The survival benefit in patients with pulmonary arterial hypertension (PAH) and obesity – the obesity paradox – cannot be explained by differences in response to treatment. Higher BMI did not affect the change in 6-minute walking distance (6MWD), but increased the risk of poorer WHO functional class after treatment.
Obesity is increasingly common in patients with PAH, but it is also associated with better survival: the obesity paradox. This meta-analysis examined whether obese patients may benefit more from existing treatments for PAH. Using individual participant data, a meta-analysis of randomized, placebo-controlled Phase III trials of PAH treatments submitted to the FDA for approval between 2000 and 2015. Primary outcomes were the change in 6MWD and WHO functional class.
A total of 5,440 participants in 17 studies were included. Overweight and obese patients had a lower baseline 6MWD and were more likely to fall into WHO functional class III or IV. Treatment was associated with a 27.01 meter increase in 6MWD (95% CI 21.58-32.45; p < 0.001) and a lower risk of poorer WHO functional class (OR 0.58; 95%- CI 0.48-0.70; p < 0.001). For each increment of 1 kg/m2 in BMI, the 6MWD decreased by 0.66 meters (p = 0.07); there was no significant influence of BMI on the 6MWD response (p for interaction 0.34). A higher BMI reduced response to treatment such that any increase of 1 kg/m2 in BMI the risk of a poorer WHO functional class increased by 3% (OR 1.03; p for interaction 0.06).
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McCarthy BE, McClelland RL, Appleby DH, et al. BMI and Treatment Response in Patients With Pulmonary Arterial Hypertension: A Meta-analysis. Chest. 2022;162:436-47.