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Abstract
Objective
Pulmonary hypertension (PH) develops frequently in connective tissue diseases (CTD) and is an important prognostic factor. The aim of this study was to assess the prevalence of PH in patients with CTD by non-invasive echocardiography and analyze the potential biomarkers for helping to detect PH.
Methods
All Korean patients with CTD who had dyspnea on exertion or interstitial lung disease (ILD) were screened for PH with echocardiography and clinical data were collected from four hospitals.
Results
Among 196 patients with CTD, 108 (55.1%) had ILD and 21 had PH defined as ＞40 mmHg. Of the 21 patients with PH, 10, 4, and 3 patients had systemic sclerosis, systemic lupus erythematosus, and mixed connective tissue disease, respectively. There was no difference in the incidence of PH according to the presence of ILD; 12 patients (11.1%) with ILD had PH and 9 patients (10.2%) without ILD had PH. The results of the pulmonary function test, total cholesterol, red cell volume distribution width, alkaline phosphatase, and the New York Heart Association (NYHA) functional class III or IV differed significantly according to the presence of PH. In multiple regression analysis, NYHA functional class III or IV (odd ratio [OR]=7.3, p=0.009) and forced vital capacity (OR=0.97, p=0.043) were independent predictive factors of PH.
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Figure 1.
Receiver operating characteristic to predict pulmonary hypertension by echocardiography in connective tissue disease. The area under curve (AUC) of receiver operating characteristic by final model with New York Heart Association functional class III or IV and forced vital capacity was 0.767.
Table 1.
The clinical characteristics of patients (n=196)
NYHA: New York Heart Association, TRV: tricuspid regurgitation velocity, PASP: pulmonary artery systolic pressure, PFT: pulmonary function test, DLCO: lung diffusion capacity for carbon monoxide, FVC: forced vital capacity, FEV1: forced expired volume in one second, RDW: red cell volume distribution width, AST: aspartate aminotransferase, ALT: alanine aminotransferase, ALP: alkaline phosphatase.
Table 2.
The comparison of the patients with ILD and those without
| Clinical factor | ILD (n=108) | No ILD (n=88) | p-value |
|---|---|---|---|
| Age (yr) | 55.7±14.3 | 53.8±15.1 | 0.302 |
| Gender, female:male | 81:26 | 69:20 | 0.706 |
| NYHA functional class III/IV, n (%) | 9 (8.3) | 7 (8.0) | 0.848 |
| Echocardiographic finding | |||
| TRV (m/s) | 2.5±0.4 | 2.5±0.4 | 0.808 |
| PASP (mmHg) | 30.8±9.6 | 30.1±10.1 | 0.455 |
| PFT finding (%) | |||
| DLCO | 60.7±21.2 (92*) | 75.5±21.3 (79*) | ＜0.001 |
| FVC | 73.9±19.6 (96*) | 93.5±19.2 (82*) | ＜0.001 |
| FEV1 | 79.5±5.46 (96*) | 95.7±22.3 (82*) | ＜0.001 |
| FVC/DLCO | 1.3±0.4 (91*) | 1.3±0.3 (78*) | 0.346 |
| Laboratory finding | |||
| RDW (%) | 14.2±1.8 (107*) | 14.6±2.4 (88*) | 0.215 |
| AST (U/L) | 36.6±65.2 (107*) | 30.5±26.4 (88*) | 0.913 |
| ALT (U/L) | 28.5±55.5 (107*) | 22.6±14.9 (88*) | 0.160 |
| Total cholesterol (mg/dL) | 175.3±38.7 (101*) | 179.1±50.1 (88*) | 0.552 |
| ALP (U/L) | 108.5±87.9 (102*) | 105.5±93.8 (88*) | 0.481 |
| Uric acid (mg/dL) | 4.5±1.5 (97*) | 4.6±1.3 (85*) | 0.895 |
ILD: interstitial lung disease, NYHA: New York Heart Association, TRV: tricuspid regurgitation velocity, PASP: pulmonary artery systolic pressure, PFT: pulmonary function test, DLCO: lung diffusion capacity for carbon monoxide, FVC: forced vital capacity, FEV1: forced expired volume in one second, RDW: red cell volume distribution width, AST: aspartate aminotransferase, ALT: alanine aminotransferase, ALP: alkaline phosphatase.
Table 3.
The prevalence of increased PASP according to ILD pattern in CTD
Table 4.
The clinical characteristics in the patients with PAH
| Variable | PAH (n=21) | No PAH (n=175) | p-value |
|---|---|---|---|
| Age (yr) | 56.6±19.8 | 54.6±14.0 | 0.567 |
| Gender, female:male | 19:3 | 131:43 | 0.295 |
| Disease duration (mo) | 37±43.7 | 42.9±51.6 | 0.908 |
| Presence of ILD Disease | 12 (54.5) | 96 (55.2) | 0.843 |
| SSc | 10 (16.1) | 52 (83.9) | |
| RA | 2 (3.7) | 52 (96.3) | |
| SLE | 4 (9.3) | 39 (90.7) | |
| MCTD | 3 (42.9) | 4 (57.1) | |
| NYHA functional class III/IV | 8 (36.4) | 8 (4.6) | ＜0.001 |
| Echocardiography data TRV (m/s) | 3.4±0.3 | 2.38±0.2 | ＜0.001 |
| PASP (mmHg) | 52.2±10.5 | 27.8±5.6 | ＜0.001 |
| PFT data (%) | |||
| DLCO | 60.6±24.1 (13*) | 68.1±22.1 (158*) | 0.246 |
| FVC | 63.2±28.3 (18*) | 85.1±19.8 (160*) | ＜0.001 |
| FEV1 | 68.7±34.4 (18*) | 89.1±20.9 (160*) | 0.024 |
| FVC/DLCO | 1.3±0.3 (14*) | 1.3±0.4 (155*) | 0.948 |
| Laboratory data | |||
| RDW (%) | 15.1±3.1 | 14.2±1.8 | 0.041 |
| AST (U/L) | 32.0±18.7 | 34.0±54.0 | 0.736 |
| ALT (U/L) | 18.9±12.8 | 26.6±44.4 | 0.432 |
| Total cholesterol (mg/dL) | 147.7±40.1 (17*) | 179.9±43.7 (172*) | 0.004 |
| ALP (U/L) | 87.5±35.5 (20*) | 67.9±30.7 (171*) | 0.027 |
| Uric acid (mg/dL) | 5.0±1.9 (19*) | 4.4±1.2 (163*) | 0.105 |
PAH: pulmonary arterial hypertension, ILD: interstitial lung disease, SSc: systemic sclerosis, RA: rheumatoid arthritis, SLE: systemic lupus erythematosus, MCTD: mixed connective tissue disease, NYHA: New York Heart Association, TRV: tricuspid regurgitation velocity, PASP: pulmonary artery systolic pressure, PFT: pulmonary function test, DLCO: lung diffusion capacity for carbon monoxide, FVC: forced vital capacity, FEV1: forced expired volume in one second, RDW: red cell volume distribution width, AST: aspartate aminotransferase, ALT: alanine aminotransferase, ALP: alkaline phosphatase. Pulmonary hypertension: pulmonary artery systolic pressure ＞40 mmHg.
Table 5.
The logistic regression analysis for PAH in connective tissue disease
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