Table 1.
A Summary of Clinical Study Data Demonstrating the Adverse Functional Consequences of Resting Pulmonary Artery Pressure Levels below the Current Diagnostic Threshold for Pulmonary Hypertension
| Study (Reference) | Patients (N) | Clinical Phenotype | PA Pressure (mm Hg) | Diagnostic Modality | Outcome Measure | |
|---|---|---|---|---|---|---|
| Weitzenblum et al., 1981 (12) | 175 | COPD | mPAP: ≤20 vs. >20 | RHC | ↑Unadj. mortality | |
| 7-yr survival, 56% vs. 29%; P < 0.01 | ||||||
| Gladwin et al., 2004 (5) | 195 | SCD | TR jet velocity: <2.5 vs. ≥2.5 m/s | ECHO | ↑Adj. mortality | |
| RR, 10.1 (2.2–47.0) | ||||||
| P < 0.001 | ||||||
| Hamada et al., 2007 (6) | 68 | IPF | mPAP: <17 vs. >17 | RHC | ↑Unadj. mortality | |
| Relative risk, 2.20 (1.40–3.45); P < 0.001 | ||||||
| Lam et al., 2009 (13) | 2,042 | Random sample, Olmsted County | PASP: 15–23 vs. 24–25; 26–29; 30–32 | ECHO | ↑Adj. mortality | |
| HR, 1.46/10 mm Hg ↑PASP; P = 0.017 | ||||||
| Kovacs et al, 2009 (10) | 29 | Scleroderma-PAH/-lung disease | mPAP: <17 vs. >17 | RHC | ↓pVo2 | |
| ↓6-MWD | ||||||
| Mutlak et al., 2012 (14) | 1,054 | Post-MI | PASP: ≤35 vs. >35 | ECHO | ↑Heart failure admission | |
| HR, 3.10 (1.87–5.14); P < 0.0001 | ||||||
| Heresi et al., 2013 (15) | 1,491 | Referral population at risk for PH | mPAP: 10–20 vs. 21–24 | RHC | ↑Mortality | |
| Kimura et al., 2013 (16) | 101 | IPF | mPAP: ≤20 vs. >20 | RHC | ↑Adj. mortality | |
| HR, 1.064 (1.015–1.116); P = 0.010 | ||||||
| Valerio et al., 2013 (17) | 228 | Scleroderma | mPAP: ≤20 vs. 21–24 | RHC | ↑Progression to resting PH | |
| Damy et al., 2016 (18) | 1,780 | SCD or β-thalassemia | TR jet velocity: <2.5 vs. ≥2.5 m/s | ECHO | ↑Mortality | |
| Kovacs et al., 2016 (19) | 141 | Referral population at risk for PH | mPAP: <21 vs. 21–24 | RHC, iCPET | ↑PVR | |
| ↑mPAP/CO | ||||||
| ↑TPG/CO | ||||||
| ↓pVo2 | ||||||
| ↓6-MWD | ||||||
| Lau et al., 2016 (20) | 290 | Referral population with unexplained dyspnea or PH risk | mPAP: <21 vs. 21–24 | RHC, iCPET | ↓Exercise workload | |
| ↓6-MWD | ||||||
| ↑PVR at peak exercise | ||||||
| ↑mPAP at peak exercise | ||||||
| Maron et al., 2016 (7) | 21,727 | Referral population Veterans Affairs | mPAP: ≤18 vs. 19–24 | RHC | ↑Adj. mortality | |
| HR, 1.23 (1.12–1.36); P < 0.0001 | ||||||
| ↓Adj. Event-free survival | ||||||
| HR Hosp., 1.07 (1.01-1.12); P = 0.0149 | ||||||
| Assad et al., 2017 (8) | 4,343 | Referral population at risk for PH | mPAP: ≤18 vs. 19–24 | RHC | ↑Adj. mortality | |
| HR, 1.31 (1.04–1.65) | ||||||
| P = 0.001 | ||||||
| ↑Progression to resting PH | ||||||
| Women have ↑HR for mortality for given mPAP | ||||||
| ↑PVR | ||||||
| ↑PAWP | ||||||
| ↓PA capacitance | ||||||
| Douschan et al., 2017 (3) | 547 | Referral population at risk for PH | mPAP: ≤17.3 vs. 20.6–24.9 | RHC | ↑Adj. mortality | |
| HR, 2.37 (1.14–4.97); P = 0.022 | ||||||
| ↓6-MWD | ||||||
| Lamia et al., 2017 (21) | 44 | Borderline PH, PAH, healthy controls | Matched healthy controls vs. patients with mPAP ≥20–24 on RHC | ECHO | ↑RV dyssynchrony | |
| Oliveira et al., 2017 (22) | 312 | Referral population at risk for PH | mPAP: <13, 13–16, 17–20, 21–24 | RHC, iCPET | ↓pVo2 | |
| ↑mPAP at peak exercise | ||||||
| ↑PVR at rest and peak exercise | ||||||
| ↓PA capacitance at rest | ||||||
| ↓CI at peak exercise |
Definition of abbreviations: 6-MWD = 6-minute-walk distance; Adj. = adjusted; CI = cardiac index; CO = cardiac output; COPD = chronic obstructive pulmonary disease; ECHO = echocardiography; Hosp. = hospitalization; iCPET = invasive cardiopulmonary exercise test; HR = hazard ratio; IPF = idiopathic pulmonary fibrosis; MI = myocardial infarction; mPAP = mean pulmonary artery pressure; PA = pulmonary artery; PAH = pulmonary arterial hypertension; PASP = pulmonary artery systolic pressure; PAWP = pulmonary artery wedge pressure; PH = pulmonary hypertension; pVo2 = peak volume of oxygen consumption; PVR = pulmonary vascular resistance; RHC = right heart catheterization; RR = rate ratio; RV = right ventricle; SCD = sickle cell disease; TPG = transpulmonary gradient; TR = tricuspid regurgitation; Unadj. = unadjusted.
Outcome measure data may include RR, HR, or relative risk (95% confidence interval). Modified from Reference 11.