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Sex and haemodynamics in pulmonary arterial hypertension.

ABSTRACT: Female sex is a risk factor for pulmonary arterial hypertension (PAH), yet females have better survival than males. We sought to determine if sex was associated with baseline haemodynamics in subjects with PAH, and whether age modified these relationships. We conducted a pooled analysis from 11 randomised trials submitted to the US Food and Drug Administration. The study sample included 1211 subjects with idiopathic PAH, 25% of whom were males, and 489 subjects with connective tissue disease-associated PAH, 13% of whom were males. After multivariable adjustment, right atrial pressure was 1.36 mmHg higher (95% CI 0.44-2.27, p=0.004), cardiac index was -0.14 L · min(-1) · m(-2) lower (95% CI -0.23-0.04, p=0.01) and pulmonary vascular resistance was 1.23 Wood units higher (95% CI 0.18-2.27, p=0.02) in males compared with females. Younger males had 5.43 mmHg (95% CI 2.20-8.66, p=0.001) higher mean pulmonary arterial pressures than younger females, but these relationships were attenuated after age 45 years. In the subgroup of connective tissue disease-associated PAH, males may have had higher right atrial pressure. These findings implicate age as a modifier and provide further evidence of sexual dimorphism in PAH.

SUBMITTER: Ventetuolo CE

PROVIDER: S-EPMC4338984 | biostudies-literature | 2014 Feb

REPOSITORIES: biostudies-literature

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Sex and haemodynamics in pulmonary arterial hypertension.

Ventetuolo Corey E CE Praestgaard Amy A Palevsky Harold I HI Klinger James R JR Halpern Scott D SD Kawut Steven M SM

The European respiratory journal 20130815 2

Female sex is a risk factor for pulmonary arterial hypertension (PAH), yet females have better survival than males. We sought to determine if sex was associated with baseline haemodynamics in subjects with PAH, and whether age modified these relationships. We conducted a pooled analysis from 11 randomised trials submitted to the US Food and Drug Administration. The study sample included 1211 subjects with idiopathic PAH, 25% of whom were males, and 489 subjects with connective tissue disease-ass ...[more]

PMID: 23949961

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Project description:Rationale: Sex-based differences in pulmonary arterial hypertension (PAH) are known, but the contribution to disease measures is understudied. Objectives: We examined whether sex was associated with baseline 6-minute-walk distance (6MWD), hemodynamics, and functional class. Methods: We conducted a secondary analysis of participant-level data from randomized clinical trials of investigational PAH therapies conducted between 1998 and 2014 and provided by the U.S. Food and Drug Administration. Outcomes were modeled as a function of an interaction between sex and age or sex and body mass index (BMI), respectively, with generalized mixed modeling. Results: We included a total of 6,633 participants from 18 randomized clinical trials. A total of 5,197 (78%) were female, with a mean age of 49.1 years and a mean BMI of 27.0 kg/m2. Among 1,436 males, the mean age was 49.7 years, and the mean BMI was 26.4 kg/m2. The most common etiology of PAH was idiopathic. Females had shorter 6MWD. For every 1 kg/m2 increase in BMI for females, 6MWD decreased 2.3 (1.6-3.0) meters (P < 0.001), whereas 6MWD did not significantly change with BMI in males (0.31 m [-0.30 to 0.92]; P = 0.32). Females had lower right atrial pressure (RAP) and mean pulmonary artery pressure, and higher cardiac index than males (all P < 0.03). Age significantly modified the sex by RAP and mean pulmonary artery pressure relationships. For every 10-year increase in age, RAP was lower in males (0.5 mm Hg [0.3-0.7]; P < 0.001), but not in females (0.13 [-0.03 to 0.28]; P = 0.10). There was a significant decrease in pulmonary vascular resistance (PVR) with increasing age regardless of sex (P < 0.001). For every 1 kg/m2 increase in BMI, there was a 3% decrease in PVR for males (P < 0.001), compared with a 2% decrease in PVR in females (P < 0.001). Conclusions: Sexual dimorphism in subjects enrolled in clinical trials extends to 6MWD and hemodynamics; these relationships are modified by age and BMI. Sex, age, and body size should be considered in the evaluation and interpretation of surrogate outcomes in PAH.

Dataset Information

Sex and haemodynamics in pulmonary arterial hypertension.

Publications

Sex and haemodynamics in pulmonary arterial hypertension.

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