• Chest · Jan 2021

    BMI is causally associated with pulmonary artery pressure but not hemodynamic evidence of pulmonary vascular remodeling.

    • Timothy E Thayer, Rebecca T Levinson, Shi Huang, Tufik Assad, Eric Farber-Eger, Quinn S Wells, Jonathan D Mosley, and Evan L Brittain.
    • Division of Cardiovascular Medicine, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN.
    • Chest. 2021 Jan 1; 159 (1): 302-310.

    BackgroundThere is an unclear relationship of obesity to the pathogenesis and severity of pulmonary arterial hypertension (PAH) and pulmonary venous hypertension (PVH).Research QuestionIs BMI casually associated with pulmonary artery pressure (PAP) and/or markers of pulmonary vascular remodeling?Study Design And MethodsThe study design was a two-sample inverse-variance weighted Mendelian randomization. We constructed two BMI genetic risk scores from genome-wide association study summary data and deployed them in nonoverlapping cohorts of subjects referred for right heart catheterization (RHC) or echocardiography. A BMI highly polygenic risk score (hpGRS) optimally powered to detect shared genetic architecture of obesity with other traits was tested for association with RHC parameters including markers of pulmonary vascular remodeling. A BMI strict genetic risk score (sGRS) composed of high-confidence genetic variants was used for Mendelian randomization analyses to assess if higher BMI causes higher PAP.ResultsAmong all subjects, both directly measured BMI and hpGRS were positively associated with pulmonary arterial pressures but not markers of pulmonary vascular remodeling. Categorical analyses revealed BMI and hpGRS were associated with PVH but not PAH. Mendelian randomization of the sGRS supported that higher BMI is causal of higher systolic pulmonary artery pressure (sPAP). Sensitivity analyses showed sPAP-BMI sGRS relationship was preserved when either individuals with PAH or PVH were excluded. In the echocardiographic cohort, BMI and hpGRS were positively associated with estimated PAP and markers of left heart remodeling.InterpretationBMI is a modifier of pulmonary hypertension severity in both PAH and PVH but is only involved in the pathogenesis of PVH.Copyright © 2020 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

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