The Effect of Long Term Inhaled Corticosteroids on the Risk of Cardiovascular Morbidities
Condition: Asthma
MeSH terms: Asthma
Study type: Observational

Summary: 
      Cardiovascular disease is a major cause of morbidity and mortality worldwide. It is the
      second leading cause of death in Hong Kong. The disease burden is huge and effective control
      measures should target at prevention level. As the disease pathophysiology is linked to
      chronic low grade systemic inflammation, any therapeutics having the potential to reduce
      systemic inflammation should be vigorously explored.

      The use of long-term inhaled corticosteroid (ICS) treatment in recent 2 decades has become
      the cornerstone in the treatment of most patients with persistent asthma with reduction in
      its mortality and hospital utilization. The long term safety of ICS in adults is generally
      very high.

      Recent epidemiological studies utilizing large numbers of patients with asthma have shown
      that long term use of ICS is independently associated with a protective effect towards the
      development of myocardial infarction and cardiovascular mortality, with protective risk at
      0.35 (95%CI 0.13-0.93). This effect is possibly mediated through the reduction of low grade
      systemic inflammation as reflected by plasma hs-CRP, from systemic absorption of the ICS.

      The purpose of this study is to explore the potential protective effect of ICS on
      cardiovascular morbidities and its underlying link with systemic inflammation in Chinese
      adults with asthma compared with matched controls from the general population.
    

Detailed description: 
      Globally, cardiovascular disease is a major cause of mortality and morbidity. In the past 2
      decades in Hong Kong, it has been the second leading cause of death, with death rate reaching
      50/100,000 population in 2006, and the third leading cause of hospitalizations in Hospital
      Authority Hospitals between 2001-2005. The disease burden is huge and effective control
      measures should target at prevention level.

      There has been substantial evidence from landmark epidemiological studies in the past 10
      years that chronic low grade systemic inflammation, predominantly based on plasma hs-CRP, is
      an independent predictor for the development of hypertension, myocardial infarction, stroke,
      cardiovascular death and peripheral vascular disease. A dose-dependent risk association
      between hs-CRP and these cardiovascular morbidities has also been consistently demonstrated.

      Asthma is a chronic inflammatory airway disorder associated with airflow obstruction and
      bronchial hyper-responsiveness, which affects about 10% of population in Hong Kong. It is a
      major respiratory disease in Hong Kong that carries significant morbidity and high
      hospitalization burden in all ages. The use of long-term inhaled corticosteroid (ICS)
      treatment in recent decades has become the cornerstone in the treatment of most patients with
      persistent asthma with reduction in its mortality and hospital utilization. The ultimate goal
      of treatment is to achieve optimal control of airway inflammation and to reduce mortality and
      morbidity.

      Although the pathogenesis of asthma is incompletely understood, studies have shown that it is
      associated airway inflammation and a state of increased free radical formation, because cells
      derived from airways and peripheral blood of patients with asthma generate increased amount
      of reactive oxygen species, the level of which is related to severity of asthma. Recent
      preliminary studies have indicated that, apart from the presence of chronic airway
      inflammation, asthma may also be associated with chronic low grade systemic inflammation and
      increased oxidative stress. Intuitively, this asthma-related systemic inflammation may
      increase the risk for development of cardiovascular and cerebrovascular diseases.

      Despite the propensity of asthma towards cardiovascular morbidity, recently, several
      epidemiological studies utilizing large numbers of patients with asthma have shown that long
      term use of ICS is independently associated with a protective effect towards the development
      of myocardial infarction and cardiovascular mortality, with protective risk at 0.35 (95%CI
      0.13-0.93). This effect is possibly mediated through the reduction of low grade systemic
      inflammation as reflected by plasma hs-CRP from systemic absorption of the ICS.

      This potential effect of ICS on reduction of chronic low grade systemic inflammation has an
      invaluable implication for its future application as a preventive medicine against the
      development of cardiovascular morbidities and mortality, especially in high risk patients.

      ICS have been launched for more than 20 years, and is currently the first-line treatment for
      asthma. Their systemic side effects are much less than that of oral corticosteroids. Long
      term safety of ICS in adults is generally very high, but mild increases in risk of
      osteoporosis, cataracts and glaucoma have been reported in patients with high dose ICS use.

      The purpose of this study is to explore the potential protective effect of ICS on
      cardiovascular morbidities and its underlying link with systemic inflammation in Chinese
      adults with asthma compared with matched controls from the general population.
    

Observational model: Case-Control
Time perspective: Cross-Sectional
Sampling method: Non-Probability Sample
Study population: 
        Asthma patients will be recruited from asthma clinics of 4 centres in Hong Kong, including
        Queen Mary Hospital, Queen Elizabeth Hospital, Kowloon Hospital and Kwong Wah Hospital.

        Matched controls at 1:1 ratio from the general population database of Cardiovascular Risk
        Factor Prevalence Study II (CRISPSII) will be selected. Matching critera: age +/-5 years;
        same gender and BMI+/-10%.
      
Biospecimen description: 
      Whole blood, plasma, serum and DNA
    
Keywords: Asthma; Inhaled corticosteroids; Cardiovascular morbidities; Systemic inflammation