RSV and Heart Health
Can Hormone Replacement Therapy Help Treat Pulmonary Hypertension In Women?
Researchers estimate that about 1% of the global population has pulmonary hypertension — a disease caused by high blood pressure in the blood vessels that deliver oxygen to the lungs.
Past studies show that pulmonary hypertension is more common in females, for which there is currently no cure.
Scientists believe the hormone estrogen may play an important role in pulmonary hypertension in females.
Now, researchers from The University of Arizona College of Medicine Tucson report during a presentation at the American Thoracic Society 2024 International Conference that hormone replacement therapy (HRT) may improve pulmonary hypertension symptoms in females. The findings have not yet been published in a peer-reviewed scientific journal.
For this study, researchers recruited a total of 742 female participants. Those who had pulmonary hypertension were classified into the five groups established by the World Symposium on Pulmonary Hypertension:
"Pulmonary hypertension is a progressive disease that can significantly impact one's quality [of life] despite current treatments," Audriana Hurbon, MD, assistant clinical professor in the Department of Medicine at The University of Arizona College of Medicine Tucson and corresponding author of this study told Medical News Today.
"Because we know that in Group 1 pulmonary hypertension women can be affected more often than men, we also know that once affected we have observed less severe disease than (men). We wanted to explore a suspected hormonal contribution to this observation."
Other female participants included those with risk factors for pulmonary hypertension but who did not have this disease and healthy controls.
Researchers examined the impact of both exogenous and endogenous hormone exposure on pulmonary hypertension.
"Because we wanted to explore the suspected hormonal impact, endogenous hormone exposure was defined as one's lifetime duration of menses, and exogenous hormone exposure was defined as one ever having used hormone replacement therapy (HRT)," Hurbon explained.
Upon analysis, Hurbon and her team discovered that average pulmonary arterial pressure decreased with a greater lifetime duration of menstruation across all pulmonary hypertension groups.
"We wanted to assess whether there was a difference between pulmonary vascular disease — where we looked at pulmonary arterial pressure and pulmonary vascular resistance, which was measured by right heart catheterization — and also right ventricular function — defined by measurement of right ventricular fractional shortening from echocardiography and right ventricular ejection fraction from cardiac MRI — between those who had greater lifetime duration of menses and use of HRT," Hurbon said.
"Ultimately there was no statistically significant difference with lifetime duration of menses in regard to pulmonary vascular disease, but we did observe improvement with right ventricular ejection fraction."
Researchers found an association between the use of hormone replacement therapy and lower mean pulmonary artery pressure, higher right ventricular fractional shortening, and right ventricular ejection fraction.
"So far, our preliminary data has been positive with improvement (in) mean pulmonary arterial pressure, pulmonary vascular resistance, right ventricular ejection fraction, and right ventricular fractional shortening with the use of HRT in the pulmonary hypertension cohort," Hurbon said.
"We didn't observe a difference with the healthy controls or comparator — one with risk factors for pulmonary hypertension but does not have the disease — with increased lifetime duration of menses or with use of HRT. These findings were consistent with our hypothesis that suggests that hormones could be protective with this pulmonary hypertension subgroup."
Additionally, those in the pulmonary hypertension Group 1 had lower mean pulmonary artery pressure, pulmonary vascular resistance, and higher right ventricular ejection fraction if exposed to HRT.
"Additional studies are needed to further explore this," Hurbon said. "Preliminary data suggests that these findings are most notable with Group 1 pulmonary hypertension compared to the other subgroups of pulmonary hypertension."
After reviewing this study, Nicole Weinberg, MD, a board certified cardiologist at Providence Saint John's Health Center in Santa Monica, CA, told MNT the findings may cause controversy, noting the following:
"We know that hormones do have some pros and cons, and it's something that I feel we've struggled with in the world of preventative health — for every positive study, there's a negative study," Weinberg continued. "I think hormones, for one thing, are vasodilating medications — they can cause your blood vessels to plump. So if you think about a disease process like pulmonary hypertension, that is a facet of the drugs that we use for pulmonary hypertension, that can be very beneficial to cause more blood flow due to the circulation that's being compromised."
"The flip side of it is the induction of actual hormones can cause increased clotting risks and things like that, that we already worry about quite significantly in this group of patients," Weinberg continued. "So it'll be interesting to see when they flesh out further research data where this ends up."
There is also controversy regarding the use of HRT and the cardiovascular system.
While some studies say that HRT may help protect the body from cardiovascular disease, other studies say differently, such as a recent study reported that HRT may not help prevent heart disease.
MNT also spoke with Cheng-Han Chen, MD, a board certified interventional cardiologist and medical director of the Structural Heart Program at MemorialCare Saddleback Medical Center in Laguna Hills, CA, about this study.
As public hypertension is a notoriously difficult condition to treat, Chen said this study provides a useful new avenue of research into new approaches for this condition.
"These findings will not affect how we approach hormone replacement therapy simply because it's too early of a stage of research," he continued. "Right now the decision to start therapies will still be rather individualized and mostly revolve around patients with severe menopausal symptoms that affect their quality of life."
"Future research should focus on confirming this relationship between estrogen and improving pulmonary hypertension, preferably with randomized control trials," Chen noted.
Pulmonary Arterial Hypertension Diagnosis Results In Lost Work Productivity
Patients with pulmonary arterial hypertension with commercial insurance lose time from work to seek treatment.
Patients with pulmonary arterial hypertension who have commercial insurance lose more than 8% of annual workdays to seek treatment and other healthcare services, according to a poster presented recently at the American Thoracic Society 2024 International Conference.
Pulmonary arterial hypertension is a rare, progressive and life-threatening disease in which blood vessels in the lungs narrow, causing strain on the heart. About 40,000 people in the United States are living with PAH. The five-year mortality rate is about 43%.
In this retrospective study, which was sponsored by Merck, researchers assessed claims data from adult patients treated between Jan. 1, 2019, and Nov. 30, 2020, for patients who have commercial insurance. Researchers used data from Milliman's Consolidated Health Cost Guidelines Source Databased and IBM's MarketScan.
Researchers, led by Anna Watzker, associate director, outcomes research at Merck, identified 1,174 commercially insured patients for analysis. In 2019, they identified a total of 19,525 lost workdays, or about 8.7% of all available workdays. In 2020, there were 14,738 lost workdays, or about 8.2% of total available days.
On average, patients had 18.2 lost days in 2019 and 18.5 lost days in 2020. Based on median household income, researchers valued this lost work time at $6,614 per patient in 2019 and $6,587 per patient in 2020.
"Pulmonary arterial hypertension (PAH) is associated with an overall significant economic societal burden," researchers wrote. "Our data add to the growing evidence of indirect healthcare resource utilization from productivity loss, which should be considered in the overall PAH economic burden. The impact could be even higher when accounting for PAH-related sick leaves, effect on work productivity, and loss of employment."
Researchers said that one of the limitations of the study was that it relied on claims data from Milliman and IBM. Analysis using different sources, payer markets, and time periods may produce different results, researchers said. In addition, this study estimated productivity loss only due healthcare visits and did not account for other reasons for missed work.
There hasn't been a lot of recent research on the impact of pulmonary arterial hypertension on employment and work productivity. One study from 2014 found that productivity loss among workers with pulmonary arterial hypertension was 44% higher than employers who did not have the disease.
More recent research analyzed workplace productivity in PAH outside of the United States. One study, published online in February 2022 in Frontiers in Psychiatry, surveyed patients in Germany about education, employment, productivity and quality of life. Researchers found that employment and work productivity of patients is impaired.
Another study, published in October 2022 in the European Heart Journal, focused on PAH patients in Sweden. This study was a retrospective observational case-control study of patients in the Swedish PAH registry, and found pulmonary arterial hypertension resulted in a heavy economic burden, with medications, disability and sick leave as the main cost drivers. Ten-year mean sick leave days was five times higher for PAH patients compared with controls. This study also found that costs for hospitalizations and outpatient visits increased three prior to a diagnosis of PAH.
Hormone Replacement Therapy May Benefit Some Women With Pulmonary Hypertension
Preliminary data suggest people with Group 1 pulmonary hypertension had improved outcomes if they had ever received hormone replacement therapy.
New evidence suggests the use of hormone replacement therapy (HRT) may lead to benefits in certain women with pulmonary hypertension. The findings add to a long debate over the role of hormones like estrogen in the course of the disease.
During a presentation at the American Thoracic Society's 2024 International Conference in San Diego, investigators said HRT appeared to improve pulmonary vascular disease and right ventricular (RV) function in a cohort of 742 women who participated in the study
Corresponding author Audriana Hurbon, M.D., of the University of Arizona College of Medicine, explained along with colleagues that previous research has indicated women with World Symposium Group 1 pulmonary hypertension have improved preservation of RV function compared to men in the same disease group. Yet, Hurbon and colleagues said it was not clear whether the preservation of RV function was linked with endogenous and/or exogenous exposure to female hormones, and it was not known if the apparent benefits of female hormones applied to all groups of pulmonary hypertension or merely to Group 1.
"While it is accepted that in World Symposium Group 1 pulmonary hypertension female sex is associated with preservation of right ventricular function, the role of estrogen in pulmonary hypertension has been controversial," Hurbon explained, in a press release. "Additionally, we know that women are affected by pulmonary hypertension more often than men, but when compared to each other, women seem to present less severely than men."
The more than 700 participants in Hurbon's research were part of the National Heart Lung and Blood Institute-funded Pulmonary Vascular Disease Phenomics (PVDOMICS) Study. The women represented all five World Symposium disease groups, along with healthy controls and comparators who had risk factors for pulmonary hypertension but had not been diagnosed with the disease.
The authors set out to compare participants using mean pulmonary artery pressure on right heart catheterization to measure pulmonary vascular disease related to pulmonary hypertension, and characterizing RV function based on RV fractional shortening and RV ejection fraction from echocardiography.
Endogenous hormone exposure was quantified based on self-reported lifetime duration of menses. Participants were considered to have exogenous exposure to hormones if they had ever received HRT.
Hurbon and colleagues found that people with greater lifetime duration of menses had decreased average pulmonary arterial pressure regardless of which pulmonary hypertension group they belonged in. Specifically, they found mean pulmonary arterial pressure was 47±14 mmHg for participants with 20-30 years of menses, versus 37±13 mmHg for participants with more than 50 years of menses.
Additionally, participants who had taken HRT had lower mean pulmonary artery pressure (35±11 vs 42±14, P = 0.002) and pulmonary vascular resistance (5±3 vs 7±4, P = 0.006) and higher RV fractional shortening (37±11 vs 32±9, P = 0.001) and RV ejection fraction (48±13 vs 40±12 %, P < 0.0001). However, when broken out by subgroup, the investigators only found statistically significant impacts in patients with Group 1 pulmonary hypertension.
Hurbon said in the press release that further analysis also suggests that older age and HRT exposure may have a positive "synergistic effect."
"This could support a theory suggesting a threshold of estrogen exposure necessary for a protective effect," she said.
The authors described their findings as preliminary, but they said their data suggest more research is needed to better understand the potential impacts of HRT, both positive and potentially negative, on patients with pulmonary hypertension.
"We hope this study will be a catalyst for further exploration of the mechanisms of female reproductive hormones to identify therapeutic targets for right ventricular preservation in pulmonary hypertension," Hurbon said.
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