Why is late-onset asthma so dangerous?

Patients who develop asthma at age 18 or older, but not before, are at increased risk of CVD events including death, according to a Wisconsin Sleep Cohort analysis^[1].

Longitudinal follow-up for 13.9 years among 1269 participants revealed that late-onset asthmatics had a 1.6-fold higher adjusted risk of MI, angina, stroke, coronary revascularization, heart failure, or CVD death than nonasthmatics (hazard ratio [HR] 1.57, 95% CI 1.01–2.45; P=0.045).

There was no difference in CVD events between those with early-onset asthma and nonasthmatics (HR 0.94, 95% 0.46–1.92; P=0.873).

"Given the public-health burden of asthma, further investigations into the mechanisms of this association in specific asthma phenotypes are needed," lead author Dr Matthew Tattersall (University of Wisconsin-Madison) and colleagues note.

The study was published online August 24, 2016 in the Journal of the American Heart Association.

Prior studies looking into a possible association between CVD and asthma have yielded mixed results, with some reporting a consistent association, others limited associations with specific end points, and some no association at all. This may be, in part, because early- and late-onset asthma are often lumped together but are in fact substantially different disease processes that vary in their risk factors, pathophysiology, and responses to treatment, the investigators observe.

Two previous reports, however, have looked specifically at the age of asthma onset and CVD risk. TheAtherosclerosis Risk in Communities (ARIC) study^[2] found that only women with adult-onset asthma had a higher risk of coronary heart disease or stroke, while an analysis^[3] of 1999–2006 NHANES data found an increased risk of CVD with adult-onset asthma.

In both studies there was a significant effect modification by sex in the association of late-onset asthma and CVD. There was no effect modification by sex in the present study, but it was smaller and may not have been adequately powered to detect this, the investigators note.

"Despite the study size, we saw a similar magnitude of association in fully adjusted models, further strengthening the support for the association of late-onset asthma and CVD," they add.

Notably, participants with late-onset asthma compared with those with no asthma were significantly more likely to be female (67% vs 44%), have a higher body-mass index (BMI), (32.2 vs 29.4 kg/m²), and be taking antihypertensives (22% vs 13%; P values for all <0.05).

The mean age of asthma diagnosis among the 166 participants with asthma was 39.5 years in the late-onset group and 8.9 years in the early-onset group.

Because the age definition for late-onset asthma varies in the literature, sensitivity analyses were performed that varied the threshold for adult-onset asthma to age >12 years or age >21 years, and once again there was a similar magnitude of association between late-onset asthma and CVD risk, Tattersall and colleagues note.

A measure of obstructive sleep apnea (OSA) severity was also added to the final models because of the potential for OSA to confound or mediate an association between asthma and CVD, but doing so resulted in only a minimal (<4%) change in the magnitude of the asthma coefficient in both the early- and late-onset asthma models.

Exploratory analyses also found no association between CVD events and presence of gastroesophageal reflux disease, hours of physical activity per week, or year of study entry.

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