Stress Doppler Echocardiography in Relatives of Patients With Idiopathic and Familial Pulmonary Arterial Hypertension Results of a Multicenter European Analysis of Pulmonary Artery Pressure Response to Exercise and Hypoxia

被引：178

作者：

Gruenig, Ekkehard ^{[1
]}

Weissmann, Sylvia ^{[4
]}

Ehlken, Nicola ^{[1
]}

Fijalkowska, Anna ^{[7
]}

Fischer, Christine ^{[3
]}

Fourme, Thierry ^{[5
]}

Galie, Nazzareno ^{[8
]}

Ghofrani, Ardeschir ^{[4
]}

Harrison, Rachel E. ^{[9
]}

Huez, Sandrine ^{[6
]}

Humbert, Marc ^{[5
]}

Janssen, Bart ^{[3
]}

Kober, Jaroslaw ^{[7
]}

Koehler, Rolf ^{[3
]}

Machado, Rajiv D. ^{[9
]}

Mereles, Derliz ^{[2
]}

Naeije, Robert ^{[6
]}

Olschewski, Horst ^{[11
]}

Provencher, Steeve ^{[5
,10
]}

Reichenberger, Frank ^{[4
]}

Retailleau, Kathleen ^{[6
]}

Rocchi, Guido ^{[8
]}

Simonneau, Gerald ^{[5
]}

Torbicki, Adam ^{[7
]}

Trembath, Richard ^{[9
]}

Seeger, Werner ^{[4
]}

机构：

[1] Heidelberg Univ, Thoraxclin, Heidelberg, Germany

[2] Heidelberg Univ, Dept Cardiol, D-6900 Heidelberg, Germany

[3] Heidelberg Univ, Inst Human Genet, D-6900 Heidelberg, Germany

[4] Univ Giessen, Lung Ctr, Giessen, Germany

[5] Univ Paris 11, Hop Antoine Beclere, Clamart, France

[6] Univ Brussels, Dept Physiol, Brussels, Belgium

[7] Natl Inst TB & Lung Dis, Warsaw, Poland

[8] Univ Bologna, Dept Cardiol, Bologna, Italy

[9] Kings Coll London, Inst Human Genet, London WC2R 2LS, England

[10] Univ Laval, Inst Cardiol & Pneumol, Quebec City, PQ, Canada

[11] Graz Univ, Dept Pulmonol, Graz, Austria

来源：

CIRCULATION | 2009年 / 119卷 / 13期

关键词：

echocardiography; stress; genetics; hypertension; pulmonary; hypoxia; pulmonary heart disease; SYSTOLIC PRESSURE; HIGH-ALTITUDE; NONINVASIVE EVALUATION; DISEASE; BMPR2; MUTATIONS; DIAGNOSIS; RECEPTOR; LOCUS;

D O I：

10.1161/CIRCULATIONAHA.108.800938

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Background-This large, prospective, multicentric study was performed to analyze the distribution of tricuspid regurgitation velocity (TRV) values during exercise and hypoxia in relatives of patients with idiopathic and familial pulmonary arterial hypertension (PAH) and in healthy control subjects. We tested the hypothesis that relatives of idiopathic/familial PAH patients display an enhanced frequency of hypertensive TRV response to stress and that this response is associated with mutations in the bone morphogenetic protein receptor II (BMPR2) gene. Methods and Results-TRV was estimated by Doppler echocardiography during supine bicycle exercise in normoxia and during 120 minutes of normobaric hypoxia (FIO2 = 12%; approximate to 4500 m) in 291 relatives of 109 PAH patients and in 191 age-matched control subjects. Mean maximal TRVs were significantly higher in PAH relatives during both exercise and hypoxia. During exercise, 10% of control subjects but 31.6% of relatives (P < 0.0001) exceeded the 90% quantile of mean maximal TRV seen in control subjects. Hypoxia revealed hypertensive TRV in 26% of relatives (P = 0.0029). Among control subjects, TRV at rest was not related to age, sex, body mass index, systemic blood pressure, smoking status, or heart rate. Within kindreds identified as harboring deleterious mutations of the BMPR2 gene, a hypertensive TRV response occurred significantly more often compared with those without detected mutations. Conclusions-Pulmonary hypertensive response to exercise and hypoxia in idiopathic/familial PAH relatives appears as a genetic trait with familial clustering, being correlated to but not caused by a BMPR2 mutation. The suitability of this trait to predict manifest PAH development should be addressed in long-term follow-up studies. (Circulation. 2009; 119: 1747-1757.)

引用

页码：1747 / 1757

页数：11

共 34 条

[1] Appetite-suppressant drugs and the risk of primary pulmonary hypertension [J].