From the Guidelines
Elevated pulmonary vascular resistance (PVR) in females is most commonly caused by pulmonary arterial hypertension (PAH), which affects women more frequently than men, particularly during childbearing years, with a female-to-male ratio of approximately 4:1, as reported in the most recent guidelines 1. The causes of elevated PVR in females can be multifactorial, including:
- Pulmonary arterial hypertension (PAH), which is more prevalent in women, especially during childbearing years
- Left heart disease
- Lung diseases like COPD or interstitial lung disease
- Chronic thromboembolic pulmonary hypertension
- Connective tissue disorders such as systemic sclerosis and lupus, which are more prevalent in women
- Autoimmune conditions, particularly those affecting the vasculature
- Pregnancy, which can exacerbate PVR due to increased cardiac output and blood volume
- Genetic factors, such as mutations in the bone morphogenetic protein receptor-2 (BMPR2) gene, which can increase the risk of developing PAH, as noted in a study published in Circulation 1
- Hormonal factors, with estrogen potentially modifying disease expression and progression, as suggested by research in the field 1
It is essential to note that the pathogenesis of PAH is complex and involves various biochemical pathways and cell types, including endothelial dysfunction, smooth muscle cell proliferation, and inflammation, as discussed in a report by the American College of Cardiology Foundation Task Force on Expert Consensus Documents and the American Heart Association 1. Treatment of elevated PVR in females depends on the underlying cause and may include vasodilators like sildenafil or tadalafil, or endothelin receptor antagonists like bosentan, as recommended in the guidelines 1. Effective contraception is crucial for women of childbearing age with elevated PVR, as pregnancy can significantly worsen pulmonary hypertension, and some medications used to treat elevated PVR are teratogenic.
From the Research
Causes of Elevated Pulmonary Vascular Resistance (PVR) in Females
- The exact causes of elevated PVR in females are not fully understood, but several factors are thought to contribute to its development, including an imbalance between vasodilators and vasoconstrictors 2, 3.
- Pulmonary vascular vasoconstriction, smooth muscle cell proliferation, and thrombosis are also thought to play a role in the development of elevated PVR 2.
- The pathology of PAH is characterized by an imbalance between locally produced vasodilators (such as nitric oxide, prostacyclin, and vasoactive intestinal peptide) and vasoconstrictors (such as thromboxane A2, endothelin, and serotonin) 2, 3.
- Females have a higher incidence of PAH, which is reflected globally across registries in the United States, Europe, and Asia 4.
- Special considerations should be given to women with PAH regarding sexual health, contraception, family planning, and treatment before, during, and after pregnancy 4.
- Pulmonary arterial smooth muscle cell (PASMC) phenotypic switch from a contractile to a synthetic and proliferative phenotype is an important factor in pulmonary artery remodeling, which can contribute to elevated PVR 5.
- Excessive pulmonary artery remodeling, perivascular fibrosis, and inflammation can also contribute to elevated PVR 5.