Effect of Therapy on Angiogenic Growth Factor Levels
The effect of medical therapy for PAH on growth factor levels was analyzed. Twelve patients (PPH, 6 patients; PAH-other, 6 patients) were not receiving prostanoid therapy, calcium-channel blockers, or endothelin blockers at the time of study (de novo patients). The median plasma bFGF level in this group of patients was significantly increased compared to control subjects (1.91 pg/mL, p = 0.02), as was the median urine bFGF level (2,338 pg/L, p = 0.002). The bFGF levels in these de novo patients were not significantly different from patients who were receiving specific therapy for PAH. Sixty-one percent of patients were receiving IV prostacyclin at the time samples were obtained for the cohort. Patients with PAH receiving prostacyclin had qualitatively higher median levels of plasma VEGF (42.9 pg/mL vs 25.4 pg/mL, p = 0. 09) than did patients not receiving prostacyclin, although this did not reach statistical significance. This trend remained when analyzed for the PPH subgroup (48.1 pg/mL vs 28.8 pg/mL, p = 0.13). When adjusted for covariates associated with severity of disease, the effect of prostacyclin on plasma VEGF was diminished, and prostacyclin was not independently associated with altered growth factor levels. Calcium-channel blocker therapy or anticoagulation with warfarin did not affect growth factor levels. Click Here
Correlation of Growth Factor Levels to Clinical and Hemodynamic Variables
Levels of both bFGF and VEGF were analyzed for correlation to clinical and hemodynamic variables. In patients with PPH but not other forms of PAH, there was a modest correlation between mean pulmonary artery pressure (PAP) and plasma bFGF levels (r = 0.28, p = 0.04). We found a significant relationship between functional capacity and plasma bFGF in patients with PPH. In patients with poor functional capacity (WHO classes 3 or 4), median plasma bFGF was 4.2 pg/mL, compared to 0.5 pg/mL in patients with classes 1 or 2 (p < 0.003) [Fig 4].
Figure 4. Plasma bFGF levels (median, IQR) according to functional capacity (WHO classes 1-2 vs WHO classes 3-4). There is a significant increase in plasma bFGF in patients with poor functional capacity (p = 0.003).