肺高压的生化标志物 biochemical markers of pulmonary hypertension...

肺高压的生化标志物Biochemical Markers of Pulmonary Hypertension

吉林大学白求恩第一医院心血管病中心 /肺血管病中心

郑 杨 张尉华

血清生化标志物•肌钙蛋白↑→心肌损伤•脑利钠肽↑→心功能不全• D-二聚体↑→ VTE……

Guidelines for pulmonary hypertension, ESC 2009

7.2 Evaluation of severity

• 7.2.3 Biochemical markers• Biochemical markers emerged within the last decade as an attractive non-invasive tool for assessment and monitoring of RV dysfunction in patients with PH.

尿酸（ Uric acid）

Chest 2000,117: 19-24

尿酸（ Uric acid）

Chest 2000,117: 19-24

尿酸（ Uric acid）

Chest 2000, 117: 19-24

尿酸（ Uric acid）

Chest 2000, 117: 19-24

Change in the serum UA levels in the patients chronically treated with continuous IV prostacyclin infusion.

尿酸（ Uric acid）

Conclusion There is a positive correlation between the RAP elevation and the serum UA levels in patients with PPH. Serum UA levels drop in some, but not all PPH patients during chronic prostacyclin infusion therapy.

Chest 2000, 117: 19-24

尿酸（ Uric acid）

Int Heart J 2007, 48(4): 523-532

(≥ 4.7 mg/dL)

尿酸（ Uric acid） Conclusion Elevated serum UA levels are associated with poor prognosis and can serve as a prognostic predictor for patients with PAH secondary to connective tissue disease.

Int Heart J 2007, 48(4): 523-532

尿酸（ Uric acid）

Am J Physiol Cell Physiol 2008, 295: C1183-C1190

尿酸（ Uric acid）

Am J Physiol Cell Physiol 2008, 295: C1183-C1190

尿酸（ Uric acid）

Am J Physiol Cell Physiol 2008, 295: C1183-C1190

脑利钠肽（ BNP）

• Plasma BNP was measured in 60 patients with PPH at diagnostic catheterization, together with atrial natriuretic peptide, norepinephrine, and epinephrine.

• Measurements were repeated in 53 patients after a mean follow-up period of 3 months.

Circulation 2000,102;865-870

脑利钠肽（ BNP）

Circulation 2000,102;865-870

脑利钠肽（ BNP）

Circulation 2000,102;865-870

脑利钠肽（ BNP） Conclusions A high level of plasma BNP, and in particular, a further increase in plasma BNP during follow-up, may have a strong, independent association with increased mortality rates in patients with PPH.

Circulation 2000,102;865-870

N末端 -脑利钠肽前体（ NT-proBNP）

European Heart Journal 2006,27:1485–1494

N末端 -脑利钠肽前体（ NT-proBNP）

European Heart Journal 2006,27:1485–1494

N末端 -脑利钠肽前体（ NT-proBNP）

European Heart Journal 2006,27:1485–1494

N末端 -脑利钠肽前体（ NT-proBNP）

Conclusion Raised N-TproBNP levels are directly related to the severity of PAH. Baseline and serial changes in N-TproBNP levels are highly predictive of survival.

European Heart Journal 2006,27:1485–1494

N末端 -脑利钠肽前体（ NT-proBNP）

Chest 2006,129:1313-1321

55 patients with a mean age of 41 years and severe PH (including 36 patients with IPAH) were followed up for up to 36 months.

N末端 -脑利钠肽前体（ NT-proBNP）

Chest 2006,129:1313-1321

PH IPAH

N末端 -脑利钠肽前体（ NT-proBNP）

Chest 2006,129:1313-1321

Conclusions A serum NT-proBNP level of > 1,400 pg/mL was found to be useful in identifying patients with poor long-term prognosis both in the whole studied group and in the IPAH subgroup.

肌钙蛋白（ Troponin）

Circulation 2003,108:844-848

Initial evaluation of 56 clinically stable patients with pulmonary arterial (51patients) or inoperable chronic thromboembolic (5 patients) PH included cTnT test, allowing detection of its serum levels 0.01 ng/mL.

肌钙蛋白（ Troponin）

Circulation 2003,108:844-848

Conclusions—Detectable cTnT is an independent marker of increased mortality risk in patients with chronic precapillary PH, supporting the role of progressive myocyte injury in the vicious circle leading to hemodynamic destabilization.

生长分化因子 -15 （ GDF-15）

Growth-differentiation factor (GDF)-15 is a stress-responsive, transforming growth factor-β–related cytokine. Circulating levels of GDF-15 provide independent prognostic information in patients with acute pulmonary embolismand chronic left-sided heart failure.

Am J Respir Crit Care Med 2008, 178:534–541

生长分化因子 -15 （ GDF-15）

GDF-15 is a promising new biomarker in idiopathic pulmonary arterial hypertension.

Am J Respir Crit Care Med 2008, 178:534–541

生长分化因子 -15 （ GDF-15）

GDF-15 is a promising new biomarker in idiopathic pulmonary arterial hypertension.

Am J Respir Crit Care Med 2008, 178:534–541

胆红素（ Bilirubin）

The subjects were 37 patients with PAH (8 men and 29 women; 18 with idiopathic PAH and 19 with connective tissue disease-associated PAH).

BMC Pulmonary Medicine 2010, 10:22

胆红素（ Bilirubin）

Conclusion Elevated serum bilirubin is a risk factor for death in patients with PAH.

BMC Pulmonary Medicine 2010, 10:22-27

hyperbilirubinemia

(serum total bilirubin > 1.2 mg/dL)

高密度脂蛋白胆固醇（ HDL-C）

Am J Respir Crit Care Med. 2010 Sep 1;182(5):661-8. Epub 2010 May 6.

Plasma levels of high-density lipoprotein cholesterol and outcomes in pulmonary arterial hypertension.

Heresi GA, Aytekin M, Newman J, DiDonato J, Dweik RA.

Am J Respir Crit Care Med 2010,182(5): 661-668

高密度脂蛋白胆固醇（ HDL-C）• High HDL-C(> 35 mg/dl) was associated with decreased

mortality (P = 0.001) and less clinical worsening (P = 0.02).

• HDL-C remained a significant predictor of survival after adjusting for cardiovascular risk factors, C-reactive protein, indices of insulin resistance, and severity of PAH (all P < 0.05).

• Low plasma HDL-C is associated with higher mortality and clinical worsening in PAH.

Am J Respir Crit Care Med 2010,182(5): 661-668

总结• 肺高压（ PH）的血清标志物是反映 PH患者右心功能，评估预后的无创检验方法。

• 血清尿酸、脑利钠肽、肌钙蛋白升高分别代表周围循环灌注不足、心室壁张力增高和心肌损伤是判断 PH患者预后的重要血清生化标志物。

• GDF-15、胆红素升高， HDL-C下降与 PH患者预后不良相关，可作为判断 PH患者预后的新的生化标志物。

谢谢

23/4/21