Although higher body mass index (BMI) is causally associated with higher pulmonary artery pressure, it is not associated with pulmonary vascular remodeling, according results of an analysis published in CHEST.
Researchers conducted a 2-sample, inverse-variance weighted, Mendelian randomization study to explore whether BMI is causally linked to pulmonary arterial pressure and/or to markers of pulmonary vascular remodeling.
They constructed 2 BMI genetic risk scores from existing genome-wide association study summary data and used them in nonoverlapping cohorts of patients who were referred for right heart catheterization (RHC) or echocardiography. The 2 risk scores consisted of a “strict” genetic risk score (BMI_sGRS) and a “highly polygenic” risk score (BMI_hpGRS). The BMI_hpGRS was optimally powered to detect shared genetic architecture of obesity with other characteristics, and assessed its association with RHC parameters, including markers of pulmonary vascular remodeling. The BMI_sGRS included high-confidence genetic variants and was used for Mendelian randomization analyses to evaluate whether higher BMI causes higher pulmonary arterial pressure.
A total of 1043 individuals with existing Multi-Ethnic Global Array genotyping data who had been referred for RHC, were unrelated, and were of European ancestry were included in the analysis. The median participant age was 60±14 years; 52% were men. In this patient population, 12% had pulmonary arterial hypertension (PAH), 40% had pulmonary venous hypertension (PVH), 6% had PH related to lung disease, and 42% did not have pulmonary hypertension (PH).
Results of the study demonstrated that in all participants, both directly measured BMI and BMI_hpGRS were positively associated with pulmonary arterial pressures but not with markers of pulmonary vascular remodeling. Further, based on categorical analyses, BMI and BMI_hpGRS were associated with PVH but not with PAH.
According to Mendelian randomization of BMI_sGRS, higher BMI caused higher pulmonary arterial pressure. Repeat Mendelian randomization, in which individuals with PVH were excluded, revealed that BMI likely affects pulmonary artery pressure via mechanisms that are distinct from left heart disease. The relationship between the BMI_hpGRS and echocardiographic estimates of pulmonary artery pressure was reproduced in a separate cohort.
According to the researchers, the results are significant because they demonstrate the lack of a clinical or genetic association between obesity and pulmonary vascular disease in humans, and reinforce the notion that higher BMI causes increased pulmonary arterial pressure, which, in turn, may have therapeutic implications for both PAH and PVH. In addition, BMI may be a modifier of PH severity in both PAH and PVH, but is involved only in the pathogenesis of PVH.
A drawback of the current study is that the generalizability of its findings to populations of non-European descent is limited, since the cohorts were all of European descent. Additionally, the invasive hemodynamic cohort was filled with individuals who had heart failure and PH because it included patients who had been referred for a clinically indicated RHC.
The investigators concluded that based on the findings of the current study, higher BMI is not linked to pulmonary vascular remodeling, but it is causally associated with higher pulmonary artery pressure.
Thayer TE, Levinson RT, Huang S, et al. BMI is causally associated with pulmonary artery pressure but not hemodynamic evidence of pulmonary vascular remodeling. CHEST. Published online July 23, 2020. doi:10.1016/j.chest.2020.07.038