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The association of allergic asthma and carotid intima-media thickness in adolescence: data of the prospective early vascular ageing (EVA)-Tyrol cohort study

BMC Cardiovascular Disorders volume 22, Article number: 11 (2022) Cite this article

Abstract

Background

In recent years, there has been increasing evidence that asthma is associated with atherosclerosis and cardiovascular disease. However, data in children and adolescents are scarce and conflicting. We aimed to assess the impact of asthma with and without an allergic component on the carotid intima-media thickness in a large pediatric population.

Methods

The community-based early vascular ageing-Tyrol cohort study was performed between May 2015 and July 2018 in North, East (Austria) and South Tyrol (Italy) and recruited youngster aged 14 years and above. Medical examinations included anthropometric measurements, fasting blood analysis, measurement of the carotid intima-media thickness by high-resolution ultrasound, and a physician guided interview.

Results

The mean age of the 1506 participants was 17.8 years (standard deviation 0.90). 851 (56.5%) participants were female. 22 subjects had a physician diagnosis of non-allergic asthma, 268 had inhalative allergies confirmed by a positive radio-allergo-sorbent-test and/or prick test, and 58 had allergic asthma. Compared to healthy controls, participants with non-allergic asthma (411.7 vs. 411.7 µm; p = 0.932) or inhalative allergy (420.0 vs. 411.7 µm; p = 0.118) did not have significantly higher carotid intima-media thickness (cIMT). However, participants with allergic asthma had significantly higher cIMT (430.8 vs. 411.7; p = 0.004) compared to those without and this association remained significant after multivariable adjustment for established cardiovascular risk factors.

Conclusion

Allergic asthma in the youth is associated with an increased carotid intima-media thickness. Physicians should therefore be aware of allergic asthma as a potential cardiovascular risk factor in children and adolescents.

Trial Registration Number The EVA-Tyrol Study has been retrospectively registered at clinicaltrials.gov under NCT03929692 since April 29, 2019.

Peer Review reports

Background

Asthma and cardiovascular disease (CVD) are highly prevalent conditions worldwide [1, 2]. In recent years, evidence has accumulated that asthma is associated with CVD [3,4,5,6,7,8,9,10]. However, available epidemiological and clinical data are not univocal in supporting this hypothesis [11, 12], and pathophysiological links between these two diseases remain poorly defined. Given the important role of inflammatory processes and the immune system in human atherogenesis [13, 14], it is plausible that subjects suffering from chronic inflammation—a hallmark characteristic of asthma—are more prone to CVD [15]. In addition, asthma has been associated with several cardiovascular risk factors (CVRF) such as elevated body-mass index (BMI) [16, 17] and biomarkers that were also associated with CVD like high levels of tumor necrosis factor-α [18, 19], Interleukin 6 [20], and fibrinogen [5, 21].

Considering the recent estimated prevalence of 8.3% for asthma in children and adolescents in the United States [22], asthma is a major health burden. Although atherosclerosis may originate in childhood [23], data on atherosclerotic vascular changes in children and adolescents with asthma are scarce and conflicting [24,25,26,27,28].

With data of the Atherosclerosis Risk Factors in Male Youngsters (ARMY) study (participants aged 17 and 18 years) and the Bruneck study (men and women aged 40–70 years), we have previously demonstrated a significant association between atherosclerosis and the common allergic diseases asthma and allergic rhinitis [24]. However, differentiation between asthma with and without an allergic component was not possible due to the low number of asthmatics in these populations.

The purpose of the present study was to investigate the impact of asthma with and without an allergic component on carotid intima-media thickness (cIMT), a marker of early subclinical atherosclerosis [29] and predictor for future vascular events [30], in the early vascular ageing (EVA)-Tyrol cohort of healthy young adolescents.

Methods

Data that support the findings of this study are available from the corresponding author upon request.

Study design and participants

The EVA-Tyrol cohort study was a community-based non-randomized, controlled trial performed between May 2015 and July 2018 in North, East (Austria) and South Tyrol (Italy) aiming to assess the efficacy of a health promotion intervention on CVRF, behaviors as well as on vascular wall changes in healthy adolescents. The study protocol including detailed methods has been published [31]. In brief, students attending 9th or 10th grade (target age 14–16 years) and apprentices of the same age were invited to participate. Baseline examinations were performed between May 2015 and December 2016. After approximately two years (target age 16–18 years), follow-up was performed between August 2017 and July 2018. Simultaneously, another group of adolescents took part as participants in the control group. To achieve a representative sample of adolescents homogenous in age, participants of the intervention group as well as the control group were included in the present exploratory analysis.

The study was approved by the local ethics committee of the Medical University of Innsbruck (approval number AN 2015-0005 345/4.13) and was executed in agreement with the Declaration of Helsinki. The trial has been registered at clinicaltrials.gov (NCT03929692). All participants provided a written informed consent or if the participants had not attained age of majority, the consent was additionally provided by a parent or legal guardian.

Diagnosis of asthma and allergy

The medical history of allergies and asthma was assessed in a physician guided, face-to-face interview. Consistent with other studies [4, 12] and the previous finding that, in the absence of pulmonary function testing, self-reported questions about physician diagnosed asthma have the highest diagnostic value for asthma diagnosis [32], we defined asthma as prevalent if the participants either answered positive to the question: "Has a doctor ever told you that you have asthma?” and/or the participant reported an ongoing anti-asthmatic drug therapy, both on a regular basis or on demand. The presence of an allergy was defined if an inhaled allergen was self-reported to cause repeated clinical symptoms and the diagnosis was confirmed by a positive radio-allergo-sorbent-test (RAST) or prick test. Allergic asthma was recorded if both asthma and allergy were present.

Anthropometry

For measurement of height with a Harpenden stadiometer (Holtain, Crymych, United Kingdom) and weight with calibrated medical precision scales, participants were clothed with light indoor clothes without shoes. The calculation of BMI was done by dividing the body weight in kilograms by the square of height in meters. According to the recommendations of the WHO [33] waist circumference was measured with a stretch-resistant tape to the nearest 0.1 cm. After 5 min of rest systolic and diastolic blood pressure were calculated as the mean of 3 independent measurements on the left and right upper arm in a sitting position (automated oscillometric device OMRON M4-I, Omron Healthcare Co., Lake Forest, Illinois, USA).

Assessment of lifestyle risk factors

We assessed behavioral risk factors by standardized medical interviews with questionnaires adapted from the Atherosclerosis Risk Factors in Female Youngsters (ARFY), Atherosclerosis Risk Factors in Male Youngsters (AMRY) and Bruneck studies [34,35,36]. Smoking and physical activity were assessed in physician-guided interviews. Cigarette pack years were calculated by multiplying the number of packs of cigarettes smoked per day by the number of years the person has smoked. The average number of minutes per day of moderate- or vigorous exercise (i.e., leading to an increased heart rate and/or sweating) served as metric for physical activity.

Laboratory methods

Overnight fasting blood samples were cooled and delivered to the Central Institute for Medical and Chemical Laboratory Diagnosis of the Medical University of Innsbruck, Austria immediately. A standard enzymatic colorimetric assay (Cobas 8000, Roche Diagnostics, Rotkreuz, Switzerland) was used to measure total cholesterol, high-density lipoprotein-cholesterol (HDL-C), low-density lipoprotein-cholesterol (LDL-C), and triglyceride. According to the recommendations of the international federation of Clinical Chemistry and Laboratory Medicine we measured Alanine aminotransferase (ALT) (Cobas 8000, Roche Diagnostics, Rotkreuz, Switzerland). Measurement of C-reactive protein (CRP) was conducted with a particle-enhanced immunological clouding assay (Cobas 8000, Roche Diagnostics, Rotkreuz, Switzerland).

High-resolution ultrasound

Intima-media thickness was measured on the far-wall of the common carotid arteries (cIMT) visualized by high-resolution ultrasound (6.0–13.0 MHz linear probe, GE 12L-RS, on a Vivid q ultrasound device,both General Electric Healthcare, Chicago, Illinois, USA). Three representative measurements in longitudinal images on the distal 4 cm on both sides were done on digitally stored images by a single rater, experienced in ultrasound techniques without information on clinical characteristics of the participant. The mean from all six measurements was used for the present analysis (cIMTMEAN).

Statistical analysis

For statistical analysis we used SPSS version 27.0 (IBM Corporation, Armonk, New York, USA) and R version 4.0.3 (R Foundation for Statistical Computing, Vienna, Austria). Our primary outcome parameter was cIMTMEAN. Participants without valid cIMT measurements were excluded from our analysis. Characteristics of the study cohort are presented as number (percentage), mean ± standard deviation or median (Q25–Q75). Power analysis indicates that, given standard deviations of cIMTMEAN within and sample sizes of subgroups (allergic asthma, controls), we were powered to detect a difference in cIMTmean between groups of at least 19.7 µm, at an alpha level of 0.05, with power of 0.8. Univariate analysis was performed using the Welch-t-test and the Chi-squared test. For multivariable linear regression analysis variables known to impact cIMT (dependent variable) in our study cohort (age, sex, size, systolic blood pressure, physical activity, cigarette pack years, LDL-C, ALT) [37] as well as other common CVRF (waist circumference, CRP)were included as independent variables/confounders into the model. In addition, subgroups (non-allergic asthma, inhalative allergy, allergic asthma) and controls (free of any asthma and inhalative allery) were separately included as dichotomous independent variable. Variables not meeting the assumptions of a normal distribution were loge-transformed. All models were inspected for collinearity by variance inflation factors (VIF). Subsequently, the conditions of linearity of the relationship between dependent and independent variables, as well as homoscedasticity, independence and normality of the errors were tested and satisfied. Hence, a multiple linear regression model was finally calculated to assess the impact of the independent variables/confounders on the cIMTMEAN as the primary outcome parameter. p Values < 0.05 were considered as statistically significant.

Results

A flow chart of the study population is shown in Fig. 1. Of the 1529 subjects included in the present analysis, 1000 (65.4%) were in the intervention group and 529 were in the control group. Ultrasound measurement of cIMT was available in 1521 (99.5%) and information on asthma and allergy in 1514 (99.0%) participants leaving 1506 (98.5%) with a complete dataset for the present analysis. The mean age of the participants at the time of examination was 17.8 years (Standard deviation 0.9, range 16–23 years). 851 (56.5%) participants were female. Median cIMTMEAN was 413.3 µm (381.7–446.7) in the whole study population (males: 426.7 µm (395.0–461.7), females: 405.0 µm (375.0–436.7); univariable p < 0.001). Further characteristics of the study population are shown in Table 1.

Fig. 1
figure 1

From: The association of allergic asthma and carotid intima-media thickness in adolescence–Data of the prospective early vascular ageing (EVA)-Tyrol cohort study

Full size image
Table 1 Characteristics of the study population
Full size table

22 participants (representing 1.5% of all participants with a complete dataset) reported a physician diagnosis of asthma without an allergic component (non-allergic asthma). Among those, 16 (72.7%) subjects received anti-asthmatic medication. In both models, univariable and multivariable, participants with non-allergic asthma did not have significantly higher cIMTMEAN compared to those without (411.7 vs. 411.7 µm; p = 0.932, adjusted R2 = 0.11) (Table 2). In participants with non-allergic asthma median cIMTMEAN was 411.7 µm (388.8–439.6) [males: 438.3 µm (411.7–456.7), females: 400.0 µm (365.0–433.3); univariable p = 0.011].

Table 2 Association between asthma, inhalative allergy, allergic asthma and cIMTMEAN
Full size table

268 participants (representing 19.0% of all participants with a complete dataset) had a physician diagnosis of inhalative allergy confirmed by a positive RAST and/or skin prick-test. Anti-allergic medication was taken permanently by 14 (5.2%) and on demand by 131 (48.9%) subjects. Again, in both models, cIMTMEAN was not significantly higher in those subjects with inhalative allergic disorders compared to those without (420.0 vs. 411.7 µm; p = 0.118, adjusted R2 = 0.12) (Table 2). Median cIMTMEAN in this subgroup was 420.0 µm (385.0–449.6) [males: 428.3 µm (401.7–466.7), females: 406.7 µm (375.8–430.0); univariable p < 0.001].

58 participants (representing 3.9% of all participants with a complete dataset) had a physician diagnosis of allergic asthma (i.e., simultaneous diagnosis of asthma and inhalative allergy). Among those, 56 (96.6%) subjects received anti-allergic and/or anti-asthmatic medication. Median cIMTMEAN was 430.8 µm (399.6–463.8) [males: 445.8 µm (401.3–477.9), females: 416.7 µm (397.1–444.2); univariable p = 0.091] As primary outcome parameter, cIMTMEAN was significantly higher in subjects with allergic asthma compared to those without (430.8 vs. 411.7 µm; univariable p = 0.004) and this association remained significant (multivariable p = 0.026, adjusted R2 = 0.12) after adjustment for established CVRF including age, sex, size, waist circumference, systolic blood pressure, physical activity, cigarette pack years, LDL-C, ALT, and CRP (Table 2). If only variables are included in the multivariable model, that significantly differ in the univariable analysis between participants with allergic asthma and those without asthma or inhalative allergies (sex, systolic blood pressure, physical activity, LDL-C, current smoker) or if waist circumference is replaced by weight, the significance level does not change significantly (p = 0.039 adjusted R2 = 0.07 or p = 0.027, adjusted R2 = 0.09).

Discussion

In our large EVA-Tyrol cohort of healthy young adolescents, we could demonstrate an association between cIMT and allergic asthma, but not inhalative allergy or non-allergic asthma. A possible link between asthma and atherosclerosis has been a matter of debate for three decades. Several previous studies have demonstrated an association between asthma and an increased risk of CVD in adults [3,4,5,6,7,8,9,10]. However, the strength of this association varies widely and some of the results are limited to specific subgroups such as smokers [38] or women [39,40,41,42]. In addition, there are also studies that show no association between the two conditions [11, 12].

So far, only few studies have investigated the association between asthma and cIMT in pediatric populations. Cakmak et al. demonstrated that children with mild asthma had thicker cIMT than those without, but these results were not adjusted for potential confounders [25]. The Swiss Study on Air Pollution and Lung and Heart Disease In Adults (SAPALDIA)-Youth study came to a similar conclusion, although an increased cIMT was demonstrated for adolescent boys but not girls with asthma [27]. We have previously shown that in our cohort male sex is independently associated with an increased cIMT [37]. Even though there is a male preponderance in participants with allergic asthma, our finding remains robust when adjusting for potential confounders including sex.

Data on the effect of an allergic component on cIMT in asthmatic disease are even scarcer. To the best of our knowledge, only one small case–control study has previously investigated the association of allergic asthma and asthma in general with cIMT in children. In a modest sample size of 89 adolescents, increased cIMT was demonstrated in asthmatics with and without an allergic component compared to a healthy control group. In addition, asthmatics with an allergic component tended to have higher cIMT compared to those without, which fits well to our findings [43].

Based on these results and a previous study, which demonstrated an association of persistent asthma, but not intermittent asthma, with CVD events [4], it is tempting to speculate that due to high cumulative exposure to inhalative allergens and the resulting inflammatory processes, atherosclerotic vascular changes are detectable earlier in asthmatics with a strong allergic component than in those without.

A link between allergic asthma and atherosclerosis is not surprising. Atherosclerosis itself has been long recognized as an inflammatory process [13, 14] and chronic inflammatory diseases [15, 44] as well as autoimmune processes [14, 45] are linked to atherosclerosis and CVD. Regarding the pathophysiological background, three possible pathways could be discussed.

At the level of inflammatory mediators, the arachidonic acid metabolism is important because it can be associated with asthma as well as CVD. Polymorphisms in the 5-lipoxygenase-activating protein have been demonstrated to be associated with coronary heart disease [46] and 5-lipoxygenase inhibition showed protective effects in animal models of myocardial infarction [47] and atherosclerosis [48]. Mutations with decreased function in the human Phospholipases A2 gene—another key enzyme in the arachidonic acid metabolism—have been linked to atherosclerosis, coronary heart disease, stroke as well as asthma [49].

Another mechanism triggered mainly by inflammatory mediators is smooth-muscle remodeling. Hyperplasia and abnormal contraction of smooth muscle cells leading to airway obstruction in asthma are also recognized as features of vascular remodeling and endothelial abnormalities [50]. This pathophysiological mechanism may also explain the elevated blood pressure levels in allergic asthmatics compared to healthy controls in our study population. Previous studies have already reported an increased incidence of hypertension in adults with asthma or inhalative allergies [51, 52]. However, this association was not observed in all studies, particularly those with pediatric study cohorts [43, 53]. In our analysis, the association between allergic asthma and cIMTMEAN was independent of blood pressure levels, making it unlikely that blood pressure is the sole link between asthma and cIMTMEAN.

On a cellular level, the presence of the same sets of inflammatory cells in both the asthmatic bronchoalveolar and atherosclerotic vessel wall suggests that inflammatory cells share similar activities in both diseases [54]. Possible key roles play Immunoglobulin E (IgE)-triggered mast cells [55] and eosinophil leucocytes [56]. Through the release of chemokines and cytokines, both groups of cells elicit vascular permeability and increase the entry of LDL and inflammatory cells into the arterial wall fostering foam cell accumulation and atherosclerosis [55, 56].

Considering the described inflammatory links between asthma and atherosclerosis, the possibility arises that anti-inflammatory drugs could control both asthma and its disadvantageous effect on the vasculature. Previous small scale pharmacotherapeutic studies have already shown the potential benefit of various drug-based therapies, including inhaled corticosteroids [57, 58], lipid lowering statins [59], and 5-lipoxygenase inhibitor [60], yet sufficient powered randomized-controlled trials are lacking.

The strengths of our study include the large, homogeneous study cohort and a physician guided diagnosis of asthma from a face-to-face interview, as well as the requirement of diagnostic confirmation of the inhalative allergic component by a positive RAST and/or a prick-test. Still the absolute number of participants with allergic asthma was low, not allowing to further explore subgroups with different anti-allergic or anti-asthmatic treatment. Further limitations are the lack of determination of the duration and severity of asthma as well as the lack of determination of total and specific IgE-levels as markers for the degree of atopic sensitization.

Conclusions

In summary, our analysis revealed significant associations between allergic asthma and increased cIMT in adolescents. Physicians should therefore be aware of allergic asthma as a potential CVRF in children and adolescents. The role of early and consequent anti-inflammatory treatment in prevention of CVD is unclear and merits further studies.

Availability of data and material

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request after appropriate ethics vote and signing of a data transfer agreement.

Abbreviations

ALT:

Alanine aminotransferase

ARFY:

Atherosclerosis risk factors in female youngsters

ARMY:

Atherosclerosis risk factors in male youngsters

BMI:

Body-mass index

cIMT:

Carotid intima-media thickness

cIMTMEAN :

Mean carotid intima-media thickness

CRP:

C-reactive protein

CVD:

Cardiovascular disease

CVRF:

Cardiovascular risk factor

EVA:

Early Vascular Ageing

HDL-C:

High-density lipoprotein cholesterol

IgE:

Immunoglobulin E

LDL-C:

Low-density lipoprotein cholesterol

RAST:

Radio-allergo-sorbent-test

References

  1. Masoli M, Fabian D, Holt S, Beasley R. The global burden of asthma: executive summary of the GINA Dissemination Committee report. Allergy. 2004;59(5):469–78. https://doi.org/10.1111/j.1398-9995.2004.00526.x.

    Article  PubMed  Google Scholar 

  2. Benjamin EJ, Blaha MJ, Chiuve SE, Cushman M, Das SR, Deo R, de Ferranti SD, Floyd J, Fornage M, Gillespie C, et al. Heart disease and stroke statistics-2017 update: a report from the American Heart Association. Circulation. 2017;135(10):e146–603. https://doi.org/10.1161/CIR.0000000000000485.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Iribarren C, Tolstykh IV, Miller MK, Sobel E, Eisner MD. Adult asthma and risk of coronary heart disease, cerebrovascular disease, and heart failure: a prospective study of 2 matched cohorts. Am J Epidemiol. 2012;176(11):1014–24. https://doi.org/10.1093/aje/kws181.

    Article  PubMed  Google Scholar 

  4. Tattersall MC, Guo M, Korcarz CE, Gepner AD, Kaufman JD, Liu KJ, Barr RG, Donohue KM, McClelland RL, Delaney JA, et al. Asthma predicts cardiovascular disease events: the multi-ethnic study of atherosclerosis. Arterioscler Thromb Vasc Biol. 2015;35(6):1520–5. https://doi.org/10.1161/ATVBAHA.115.305452.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Tuleta I, Skowasch D, Aurich F, Eckstein N, Schueler R, Pizarro C, Schahab N, Nickenig G, Schaefer C, Pingel S. Asthma is associated with atherosclerotic artery changes. PLoS ONE. 2017;12(10):e0186820. https://doi.org/10.1371/journal.pone.0186820.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Strand LB, Tsai MK, Wen CP, Chang SS, Brumpton BM. Is having asthma associated with an increased risk of dying from cardiovascular disease? A prospective cohort study of 446 346 Taiwanese adults. BMJ Open. 2018;8(5):e019992. https://doi.org/10.1136/bmjopen-2017-019992.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Pollevick ME, Xu KY, Mhango G, Federmann EG, Vedanthan R, Busse P, Holguin F, Federman AD, Wisnivesky JP. The relationship between asthma and cardiovascular disease: an examination of the Framingham offspring study. Chest. 2020. https://doi.org/10.1016/j.chest.2020.11.053.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Chung WS, Shen TC, Lin CL, Chu YH, Hsu WH, Kao CH. Adult asthmatics increase the risk of acute coronary syndrome: a nationwide population-based cohort study. Eur J Intern Med. 2014;25(10):941–5. https://doi.org/10.1016/j.ejim.2014.10.023.

    Article  PubMed  Google Scholar 

  9. Chung WS, Lin CL, Chen YF, Ho FM, Hsu WH, Kao CH. Increased stroke risk among adult asthmatic patients. Eur J Clin Invest. 2014;44(11):1025–33. https://doi.org/10.1111/eci.12336.

    Article  PubMed  Google Scholar 

  10. Xu M, Xu J, Yang X. Asthma and risk of cardiovascular disease or all-cause mortality: a meta-analysis. Ann Saudi Med. 2017;37(2):99–105. https://doi.org/10.5144/0256-4947.2017.99.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Bellia V, Pedone C, Catalano F, Zito A, Davì E, Palange S, Forastiere F, Incalzi RA. Asthma in the elderly: mortality rate and associated risk factors for mortality. Chest. 2007;132(4):1175–82. https://doi.org/10.1378/chest.06-2824.

    Article  PubMed  Google Scholar 

  12. Schanen JG, Iribarren C, Shahar E, Punjabi NM, Rich SS, Sorlie PD, Folsom AR. Asthma and incident cardiovascular disease: the Atherosclerosis Risk in Communities Study. Thorax. 2005;60(8):633–8. https://doi.org/10.1136/thx.2004.026484.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Ross R. Atherosclerosis—an inflammatory disease. N Engl J Med. 1999;340(2):115–26. https://doi.org/10.1056/NEJM199901143400207.

    Article  CAS  PubMed  Google Scholar 

  14. Wick G, Knoflach M, Xu Q. Autoimmune and inflammatory mechanisms in atherosclerosis. Annu Rev Immunol. 2004;22:361–403. https://doi.org/10.1146/annurev.immunol.22.012703.104644.

    Article  CAS  PubMed  Google Scholar 

  15. Kiechl S, Egger G, Mayr M, Wiedermann CJ, Bonora E, Oberhollenzer F, Muggeo M, Xu Q, Wick G, Poewe W, et al. Chronic infections and the risk of carotid atherosclerosis: prospective results from a large population study. Circulation. 2001;103(8):1064–70. https://doi.org/10.1161/01.cir.103.8.1064.

    Article  CAS  PubMed  Google Scholar 

  16. Lampalo M, Majer M, Ferara N, Milošević M, Barišić Kutija M, Jukić I. Gender differences in relationship between body mass index and asthma. Psychiatr Danub. 2019;31(Suppl 5):786–91.

    PubMed  Google Scholar 

  17. Souza ECC, Pizzichini MMM, Dias M, Cunha MJ, Matte DL, Karloh M, Maurici R, Pizzichini E. Body mass index, asthma, and respiratory symptoms: a population-based study. J Bras Pneumol. 2020;46(1):e20190006. https://doi.org/10.1590/1806-3713/e20190006.

    Article  PubMed  PubMed Central  Google Scholar 

  18. Berry M, Brightling C, Pavord I, Wardlaw A. TNF-alpha in asthma. Curr Opin Pharmacol. 2007;7(3):279–82. https://doi.org/10.1016/j.coph.2007.03.001.

    Article  CAS  PubMed  Google Scholar 

  19. Brightling C, Berry M, Amrani Y. Targeting TNF-alpha: a novel therapeutic approach for asthma. J Allergy Clin Immunol. 2008;121(1):5–12. https://doi.org/10.1016/j.jaci.2007.10.028.

    Article  CAS  PubMed  Google Scholar 

  20. Peters MC, McGrath KW, Hawkins GA, Hastie AT, Levy BD, Israel E, Phillips BR, Mauger DT, Comhair SA, Erzurum SC, et al. Plasma interleukin-6 concentrations, metabolic dysfunction, and asthma severity: a cross-sectional analysis of two cohorts. Lancet Respir Med. 2016;4(7):574–84. https://doi.org/10.1016/S2213-2600(16)30048-0.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Carriero V, Bertolini F, Sprio AE, Bullone M, Ciprandi G, Ricciardolo FLM. High levels of plasma fibrinogen could predict frequent asthma exacerbations. J Allergy Clin Immunol Pract. 2020;8(7):2392-2395.e2397. https://doi.org/10.1016/j.jaip.2020.02.034.

    Article  PubMed  Google Scholar 

  22. Akinbami LJ, Simon AE, Rossen LM. Changing trends in asthma prevalence among children. Pediatrics. 2016;137(1):1–7. https://doi.org/10.1542/peds.2015-2354.

    Article  Google Scholar 

  23. Strong JP, Malcom GT, McMahan CA, Tracy RE, Newman WP 3rd, Herderick EE, Cornhill JF. Prevalence and extent of atherosclerosis in adolescents and young adults: implications for prevention from the Pathobiological Determinants of Atherosclerosis in Youth Study. JAMA. 1999;281(8):727–35. https://doi.org/10.1001/jama.281.8.727.

    Article  CAS  PubMed  Google Scholar 

  24. Knoflach M, Kiechl S, Mayr A, Willeit J, Poewe W, Wick G. Allergic rhinitis, asthma, and atherosclerosis in the Bruneck and ARMY studies. Arch Intern Med. 2005;165(21):2521–6. https://doi.org/10.1001/archinte.165.21.2521.

    Article  PubMed  Google Scholar 

  25. Cakmak A, Zeyrek D, Cece H, Erel O. The relationship between carotid intima media thickness and oxidative stress in asthmatic children. Asian Pac J Allergy Immunol. 2010;28(4):256–61.

    PubMed  Google Scholar 

  26. Steinmann M, Abbas C, Singer F, Casaulta C, Regamey N, Haffner D, Fischer DC, Simonetti GD. Arterial stiffness is increased in asthmatic children. Eur J Pediatr. 2015;174(4):519–23. https://doi.org/10.1007/s00431-014-2423-2.

    Article  PubMed  Google Scholar 

  27. Dratva J, Caviezel S, Schaffner E, Stolz D, Rothe T, Kuenzli N, Schmidt-Trucksäss A, Zemp E, Probst-Hensch N. Is there a gender-specific association between asthma and carotid intima media thickness in Swiss adolescents? Eur J Pediatr. 2018;177(5):699–707. https://doi.org/10.1007/s00431-018-3107-0.

    Article  PubMed  Google Scholar 

  28. Akyüz Özkan E, Serin H, Khosroshahi HE, Kılıç M, Ekim M, Beysel P, Geçit UA, Domur E. Arterial stiffness, distensibility, and strain in asthmatic children. Med Sci Monit 2016, 22:251–257. https://doi.org/10.12659/msm.895502.

  29. Raitakari OT, Juonala M, Kähönen M, Taittonen L, Laitinen T, Mäki-Torkko N, Järvisalo MJ, Uhari M, Jokinen E, Rönnemaa T, et al. Cardiovascular risk factors in childhood and carotid artery intima-media thickness in adulthood: the Cardiovascular Risk in Young Finns Study. JAMA. 2003;290(17):2277–83. https://doi.org/10.1001/jama.290.17.2277.

    Article  CAS  PubMed  Google Scholar 

  30. Lorenz MW, Markus HS, Bots ML, Rosvall M, Sitzer M. Prediction of clinical cardiovascular events with carotid intima-media thickness: a systematic review and meta-analysis. Circulation. 2007;115(4):459–67. https://doi.org/10.1161/CIRCULATIONAHA.106.628875.

    Article  PubMed  Google Scholar 

  31. Bernar B, Gande N, Stock KA, Staudt A, Pechlaner R, Geiger R, Griesmacher A, Kiechl S, Knoflach M, Kiechl-Kohlendorfer U. The Tyrolean early vascular ageing-study (EVA-Tyrol): study protocol for a non-randomized controlled trial: effect of a cardiovascular health promotion program in youth, a prospective cohort study. BMC Cardiovasc Disord. 2020;20(1):59. https://doi.org/10.1186/s12872-020-01357-9.

    Article  PubMed  PubMed Central  Google Scholar 

  32. Torén K, Brisman J, Järvholm B. Asthma and asthma-like symptoms in adults assessed by questionnaires. A literature review. Chest. 1993;104(2):600–8. https://doi.org/10.1378/chest.104.2.600.

    Article  PubMed  Google Scholar 

  33. Nishida C, Ko GT, Kumanyika S. Body fat distribution and noncommunicable diseases in populations: overview of the 2008 WHO Expert Consultation on Waist Circumference and Waist-Hip Ratio. Eur J Clin Nutr. 2010;64:2–5. https://doi.org/10.1038/ejcn.2009.139.

    Article  CAS  PubMed  Google Scholar 

  34. Knoflach M, Kiechl S, Kind M, Said M, Sief R, Gisinger M, van der Zee R, Gaston H, Jarosch E, Willeit J, et al. Cardiovascular risk factors and atherosclerosis in young males: ARMY study (Atherosclerosis Risk-Factors in Male Youngsters). Circulation. 2003;108(9):1064–9. https://doi.org/10.1161/01.CIR.0000085996.95532.FF.

    Article  PubMed  Google Scholar 

  35. Knoflach M, Kiechl S, Penz D, Zangerle A, Schmidauer C, Rossmann A, Shingh M, Spallek R, Griesmacher A, Bernhard D, et al. Cardiovascular risk factors and atherosclerosis in young women: atherosclerosis risk factors in female youngsters (ARFY study). Stroke. 2009;40(4):1063–9. https://doi.org/10.1161/STROKEAHA.108.525675.

    Article  CAS  PubMed  Google Scholar 

  36. Kiechl S, Willeit J. The natural course of atherosclerosis. Part I: incidence and progression. Arterioscler Thromb Vasc Biol. 1999;19(6):1484–90. https://doi.org/10.1161/01.atv.19.6.1484.

    Article  CAS  PubMed  Google Scholar 

  37. Staudt A, Stock K, Gande N, Bernar B, Hochmayr C, Pechlaner R, Kiechl SJ, Geiger R, Griesmacher A, Anliker M, et al. Impact of lifestyle and cardiovascular risk factors on early atherosclerosis in a large cohort of healthy adolescents: the early vascular ageing (EVA)-Tyrol study. Atherosclerosis. 2020;305:26–33. https://doi.org/10.1016/j.atherosclerosis.2020.05.011.

    Article  CAS  PubMed  Google Scholar 

  38. Çolak Y, Afzal S, Nordestgaard BG, Lange P. Characteristics and prognosis of never-smokers and smokers with asthma in the Copenhagen general population study. a prospective cohort study. Am J Respir Crit Care Med. 2015;192(2):172–81. https://doi.org/10.1164/rccm.201502-0302OC.

    Article  PubMed  Google Scholar 

  39. Iribarren C, Tolstykh IV, Eisner MD. Are patients with asthma at increased risk of coronary heart disease? Int J Epidemiol. 2004;33(4):743–8. https://doi.org/10.1093/ije/dyh081.

    Article  PubMed  Google Scholar 

  40. Onufrak SJ, Abramson JL, Austin HD, Holguin F, McClellan WM, Vaccarino LV. Relation of adult-onset asthma to coronary heart disease and stroke. Am J Cardiol. 2008;101(9):1247–52. https://doi.org/10.1016/j.amjcard.2007.12.024.

    Article  PubMed  PubMed Central  Google Scholar 

  41. Onufrak S, Abramson J, Vaccarino V. Adult-onset asthma is associated with increased carotid atherosclerosis among women in the Atherosclerosis Risk in Communities (ARIC) study. Atherosclerosis. 2007;195(1):129–37. https://doi.org/10.1016/j.atherosclerosis.2006.09.004.

    Article  CAS  PubMed  Google Scholar 

  42. Wang L, Gao S, Yu M, Sheng Z, Tan W. Association of asthma with coronary heart disease: a meta analysis of 11 trials. PLoS ONE. 2017;12(6):e0179335. https://doi.org/10.1371/journal.pone.0179335.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Tattersall MC, Evans MD, Korcarz CE, Mitchell C, Anderson E, DaSilva DF, Salazar LP, Gern JE, Jackson DJ, Lemanske RF Jr, et al. Asthma is associated with carotid arterial injury in children: the Childhood Origins of Asthma (COAST) Cohort. PLoS ONE. 2018;13(9):e0204708. https://doi.org/10.1371/journal.pone.0204708.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Raggi P, Genest J, Giles JT, Rayner KJ, Dwivedi G, Beanlands RS, Gupta M. Role of inflammation in the pathogenesis of atherosclerosis and therapeutic interventions. Atherosclerosis. 2018;276:98–108. https://doi.org/10.1016/j.atherosclerosis.2018.07.014.

    Article  CAS  PubMed  Google Scholar 

  45. Shoenfeld Y, Gerli R, Doria A, Matsuura E, Cerinic MM, Ronda N, Jara LJ, Abu-Shakra M, Meroni PL, Sherer Y. Accelerated atherosclerosis in autoimmune rheumatic diseases. Circulation. 2005;112(21):3337–47. https://doi.org/10.1161/CIRCULATIONAHA.104.507996.

    Article  PubMed  Google Scholar 

  46. Huang H, Zeng Z, Li J, Zhang L, Chen Y. Variants of arachidonate 5-lipoxygenase-activating protein (ALOX5AP) gene and risk of coronary heart disease: a meta-analysis. Arch Med Res. 2010;41(8):634–41. https://doi.org/10.1016/j.arcmed.2010.11.001.

    Article  CAS  PubMed  Google Scholar 

  47. Abueid L, Uslu Ü, Cumbul A, Velioğlu Öğünç A, Ercan F, Alican İ. Inhibition of 5-lipoxygenase by zileuton in a rat model of myocardial infarction. Anatol J Cardiol 2017, 17(4):269–275. https://doi.org/10.14744/AnatolJCardiol.2016.7248.

  48. Mehrabian M, Allayee H, Wong J, Shi W, Wang XP, Shaposhnik Z, Funk CD, Lusis AJ. Identification of 5-lipoxygenase as a major gene contributing to atherosclerosis susceptibility in mice. Circ Res. 2002;91(2):120–6. https://doi.org/10.1161/01.res.0000028008.99774.7f.

    Article  CAS  PubMed  Google Scholar 

  49. Khan MI, Hariprasad G. Human secretary phospholipase A2 mutations and their clinical implications. J Inflamm Res. 2020;13:551–61. https://doi.org/10.2147/JIR.S269557.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Christiansen SC, Zuraw BL. Treatment of hypertension in patients with asthma. N Engl J Med. 2019;381(11):1046–57. https://doi.org/10.1056/NEJMra1800345.

    Article  CAS  PubMed  Google Scholar 

  51. Dogra S, Ardern CI, Baker J. The relationship between age of asthma onset and cardiovascular disease in Canadians. J Asthma. 2007;44(10):849–54. https://doi.org/10.1080/02770900701752391.

    Article  PubMed  Google Scholar 

  52. Aung T, Bisognano JD, Morgan MA. Allergic respiratory disease as a potential co-morbidity for hypertension. Cardiol J. 2010;17(5):443–7.

    PubMed  Google Scholar 

  53. Roelofs R, Gurgel RQ, Wendte J, Polderman J, Barreto-Filho JA, Solé D, Motta-Franco J, De Munter J, Agyemang C. Relationship between asthma and high blood pressure among adolescents in Aracaju. Brazil J Asthma. 2010;47(6):639–43. https://doi.org/10.3109/02770901003734306.

    Article  PubMed  Google Scholar 

  54. Liu CL, Zhang JY, Shi GP. Interaction between allergic asthma and atherosclerosis. Transl Res. 2016. https://doi.org/10.1016/j.trsl.2015.09.009.

  55. Hermans M, Lennep JRV, van Daele P, Bot I. Mast cells in cardiovascular disease: from bench to bedside. Int J Mol Sci 2019. https://doi.org/10.3390/ijms20143395.

  56. Marx C, Novotny J, Salbeck D, Zellner KR, Nicolai L, Pekayvaz K, Kilani B, Stockhausen S, Bürgener N, Kupka D, et al. Eosinophil-platelet interactions promote atherosclerosis and stabilize thrombosis with eosinophil extracellular traps. Blood. 2019;134(21):1859–72. https://doi.org/10.1182/blood.2019000518.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Otsuki M, Miyatake A, Fujita K, Hamasaki T, Kasayama S. Reduced carotid atherosclerosis in asthmatic patients treated with inhaled corticosteroids. Eur Respir J. 2010;36(3):503–8. https://doi.org/10.1183/09031936.00090009.

    Article  CAS  PubMed  Google Scholar 

  58. Suissa S, Assimes T, Brassard P, Ernst P. Inhaled corticosteroid use in asthma and the prevention of myocardial infarction. Am J Med. 2003;115(5):377–81. https://doi.org/10.1016/s0002-9343(03)00393-0.

    Article  CAS  PubMed  Google Scholar 

  59. Huang CC, Chan WL, Chen YC, Chen TJ, Chou KT, Lin SJ, Chen JW, Leu HB. Statin use in patients with asthma: a nationwide population-based study. Eur J Clin Invest. 2011;41(5):507–12. https://doi.org/10.1111/j.1365-2362.2010.02434.x.

    Article  PubMed  Google Scholar 

  60. Tardif JC, L’Allier PL, Ibrahim R, Grégoire JC, Nozza A, Cossette M, Kouz S, Lavoie MA, Paquin J, Brotz TM, et al. Treatment with 5-lipoxygenase inhibitor VIA-2291 (Atreleuton) in patients with recent acute coronary syndrome. Circ Cardiovasc Imaging. 2010;3(3):298–307. https://doi.org/10.1161/CIRCIMAGING.110.937169.

    Article  PubMed  Google Scholar 

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Acknowledgements

Consortium Members of the “EVA-Tyrol Study Group”: Carmen Reiter1, Christina Schreiner1, Julia Klingenschmid1, Julia Marxer1 Martina Kothmayer1 Maximilian Pircher1, Manuela Bock-Bartl2, Mandy Asare3, Maximilian Bohl3, Raimund Pechlaner3. Affiliations of the consortium members: 1Department of Pediatrics II, Medical University of Innsbruck, Anichstrasse 35, 6020 Innsbruck, Austria. 2VASCage, Research Centre on Vascular Ageing and Stroke, Innrain 66a, 6020 Innsbruck, Austria. 3Department of Neurology, Medical University of Innsbruck, Anichstrasse 35, 6020 Innsbruck, Austria

Funding

This study is supported by VASCage – Research Centre on Vascular Ageing and Stroke. VASCage is a COMET Centre within the Competence Centers for Excellent Technologies (COMET) program and funded by the Federal Ministry for Climate Action, Environment, Energy, Mobility, Innovation and Technology, the Federal Ministry for Digital and Economic Affairs, and the federal states of Tyrol, Salzburg and Vienna. COMET is managed by the Austrian Research Promotion Agency (Österreichische Forschungsförderungsgesellschaft). The funding body had no influence in the design of the study and collection, analysis, and interpretation of data and in writing the manuscript.

Author information

Authors and Affiliations

  1. Department of Pediatrics II, Medical University of Innsbruck, Anichstrasse 35, 6020, Innsbruck, Austria

    Bernhard Winder, Benoît Bernar, Nina Gande, Anna Staudt, Katharina Stock, Christoph Hochmayr, Ursula Kiechl-Kohlendorfer, Carmen Reiter, Christina Schreiner, Julia Klingenschmid, Julia Marxer, Martina Kothmayer & Maximilian Pircher

  2. VASCage, Research Centre on Vascular Ageing and Stroke, Innrain 66a, 6020, Innsbruck, Austria

    Bernhard Winder, Sophia J. Kiechl, Nadja M. Gruber, Stefan Kiechl, Michael Knoflach & Manuela Bock-Bartl

  3. Department of Neurology, Medical University of Innsbruck, Anichstrasse 35, 6020, Innsbruck, Austria

    Sophia J. Kiechl, Stefan Kiechl, Michael Knoflach, Mandy Asare, Maximilian Bohl & Raimund Pechlaner

  4. Department of Pediatrics I, Medical University of Innsbruck, Anichstrasse 35, 6020, Innsbruck, Austria

    Benoît Bernar

  5. Department of Pediatrics III, Medical University of Innsbruck, Anichstrasse 35, 6020, Innsbruck, Austria

    Katharina Stock & Ralf Geiger

  6. Central Institute of Clinical Chemistry and Laboratory Medicine (ZIMCL), Medical University of Innsbruck, Anichstrasse 35, 6020, Innsbruck, Austria

    Andrea Griesmacher & Markus Anliker

Authors
  1. Bernhard Winder
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  2. Sophia J. Kiechl
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  3. Nadja M. Gruber
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  4. Benoît Bernar
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  5. Nina Gande
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  6. Anna Staudt
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  7. Katharina Stock
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  8. Christoph Hochmayr
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  9. Ralf Geiger
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  12. Stefan Kiechl
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  14. Michael Knoflach
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Consortia

the Early Vascular Ageing (EVA)-Tyrol Study Group

  • Carmen Reiter
  • , Christina Schreiner
  • , Julia Klingenschmid
  • , Julia Marxer
  • , Martina Kothmayer
  • , Maximilian Pircher
  • , Manuela Bock-Bartl
  • , Mandy Asare
  • , Maximilian Bohl
  •  & Raimund Pechlaner

Contributions

BW was involved in EVA-Tyrol data collection, analyzed, and interpreted the data in collaboration with all authors, and was responsible for writing the first and all subsequent drafts and the submitted paper. SJK, BB, NG, KS, and CH were involved in the EVA-Tyrol data collection and contributed to the drafting of the manuscript. AS was involved in EVA-Tyrol data collection, performed all cIMT measurements on digitally stored images, and contributed to the drafting of the manuscript. NMG supervised the statistical analysis and contributed to the drafting of the manuscript. RG coordinated the investigations in South Tyrol (Italy), participated in EVA-Tyrol data collection, and contributed to the drafting of the manuscript. AG and MA coordinated the collaboration with the Central Institute for Clinical Chemistry and Laboratory Medicine (ZIMCL) and contributed to the drafting of the manuscript. SK directs the scientific program of the Research Center on Vascular Ageing and Stroke (VASCage) and contributed to the drafting of the manuscript. UKK is one of the two primary investigators of the EVA-Tyrol study. She developed the study protocol and supervised the data collection as well as the writing of the submitted paper. MK is one of the two primary investigators of the EVA-Tyrol study. He developed the study protocol and supervised the data collection as well as the writing of the first and all subsequent drafts and the submitted paper. All members of the EVA-Tyrol Study Group were involved in EVA-Tyrol data collection and management. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Michael Knoflach.

Ethics declarations

Ethics approval and consent to participate

The study was approved by the local ethics committee of the Medical University of Innsbruck (approval number AN 2015-0005 345/4.13) and was executed in agreement with the Declaration of Helsinki and Good Clinical Practice. All participants provided a written informed consent for the publication of their data or, if the participants had not attained age of majority, the consent was additionally provided by a parent or legal guardian.

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Not applicable.

Competing interests

The authors declare that they have no competing interests.

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Winder, B., Kiechl, S.J., Gruber, N.M. et al. The association of allergic asthma and carotid intima-media thickness in adolescence: data of the prospective early vascular ageing (EVA)-Tyrol cohort study. BMC Cardiovasc Disord 22, 11 (2022). https://doi.org/10.1186/s12872-021-02452-1

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Keywords

BMC Cardiovascular Disorders

ISSN: 1471-2261

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