Physical Activity and Its Association with Traditional Outcome Measures in Pulmonary Arterial Hypertension

Abstract

Rationale: Limitation of physical activity is a common presenting complaint for patients with pulmonary arterial hypertension (PAH). Physical activity is thought to be determined by cardiopulmonary function, yet there are limited data that investigate this relationship. Objectives: We aimed to study the relationship between right ventricular function and daily activity and its impact on health-related quality of life (HRQoL) in PAH. Methods: Baseline data for 55 patients enrolled in PHANTOM (Pulmonary Hypertension and Anastrozole), an ongoing multicenter randomized controlled trial of anastrozole in PAH, were used. Postmenopausal women and men were eligible and underwent 6-minute walk testing and echocardiography and completed HRQoL questionnaires. Each patient wore an accelerometer for 7 days. Multivariable linear regression models were used to study the association between tricuspid annular plane systolic excursion (TAPSE) and vector magnitude counts, and between daily activity and HRQoL. Principal component analysis and K-means clustering were used to identify activity-based phenotypes. K-nearest neighbors classification was applied to an independent cross-sectional cohort from the University of Pennsylvania. Results: The mean age of patients in PHANTOM was 61 years. In total, 67% were women with idiopathic PAH as the most common etiology. A 0.4-cm increase in TAPSE was associated with an increase in daily vector magnitude counts (β: 34,000; 95% confidence interval [CI], 900-67,000; P = 0.004) after adjustment for age, sex, body mass index, etiology of PAH, and wear time. A 1-SD increase in vector magnitude counts was associated with higher 6-minute walk distance (β: 56.1 m; 95% CI, 28.6-83.7; P < 0.001) and lower emPHasis-10 scores (β: -3.3; 95% CI, 0.3-6.4; P = 0.03). Three activity phenotypes, low, medium, and high, were identified. The most active phenotype had greater 6-minute walk distances (P = 0.001) and lower emPHasis-10 scores (P = 0.009) after adjustment for age, sex, body mass index, World Health Organization functional class, and parenteral prostacyclin use. Phenotypes of physical activity were reproduced in the second cohort and were independently associated with 6-minute walk distance. Conclusions: Better right ventricular systolic function was associated with increased levels of activity in PAH. Increased daily activity was associated with greater 6-minute walk distance and better HRQoL. Distinct activity-based phenotypes may be helpful in risk stratification of patients with PAH or provide novel endpoints for clinical trials.

Keywords: accelerometry; physical activity; pulmonary hypertension; quality of life.

Figure 1.

Vector magnitude counts over a 7-day period from (A) PHANTOM (Pulmonary Hypertension and Anastrozole) and (B) Penn (Pennsylvania) cohort. These heatmaps show vector magnitude counts for subjects across the 7-day study period. Each row represents data from an individual patient. Each graphical square depicts the median vector magnitude counts for that hour over the 7-day study period.

Figure 2.

Multivariable linear regression models of tricuspid annular plane systolic excursion (TAPSE) with (A) vector magnitude counts and (B) step counts after adjusting for age, sex, body mass index, connective tissue disease as etiology of pulmonary arterial hypertension and accelerometer wear time in PHANTOM (Pulmonary Hypertension and Anastrozole). (β coefficients reported per 0.4-cm increase in TAPSE. Gray area represents the 95% confidence interval [CI].)

Figure 3.

Expected mean estimates for (A) vector magnitude counts and (B) step counts by right ventricular dysfunction based on regression models after adjusting for age, sex, body mass index, connective tissue disease as etiology of pulmonary arterial hypertension, and accelerometer wear time in PHANTOM (Pulmonary Hypertension and Anastrozole). RV = right ventricular.

Figure 4.

Multivariable linear regression models of 6-minute walk distance with (A) vector magnitude counts and (B) step counts and emPHasis-10 scores with (C) vector magnitude counts and (D) step counts after adjusting for age, sex, body mass index, connective tissue disease as etiology of pulmonary arterial hypertension, and accelerometer wear time in PHANTOM (Pulmonary Hypertension and Anastrozole). (β coefficients reported for a 10,000 increase in vector magnitude counts and 1,000 increase in step counts; gray area represents the 95% confidence interval [CI].) 6MWD = 6-minute walk distance; E-10 = emPHasis-10.

Figure 5.

(A) K-means clustering (PHANTOM [Pulmonary Hypertension and Anastrozole]); (B) K-nearest neighbors clustering (Penn Cohort). PC = principal component.

Figure 6.

(A–D) Expected mean estimates for 6-minute walk distance and emPHasis-10 from PHANTOM (Pulmonary Hypertension and Anastrozole) (A and B) and Penn (Pennsylvania) Cohort (C and D) with activity levels based on regression models adjusted for age, sex, body mass index, World Health Organization functional class, and use of parenteral prostacyclin analog therapy. 6MWD = 6-minute walk distance; E-10 = emPHasis-10.