Prevalence and Clinical Implications of Excess Adiposity in Group 1 Pulmonary Hypertension.

Excess adiposity was highly prevalent in group 1 PH patients, with prevalence varying substantially by measurement method.

• Among 418 group 1 PH patients, 158 (38%) had BMI ≥30 kg/m²
• Among those with waist circumference measurement (n=375), 287 (77%) had excess adiposity by elevated waist/height ratio
• 214 (57%) had elevated waist circumference
• Excess adiposity was present in 4 out of 5 patients by waist/height ratio, compared to only 2 out of 5 by traditional BMI criteria

Insulin resistance co-occurred frequently with obesity but was also present in a substantial minority of non-obese group 1 PH patients.

• Among the 158 patients with BMI ≥30 kg/m², 94 (60%) had IR (HOMA-IR ≥2.6)
• Among the 260 patients with BMI <30 kg/m², 74 (28%) had IR
• IR was defined using a HOMA-IR threshold of ≥2.6

Patients with obesity had worse quality of life, exercise capacity, and left heart remodeling compared to non-obese group 1 PH patients.

• Differences in quality of life, exercise capacity, and left heart remodeling were statistically significant (P<0.0001 for all)
• Obese patients had higher resting and dynamic pulmonary capillary wedge pressure (PCWP), right atrial pressure, and cardiac output (P<0.0001 for all)

Higher PCWP response with obesity persisted after adjusting for insulin resistance, whereas IR itself was not independently associated with PCWP response.

• IR-adjusted PCWP was +2.5 mm Hg (95% CI, +1.4 to +3.6; P<0.0001) higher in obese versus non-obese patients
• All adiposity indices were consistently associated with PCWP response, but IR was not
• Dynamic PCWP responses were compared using repeated-measure mixed models

Greater visceral adiposity was independently associated with worse survival in group 1 PH patients.

• Body shape index was associated with worse survival (hazard ratio, 2.01 [95% CI, 1.16–3.47]; P=0.01)
• Weight-adjusted waist index was also associated with worse survival (hazard ratio, 1.64 [95% CI, 1.10–2.46]; P=0.01)
• Both body shape index and weight-adjusted waist index are measures of visceral adiposity

Adiposity indices were consistently associated with higher right atrial pressure and cardiac output in addition to PCWP.

• Similar associations were observed between adiposity indices and higher right atrial pressure and cardiac output
• These associations were assessed using repeated-measure mixed models for dynamic hemodynamic responses
• The associations with right atrial pressure and cardiac output were also statistically significant (P<0.0001)

The study was conducted within the PVDOMICS cohort, which measured multiple adiposity and metabolic indices in group 1 PH patients.

• PVDOMICS stands for Redefining Pulmonary Hypertension Through Pulmonary Vascular Disease Phenomics
• Measures included HOMA-IR, BMI, fat mass, and waist circumference
• Dynamic pulmonary capillary wedge pressure and right atrial pressure responses were compared stratified by obesity (BMI ≥30 kg/m²) and IR status (HOMA-IR ≥2.6)
• Total group 1 PH sample size was 418 patients; waist circumference was available in 375

The authors concluded that their data support trials of adipose-reducing therapies in patients with group 1 PH and excess adiposity.

• Excess adiposity was associated with higher biventricular filling pressures, cardiac output demand, worse functional status, and reduced survival
• The effect of adiposity on hemodynamics was independent of insulin resistance
• Authors explicitly called for 'trials of adipose-reducing therapies in patients with group 1 PH and excess adiposity'