Global Burden of Pulmonary Arterial Hypertension in Older Adults and Its Causal Association With Body Mass Index

ABSTRACT

Pulmonary arterial hypertension (PAH) is a severe cardiopulmonary disease associated with substantial morbidity and mortality. However, the global burden, future trajectory, and potentially modifiable risk factors for PAH among older adults remain insufficiently characterized. This study aimed to quantify the global burden and projected trends of PAH among adults aged ≥ 60 years and investigate the causal association between body mass index (BMI) and PAH risk using Mendelian randomization (MR). We extracted PAH burden estimates from the Global Burden of Disease (GBD) 2021 study across 204 countries and territories, 21 GBD regions, and five socio‐demographic index (SDI) strata. Temporal trends were assessed using age‐standardized rates and average annual percent changes (AAPCs), while demographic decomposition and Bayesian age‐period‐cohort (BAPC) models were applied to evaluate drivers of burden changes and future trajectories. Two‐sample MR analyses were performed using genome‐wide significant BMI‐associated genetic variants as instrumental variables and PAH genome‐wide association study summary statistics from FinnGen. Between 1990 and 2021, global incident cases of PAH among adults aged ≥ 60 years increased from 6771.01 (95% uncertainty interval [UI]: 4577.81–9656.55) to 15,622.29 (95% UI: 10,546.44–22,296.65), and deaths increased from 6812.93 (95% UI: 5305.00–8473.04) to 15,443.42 (95% UI: 11,746.25–18,388.02). Although the age‐standardized mortality, prevalence, and disability‐adjusted life year (DALY) rates declined, the age‐standardized incidence rate showed a slight increase (AAPC = 0.07%, 95% CI: 0.05–0.09). Marked geographic and SDI‐related disparities were observed, with population growth and aging identified as the predominant contributors to the rising absolute burden. BAPC modeling projected continued increases in absolute PAH cases through 2050 despite declining age‐standardized mortality and DALY rates. In addition, MR analyses provided suggestive evidence for a positive association between genetically predicted higher BMI and increased PAH risk (inverse‐variance weighted odds ratio [IVW OR] = 1.84, 95% CI: 1.11–3.05, p  = 0.018). Among older adults, the global absolute burden of PAH has increased substantially over the past three decades and is expected to continue rising, largely driven by population aging and growth. Genetic evidence further suggests that elevated BMI may represent a potentially modifiable risk factor for PAH. These findings highlight the need for enhanced surveillance, improved diagnostic strategies, equitable healthcare access, and targeted metabolic risk management to address the growing burden of PAH in aging populations.