Asthma linked to deleterious atherosclerotic changes

Liz Meszaros, MDLinx | March 14, 2018

Asthma—especially severe asthma—is associated with pathological arterial changes, including a significantly increased atherosclerotic plaque burden, according to results from a study published in PLoS One.


Atherosclerosis warning

Asthma is associated with preatherosclerotic vessel changes.

Although patients with asthma seem to have an increased risk for cardiovascular complications, and asthma is associated with changes in both functional and structural vasculature, studies that link asthma with atherosclerosis are inconsistent. Asthma medications may also, in turn, affect the vascular system. For example, oral cortisone may have negative effects, while inhaled cortisone may actually be protective.

“Against this background, the aim of our present work was to evaluate functional and structural atherosclerotic vessel changes in patients with mild-to-moderate and severe asthma compared to control individuals. Additionally, we aimed to determine the levels of cardiovascular risk markers in blood,” wrote the researchers, led by Izabela Tuleta, Department of Internal Medicine II-Cardiology, Pulmonology, and Angiology, University of Bonn, Bonn, Germany.

Tuleta and colleagues included 82 consecutive outpatients who had allergic asthma and 21 nonasthmatic controls. They defined allergic asthma as an increase in forced expiratory volume in 1 second (FEV1) of more than 12% after administration of a short acting ß2-agonist, or a decrease in FEV1 of over 200 ml upon bronchial challenge and the presence of at least three allegro-allergens upon specific immunoglobulin E (IgE) blood measurements or on skin prick testing.

They divided asthma patients into two groups:

  • Patients with mild-to-moderate asthma, currently on inhaled therapy, with no treatment with omalizumab or oral cortisone (n=24), and
  • Patients with severe asthma, currently taking maximal inhaled therapy combined with present or past treatment with omalizumab and/or oral cortisone (n=58).

Researchers used central pulse wave velocity and ankle-brachial index (ABI) to assess vessel stiffness with mean ABI values greater than 1.3 denoting increased vascular stiffness. Atherosclerotic plaques were assessed by color-coded duplex sonography.

Subjects underwent standard laboratory blood testing to assess cardiovascular risk and asthma makers, including total cholesterol, HDL and LDL cholesterol, lipoprotein(a), C-reactive protein (CRP), interleukin-6, soluble interleukin-2 receptor, IgE, fibrinogen, d-dimer, leukocytes, lymphocytes, eosinophils, hemoglobin, and thrombocytes.

Patients with asthma, especially those with severe asthma, had increased arterial stiffness and greater atherosclerosis compared with controls. For example, central pulse wave velocity was 5.81 m/s in patients with mild-to-moderate asthma, compared with 6.45 m/s in those with severe asthma, and 4.91 m/s in controls (P=0.019 and P=0.005, respectively, for severe asthmatics compared with controls)

Atherosclerotic plaques were seen in more severe asthma patients than in those with mild-to-moderate asthma and controls (43.1% vs 25.0% vs 14.3%; P=0.035). Atherosclerotic vessel changes accounted for most of the peripheral artery disease found in patients with severe asthma, compared with the other two groups (36.2% vs 20.8% vs 4.8%: P=0.015). In addition, researchers found that cranial artery disease was more prevalent in asthma patients, but the differences did not reach statistical significance (25.9% vs 20.8% vs 14.3%; P=0.540).

Compared with controls, patients with asthma had higher IgE blood concentrations, significantly elevated levels of fibrinogen and leukocytes, a reduced lymphocyte fraction, and a slightly increased number of eosinophils. Patients with asthma also showed a trend of higher lipoprotein(a) and thrombocyte levels.

They found no differences, however, in classic cardiovascular risk factors, including total cholesterol, HDL, LDL, or CRP between the groups.

To assess the effects of asthmatic medications, researchers also conducted a subanalysis of patients treated with omalizumab and oral cortisone (group 1a; n=16) and compared them with patients treated with omalizumab without oral cortisone (group 1b; n=31).

The only difference in lung function between the groups was significantly lower FEV1 in group 1a patients (1.9 l vs 2.7 l, respectively; P=0.002) and predicted FEV1 % (67.0% vs 85.8%; P=0.003). Upon serum testing, researchers found no relevant differences between the two groups, aside from increased IgE levels in group 1a compared with group 1b (10.2 100 IU/ml vs 3.5 100 IU/ml; P=0.009).

Angiographic differences included worse vessel status in group 1a patients, who had a significantly higher incidence of atherosclerotic plaques (68.8% vs 32.3%; P=0.017), as well as more cranial artery disease (37.5% vs 19.4%; P=0.176) and peripheral artery disease (56.3% vs 29.0%; P=0.069).

Results from further measures of arterial stiffness and function in group 1a compared with group 1b, respectively, were:

  • central pulse wave velocity: 6.87 m/s vs. 5.87 m/s; P=0.194;
  • global radial displacement: 0.09 mm vs 0.12 mm; P =0.154;
  • global circumferential strain: 2.62% vs 3.46%; P =0.141;
  • global radial strain: 3.21% vs 3.70%; P =0.324;
  • global circumferential strain rate: 0.18 vs 0.26; P = 0.029; and
  • global radial strain rate: 0.25 vs 0.31; P =0.124.

“Interestingly, patients on the add-on combined therapy of oral corticosteroid and omalizumab (group 1a) showed even greater atherosclerotic artery alternations than the patients with the same therapy except for oral corticosteroids (group 1b). Since the lung function was more impaired in group 1a vs group 1b, it is difficult to judge if the severity of asthma, differences in the treatment or both influenced this finding,” the authors noted.

“Our data show pathological artery changes in asthma patients compared to the control collective. Specifically, asthma was not only associated with preatherosclerotic vessel alternations, such as higher arterial stiffness, but much more with increased prevalence of manifest atherosclerosis compared to nonasthma individuals,” they concluded.