Mystery Remains Around Obesity’s Association With Better PAH Outcomes

A compilation of data on patients with pulmonary arterial hypertension (PAH) is highlighting the complexities of understanding outcomes based on patient weight, according to findings published in Chest

Known as the “obesity paradox,” patients with obesity have been shown to have better PAH outcomes than patients with normal weight, and while hypotheses have landed on the potential explanation of body mass index (BMI) affecting treatment effectiveness, findings from more than 15 studies indicate otherwise.

“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,” wrote the authors of the study, which used World Health Organization functional class as well as change in 6-minute walk distance (6MWD) as primary outcomes.

Based on their findings, the researchers argued a need for more inclusive representation of patients with PAH across the weight spectrum.

Across the 17 phase 3, multicenter studies, data were available on 5400 patients, which revealed that every 1 kg/mg² increase in BMI increased the risk of worse functional class by 3%. There was no significant effect of BMI on 6MWD; with every 1 kg/m² increase in BMI, 6MWD improved by 0.66 meters.

At baseline, patients with overweight and obesity had lower 6MWD and were more likely to have worse functional class (class 3 or 4), potentially resulting from comorbidities such as diabetes, systemic hypertension, and hypothyroidism. The researchers noted that the lower 6MWD and worse functional class observed at baseline is consistent with previous research.

Patients with overweight were more likely to be male and patients with obesity were more likely to be female compared with patients with normal weight. Compared with patients with normal weight, patients with obesity were more likely to have idiopathic PAH or drug-/toxin-related PAH. They were less likely to have connective tissue disease– or congenital heart disease–related PAH.

The studies, ranging from 1998 to 2013, included fewer patients with overweight and obesity compared with the more recent Pulmonary Hypertension Association Registry cohort. According to the researchers, “The lower prevalences of overweight and obesity in these clinical trials could be due to secular trends. However, it is also possible that overweight and obese patients were excluded from these clinical trials due to inclusion/exclusion criteria. Some trials had lower cutoffs for 6MWD which may have led to selection bias, excluding predominantly overweight and obese patients who were noted to have shorter 6MWD.”

The researchers also cited the multicenter nature of the studies included in their analysis as a potential reason for this finding, explaining that it could reflect lower obesity rates outside of the United States.

Reference

McCarthy B, McClelland R, Appleby D, 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