Efforts should be made to include overweight and obese patients with PAH in clinical studies, according to a recent meta-analysis of phase 3 randomized, placebo-controlled trials of treatments for pulmonary arterial hypertension (PAH).

“PAH trials should include participants representative of all weight groups to allow for assessment of treatment heterogeneity and mechanisms,” said the authors of the study published in Chest.

They found a lower proportion of overweight or obese patients enrolled in PAH randomized clinical trials than that found in contemporary PAH registries. However, the analysis of 5440 patients from 17 trials revealed that overweight and obese patients with PAH have different baseline functional statuses when compared to normal weight in patients with PAH.

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Baseline 6-Minute Walk Distance (6MWD) scores were lower in overweight patients and even lower in obese patients than in normal-weight patients with PAH (P <.001). Moreover, overweight and obese patients with PAH were more likely to be World Health Organization (WHO) functional class 3 or 4, while normal-weight patients with PAH were more likely to be WHO functional class 1 or 2 (P =.004).

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Treatment increased the 6MWD by 27.01 m (95% CI, 21.58-32.45 m, P <.001), as well as reduced the odds of WHO functional class worsening (odds ratio [OR], 0.58, 95% CI, 0.48-0.70, P <.001). However, the improvement observed in the 6MWD was not affected by body mass index (BMI).

The analysis showed that every 1 kg/m2 increase in BMI reduced the 6MWD by 0.66 m and increased the odds of worse WHO functional class by 3%. Despite the slight effect observed for BMI in the 2 parameters, none achieved a clear statistical significance.

“This study shows that the survival benefit observed for patients with obesity and PAH (“obesity paradox”) may not be explained by differences in treatment response,” the authors concluded. The “obesity paradox” in PAH reflects the increased prevalence of obesity in PAH, albeit associated with improved survival.

Nonetheless, this study had several limitations as mentioned by the authors. One of the concerns is related to a biased sample, as it only included trials submitted to the US Food and Drug Administration for drug approval and excluded studies that did not record BMI data.


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