PAH clinical worsening associated with fewer fingernail capillaries
Findings suggest blood vessel loss not caused by disease's effect on blood flow
Having fewer very fine blood vessels in the fold of skin at the base of the fingernails appears to be linked to an increased risk of clinical worsening in pulmonary arterial hypertension (PAH), a study in the Netherlands suggests.
People with chronic thromboembolic pulmonary hypertension (CTEPH) also had fewer fine blood vessels, called capillaries, in their nail folds than healthy people, but this didn’t change after a surgical procedure to relieve high blood pressure in their lungs.
This suggests a loss of capillaries isn’t unique to PAH or directly caused by how the disease affects blood flow. Instead, shared mechanisms may cause changes to both the pulmonary arteries that supply the lungs and the capillaries throughout the body. The study, “Low nailfold capillary density in patients with pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension: biomarker of clinical outcome?” was published in Scientific Reports.
PAH occurs when small blood vessels in the lungs become narrower, resulting in high blood pressure in the pulmonary arteries. The disease can result from inherited genetic mutations, where it’s called heritable PAH, or when the cause of the narrowing is unknown, called idiopathic PAH.
Usually regarded as a disease that only affects the lungs, PAH often occurs in people with fewer capillaries in the folds of their fingernails, suggesting microangiopathy, that is, a disease of the small blood vessels. This has led the researchers to ask whether loss of capillaries is unique to PAH or is a result of high blood pressure in the lungs in general.
Counting the capillaries at the fingernails
To investigate this, they used a technique called nail fold capillaroscopy to count the number of capillaries in fingernail folds and see how narrow they were. The study included 30 people with PAH (23 with idiopathic PAH, seven with heritable PAH), 17 people with CTEPH, and 48 healthy people, who served as controls. CTEPH is a type of pulmonary hypertension that occurs when blood clots deposit in the pulmonary arteries, limiting or blocking blood flow. Unlike PAH, CTEPH can be treated with pulmonary endarterectomy (PEA) to remove the clots or balloon pulmonary angioplasty (BPA) to open the narrowed arteries.
Compared to controls, who had an average 10.3 capillaries per mm of their nail folds, capillary density was significantly lower in PAH (7.5 capillaries/mm) and CTEPH (8.4 capillaries/mm). There was no difference in capillary density between idiopathic and heritable PAH (7.5 vs. 7.6 capillaries/mm).
“The current study confirms that patients with [idiopathic PAH] and CTEPH are characterized by increased capillary dimensions and reduced capillary density, but extends these findings to patients with confirmed [heritable PAH],” the researchers wrote.
In PAH, the endothelial cells, smooth muscle cells, and fibroblasts that line the blood vessels grow out of control. As a result, the walls of the blood vessels thicken, narrowing the lumen, or opening, where the blood flows.
The researchers also measured the capillaries’ diameter, which on average was significantly larger in people with PAH or CTEPH than controls, indicating both fewer capillaries and changes in their structure. The researchers also looked at whether the number of capillaries was related to how severe the disease was or if it could predict how the disease may get worse. Fewer capillaries were linked to an increased risk of disease worsening in PAH.
Over a median 3.7 years, 11 of the 30 people with PAH worsened and required either additional treatment or a lung transplant, or died. Each loss of one capillary per mm doubled the risk of clinical worsening, even when adjusted for age.
Fifteen people with CTEPH underwent a surgical procedure, eight had PEA and seven had BPA. Eleven had normal mean pulmonary arterial after surgery, while four had residual high blood pressure. For seven patients who had repeat measurements, capillary density remained unchanged even after a median of 3.3 years.
“Although capillary density was associated with time to clinical worsening in patients with PAH, capillary density did not normalize after recovery of pulmonary hemodynamics [blood flow] in patients with CTEPH,” the researchers wrote. “Our findings indicate that a loss of peripheral capillaries is not specific to PAH and is not related to the hemodynamic disturbance per se, but that shared mechanisms may account for a simultaneous development of a systemic [body-wide] microangiopathy and pulmonary vascular remodeling.”
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