Review: Allergic Asthma Is a Risk Factor for Cardiovascular Diseases

Woman sitting on bed reaching for blue inhaler, asthma concept

Asthma in adulthood is associated with an increased risk of premature death and cardiovascular disease (CVD). The etiology of both diseases is chronic systemic inflammation, and accumulating evidence is revising the earlier concept that eosinophils, mast cells, and immunoglobulin E (IgE) are asthma-specific.

Guo-Ping Shi, ScD, a biochemist in the Department of Medicine at Brigham and Women’s Hospital, and colleagues review in Nature Cardiovascular Research how allergic asthma affects the risk of CVD.

Clinical Studies

Asthma is considered an allergic airway disease with predominant type 2 immune responses. Most patients have high airway and systemic eosinophilia and respond to glucocorticosteroids. Epidemiologic studies have demonstrated various degrees of association between asthma and:

  • Coronary artery atherosclerosis, angina, myocardial infarction (MI), sudden cardiac death
  • Ischemic stroke
  • Atrial fibrillation
  • Heart failure
  • Pulmonary hypertension, right ventricular dysfunction, pulmonary embolism
  • Aortic diseases
  • Peripheral arterial diseases
  • Cardiac hypertrophy
  • Hypertension

Two asthma-relevant allergies, allergic rhinitis and atopic dermatitis (eczema), have also been shown to increase the risk of CVD, as have many anti-asthma therapies. The tables in the article review the latter associations in detail.

Common Mechanisms of Asthma and CVD

The review focuses on the mechanisms of how allergic asthma may contribute to the incidence and progression of CVD and vice versa.

Eosinophils—Dr. Shi and colleagues have reported eosinophil accumulation in the infarcted heart and abdominal aortic aneurysms (AAAs). Some other intriguing evidence they cite:

  • Cardiac involvement is the most common cause of morbidity and mortality in patients with hypereosinophilia
  • Cysteinyl leukotriene modifiers, widely used in the treatment of asthma, are also showing benefits in mouse models of atherosclerosis and MI and in reducing CVD events and blood biomarkers in patients with asthma
  • Serum eosinophil cationic protein (ECP), a sensitive marker of eosinophils, has been associated with coronary atherosclerosis

However, new research also supports the beneficial role of eosinophils in CVD. Findings by Dr. Shi’s team suggest that although increased eosinophil levels in asthmatic lungs are pathogenic, eosinophil-derived interleukin-4 and ECP in diseased hearts and aortas may have reparative roles.

Mast cells are a major contributor to airway obstruction in asthma. Dr. Shi and his colleagues have found in several studies that mast cells also promote atherosclerosis and the growth of AAAs by releasing IL-6, interferon-γ (IFN-γ), and basic fibroblast growth factor after activation. However, the cellular targets may differ depending on the tissue.

In multiple experimental models of CVD, stabilizing mast cells with the over-the-counter drug cromolyn blocked pathogenesis, which suggests the potential for expanded clinical use of mast cell stabilizers.

IgE—A key IgE action in asthma is activating mast cells. Dr. Shi and colleagues have detected elevated plasma IgE levels in patients with coronary heart disease, particularly after acute MI. Furthermore, the team demonstrated the therapeutic effects of an anti-IgE antibody against CVD in mouse models of asthma.

The authors also discuss angiogenesis, obesity, and coagulation as key risk factors for CVD in patients with asthma.

Exploring the Contradictions

While asthma is considered a type 2-dominant disease, CVD generally involves type 1 predominance. Thus, whereas type 2 inflammation is pathogenic in allergic asthma, type 2 cytokines could protect against certain cardiovascular conditions.

This may imply an ameliorating rather than aggravating relationship between asthma and CVD. As already suggested in preclinical studies, a better understanding of the relationship between the two diseases should aid the development of new preventive interventions against CVD for patients with asthma.

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