Men with PH have worse right ventricular function, study finds

Differences found across PH types, include risk of transplant-free survival

Lindsey Shapiro, PhD avatar

by Lindsey Shapiro, PhD |

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Despite more women being affected by pulmonary hypertension (PH), men with the cardiovascular disease had worse right ventricular function and lower odds of transplant-free survival relative to their female counterparts, a study found.

In a large group of patients with various types of PH, sex differences in function of the right ventricle (RV) were most notable where pulmonary vascular resistance (PVR), an indicator of resistance to blood flow in the vessels of the lungs, was not severely elevated.

The study, “Male Sex Is Associated With Worse Right Ventricular Function and Survival in Pulmonary Hypertension in the Redefining Pulmonary Hypertension Through Pulmonary Vascular Disease Phenomics Cohort,” was published in CHEST Pulmonary.

PH is characterized by increased pressure in the pulmonary arteries, which carry blood from the heart’s RV to the lungs. Ultimately, this causes strain on the RV, which can eventually lead to heart failure.

Sex-based differences have been observed among patients with pulmonary arterial hypertension (PAH), or group 1 of the World Health Organization (WHO) PH classification. This type of PH is characterized by a narrowing of the pulmonary arteries.

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While women appear to be at greater risk of developing PAH, male patients have worse outcomes. It has been proposed that these divergent outcomes may be because male PAH patients have worse RV function.

Still, it is “unknown whether these sex-based differences extend to other forms of PH,” the researchers wrote.

The scientists examined RV function among a large group of PH patients who had enrolled in an earlier clinical study called PVDOMICS (NCT02980887) — Pulmonary Vascular Disease Phenomics Program — being conducted at a handful of U.S. sites.

Their analysis involved 750 PH patients, 471 of whom were women and 279 men. While 353 of them had PAH, the remaining 397 were in WHO groups 2-5, representing other forms of PH.

Females predominated in group 1, group 2 (PH due to left heart disease), and group 4 (PH due to blood clots in the lungs). Group 3, in which PH arises due to lung disease or chronic oxygen depravation, was balanced in terms of sex, and group 5 (PH due to other health conditions) showed a male predominance.

Male patients were significantly more likely to have a history of coronary artery disease, high blood pressure, and smoking. They also had significantly higher levels of NT-proBNP, a biomarker of heart failure, and lower indicators of lung function, than women.

A number of different tests were used to look at the heart’s structure and function.

Male PH patients were found to have multiple markers of worse RV function compared with female patients, including a significantly lower RV ejection fraction (RVEF), which refers to how much blood the RV is able to pump out with each beat. A number of cardiac structural differences were also observed between sexes.

These sex differences were generally consistent across PH types, and remained statistically significant in WHO groups 1-3.

In both men and women, RVEF was inversely correlated with PVR, such that when blood flow resistance was lower, the RV could pump out more blood.

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Patients followed for three years

PVR and sex were found to interact to influence RVEF. The greatest sex differences in RVEF were observed where PVR was mildly to moderately elevated, while no sex differences were seen where PVR was severely elevated.

Patients were followed for a median of three years, during which 45 patients underwent a heart or lung transplant and 137 died. After adjusting for transplant risk, the incidence of death was 17.6% for women and 27.2% for men.

In final analyses, male sex was significantly associated with a reduced transplant-free survival rate across the age spectrum. Similar to the findings with RV function, sex differences in transplant-free survival were most notably observed where PVR was only mildly elevated.

RVEF was also found to significantly influence sex-based differences in transplant-free survival, accounting for about 68% of the relationship.

“Overall, our study suggested that the RV in men is less able to compensate for mild increases in afterload [PVR],” the researchers wrote, adding that the observed “steep decline in RVEF with small increases in PVR contributes to the observed differences in mortality between men and women with PH.”

Still, “these results do not allow us to identify mechanisms behind the sex-based differences in RV function observed,” they added, noting that both biological factors such as hormones, as well as behavioral ones like diet, exercise, or family roles, could be involved.

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