Greater Carotid Plaque Burden in Asthmatic Patients: MESA

Individuals with persistent asthma have a higher burden of carotid artery plaque and higher levels of inflammatory biomarkers when compared with those without asthma, an analysis of the Multi-Ethnic Study of Atherosclerosis (MESA) shows.

The new study, which was published this week in the Journal of the American Heart Association, adds to a growing body of evidence showing that asthma may be linked to the development of atherosclerotic cardiovascular disease (ASCVD).

Matthew Tattersall, DO (University of Wisconsin, Madison), who led the analysis, said asthma can serve as a potential marker of future risk, one that should then “drive risk factor identification and modification if possible.”

“A lot of times these risk factors—cholesterol, blood pressure, body mass index, and all these other things that are modifiable—may not be as aggressively pursued,” he told TCTMD. “If asthmatics are at increased risk, which has been shown not just in this study but in many other studies, then earlier preventive counseling and attention to these modifiable risk factors would be helpful.”

The 2019 American College of Cardiology/American Heart Association primary prevention guidelines recommend physicians consider inflammatory diseases a risk-enhancing factor in the assessment of ASCVD risk. Typically, doctors are on the lookout for rheumatoid arthritis, psoriasis, HIV, lupus, and other diseases, but asthma is also an inflammatory condition, said Tattersall, one that may not be confined solely to the airway. In fact, levels of biomarkers of systemic inflammation, interleukin-6 (IL-6) and C-reactive protein (CRP), are higher in asthmatic people than in those without asthma and tend to increase during exacerbations.     

In 2014, the researchers looked into the risk of ASCVD events in patients with persistent asthma in MESA, showing that these individuals had a 60% higher risk compared with those without asthma. In another study, Tattersall and colleagues, using data from the COAST cohort, showed that asthma was associated with subclinical arterial injury in children as measured by changes in carotid intima-media thickness (IMT). The present study, which returned to the MESA cohort, is intended to fill the research gap.    

“We had adolescents with thicker IMTs, a sign of early arterial injury, and we had the other end of the spectrum, which was cardiovascular events, but we didn’t have anything to link them together,” said Tattersall.

'Maybe It Isn’t All Just Inflammation?'

The latest analysis focused on carotid plaque, which is a strong, independent predictor of cardiovascular events, in 5,029 men and women (mean age 61.6 years; 53% women). Carotid plaque, the researchers explain, is a “specific manifestation” of the atherosclerotic process and includes intimal thickening, foam cell infiltration, inflammatory cell infiltration, and fibrous cap formation.

Of the participants, 109 had persistent asthma (needing medications to modify disease activity), 388 had intermittent asthma (which didn’t require controller medications), and 4,532 did not have asthma. Carotid plaque, which was defined as discrete, focal wall thickening > 1.5 cm or focal thickening 50% or greater than surrounding IMT, was measured with B-mode ultrasound. A total plaque score (TPS) was developed to indicate the number of segments with carotid plaque present in the internal, bulb, and common segments of both carotid arteries.

Overall, carotid plaque was evident in 50.5% of people without asthma (TPS 1.29), 49.5% of those with intermittent asthma (TPS 1.25), and 67% of those with persistent asthma (TPS 2.08). People with persistent asthma also had significantly higher levels of IL-6 and CRP when compared with those without asthma. 

In an unadjusted model, persistent asthma was associated with greater odds of carotid plaque presence (OR 1.97; 95% CI 1.32-2.95). This association remained after adjusting for baseline variables, such as age, sex, and medication use, as well as IL-6 and CRP. Persistent asthma was also associated with a higher carotid TPS, as well.

The findings suggest there may be something other than inflammation that’s causing the higher plaque burden, said Tattersall.

“We adjusted our models for the inflammatory markers, and it didn’t change that association between persistent asthma and carotid plaque presence and burden,” said Tattersall. “However, it’s tough to say definitively because these are inflammatory markers measured at a single time point. They may have varied over time, but it does speak to the idea that the association may be multifactorial. Maybe it isn’t just all inflammation—maybe there’s other features that could be driving the risk?”  

Right now, other mechanisms possibly contributing to the development of atherosclerotic plaque in asthma are unknown. However, Tattersall pointed out there is research showing that asthmatic patients have a high prevalence of hypertension. While researchers have primarily focused on inflammation, “there’s clearly other features that could be at play here,” he said.