Pulmonary Arterial Hypertension: Effect of BMI on Treatment Response

A meta-analysis of the effect of BMI on treatment response among patients with pulmonary arterial hypertension found that higher BMI did not change the patient’s treatment response as measured by 6-minute walking distance (6MWD) scores, and that odds of World Health Organization functional class worsening on treatment was slightly but not significantly affected by BMI. These were among the finding of a study recently published in Chest.

Obesity, which is increasingly common among patients with pulmonary arterial hypertension, is associated with improved PAH survival, a situation clinicians often refer to as the PAH “obesity paradox.” With this in mind, study investigators hypothesized that patients with PAH who were overweight (BMI ≥25.0 and <30.0 kg/m²) and obese (BMI ≥30.0 kg/m²) would show greater improvement in 6MWD and would be more likely to improve their WHO functional class after treatment with various pulmonary vasodilators than would patients who were normal weight or underweight.

Toward that end, the investigators conducted a meta-analysis of phase 3 randomized controlled trials of PAH treatments reviewed by the FDA from 2000 to 2015 to determine whether BMI impacted treatment effectiveness. The analysis involved data from 5440 individuals pooled from 17 trials, with WHO functional class and 6MWD as the primary outcomes of interest. At baseline, patients with pulmonary arterial hypertension (PAH) who were overweight/obese had lower 6-minute walk distance scores (6MWD) and a worse World Health Organization (WHO) functional class rating (class III or IV) than did PAH patients of normal weight.

The investigators found that for the cohort as a whole, treatment was correlated with a 27.01-meter increase in 6MWD (P <.001), as well as decreased chances of a worse WHO functional class (P <.001). In assessing the effect of BMI on 6MWD, the investigators determined that 6MWD was decreased by 0.66 m for each 1 kg/m2 increase in BMI (P =.07); however, BMI did not significantly affect the treatment response (P for interaction=0.34). With respect to WHO functional class, the investigators found that increased BMI reduced treatment response, with each 1 kg/m2 increase in BMI heightening odds of worse WHO functional class by 3%. Nevertheless, at the end of follow-up, increased BMI was not significantly related to the odds of a worsening in WHO functional class.

The investigators concluded: “We hypothesized that patients with higher BMI would derive greater benefit from active PAH treatment, however we did not find an interaction between treatment and BMI in terms of 6MWD. If anything, we found that heavier patients had less of an impact of active treatment on the odds of worsening functional class compared to placebo.”

As possible explanations for these results, the investigators postulated that: 1) overweight and obese patients might be underdosed due to the fixed dosing prescribed by the medications studied; or 2) treatment response in patients who were obese and overweight could have negatively affected by the presence of comorbidities such as

systemic hypertension or diabetes mellitus, or by the system inflammation associated with obesity. “These findings highlight the need for inclusion of patients at the extremes of weight continuum in drug treatment trials to ensure dose efficacy across the spectrum,” the authors noted.

Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.

Reference

McCarthy BE, McClelland RL, Appleby DH, et al. Body Mass Index and Treatment Response in Patients with Pulmonary Arterial Hypertension: A Meta-Analysis. Chest. Published online March 2, 2022. doi:10.1016/j.chest.2022.02.041