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.

Sex Differences in Response to Tadalafil in Pulmonary Arterial Hypertension

“…Th is diff erence did not persist among other age strata. 35 In the current study, we found no eff ect modifi cation of age (when included as a continuous variable or when stratifi ed at 56 years of age) upon the relationship between sex and odds of achieving clinically relevant changes in 6MWD. However, when compared with women .…”

“…While studies in normal populations from which predictive equations for the 6MWT have demonstrated signifi cant diff erences in 6MWD between men and women based solely upon sex, these diff erences are not pronounced in PAH. [45][46][47] As shown by Ventetuolo and colleagues, 35 at baseline assessment of . 1,200 patients with PAH enrolled in clinical trials for PAH therapy, the diff erence in mean 6MWD between men and women was , 20 m. Th us, it unlikely that the observed diff erences in odds of achieving the MID for the 6MWT are based upon baseline differences in 6MWT between men and women.…”

Regulation and Function of miR‐214 in Pulmonary Arterial Hypertension

“…tween males and females in cardiovascular responses. 1,5,7,8 Previous studies have shown different pathophysiology between male and female mice in a transgenic mouse model. 8,42,43 Furthermore, male PAH patients have decreased RV function compared with females, 6 and male rodents and swine develop more severe RVH when exposed to chronic hypoxia compared with females.…”

“…1,5,7,8 Previous studies have shown different pathophysiology between male and female mice in a transgenic mouse model. 8,42,43 Furthermore, male PAH patients have decreased RV function compared with females, 6 and male rodents and swine develop more severe RVH when exposed to chronic hypoxia compared with females. 42,44 These significant sex differences in adaptation to hypoxia may reflect the different sensitivity of males and females to oxygen deprivation and other stresses.…”

“…6 This could be due at least in part to the protective effect of estrogen on RV function. 7,8 MicroRNAs (miRNAs) are involved in multiple cellular responses during normal development and disease; they act as posttranscriptional regulators to fine-tune protein synthesis. Evidence has emerged for a key role for miRNA in regulation of the cellular processes involved in PAH.…”