Saturday, June 10, 2023
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Patients living with asthma experience higher levels of chronic inflammation compared with patients without asthma. This inflammation is manifest in chronic respiratory symptoms, but could it also promote higher rates of atherosclerosis and cardiovascular events? The authors of the current study previously addressed this question, using the same cohort of adults from the Multi-Ethnic Study of Atherosclerosis (MESA). The results of their research were published in the June 2015 issue of Arteriosclerosis, Thrombosis, and Vascular Biology.[1]
A total of 6792 adults were followed for a composite of myocardial infarction, stroke, angina, and cardiovascular death for a mean of 9.1 years. The main study variables were intermittent and persistent asthma. Although intermittent asthma was not significantly associated with a higher risk for cardiovascular events, the hazard ratio (HR) for such events associated with persistent asthma was 1.6 (95% CI, 1.01-2.5). This HR was adjusted to account for demographic, disease, and medication variables.
The burden of atherosclerosis on carotid ultrasound is predictive of future cardiovascular events. The current study reexamines the MESA cohort to establish a potential link between asthma and carotid atherosclerosis.
Persistent asthma is associated with increased carotid plaque burden and higher levels of inflammation, putting these patients at risk for atherosclerotic cardiovascular disease (ASCVD) events, new research suggests.
Using data from the MESA study, investigators analyzed more than 5000 individuals, comparing carotid plaque and inflammatory markers in those with and without asthma.
They found that carotid plaque was present in half of participants without asthma and half of those with intermittent asthma, but in close to 70% of participants with persistent asthma.
Moreover, those with persistent asthma had higher interleukin-6 (IL-6) levels compared with those without asthma or those with intermittent asthma.
“The take-home message is that the current study, paired with prior studies, highlights that individuals with more significant forms of asthma may be at higher cardiovascular risk and make it imperative to address modifiable risk factors among patients with asthma,” lead author Matthew Tattersall, DO, MS, assistant professor of cardiovascular medicine, University of Wisconsin School of Medicine and Public Health, Madison, told theheart.org | Medscape Cardiology.
The study was published online November 23 in the Journal of the American Heart Association.[2]
Limited Data
Asthma and ASCVD are “highly prevalent inflammatory diseases,” the authors write. Carotid artery plaque detected by B-mode ultrasound “represents advanced, typically subclinical atherosclerosis that is a strong independent predictor of incident ASCVD events,” with inflammation playing a “key role” in precipitating these events, they note.
Serum inflammatory markers such as C-reactive protein (CRP) and IL-6 are associated with increased ASCVD events, and in asthma, CRP and other inflammatory biomarkers are elevated and tend to further increase during exacerbations.
At this time there are limited data looking at the associations of asthma, asthma severity, and atherosclerotic plaque burden, the researchers note, so they turned to the MESA study, a multiethnic population of individuals free of prevalent ASCVD at baseline. They hypothesized that persistent asthma would be associated with higher carotid plaque presence and burden.
They also wanted to explore “whether these associations would be attenuated after adjustment for baseline inflammatory biomarkers.”
Dr Tattersall said that the current study “links our previous work studying the manifestations of asthma,” in which he and his colleagues demonstrated increased cardiovascular events among MESA participants with persistent asthma, as well as late-onset asthma participants in the Wisconsin Sleep Cohort. His group also showed that early arterial injury occurs in adolescents with asthma.[3-5]
However, there are also few data looking at the association with carotid plaque, “a late manifestation of arterial injury and a strong predictor of future cardiovascular events and asthma,” Dr Tattersall said.
He and his group therefore “wanted to explore the entire spectrum of arterial injury, from the initial increase in the carotid media thickness to plaque formation to cardiovascular events.”
To do so, they studied participants in MESA, a study of close to 7000 adults that began in 2000 and continues to follow participants today. At the time of enrollment, all participants were free from CVD.
The current analysis looked at 5029 MESA participants (mean age, 61.6 years; 53% female; 26% Black, 23% Hispanic, 12% Chinese). It compared those with persistent asthma, defined as “asthma requiring use of controller medications”; those with intermittent asthma, defined as “asthma without controller medications”; and those with no asthma.
Participants underwent B-mode carotid ultrasound to detect carotid plaques, with a total plaque score (TPS) ranging from 0 to 12. The researchers used multivariable regression modeling to evaluate the association of asthma subtype and carotid plaque burden.
Interpret Cautiously
Participants with persistent asthma were more likely to be female, have a higher body mass index, and have higher high-density lipoprotein cholesterol levels compared with those without asthma.
Participants with persistent asthma had the highest burden of carotid plaque (P≤.003 for comparison of proportions and P=.002 for comparison of means).
Table 1. Carotid plaque by asthma status
|
Type of Participant |
% With Carotid Plaque |
Total plaque score (SD) |
|---|---|---|
|
No asthma |
50.5 |
1.29 (1.80) |
|
Intermittent asthma |
49.5 |
1.25 (1.76) |
|
Persistent asthma |
67 |
2.08 (2.35) |
Moreover, participants with persistent asthma also had the highest systemic inflammatory marker levels, both CRP and IL-6, compared with those without asthma. While participants with intermittent asthma also had higher average CRP, compared with those without asthma, their IL-6 levels were comparable.
Table 2. Inflammatory markers by asthma status
|
Marker |
No Asthma Mean (SD) |
Intermittent Asthma Mean (SD) |
Persistent Asthma Mean (SD) |
|---|---|---|---|
|
CRP (mg/L) |
3.61 (5.50) |
4.54 (6.80) |
6.49 (11.20) |
|
IL-6 (pg/mL) |
1.52 (1.21) |
1.60 (1.21) |
1.89 (1.61) |
In unadjusted models, persistent asthma was associated with higher odds of carotid plaque presence (odds ratio, 1.97; 95% CI, 1.32-2.95), an association that persisted even in models that adjusted for biologic confounders (both P<.01). There also was an association between persistent asthma and higher carotid TPS (P<.001).
In further adjusted models, IL-6 was independently associated with presence of carotid plaque (P=.0001 per 1-SD increment of 1.53), as well as TPS (P<.001). CRP was “slightly associated” with carotid TPS (P=.04), but not carotid plaque presence (P=.07).
There was no attenuation after the researchers evaluated the associations of asthma subtype and carotid plaque presence or TPS and fully adjusted for baseline IL-6 or CRP (P=.02 and P=.01, respectively).
“Since this study is observational we cannot confirm causation, but the study adds to the growing literature exploring the systemic effects of asthma,” Dr Tattersall commented.
“Our initial hypothesis was that it was driven by inflammation, as both asthma and CVD are inflammatory conditions,” he continued. “We did adjust for inflammatory biomarkers in this analysis, but there was no change in the association.”
Nevertheless, Dr Tattersall and colleagues are “cautious in the interpretation,” as the inflammatory biomarkers “were only collected at one point, and these measures can be dynamic--thus, adjustment may not tell the whole story.”
Heightened Awareness
Commenting for theheart.org | Medscape Cardiology, Robert Brook, MD, professor and director of cardiovascular disease prevention, Wayne State University, Detroit, Michigan, said that the “main contribution of this study is the novel demonstration of a significant association between persistent (but not intermittent) asthma with carotid atherosclerosis in the MESA cohort, a large multiethnic population.”
These findings “support the biological plausibility of the growing epidemiological evidence that asthma independently increases the risk for cardiovascular morbidity and mortality,” added Dr Brook, who was not involved with the study.
“The main take-home message for clinicians is that, just like in [chronic obstructive pulmonary disease] (which is well-established), asthma is often a systemic condition in that the inflammation and disease process can impact the whole body,” he said.
“Healthcare providers should have a heightened awareness of the potentially increased cardiovascular risk of their patients with asthma and pay special attention to controlling their heart disease risk factors (eg, hyperlipidemia, hypertension),” Dr Brook stated.
Dr Tattersall was supported by an American Heart Association Career Development Award. The Multi-Ethnic Study of Atherosclerosis was supported by the National Heart, Lung, and Blood Institute and the National Center for Research Resources. Dr Tattersall and coauthors and Dr Brook have disclosed no relevant financial relationships.
J Am Heart Assoc. Published online November 23, 2022.
