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.
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.
Currently, there are limited data looking at the associations of asthma, asthma severity, and atherosclerotic plaque burden, they note, so the researchers 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.”
Tattersall said 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.
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,” 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 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), comparing those with persistent asthma, defined as “asthma requiring use of controller medications,” intermittent asthma, defined as “asthma without controller medications,” and no asthma.
Participants underwent B-mode carotid ultrasound to detect carotid plaques, with a total plaque score (TPS) ranging from 0-12. The researchers used multivariable regression modeling to evaluate the association of asthma subtype and carotid plaque burden.
Participants with persistent asthma were more likely to be female, have higher body mass index (BMI), and higher high-density lipoprotein (HDL) 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 .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 to those without asthma, their IL-6 levels were comparable.
Table 2. Inflammatory markers by asthma status
|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 (OR, 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,” 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, Tattersall and colleagues are “cautious in the interpretation,” since the inflammatory biomarkers “were only collected at one point, and these measures can be dynamic, thus adjustment may not tell the whole story.”
Commenting for theheart.org | Medscape Cardiology, Robert Brook, MD, professor and director of cardiovascular disease prevention, Wayne State University, Detroit, Michigan, said 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 multi-ethnic population.”
These findings “support the biological plausibility of the growing epidemiological evidence that asthma independently increases the risk for cardiovascular morbidity and mortality,” added Brook, who was not involved with the study.
“The main take-home message for clinicians is that, just like in COPD (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),” Brook stated.
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. Tattersall and co-authors and Brook declare no relevant financial relationships.
J Am Heart Assoc. Published online November 23, 2022. Abstract
Batya Swift Yasgur MA, LSW, is a freelance writer with a counseling practice in Teaneck, New Jersey. She is a regular contributor to numerous medical publications, including Medscape and WebMD, and is the author of several consumer-oriented health books as well as Behind the Burqa: Our Lives in Afghanistan and How We Escaped to Freedom (the memoir of two brave Afghan sisters who told her their story).