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Relationship between Comorbid Conditions and Outcomes in Patients with Pulmonary Arterial Hypertension: A REVEAL Analysis

Abby Poms

Michelle Turner

Harrison Farber

Michael McGoon


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Conference: 2011 PH Professional Network Symposium

Release Date: 09.22.2011

Presentation Type: Abstracts

A Poms, BS, RRT1; M Turner, MS2; H Farber, MD3; M McGoon, MD4
1. Duke University Medical Center, Durham, NC
2. ICON Late Phase & Outcomes Research, San Francisco, CA
3. Boston University School of Medicine, Boston, MA
4. Mayo Clinic, Rochester, MN

PURPOSE: To evaluate the relationship of comorbid conditions with six-minute walk distance (6MWD), functional class (FC), and survival in patients with Group 1 pulmonary hypertension, also known as pulmonary arterial hypertension (PAH), enrolled in the Registry to EValuate Early And Long-term PAH Disease Management (REVEAL).

METHODOLOGY: REVEAL is a multicenter, observational, U.S. registry designed to assess demographic, clinical, and management data on patients diagnosed with PAH. Inclusion criteria in the present analysis were age ≥19 years at enrollment, pulmonary capillary wedge pressure (PCWP) or left ventricular diastolic pressure (LVEDP) ≤15 mmHg at diagnosis, and no participation in a blinded clinical trial at enrollment. The final analysis cohort comprised 2961 subjects. The seven most common comorbidities in the REVEAL registry were targeted: hypertension, depression, diabetes, obesity (BMI ≥30 k/m2), obstructive airway disease (OAD), sleep apnea, and thyroid disease.

FINDINGS: The enrolled patients had the following characteristics: female (78.9%); Caucasian (72.2%); mean age of 53 years at enrollment; idiopathic PAH (IPAH) (45.9%); and NYHA FC II or III (34.9% and 51.1%, respectively). Patients with diabetes or OAD had the shortest 6MWD at enrollment (309.2 m and 320.2 m, respectively) in comparison to those with other comorbidities. Linear regression for 6MWD at enrollment revealed significant decrements in hypertensive, obese, diabetic, and OAD patients (P<0.001). A significantly increased likelihood of FC III/IV versus FC I/II at enrollment was observed in patients with obesity, OAD, and clinical depression (P=0.002, P<0.001, and P=0.005, respectively). Cox proportional hazards regression analyses of survival adjusted for the targeted comorbidities, including patients with hypertension and clinical depression and/or reported use of beta blockers and selective serotonin reuptake inhibitors, respectively, revealed an increased risk in patients with the comorbid condition diabetes (HR 1.75, 95% CI 1.43, 2.14; P<0.001), OAD (HR 1.34, 95% CI 1.14, 1.58; P<0.001) or clinical depression (HR 1.18, 95% CI 1.00, 1.39; P=0.045) and, surprisingly, a decreased risk in obese patients (HR 0.73, 95% CI 0.61, 0.86; P<0.001). Similar results were observed when patients with the comorbid condition hypertension or depression were considered regardless of concomitant medication use. Subcategorization of the comorbidities revealed that the increased mortality associated with OAD was driven by chronic obstructive pulmonary disease (COPD), whereas that associated with diabetes occurred primarily in individuals with Type II diabetes (P<0.001).

IMPLICATIONS: Compared with the other targeted conditions, REVEAL patients with the comorbid condition hypertension, obesity, diabetes, or OAD had a significantly worsened 6MWD, whereas patients with obesity, OAD, or clinical depression demonstrated a significantly worsened FC. Clinical depression, OAD, and diabetes resulted in an increased risk for mortality in comparison to the other comorbidity subgroups. These findings support the necessity of more aggressive therapeutic regimens in such patients.