonly coexist, increasing the risk of hospitalization and mortality compared to either condition alone. The purpose of this study was to evaluate the impact of comorbid CVD on healthcare utilization and costs in a COPD population.

      Methods

      A retrospective cohort study of COPD patients CVD ± ≥40 years of age using administrative claims data was conducted. COPD-CVD patients were matched to COPD patients without CVD (COPD-Only cohort) using propensity scores. Multivariate analyses were conducted to assess the 1-year risk of COPD exacerbations (hospitalization and/or emergency room [ER] visits), along with differences in 1-year and 2-year all-cause and COPD-related utilization and costs (2008 USD) among COPD-CVD and COPD-Only cohorts.

      Results

      Each cohort included 4594 patients. Compared to COPD-Only cohort, the COPD-CVD cohort was almost 2 times more likely to require COPD-related hospitalization (odds ratio [OR], 1.95; p < 0.001), 47% more likely to have an ER visit (OR, 1.47; p < 0.001) and 62% more likely to require hospitalization and/or ER visit (OR, 1.62; p < 0.001). Average annual all-cause medical costs per patient were $22,755 for COPD-CVD vs $8036 for COPD-Only (p < 0.001), and total costs were $27,032 vs $11,506 (p < 0.001), respectively; corresponding average COPD-related annual medical costs were $1891 vs $1060 (p < 0.001) and total costs were $3295 vs $2379 (p < 0.001).

      Conclusions

      COPD patients with CVD have significantly higher risk of COPD exacerbations and increased costs than COPD patients without CVD. This suggests a close association between COPD and CVD that warrants further exploration.

      Keywords

      Introduction

      Chronic obstructive pulmonary disease (COPD) is among the leading causes of mortality in the United States (US)—ranking as the fourth leading cause with approximately 119,000 deaths during 2000.
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      Cardiovascular morbidity and mortality in COPD.
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      Changes in cardiovascular hospitalization and comorbidity of heart failure in the United States: findings from the National Hospital Discharge Surveys 1980–2006.
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      More recently, in an observational study of patients in Italy with chronic heart failure, comorbid COPD was shown to independently increase the likelihood of death as well as the risks of non-fatal acute myocardial infarction, non-fatal stroke, or hospitalization/rehospitalization for chronic heart failure.
      • Macchia A.
      • Monte S.
      • Romero M.
      • D’Ettorre A.
      • Tognoni G.
      The prognostic influence of chronic obstructive pulmonary disease in patients hospitalised for chronic heart failure.
      A relationship between COPD severity and CVD-related morbidity and mortality has also been described.
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      • et al.
      Chronic obstructive pulmonary disease severity and cardiovascular outcomes.
      In a COPD patient cohort from the Saskatchewan Health longitudinal databases, 20% of patients with the most severe COPD (derived from the likelihood of hospitalization for COPD) were 1.27, 1.25, 1.38, and 2.28 times more likely to have an arrhythmia, ischemic heart disease, angina, and congestive heart failure, respectively, relative to the 20% of patients with the least severe COPD.
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      Chronic obstructive pulmonary disease severity and cardiovascular outcomes.
      Additionally, the patients with the most severe COPD were 1.63 times more likely to die of CVD-related causes than those in the least severe subset. Despite only a few published studies that have described the influence of CVD on COPD-related outcomes,
      • Crisafulli E.
      • Costi S.
      • Luppi F.
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      • Cilione C.
      • Coletti O.
      • et al.
      Role of comorbidities in a cohort of patients with COPD undergoing pulmonary rehabilitation.
      • Huiart L.
      • Ernst P.
      • Suissa S.
      Cardiovascular morbidity and mortality in COPD.
      • Terzano C.
      • Conti V.
      • Di Stefano F.
      • Petroianni A.
      • Ceccarelli D.
      • Graziani E.
      • et al.
      Comorbidity, hospitalization, and mortality in COPD: results from a longitudinal study.
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      • et al.
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      the available evidence together supports that CVD is correlated with hospitalization and mortality in the COPD population,
      • Huiart L.
      • Ernst P.
      • Suissa S.
      Cardiovascular morbidity and mortality in COPD.
      • Terzano C.
      • Conti V.
      • Di Stefano F.
      • Petroianni A.
      • Ceccarelli D.
      • Graziani E.
      • et al.
      Comorbidity, hospitalization, and mortality in COPD: results from a longitudinal study.
      contributes to a poor outcome following pulmonary rehabilitation,
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      • Costi S.
      • Luppi F.
      • Cirelli G.
      • Cilione C.
      • Coletti O.
      • et al.
      Role of comorbidities in a cohort of patients with COPD undergoing pulmonary rehabilitation.
      and poses an increased risk of COPD exacerbation requiring hospitalization.
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      • et al.
      Risk indexes for exacerbations and hospitalizations due to COPD.
      Although existing data indicate a correlation between comorbidity, hospitalization, and mortality, no data are available on the cost impact of comorbid CVD in the COPD population. Therefore, in postulating that comorbid COPD and CVD have a significant impact on the cost of COPD care, we sought to evaluate this issue in a managed care population by characterizing healthcare resource use, as well as direct all-cause and COPD-related costs (both total and medical).

      Methods

      This was an observational, retrospective, matched-cohort study conducted to assess healthcare resource utilization and costs among those with comorbid COPD and CVD vs COPD alone (Fig. 1). An integrated source of managed care claims from the IMS Lifelink Database that contains medical and pharmacy claims data from over 100 different managed healthcare plans (encompassing over 60 million patients) in the US was used as the data source for this study. The medical, pharmacy, and eligibility component files from this database were utilized, identifying inpatient and outpatient diagnoses and procedures, prescription records, demographic characteristics, and eligibility information. For all claims, the dates of service, as well as the amounts charged and paid for the service/drug, were available. All data were fully de-identified and compliant with the Health Insurance Portability and Accountability Act (HIPAA).
      Figure thumbnail gr1
      Figure 1Study design.
      COPD = chronic obstructive pulmonary disease; CVD = cardiovascular disease.

      Patient selection

      Identification of COPD patients was based on the presence of a pharmacy claim for a COPD maintenance medication, specifically inhaled corticosteroids (beclomethasone dipropionate, budesonide, flunisolide, fluticasone propionate, or triamcinolone acetonide), long-acting beta-agonists (formoterol fumarate, salmeterol xinafoate, or arformoterol tartrate), anticholinergics (ipratropium bromide, ipratropium bromide/albuterol, or tiotropium bromide), and/or fixed-dose combination regimens (fluticasone propionate + salmeterol xinafoate 250/50 mcg) between January 1, 2004 and June 30, 2007; the date of initial COPD medication was deemed the index COPD date. Patients were placed in the COPD-CVD cohort if they had at least 1 prescription claim for a medication used to treat CVD (Table 1) within 60 days post-index COPD date, with the date of the prescription deemed the index CVD date. Additionally, to be included in the COPD-CVD cohort, a CVD diagnosis/procedure (Table 1) during the 1-year post-index CVD date was required. Accordingly, patients were placed in the COPD with no CVD cohort (COPD-Only cohort) if they had no diagnosis/procedure or medication for CVD 1-year pre- and post-index COPD date.
      Table 1Cardiovascular Disease-related Medication Classes and Diagnostic Codes.
      Medication Classes
      • Beta-blocking agents

      • Alpha-blocking agents

      • Calcium channel blocking agents

      • Angiotensin-converting enzyme inhibitors

      • Carbonic anhydrase inhibitors

      • Diuretics

      • Antihypertensive combinations
      • Antianginal agents

      • Antiarrhythmic agents

      • Inotropic agents

      • Vasopressors

      • Thrombolytics

      • Platelet aggregation inhibitors

      • Glycoprotein platelet inhibitors

      • Heparins

      • Coumarins

      • Indanediones
      ICD-9 CM/CPT CodesCategory Description
      ‘411.xx’Other acute and subacute forms of ischemic heart disease
      ‘413.xx’Angina pectoris
      ‘414.xx’Other forms of chronic ischemic heart disease
      ‘433.xx’Occlusion and stenosis of precerebral arteries
      ‘434.xx’Occlusion of cerebral arteries
      ‘436.xx’Acute, but ill-defined, cerebrovascular disease
      ‘410.xx’Acute Myocardial Infarction
      ‘427.xx’Cardiac Arrhythmias
      ‘428.xx’Heart Failure
      ‘430.xx’Subarachnoid Hemorrhage
      ‘431.xx’Intracerebral Hemorrhage
      ‘432.xx’Other and Unspecified Intracranial Hemorrhage
      ‘435.9x’Trans Ischemic Attack
      ‘443.xx’Peripheral Vascular Disease
      ‘35450-35460’Open Transluminal Angioplasty
      ‘35470-35473’Percutaneous Transluminal Angioplasty
      ‘35474-35476’Transluminal Balloon Angioplasty
      ‘35480-35485’Open Transluminal Atherectomy
      ‘35490-35495’Percutaneous Transluminal Atherectomy
      ‘35500-35572’Vein Bypass Graft
      ‘35582-35587’In-Situ Vein Bypass Graft
      ‘35600-35671’Other Bypass Graft
      ‘33510-33514’, ‘33516-33519’, ‘33521-33523’, ‘33533-33536’Coronary Artery Bypass Graft
      ‘92980’Transcatheter placement of an intracoronary stent(s), percutaneous, with or without other therapeutic intervention, any method; single vessel
      ‘92981’Transcatheter placement of an intracoronary stent(s), percutaneous, with or without other therapeutic intervention, any method; each additional vessel
      Regardless of cohort, patients were required to be ≥40 years of age, eligible to receive healthcare services 1-year pre- and post-index COPD date, and have at least 1 medical claim with a COPD diagnosis (International Classification of Diseases, 9th Revision, Clinical Modification [ICD-9 CM] code 491.xx, 492.xx and 496.xx). Patients were excluded if they had any of the following comorbid conditions (ICD-9 CM codes) during the study period: respiratory cancer (160-163.xx, 231.xx), cystic fibrosis (277.0x), bronchiectasis (494.xx), pneumoconiosis (500-505.xx), pulmonary fibrosis (515.xx), pulmonary tuberculosis including fibrosis due to tuberculosis (011.xx), or sarcoidosis (135.xx).

      Propensity score matching

      As differences at baseline would have the potential to bias results when analyzing outcomes by cohort, patients in the COPD-CVD cohort were matched to patients in the COPD-Only cohort. This matching was performed in a 1:1 ratio using propensity scores, with the score for each patient defined as the probability of having comorbid CVD conditional on baseline variables, including demographics (age, gender), proxies for COPD severity (number of oral corticosteroid [OCS] prescriptions, number of short-acting beta-agonist [SABA] canisters, number of ipatropium [IPR] canisters, use of home oxygen therapy, COPD-related medical costs, and COPD-related pharmacy costs), and other comorbidity measures (Charlson comorbidity index, presence of asthma, number of unique medication classes, number of all prescriptions, number of unique diagnoses, all-cause medical costs, all-cause pharmacy costs) from the pre-index period. Matching proceeded using the technique of nearest available matching on the estimated propensity score, performed up to 3 decimal places (0.001). The success of the resulting propensity score to reduce bias was assessed by evaluating the balance in the covariates between the cohorts after matching.

      Outcome measures

      All-cause and COPD-related resource utilization and costs (adjusted to 2008 USD based on medical consumer price index) were calculated in the 1-year post-index date (index CVD date for the COPD-CVD cohort and index COPD date for the COPD-Only cohort), with costs also calculated for the 2-year post-index period. The examined outcomes were all-cause and COPD-related (based on the primary COPD diagnosis and COPD-related medications) total and medical costs, and the numbers of all-cause and COPD-related physician office visits, emergency room (ER) visits, inpatient hospitalizations, and hospital-based outpatient (OP) visits. The risk of COPD-related hospitalization and/or ER visit (reflecting COPD-related exacerbation) was also examined among both cohorts.

      Statistical analysis

      Standard summary statistics (means and proportions) were used to report baseline characteristics, including demographics (age, gender, and region of residence); comorbidity measures (Charlson comorbidity index, number of unique diagnoses and prescription classes, total number of prescriptions, and presence of asthma); number of all-cause, and COPD-related, hospitalizations and physician office, ER, and OP hospital visits; and all-cause, and COPD-related, medical and pharmacy costs (adjusted to 2008 USD). In addition, proxies for COPD severity, including number of canisters of inhaled SABAs and of inhaled ipratropium or ipratropium/albuterol, number of prescriptions of OCS, and use of home oxygen therapy, were reported via summary statistics.
      Baseline characteristics were compared between cohorts using paired t tests or Wilcoxon signed rank tests (for continuous variables) and McNemar’s tests (for categorical variables). Univariate outcome measures were compared between cohorts using paired t tests for continuous variables, whereas categorical variables were compared using McNemar’s tests.
      Generalized linear models using a gamma distribution with a log-link were used to obtain adjusted costs. Conditional logistic regression models were used to assess the risk of COPD-related hospitalization and/or ER visit over a 1-year follow-up period. Conditional negative binomial regression models were used to assess number of visits. All models controlled for any differences in baseline characteristics across cohorts that still existed after the match. In addition, cost models controlled for 1-year pre-period costs. All statistical tests were based on a 2-sided hypothesis of no difference between treatment groups at a significance level of 0.05.

      Results

      Post-propensity score matching, there were 4594 patients per cohort. The cohorts were similar in terms of mean age and gender distribution, and most comorbidity and COPD severity measures (Table 2). There were, however, significant differences regarding geographic region, and comorbidity measures (such as mean numbers of unique prescription classes and unique diagnoses).
      Table 2Baseline Characteristics After Propensity Score Matching.
      CharacteristicCOPD-CVD (N = 4594)COPD-Only (N = 4594)
      Mean age (SD)63.9 (10.0)63.8 (10.3)
      Male50.2%48.7%
      Region∗
       East28.7%28.2%
       Midwest38.7%35.0%
       South17.0%17.2%
       West15.6%19.6%
      Asthma17.3%18.4%
      Oxygen therapy14.0%13.7%
      Mean no. of OCS prescriptions (SD)0.6 (1.7)0.7 (1.4)
      Mean no. of SABA canisters (SD)1.3 (4.1)1.3 (3.4)
      Mean no. of IPR canisters (SD)1.3 (4.2)1.2 (3.8)
      Mean Charlson index (SD)1.2 (1.3)1.2 (1.5)
      Mean no. of unique prescription classes (SD)5.8 (3.8)6.2∗ (4.0)
      Mean no. of prescriptions (SD)25.2 (25.8)25.8 (24.9)
      Mean no. of unique diagnoses (SD)11.6 (6.5)11.9∗ (7.1)
      Mean COPD-related medical costs (SD)$1472 ($4969)$1413 ($7379)
      Mean COPD-related prescription costs (SD)$484 ($1027)$499 ($808)
      Mean all-cause medical costs (SD)$10,751 (16341)$10,033∗ (19972)
      Mean all-cause pharmacy costs (SD)$2165 (3333)$2302∗ (3158)
      IPR = ipratropium; OCS = oral corticosteroids; SABA = short-acting beta-agonist; SD = standard deviation. All characteristics measured in the 1-year pre-index COPD date.
      p < 0.05 when compared to COPD-CVD comorbid cohort.
      Given the statistically significant differences in baseline characteristics after the propensity score matching, all outcome measures were analyzed using multivariate statistics.
      Adjusted annual all-cause and COPD-related visits are summarized in Table 3. The average number of annual all-cause physician office visits was 31% higher (incidence rate ratio [IRR], 1.31; 95% confidence interval [CI], 1.27–1.36) for the COPD-CVD cohort when compared with that for the COPD-Only cohort. Likewise, for the COPD-CVD cohort relative to the COPD-Only cohort, the average number of annual all-cause ER visits were 68% higher (IRR, 1.68; 95% CI, 1.52–1.85), all-cause OP visits were 56% higher (IRR, 1.56; 95% CI, 1.49–1.64), and all-cause hospitalization was 3 times higher (IRR, 3.11; 95% CI, 2.80–3.45). Regarding annual COPD-related physician office visits, the average number was 7% higher (IRR, 1.07; 95% CI, 1.03–1.12) for the COPD-CVD cohort compared to the COPD-Only cohort, with annual COPD-related ER visits increased by 36% (IRR, 1.36; 95% CI, 1.12–1.66), COPD-related OP visits increased by 33% (IRR, 1.33; 95% CI, 1.14–1.55), and COPD-related hospitalizations were 2 times higher (IRR, 2.01; 95% CI, 1.58–2.55) for the COPD-CVD cohort when compared to the COPD-Only cohort.
      Table 3Adjusted Annual All-Cause and COPD-Related Health Care Utilization.
      COPD-CVD (N = 4594)COPD-Only (N = 4594)
      Mean (95% CI) no. of all-cause:
      Physician office visits13.01 (12.72, 13.31)9.90∗ (9.70, 10.12)
      Emergency room visits0.54 (0.51, 0.58)0.32∗ (0.30, 0.35)
      Inpatient hospitalizations0.41 (0.39, 0.44)0.13∗ (0.12, 0.15)
      Outpatient hospital visits6.22 (6.01, 6.43)3.98∗ (3.85, 4.12)
      Mean (95% CI) no. of COPD-related:
      Physician office visits2.87 (2.79, 2.96)2.67∗ (2.60, 2.75)
      Emergency room visits0.08 (0.07, 0.09)0.06∗ (0.05, 0.07)
      Inpatient hospitalizations0.05 (0.05, 0.06)0.03∗ (0.02, 0.03)
      Outpatient hospital visits0.64 (0.57, 0.71)0.48∗ (0.43, 0.53)
      CI = confidence interval; SD = standard deviation.
      p < 0.05 when compared to the COPD-CVD comorbid cohort (based on conditional negative binomial regression controlling for region, number of unique prescription classes, number of unique diagnoses, presence of intensive care unit stay for COPD, and number of visits [dependent on outcome of interest] in the 1-year pre-index period).
      Results of the analyses that assessed the risk of a COPD-related hospitalization and/or ER visit are presented in Fig. 2. Patients in the COPD-CVD cohort were 95% more likely to have a COPD-related hospitalization (odds ratio [OR], 1.95; 95% CI, 1.55–2.45; p < 0.001), 47% more likely to have an ER visit (OR, 1.47; 95% CI, 1.23–1.75; p < 0.001), and 62% more likely to have a hospitalization and/or ER visit (OR, 1.62; 95% CI, 1.40–1.88; p < 0.001) as compared with the COPD-Only cohort.
      Figure thumbnail gr2
      Figure 2Adjusted risk of COPD-related emergency room visit and/or hospitalization. OR = odds ratio.
      Mean adjusted annual all-cause medical and total healthcare costs were approximately 2.5 times higher for the COPD-CVD cohort when compared with the COPD-Only cohort (Table 4), whereas annual COPD-related medical costs were 78% higher and COPD-related total costs were 38% higher. Through the 2-year period, the COPD-CVD cohort continued to have higher all-cause total healthcare and medical costs (Fig. 3A) and higher COPD-related total and medical costs (Fig. 3B) relative to the COPD-Only cohort.
      Table 4Adjusted Annual All-Cause and COPD-Related Healthcare Costs (2008 USD).
      COPD-CVD (N = 4594)COPD-Only (N = 4594)
      Mean (95% CI) all-cause healthcare costs:
      Medical costs$22,755 ($22,579, $22,930)$8036∗ ($7974, $8098)
      Total costs$27,032 ($26,857, $27,206)$11,506∗ ($11,432, $11,581)
      Mean (95% CI) COPD-related healthcare costs:
      Medical costs$1891 ($1868, $1915)$1060∗ ($1046, $1073)
      Total costs$3295 ($3265, $3324)$2379∗ ($2357, $2400)
      CI = confidence interval. Annual costs are during 1-year of follow-up.
      p < 0.001 when compared to the COPD-CVD comorbid cohort (based on generalized linear model with a gamma distribution and log-link controlling for region, number of unique prescription classes, number of unique diagnoses, presence of intensive care unit stay for COPD, and costs [dependent on outcome of interest] in the 1-year pre-index period).
      Figure thumbnail gr3
      Figure 3Adjusted all-cause healthcare costs (A) and COPD-related healthcare costs (B) in 1-year and 2-year follow-up (2008 USD).

      Discussion

      To our knowledge, there have been no published studies focused on both healthcare utilization and cost for COPD patients with or without CVD. This study showed significant increases in all utilization and cost outcomes examined in a commercial managed care setting for patients with comorbid COPD and CVD relative to those with COPD only. Patients with comorbid COPD-CVD had twice the risk of a COPD-related hospitalization and approximately 50% greater risk of a COPD-related ER visit than those without CVD. The COPD-CVD cohort had total annual direct costs that were 135% greater than those without CVD, whereas COPD-related total costs were 38% greater. Our study confirms previous observations that the addition of CVD to COPD results in a substantial increase in COPD-specific utilization, translating to substantial increases in COPD-specific costs.
      The propensity for patients with COPD to also have CVD is well-documented in the published literature,
      • Crisafulli E.
      • Costi S.
      • Luppi F.
      • Cirelli G.
      • Cilione C.
      • Coletti O.
      • et al.
      Role of comorbidities in a cohort of patients with COPD undergoing pulmonary rehabilitation.
      • Hernandez C.
      • Jansa M.
      • Vidal M.
      • Nuñez M.
      • Bertran M.J.
      • Garcia-Aymerich J.
      • et al.
      The burden of chronic disorders on hospital admissions prompts the need for new modalities of care: a cross-sectional analysis in a tertiary hospital.
      • Holguin F.
      • Folch E.
      • Redd S.C.
      • Mannino D.M.
      Comorbidity and mortality in COPD-related hospitalizations in the United States, 1979–2001.
      • Huiart L.
      • Ernst P.
      • Suissa S.
      Cardiovascular morbidity and mortality in COPD.
      • Liu L.
      Changes in cardiovascular hospitalization and comorbidity of heart failure in the United States: findings from the National Hospital Discharge Surveys 1980–2006.
      • Macchia A.
      • Monte S.
      • Romero M.
      • D’Ettorre A.
      • Tognoni G.
      The prognostic influence of chronic obstructive pulmonary disease in patients hospitalised for chronic heart failure.
      • Terzano C.
      • Conti V.
      • Di Stefano F.
      • Petroianni A.
      • Ceccarelli D.
      • Graziani E.
      • et al.
      Comorbidity, hospitalization, and mortality in COPD: results from a longitudinal study.
      yet the underlying reason for this coexistence has not been fully elucidated, with the influence of shared risk factors (eg, smoking, sedentary lifestyle) as one potential explanation.
      • Maclay J.D.
      • McAllister D.A.
      • Macnee W.
      Cardiovascular risk in chronic obstructive pulmonary disease.
      However, as airflow limitation has been identified as an independent risk factor for CVD, it is possible that the systemic consequences of COPD influence the underlying pathogenesis of CVD.
      • Maclay J.D.
      • McAllister D.A.
      • Macnee W.
      Cardiovascular risk in chronic obstructive pulmonary disease.
      Although outstanding questions remain pertaining to the mechanism(s) linking COPD and CVD, an accumulating number of studies have demonstrated the adverse impacts of both (1) CVD on mortality and hospitalization in the COPD population
      • Huiart L.
      • Ernst P.
      • Suissa S.
      Cardiovascular morbidity and mortality in COPD.
      • Terzano C.
      • Conti V.
      • Di Stefano F.
      • Petroianni A.
      • Ceccarelli D.
      • Graziani E.
      • et al.
      Comorbidity, hospitalization, and mortality in COPD: results from a longitudinal study.
      • Niewoehner D.E.
      • Lokhnygina Y.
      • Rice K.
      • Kuschner W.G.
      • Sharafkhaneh A.
      • Sarosi G.A.
      • et al.
      Risk indexes for exacerbations and hospitalizations due to COPD.
      and (2) COPD on CVD-related mortality and hospitalization.
      • Macchia A.
      • Monte S.
      • Romero M.
      • D’Ettorre A.
      • Tognoni G.
      The prognostic influence of chronic obstructive pulmonary disease in patients hospitalised for chronic heart failure.
      • Curkendall S.M.
      • DeLuise C.
      • Jones J.K.
      • Lanes S.
      • Stang M.R.
      • Goehring Jr., E.
      • et al.
      Cardiovascular disease in patients with chronic obstructive pulmonary disease, Saskatchewan Canada cardiovascular disease in COPD patients.
      • Sidney S.
      • Sorel M.
      • Quesenberry Jr., C.P.
      • DeLuise C.
      • Lanes S.
      • Eisner M.D.
      COPD and incident cardiovascular disease hospitalizations and mortality: Kaiser Permanente Medical Care Program.
      • Curkendall S.M.
      • Lanes S.
      • de Luise C.
      • Stang M.R.
      • Jones J.K.
      • She D.
      • et al.
      Chronic obstructive pulmonary disease severity and cardiovascular outcomes.
      For example, in a US Veterans Affairs population with moderate-to-severe COPD, comorbid CVD was among the variables associated with increased risk of hospitalization for COPD exacerbation in multivariate analysis, with a relative hazard of 2.10 (95% CI, 1.28–3.46; p = 0.004).
      • Niewoehner D.E.
      • Lokhnygina Y.
      • Rice K.
      • Kuschner W.G.
      • Sharafkhaneh A.
      • Sarosi G.A.
      • et al.
      Risk indexes for exacerbations and hospitalizations due to COPD.
      Results of our analysis were similar with patients in the COPD-CVD cohort being almost 2 times more likely to have a COPD-related hospitalization. Prior research has also suggested that CVD makes a larger contribution to hospitalization
      • Huiart L.
      • Ernst P.
      • Suissa S.
      Cardiovascular morbidity and mortality in COPD.
      and/or mortality
      • Huiart L.
      • Ernst P.
      • Suissa S.
      Cardiovascular morbidity and mortality in COPD.
      • Terzano C.
      • Conti V.
      • Di Stefano F.
      • Petroianni A.
      • Ceccarelli D.
      • Graziani E.
      • et al.
      Comorbidity, hospitalization, and mortality in COPD: results from a longitudinal study.
      rates than COPD-related complications in the COPD population. Our economic analysis mirrored these conclusions from prior research. Specifically, we found the medical component to comprise a higher proportion of the total for all-cause (84%) compared to COPD-related costs (54%).
      In terms of the impact of COPD on CVD-related mortality and hospitalization, a study of patients aged ≥55 years with COPD within the Saskatchewan Health longitudinal databases revealed that overall CVD-related hospitalization was twice as frequent and heart failure-related hospitalization 3 times as frequent among patients with CVD compared with the general population.
      • Huiart L.
      • Ernst P.
      • Suissa S.
      Cardiovascular morbidity and mortality in COPD.
      Although our study did not specifically measure CVD-related hospitalizations, we did show that patients with both COPD and CVD had 3 times more all-cause inpatient hospitalizations compared to COPD patients without CVD.
      The coexistence of COPD and CVD presents many diagnostic challenges, with clinical signs and symptoms requiring careful interpretation (in conjunction with objective evidence of each condition) and both representing chronic progressive diseases complicated by exacerbations.
      • Hawkins N.M.
      • Petrie M.C.
      • Jhund P.S.
      • Chalmers G.W.
      • Dunn F.G.
      • McMurray J.J.
      Heart failure and chronic obstructive pulmonary disease: diagnostic pitfalls and epidemiology.
      Both CVD and COPD may often go undiagnosed until a sentinel event occurs that leads to the diagnosis of one, and occasionally both, conditions. Our findings emphasize the importance of the coexistence of both conditions, and suggest that the presence of one condition should lead clinicians to examine the possibility for the presence of the other until proven otherwise. This is especially true since some symptoms of CVD and COPD, such as dyspnea, may often overlap. However, additional research is needed to determine if treatment of one comorbidity can affect the course of the other.
      We acknowledge several limitations of our study. The propensity score matching was a strength of the analytic approach, yet patients in the post-matching comparison cohorts still had some differences with respect to certain baseline characteristics; our adjustment for these differences in the multivariate analysis reduces, but does not eliminate, the potential for residual confounding. As with any retrospective, observational series lacking rigorous prospective assessment of the primary outcomes, potential under-diagnosis of CVD could have resulted in an underestimation of the direct costs of comorbid COPD-CVD. Additionally, this study does not illustrate the full economic burden of comorbid COPD-CVD, given that the data source precluded the calculation of indirect costs (a substantial contributor to the economic burden of COPD
      • Foster T.S.
      • Miller J.D.
      • Marton J.P.
      • Caloyeras J.P.
      • Russell M.W.
      • Menzin J.
      Assessment of the economic burden of COPD in the U.S.: a review and synthesis of the literature.
      ). The results are also limited in that they do not provide any insight into the relative contribution of specific types of CVD or other non-CVD comorbidities to the increased hospitalizations and costs observed in the COPD-CVD cohort. Lastly, as with any claims database analysis, a lack of clinical parameters such as smoking status may affect the estimates of economic burden.
      In conclusion, in the setting of COPD and comorbid CVD, the risk of COPD-related exacerbations and average all-cause and COPD-related expenditures are higher than those encountered with COPD alone.

      Conflicts of interest

      Anand A. Dalal is an employee of GlaxoSmithKline (GSK) and owns company stock. Nicole A. Hanania has received research grant support from GSK and has also served as a consultant and on the speaker bureau of GSK. Manan Shah and Orsolya Lunacsek are employees of Xcenda, LLC, a company that received funding from GSK to conduct this research.

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