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Original Research: Pulmonary Vascular Disease |

Comorbid Conditions and Outcomes in Patients With Pulmonary Arterial HypertensionPulmonary Arterial Hypertension Comorbidities: A REVEAL Registry Analysis FREE TO VIEW

Abby D. Poms, BS, RRT; Michelle Turner, MS; Harrison W. Farber, MD, FCCP; Leslie A. Meltzer, PhD; Michael D. McGoon, MD, FCCP
Author and Funding Information

From the Duke University School of Medicine (Ms Poms), Durham, NC; ICON Late Phase & Outcomes Research (Ms Turner), San Francisco, CA; Boston University School of Medicine (Dr Farber), Boston, MA; Actelion Pharmaceuticals US, Inc (Dr Meltzer), South San Francisco, CA; and Mayo Clinic (Dr McGoon), Rochester, MN.

Correspondence to: Abby D. Poms, BS, RRT, Duke University School of Medicine, Box 102351, Durham, NC 27710; e-mail: abby.poms@duke.edu


Funding/Support: Funding and support for the REVEAL Registry was provided by Cotherix Inc and its affiliate Actelion Pharmaceuticals US Inc. Funding for preparation of this manuscript was provided by Actelion Pharmaceuticals US Inc.

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


Chest. 2013;144(1):169-176. doi:10.1378/chest.11-3241
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Published online

Background:  Comorbidities can affect disease progression and/or response to treatment in various conditions. Comorbid conditions are prevalent in patients with pulmonary arterial hypertension (PAH); however, their effect on patient outcomes remains unknown.

Methods:  We evaluated the effect on functional class (FC), 6-min walk test distance (6MWD), and survival of the seven most common, comorbid conditions at enrollment in patients with PAH from the Registry to Evaluate Early and Long-term PAH Disease Management (REVEAL Registry): hypertension, clinical depression, type 2 diabetes mellitus (diabetes), obesity, COPD, sleep apnea, and thyroid disease.

Results:  Patients with COPD or diabetes had the shortest 6MWD at enrollment (304.5 and 304.6 m, respectively) vs other comorbidities. Adjusted linear regression for 6MWD at enrollment revealed significant reductions among patients who were hypertensive, obese, diabetic, or had COPD (P < .001). A larger proportion of patients who were obese or had COPD were FC III/IV vs FC I/II at enrollment (P < .001). There was a greater risk for death among patients with diabetes (hazard ratio [HR], 1.73; 95% CI, 1.40-2.13; P < .001) or COPD (HR, 1.59; 95% CI, 1.34-1.90; P < .001), but there was a reduced risk for death in patients who were obese (HR, 0.73; 95% CI, 0.61-0.86; P < .001).

Conclusions:  Compared with other analyzed comorbidities in patients with PAH, hypertension, obesity, diabetes, and COPD were associated with significantly worse 6MWD; obesity and COPD were associated with worse FC; and diabetes and COPD were associated with increased risk for death. Further investigation of the effects of treating these comorbidities in patients with PAH is warranted.

Trial registry:  ClinicalTrials.gov; Identifier: NCT00370214; URL: www.clinicaltrials.gov

Figures in this Article

The Registry to Evaluate Early and Long-term Pulmonary Arterial Hypertension Disease Management (REVEAL Registry) is a multicenter, observational, US-based registry designed to provide current information about the demographics and clinical course of the patient population diagnosed with pulmonary arterial hypertension (PAH), defined as group 1 pulmonary hypertension.1,2 PAH is characterized by increased pressure in the pulmonary circulation, which leads to right-sided heart failure and ultimately, death.3 Outcomes in patients with PAH have been shown to vary among PAH subtypes. For example, PAH associated with portopulmonary hypertension (PoPH) or with connective tissue disease (CTD) portends a worse survival in comparison with that observed for patients with PAH associated with congenital heart disease (CHD).48 These findings suggest that the presence of other conditions that commonly coexist in patients with PAH might affect outcomes, including comorbid conditions that are not associated with the diagnosis of PAH.

Comorbid disease states have been examined in a broad range of clinical conditions, such as COPD, cancer, and rheumatoid arthritis,913 with respect to their effects on patient responses to treatment and outcomes. In many of these studies, the presence of certain comorbidities has been associated with significantly worsened outcomes or poorer responses to therapy. For example, in patients with COPD, osteoporosis is associated with a poor pulmonary rehabilitation outcome and ischemic heart disease is related to a greater risk of death.11,12 Furthermore, in elderly patients with breast cancer, a large number of comorbid conditions have been associated with poor survival.10

In patients with PAH, an associated condition such as CHD, CTD, or PoPH is commonly present, potentially impacting patient responses to therapy and/or modifying established identifiers of prognosis in PAH, such as the 6-min walk test distance (6MWD) in patients with CTD.14 Consequently, an understanding of the effects of other comorbid conditions that are prevalent in patients with PAH may be important for clinicians to optimize patient care. The seven most common conditions comorbid with PAH at enrollment in the REVEAL Registry were systemic hypertension, obesity, type 2 diabetes mellitus, COPD, sleep apnea, clinical depression, and thyroid disease. In the current study, the effects of these comorbidities on patient characteristics and outcomes, including hemodynamic parameters, lung function values, the distribution of New York Heart Association (NYHA) functional class (FC), 6MWD at enrollment, and survival, were evaluated in patients with PAH.

As previously reported,1 consecutive patients diagnosed with group 1 pulmonary hypertension and meeting specific hemodynamic criteria established by right-sided heart catheterization (RHC) at participating institutions were enrolled in the REVEAL Registry. Both newly diagnosed (confirmatory RHC ≤ 3 months prior to enrollment; 27%) and previously diagnosed (confirmatory RHC > 3 months prior to enrollment; 73%) patients were enrolled.

Among the patients enrolled in the REVEAL Registry based on established guidelines,1 those included in the present study met the following additional inclusion criteria: age ≥ 19 years at enrollment, pulmonary capillary wedge pressure (PCWP) or left ventricular end-diastolic pressure ≤ 15 mm Hg at diagnosis, and no participation in a blinded clinical trial at enrollment. Data were collected retrospectively, and the results were stratified by the comorbid conditions present in at least 10% of the REVEAL Registry population. Seven comorbidities met this criterion: hypertension, clinical depression, diabetes, obesity, COPD, sleep apnea, and thyroid disease.

The comorbidity groups were established according to the following definitions. Patients with either systemic hypertension or depression were determined according to the documented presence of the respective clinical condition. Obesity was defined as BMI ≥ 30 kg/m2.15 Due to similar clinical profiles, the results for obstructive lung disease and COPD are presented together as the comorbid condition COPD. Obstructive lung disease was documented on the medical history form or in the “Other Specify” field of the current comorbid-conditions form. COPD was documented on the current comorbid-conditions form and was determined by the treating physician. Patients with COPD were only included in the registry if they had clinically confirmed group 1 PAH and COPD that was not the underlying etiology of the pulmonary hypertension. The patients comprising this group had a mean FEV1 % predicted of 69.2, which is consistent with the cutoff values used as exclusionary criteria for COPD in clinical trials evaluating treatments for group 1 PAH (eg, GRIPHON [A Multicenter, Double-Blind, Placebo-Controlled Phase 3 Study to Demonstrate the Efficacy and Safety of ACT-293987 in Patients With Pulmonary Arterial Hypertension], SERAPHIN [Long-term Single-Arm Open-Label Extension Study of the SERAPHIN Study, to Assess the Safety and Tolerability of ACT 064992 in Patients With Symptomatic Pulmonary Arterial Hypertension], and FREEDOM [A 16-Week, International, Multicenter, Double-Blind, Randomized, Placebo-Controlled Comparison of the Efficacy and Safety of Oral UT-15C Sustained Release Tablets in Combination With an Endothelin Receptor Antagonist and/or a Phosphodiesterase-5 Inhibitor in Subjects With Pulmonary Arterial Hypertension] with ClinicalTrials.gov identifiers NCT01106014,16 NCT00667823,17 and NCT00325442,18 respectively). Thyroid disease was defined as the presence of hyperthyroidism or hypothyroidism and/or having used synthetic thyroid replacement for hypothyroidism. The diabetes group comprised patients with type 2 diabetes, and the presence of sleep apnea not associated with PAH was determined based on the medical history form. Of the 599 patients in this group, 65% were treated with CPAP or bilevel pressure ventilation, 13% were treated with “other” treatment, and < 1% were treated with surgery. The remaining 21% of patients did not receive treatment, and information regarding why they were not treated was not collected. A final comparator group denoted “None of the seven analyzed” was defined as patients without any of the analyzed comorbidities.

The REVEAL Registry protocol was approved by the institutional review boards of each participating institution prior to commencement. Participation in the REVEAL Registry was voluntary. All subjects were given full and adequate verbal and written information regarding the objectives and procedures of the study, and all subjects provided written informed consent prior to study entry.

Statistical Analyses

Demographic characteristics, hemodynamic parameters, and lung function test results are presented descriptively as the mean ± SD, stratified by each of the analyzed comorbid conditions. The contribution of each comorbid condition was assessed using regression analyses that were adjusted for the comorbidities assessed concomitantly. Therefore, patients with more than one of the seven comorbidities could be included in the present analyses because the adjustments permitted dissection of the contribution of each analyzed condition. Survival from enrollment was assessed using Kaplan-Meier product-limit estimates and adjusted Cox proportional hazards modeling. Adjusted linear regression of the 6MWD was performed. Adjusted logistic regression of NYHA/World Health Organization FC III/IV vs I/II was performed. An α level of 0.05 was used to determine statistical significance. All analyses were performed in SAS version 9.1.3 (SAS Institute, Inc) using data that were locked on April 19, 2011.

Patient Demographics and Functional Parameters by Comorbid Conditions

Among 3,515 patients enrolled in the REVEAL Registry, the following patients were excluded to obtain the present cohort: patients who were aged < 19 years at enrollment (n = 160), patients with PCWP > 15 mm Hg at diagnosis (n = 294), and patients who were participating in a blinded clinical trial at enrollment (n = 102). Consequently, the present analysis comprised 2,959 patients from the REVEAL Registry. Demographic and functional parameters at enrollment are summarized in Tables 1 and 2 and in Figure 1. The enrolled patients had the following characteristics: female (78.9%), white (72.3%), a mean age of 52.7 years at enrollment, idiopathic PAH (45.9%), and NYHA FC III or IV (51.1% and 7.0%, respectively). Demographic and functional characteristics were similar among the groups, with a somewhat greater proportion of NYHA FC IV among patients with diabetes (13.9%) or COPD (13.8%) in comparison with the other comorbidity groups (Fig 1).

Table Graphic Jump Location
Table 1 —Demographics by Analyzed Comorbid Conditions

Data given as No. (%) unless otherwise indicated. APAH = associated with pulmonary arterial hypertension; CHD = congenital heart disease; CTD = connective tissue disease; PoPH = portopulmonary hypertension.

a 

Obesity was defined as BMI ≥ 30 kg/m according to established criteria.15

b 

Thyroid disease was defined as patients with hyperthyroidism or hypothyroidism and/or patients having taken synthetic thyroid replacement for hypothyroidism.

c 

This group comprises patients who did not have any of the seven analyzed comorbidities.

Table Graphic Jump Location
Table 2 —Hemodynamic and Lung Functional Parameters by Analyzed Comorbid Conditions

Values are expressed as No. (mean ± SD). mPAP = mean pulmonary artery pressure; mRAP = mean right-sided atrial pressure; PCWP = pulmonary capillary wedge pressure; PVR = pulmonary vascular resistance.

a 

Obesity was defined as BMI ≥ 30 kg/m according to established criteria.15

b 

Thyroid disease was defined as patients with hyperthyroidism or hypothyroidism and/or patients having taken synthetic thyroid replacement for hypothyroidism.

c 

This group comprises patients who did not have any of the seven analyzed comorbidities.

Figure Jump LinkFigure 1. New York Heart Association/World Health Organization FC at enrollment by analyzed comorbid conditions. aNone refers to patients with pulmonary arterial hypertension and without any of the seven analyzed, comorbid conditions. bObesity was defined as BMI ≥ 30 kg/m2 according to established criteria.15cThyroid disease was defined as patients with hyperthyroidism or hypothyroidism and/or patients having taken synthetic thyroid replacement for hypothyroidism. FC = functional class.Grahic Jump Location
FC and 6MWD by Comorbid Conditions

Unadjusted analyses revealed that patients with COPD had the shortest 6MWD at enrollment, followed by patients with diabetes. In contrast, patients with none of the seven analyzed comorbid conditions demonstrated the best 6MWD at enrollment (Fig 2). Adjusted linear regression for 6MWD at enrollment revealed significant reductions in distance walked by patients who were hypertensive, obese, or diabetic, and by those with COPD (P < .001), as compared with patients without any of the seven analyzed conditions. In addition, the comorbid conditions of obesity and COPD were associated with a significantly increased likelihood of patients being FC III/IV vs FC I/II at enrollment (P < .001 for both) (Table 3).

Figure Jump LinkFigure 2. 6MWD at enrollment stratified by the seven analyzed, comorbid conditions. Patients with pulmonary arterial hypertension and with the comorbidity COPD or diabetes demonstrated the worst 6MWD at enrollment in comparison with the other analyzed conditions. aObesity was defined as BMI ≥ 30 kg/m2 according to established criteria.15bThyroid disease is defined as patients with hyperthyroidism or hypothyroidism and/or patients having taken synthetic thyroid replacement for hypothyroidism. cNone refers to patients with PAH and without any of the seven analyzed, comorbid conditions. 6MWD = 6-min walk distance.Grahic Jump Location
Table Graphic Jump Location
Table 3 —Adjusted Regression Analyses for Survival, 6MWD at Enrollment, and FC III/IV vs I/II at Enrollment

6MWD = 6-min walk distance; FC = functional class; LSM = least-squares mean; NYHA = New York Heart Association; WHO = World Health Organization.

a 

Obesity was defined as BMI ≥ 30 kg/m according to established criteria.15

b 

Thyroid disease was defined as patients with hyperthyroidism or hypothyroidism and/or patients having taken synthetic thyroid replacement for hypothyroidism.

Survival Analysis

Three-year survival estimates of the comorbidity groups revealed an increased risk of death in patients with PAH and diabetes or COPD compared with patients without any of the seven analyzed comorbidities (Fig 3). Consistent results were obtained using a Cox proportional hazards regression analysis of survival adjusting for each of the seven analyzed comorbidities (P < .001); however, surprisingly, a decreased risk of death was observed in patients with the comorbidity of obesity (P < .001).

Figure Jump LinkFigure 3. Three-year survival from enrollment in patients with pulmonary arterial hypertension stratified by comorbid conditions. Patients with the comorbidity of diabetes or COPD had the worst 3-y survival, whereas those with the comorbidity of obesity had the best survival, as compared with the other analyzed comorbid conditions. aThis group comprises patients who do not have any of the seven most common comorbidities; bObesity was defined as BMI ≥ 30 kg/m2 according to established criteria.15Grahic Jump Location

To further examine the disparate survival results obtained for type 2 diabetes and obesity, which are commonly linked, the demographics and etiology of the following patient groups were examined: (1) patients with diabetes and obesity, (2) patients with diabetes without obesity, and (3) patients with obesity without diabetes. Interestingly, the group with obesity without diabetes demonstrated a younger age, a greater percentage of female subjects, and a smaller percentage of patients with PoPH (e-Table 1).

The presence of certain comorbidities compared with none of the analyzed comorbid conditions was associated with a worsened FC (obesity and COPD) and 6MWD (hypertension, obesity, diabetes, and COPD) in patients with PAH enrolled in the REVEAL Registry. These observations demonstrate that the presence of a specific comorbidity in patients with PAH results in a poorer prognosis in comparison with those without that comorbidity. Furthermore, patients with the comorbid condition COPD or diabetes had an increased risk for death in comparison with the other comorbidity groups. Interestingly, in contrast to the other analyzed comorbidities, the presence of obesity conferred protection in the adjusted survival analysis. The latter results are remarkable considering data from the REVEAL Registry have demonstrated that obese patients (BMI ≥ 30 kg/m2) with PAH are more likely to present in FC III or IV PAH and with greater hemodynamic impairment in comparison with nonobese patients with PAH.19 A similar “obesity paradox” has been described in various patient populations, including elderly patients undergoing coronary artery bypass surgery,20 patients with intracerebral hemorrhage,21 and those with stroke.22 The selective protective effect of obesity in some conditions might be due to metabolic changes that impact the condition examined. In the present study, the “obesity paradox” might reflect the clinical observation of weight loss in patients who are ill and/or undergoing treatment with parenteral prostacyclin.

The results of adjusted analyses showing the opposing effects of obesity and type 2 diabetes on survival are intriguing, as these conditions are commonly linked. This phenomenon may be partially explained by the greater proportion of female patients and smaller proportion of patients with PoPH observed in the group with obesity without diabetes as compared with the comparator groups (with obesity and diabetes, with diabetes without obesity, with neither obesity nor diabetes but with one of the other five analyzed comorbid conditions, with none of the seven analyzed comorbid conditions, and all patients). Additional analyses are necessary to clarify the mechanism underlying the protective effect of obesity on survival in patients with PAH.

Despite the inclusion of a comparator group, the present study has several limitations: (1) limitations typically associated with uncontrolled, observational studies; (2) the diagnosis of sleep apnea was not rigidly defined and was considered mild and/or effectively treated by the investigating physician based on the treatment data; (3) the definitions of clinical depression and hypertension were determined by the attending physician. To address the third limitation, an additional definition was assessed for each condition: clinical depression defined as patients with the comorbid condition clinical depression and/or patients with a reported use of selective serotonin reuptake inhibitors; hypertension defined as patients with the comorbid condition hypertension and/or patients with a reported use of β-blockers. Although the subgroup of patients with an expanded definition of depression was significantly more likely to be classified as FC III/IV vs FC I/II at enrollment, all other results using the expanded definitions were consistent with those presented herein (e-Tables 2, 3, and 4), strengthening our findings for patients with depression and with hypertension.

Comorbid conditions affect the course of many underlying disease states. It has been well established that the coexistence of pulmonary hypertension affects many underlying diseases such as COPD and congestive heart failure, but this is the first study to demonstrate that comorbid conditions can affect the outcome of patients with pulmonary hypertension.23,24 Our observations also have important implications for the design of clinical trials investigating the efficacy of therapeutic interventions in patients with PAH; for example, the presence of any of the seven comorbid conditions assessed herein could affect the functional capacity and survival of patients with PAH. Furthermore, the high prevalence of comorbidities in the PAH population emphasizes the need for well-designed studies that consider the impact of comorbid disease states on PAH.

Author contributions: All authors had full access to all of the data in the study and take responsibility for the integrity of the data and accuracy of the data analysis.

Ms Poms: contributed to the study design; data collection, analysis, and interpretation; drafting and critical review of the manuscript; and approval of the final version of the manuscript and served as principal author.

Ms Turner: contributed to the study design; data collection, analysis, and interpretation; drafting and critical review of the manuscript; and approval of the final version of the manuscript.

Dr Farber: contributed to the study design; data collection, analysis, and interpretation; drafting and critical review of the manuscript; and approval of the final version of the manuscript.

Dr Meltzer: contributed to the study design; data collection, analysis, and interpretation; drafting and critical review of the manuscript; and approval of the final version of the manuscript.

Dr McGoon: contributed to the study design; data collection, analysis, and interpretation; drafting and critical review of the manuscript; and approval of the final version of the manuscript.

Financial/nonfinancial disclosures: The authors have reported to CHEST the following conflicts of interest: Ms Poms serves as a consultant for clinical research studies and advisory boards for Actelion Pharmaceuticals US Inc, Gilead Sciences Inc, United Therapeutics Corp, Lung Rx Inc, Novartis AG, and GlaxoSmithKline plc. She has received honoraria for speaker’s bureau participation for Actelion Pharmaceuticals US Inc, Gilead Sciences Inc, and United Therapeutics Corp. Ms Poms has received honoraria for her service on the REVEAL Registry Steering Committee, which is supported by Actelion Pharmaceuticals US Inc on behalf of Cotherix Inc. Ms Turner is employed by ICON Late Phase & Outcomes Research (ICON plc), which receives research support from Actelion Pharmaceuticals US Inc on behalf of Cotherix Inc and other pharmaceutical companies. Dr Farber serves as a consultant for Actelion Pharmaceuticals US Inc, Gilead Sciences Inc, Novartis AG, Bayer AG, Ikaria Inc, and United Therapeutics Corp, and is on the speaker’s bureau for Actelion Pharmaceuticals US Inc and Gilead Sciences Inc. Dr Farber has received a research grant from United Therapeutics Corp and Gilead Sciences Inc and has received honoraria for his service on the REVEAL Registry Steering Committee, which is supported by Actelion Pharmaceuticals US Inc on behalf of Cotherix Inc. Dr Meltzer is a former employee of Actelion Pharmaceuticals US Inc. Dr McGoon serves as a consultant with Actelion Pharmaceuticals US Inc, Gilead Sciences Inc, Lung LLC, and GlaxoSmithKline plc. He is a member of outcome adjudication and/or data and safety monitoring committees for Actelion Pharmaceuticals US Inc, Gilead Sciences Inc, and GlaxoSmithKline plc. Dr McGoon has served as the primary investigator for grants received by his institution from Gilead Sciences Inc and Medtronic Inc. Dr McGoon has received honoraria for his service on the REVEAL Registry Steering Committee, which is supported by Actelion Pharmaceuticals US Inc on behalf of Cotherix Inc.

Role of sponsors: Funding and support for the REVEAL Registry was provided by Cotherix, Inc, and its affiliate Actelion Pharmaceuticals US, Inc. Assistance in manuscript development was provided by Scarlett Geunes-Boyer, PhD, and Jennifer M. Kulak, PhD, of inScience Communications, Springer Healthcare, and funding was provided by Actelion Pharmaceuticals US, Inc.

Other contributions: The authors wish to thank the principal investigators and their study coordinators at 55 centers across the United States for their participation in the REVEAL Registry. Their names and affiliations appear in e-Appendix 1 and the list of centers is in e-Appendix 2.

Additional information: The e-Appendixes and e-Tables can be found in the “Supplemental Materials” area of the online article.

6MWD

6-min walk distance

CHD

congenital heart disease

CTD

connective tissue disease

FC

functional class

NYHA

New York Heart Association

PAH

pulmonary arterial hypertension

PCWP

pulmonary capillary wedge pressure

PoPH

portopulmonary hypertension

REVEAL Registry

Registry to Evaluate Early and Long-term PAH Disease Management

RHC

right-sided heart catheterization

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Figures

Figure Jump LinkFigure 1. New York Heart Association/World Health Organization FC at enrollment by analyzed comorbid conditions. aNone refers to patients with pulmonary arterial hypertension and without any of the seven analyzed, comorbid conditions. bObesity was defined as BMI ≥ 30 kg/m2 according to established criteria.15cThyroid disease was defined as patients with hyperthyroidism or hypothyroidism and/or patients having taken synthetic thyroid replacement for hypothyroidism. FC = functional class.Grahic Jump Location
Figure Jump LinkFigure 2. 6MWD at enrollment stratified by the seven analyzed, comorbid conditions. Patients with pulmonary arterial hypertension and with the comorbidity COPD or diabetes demonstrated the worst 6MWD at enrollment in comparison with the other analyzed conditions. aObesity was defined as BMI ≥ 30 kg/m2 according to established criteria.15bThyroid disease is defined as patients with hyperthyroidism or hypothyroidism and/or patients having taken synthetic thyroid replacement for hypothyroidism. cNone refers to patients with PAH and without any of the seven analyzed, comorbid conditions. 6MWD = 6-min walk distance.Grahic Jump Location
Figure Jump LinkFigure 3. Three-year survival from enrollment in patients with pulmonary arterial hypertension stratified by comorbid conditions. Patients with the comorbidity of diabetes or COPD had the worst 3-y survival, whereas those with the comorbidity of obesity had the best survival, as compared with the other analyzed comorbid conditions. aThis group comprises patients who do not have any of the seven most common comorbidities; bObesity was defined as BMI ≥ 30 kg/m2 according to established criteria.15Grahic Jump Location

Tables

Table Graphic Jump Location
Table 1 —Demographics by Analyzed Comorbid Conditions

Data given as No. (%) unless otherwise indicated. APAH = associated with pulmonary arterial hypertension; CHD = congenital heart disease; CTD = connective tissue disease; PoPH = portopulmonary hypertension.

a 

Obesity was defined as BMI ≥ 30 kg/m according to established criteria.15

b 

Thyroid disease was defined as patients with hyperthyroidism or hypothyroidism and/or patients having taken synthetic thyroid replacement for hypothyroidism.

c 

This group comprises patients who did not have any of the seven analyzed comorbidities.

Table Graphic Jump Location
Table 2 —Hemodynamic and Lung Functional Parameters by Analyzed Comorbid Conditions

Values are expressed as No. (mean ± SD). mPAP = mean pulmonary artery pressure; mRAP = mean right-sided atrial pressure; PCWP = pulmonary capillary wedge pressure; PVR = pulmonary vascular resistance.

a 

Obesity was defined as BMI ≥ 30 kg/m according to established criteria.15

b 

Thyroid disease was defined as patients with hyperthyroidism or hypothyroidism and/or patients having taken synthetic thyroid replacement for hypothyroidism.

c 

This group comprises patients who did not have any of the seven analyzed comorbidities.

Table Graphic Jump Location
Table 3 —Adjusted Regression Analyses for Survival, 6MWD at Enrollment, and FC III/IV vs I/II at Enrollment

6MWD = 6-min walk distance; FC = functional class; LSM = least-squares mean; NYHA = New York Heart Association; WHO = World Health Organization.

a 

Obesity was defined as BMI ≥ 30 kg/m according to established criteria.15

b 

Thyroid disease was defined as patients with hyperthyroidism or hypothyroidism and/or patients having taken synthetic thyroid replacement for hypothyroidism.

References

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