These findings are surprising as when steroids are administered via the lungs there is only minimal absorption outside the respiratory tract. This is the first study to show protective effects of inhaled steroids on the progression of atherosclerosis, report Dr Michio Otsuki and his colleagues of Osaka University Graduate School of Medicine and Miyatake Asthma Clinic, Japan.
In the study published ahead of print in the European Respiratory Journal asthma patients treated with inhaled corticosteroids (ICS) were found to have fewer atherosclerotic changes in their carotid arteries compared to non-asthmatic control subjects with matched atherosclerosis risk factors.
Because of their potent anti-inflammatory action, ICS are the mainstay of treatment in asthma, a chronic inflammatory disorder of the airways. In contrast to oral corticosteroids, corticosteroids applied via inhaler have been thought to have little effect on tissues other than the airways.
It is generally accepted that inflammation plays an important role in the aetiology of atherosclerosis. However, administration of corticosteroids to combat inflammation has the potential to worsen several known coronary risk factors, including hypertension, hypercholesterolaemia and hypertriglyceridaemia, and to further impair abnormal glucose tolerance.
On the other hand, steroids may prevent the initiation and progression of atherosclerosis, due to their anti-inflammatory properties. "Steroids exert direct inhibitory effects on the expression of adhesion molecules in vascular endothelial cells such as intercellular adhesion molecule-1, E-selectin, and vascular cell adhesion molecule-1, all of which are thought to be involved in the early process of atherosclerosis," explains Dr Otsuki. Additionally, ICS activate the endothelial nitric oxide synthase, another mechanism by which they might exert positive effects on the cardiovascular system.
Although concentrations of ICS entering the circulation are very low, they may well have the potential to inhibit atherosclerosis-related inflammation, since this type of inflammation is chronic and moderate.
Included in the study were 150 non-hospitalised Japanese asthma patients and 150 controls. The asthma patients had been on ICS for the previous two years. The ICS prescribed were mainly fluticasone, budesonide and ciclesonide.
Subjects‘ carotid arteries were evaluated by a blinded examiner using high-resolution ultrasound, and parameters such as the intima and media thickness (IMT) were measured. Carotid atherosclerosis was defined as mean IMT ?1.1 mm and/or the presence of a plaque lesion.
On ultrasound, 20% of asthma patients were found to have one or more atheromatous plaques in their carotid arteries compared with 29.3% of controls (p=0.06). The carotid IMT, a surrogate marker of atherosclerosis, was significantly lower in asthma patients compared to controls. Atherosclerotic change of the carotid arteries was significantly lower in the asthma patients than in the control subjects (p = 0.03). Fifty-one asthma patients (34%) had confirmed carotid atherosclerosis compared to 69 (46%) in the control group.
After calculating the mean daily ICS dose that each asthma patient had been receiving over the previous two years, the researchers were able to show that the dosage of inhaled corticosteroids inversely correlated with the risk of atherosclerosis.
"These findings confirm that inhaled corticosteroids absorbed into the circulation repress atherosclerosis progression via their anti-inflammatory effects."
"Inhaled corticosteroids possess some unique characteristics such as a higher affinity for the glucocorticoid receptor and stronger anti-inflammatory effects on bronchial epithelial cells. Although inhaled corticosteroids are only minimally absorbed into the systemic circulation, they may exert some direct actions on vessel walls and thereby exhibit anti-atherogenic properties," comments Dr Otsuki.
Title of the original article: "Reduced Carotid Atherosclerosis in Asthmatic Patients Treated with Inhaled Corticosteroids."