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Wen-Hui Wu,
Lu Yang,
Fu-Hua Peng,
Jing Yao,
Li-Ling Zou,
Dong Liu,
Xin Jiang,
Jue Li,
Lan Gao,
Jie-Ming Qu,
Steven M Kawut,
Zhi-Cheng Jing
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ABSTRACT: RATIONALE: Lower socioeconomic status (SES) confers a heightened risk of common cardiovascular and pulmonary diseases and increased mortality. The association of SES with outcomes in patients with pulmonary arterial hypertension (PAH) is less clear. OBJECTIVES: To determine the association between SES and outcomes in PAH patients. METHODS: We performed a prospective cohort study at a national referral center for PAH patients in China. Two hundred and sixty-two consecutive incident patients aged 18 to 65 years with a diagnosis of idiopathic PAH were recruited between January 2007 and June 2011 and followed-up until November 2011. The primary endpoint was all-cause mortality. A SES score for each patient was derived from their educational level, annual household income, occupation, and medical reimbursement rate. MEASUREMENTS AND MAIN RESULTS: Patients with a lower SES had higher unadjusted mortality rates with 3-year survival estimates of 50.1%, 70.8%, and 86.0% in increasing tertiles of SES (P for trend <0.001). After adjustment for clinical features, hemodynamics, and type of PAH treatment, the hazard ratios for death were 2.98 (95% confidence interval [CI], 1.51 to 5.89) in the lowest tertile of SES, and 1.80 (95% CI, 0.89 to 3.63) in the middle tertile of SES compared with the upper tertile (P for trend = 0.006). CONCLUSIONS: A lower SES is strongly associated with a higher risk of death in idiopathic PAH. This association was independent of clinical characteristics, hemodynamics, and treatment. Addressing the health disparities associated with a lower SES may improve the outcomes of patients with PAH.
American Journal of Respiratory and Critical Care Medicine 12/2012; · 11.08 Impact Factor
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ABSTRACT: Pulmonary hypertension (PH) continues to be a serious clinical problem with high mortality. As oestrogen is a potential vasodilator of the pulmonary circulation, this study examined the mechanisms by which 17β-oestradiol improves monocrotaline (MCT)-induced PH.Female Sprague-Dawley rats underwent bilateral ovariectomy or sham operations. The rats received MCT (50 mg·kg(-1)) and were treated with 17β-oestradiol (1 mg·kg(-1)·day(-1)) for 5 weeks or only from Week 4 to Week 5. Plasma 17β-oestradiol concentrations were decreased in sham-operated, MCT-treated rats compared with sham-operated rats (17.7±4.7 vs 50.3±15.4 pg·mL(-1); p=0.029). The 17β-oestradiol anabolic enzyme cytochrome P450 (CYP) 19 was decreased by MCT treatment, while the catabolic enzymes CYP 1A1 and 1B1 were increased. Ovariectomized and MCT-treated rats had more severe PH. 17β-oestradiol suppressed pulmonary arterial smooth muscle cell proliferation and macrophage infiltration, and enhanced apoptosis by increasing nitric oxide and prostacyclin levels and reducing endothelin-1 levels. PI3K and Akt phosphorylations were markedly increased but were inhibited by 17β-oestradiol treatment in PH rats.Oestrogen deficiency may aggravate development of PH. 17β-oestradiol improved PH via activation of the PI3K/Akt pathway to regulate nitric oxide, prostacyclin and endothelin-1 expression.
European Respiratory Journal 08/2012; · 5.89 Impact Factor
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ABSTRACT: Background- BMPR2 mutations predispose to idiopathic and heritable pulmonary arterial hypertension (IPAH and HPAH). The influence of BMPR2 mutations on clinical outcome is not concordant in different ethnic groups. Although the BMPR2 mutation spectrum and mutation rate in Chinese PAH patients has been reported previously, the influence of genotype on phenotype and whether this influence is associated with sex have not been investigated. Methods and Results- We analyzed data from 305 PAH patients considered as either idiopathic or heritable who underwent genetic counseling in Shanghai Pulmonary Hospital. The clinical, functional, and hemodynamic characteristics of BMPR2 mutation carriers and noncarriers were compared. The more severe hemodynamic compromise at diagnosis in BMPR2 mutation carriers versus noncarriers is concordant with other ethnic groups. In the Chinese PAH cohort, BMPR2 mutations were associated with a higher risk of mortality after adjustment for age and sex (hazard ratio, 1.971; 95% confidence interval, 1.121-3.466; P=0.018). The overall survival difference between mutation carriers and noncarriers was more obvious in male patients, which was reflected by a higher mortality risk of male mutation carriers than that of male noncarriers after adjustment for age at diagnosis (hazard ratio, 3.702; 95% confidence interval, 1.416-9.679; P=0.008). In females, this trend did not reach statistical significance. Conclusions- BMPR2 mutations influence phenotype more obviously in male PAH patients. The pathogenesis of female PAH patients is more complicated, and the influence of BMPR2 mutations may be modified by other unknown factors, making disparities in the prognosis between female mutation carriers and noncarriers less evident.
Circulation Cardiovascular Genetics 08/2012; 5(5):511-8. · 6.11 Impact Factor
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ABSTRACT: To establish an easy and repeatable method for determination of pulmonary vascular resistance in normal and pulmonary arterial hypertension (PAH) rats.
Forty-five Sprague-Dawley rats were randomly assigned into three groups: control group, low dose monocrotaline (MCT) group (50 mg/kg) and high dose MCT group (60 mg/kg). Rats in PAH groups received single subcutaneous injection of MCT. We measured pulmonary artery pressure by right heart catheterization using an improved hand-made PE-50 catheter. Cardiac output was calculated through thermodilution method. Pulmonary vascular resistance equals the mean pulmonary artery pressure divided by cardiac output.
The total percentages of success to detect pulmonary artery pressure, cardiac output and pulmonary vascular resistance were 98%, 100% and 96% respectively in 3 groups. Twenty-one days after MCT injection, mean pulmonary artery pressure significantly increased in MCT group compared to control group [(43.1 ± 0.8), (54.8 ± 2.2) vs. (17.4 ± 1.0) mm Hg (1 mm Hg = 0.133 kPa), P < 0.001], and the mPAP was also significantly higher in high dose MCT group than in low dose MCT group (P < 0.001). Cardiac output was significantly lower in PAH rats than in control rats [(77.5 ± 6.9), (71.0 ± 6.7) vs. (126.8 ± 3.9) ml/min, P < 0.001]. Pulmonary vascular resistance was significantly increased in PAH rats compared with control rats [(0.56 ± 0.06), (0.76 ± 0.08) vs. (0.13 ± 0.01) mm Hg×min(-1)×ml(-1), P < 0.001]. There were significant differences in both MCT-treated groups (P = 0.01).
Pulmonary vascular resistance in rats could be reliably detected using the improved hand-made PE-50 right heart catheter.
Zhonghua xin xue guan bing za zhi [Chinese journal of cardiovascular diseases] 10/2011; 39(10):901-4.
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ABSTRACT: To investigate the effect of GDG on the secondary structure of plasminogen and plasminogen activators, circular dichroism and SDS-PAGD were applied. The results show that the secondary structures of prourokinase and streptokinase were changed by GDG. The amount of alpha-helix, beta-sheet, beta-turn and random coil of fibrinolytic factors relates with the different concentrations of GDG in the study. GDG has no effects on the secondary structure of plasmin and plasminogen. GDG enhancing the interactivation of plasminogen and prourokinase was indicated by SDS-PAGE. It was found that GDG significantly affected the activity of prourokinase and streptokinase, and increased intrinsic fluorescence of prourokinase.
Guang pu xue yu guang pu fen xi = Guang pu 08/2010; 30(8):2171-4. · 0.84 Impact Factor
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ABSTRACT: To analyze the diagnostic value of electrocardiogram (ECG) in patients with pulmonary artery hypertension (PAH) confirmed by right-heart catheterization (RHC).
A total of 64 patients with suspected PAH [sPAP > or = 36 mm Hg (1 mm Hg = 0.133 kPa) estimated by echocardiography] were enrolled in this study. All patients were examined by 12-lead ECG within half an hour before RHC.
PAH was excluded in 26 patients and confirmed in 38 patients. ECG analysis showed that S amplitude > 0.21 mV in lead I, QRS axis > 87 degrees , R(V1) + S(V5) > 0.76 mV were good parameters for diagnosing PAH with sensibility and specificity of 89%, 81%; 86%, 92%; 84%, 83%, respectively. QRS axis was positively correlated with mean pulmonary artery pressure (mPAP) (r = 0.75, P < 0.001), R(V1) + S(V5) was positively correlated with pulmonary vascular resistance (PVR) (r = 0.74, P < 0.001), R(V1) + S(V5) and S amplitude in lead I was negatively correlated with cardiac index (CI) (r = -0.62, P < 0.001).
ECG combined with echocardiography are adequate screening tools to rule out the presence of PAH. QRS axis, R(V1) + S(V5) and S amplitude in lead I were significantly correlated with hemodynamic parameters derived from RHC in PAH patients.
Zhonghua xin xue guan bing za zhi [Chinese journal of cardiovascular diseases] 04/2010; 38(4):346-9.
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ABSTRACT: To investigate the efficacy of L-carnitine in patients with right-sided heart failure induced by pulmonary arterial hypertension (PAH).
A total of 66 pulmonary arterial hypertension patients (14 idiopathic, 36 congenital heart disease associated and 16 connective-tissue disease associated PAH, WHO heart functional class III, n = 38 or IV, n = 28) were enrolled in this study and divided into control group (26 cases) and L-carnitine group (40 cases). All patients received conventional treatment according to guideline for treatment of right-sided heart failure. The patients in L-carnitine group received 5 g/d L-carnitine intravenously for seven days. Six-minute walking distance, WHO heart functional class, physical examination, and serum markers were evaluated at baseline and 7 days after enrollment.
Compared to the baseline, six-minute walking distance was significantly increased (75 m vs. 45 m, P < 0.05), WHO heart functional class significantly improved (improved 2 classes in 16 patients, improved 1 class in 13, no improved in 6, worsen in 5 vs. 3, 8, 9, 6 respectively in the control, P = 0.04), BNP level significant decreased (58.16 ng/L vs. 33.29 ng/L, P = 0.01) and systolic blood pressure significantly increased [8.1 mm Hg vs. 2.4 mm Hg (1 mm Hg = 0.133 kPa), P = 0.03] in L-carnitine group compared with those in control group. No patient was withdrawn from this study for safety reasons.
L-carnitine could improve short-term exercise capacity and WHO heart functional class in right-sided heart failure patients induced by PAH.
Zhonghua xin xue guan bing za zhi [Chinese journal of cardiovascular diseases] 02/2010; 38(2):152-5.
