Is there a gender-specific association between asthma and carotid intima media thickness in Swiss adolescents?
Respiratory diseases are associated with increased cardiovascular risk in adults, but little is known on the early impact on the vasculature in youth. The SAPALDIA Youth study, the offspring study of the Swiss Study on Air Pollution and Lung and Heart Disease In Adults (SAPALDIA), investigated the association between physician-diagnosed asthma status and common carotid artery intima media thickness (CIMT). Offspring underwent standardized clinical protocols and provided information on early life factors, health, and lifestyle. The association between per subject averages of CIMT and asthma was estimated using mixed linear regression analyses adjusting for main confounders, testing for interaction with gender and age. Of 257 offspring (mean age 15 years, 53% female), 11.5% reported doctor-diagnosed asthma (male 17%, female 7%). Mean CIMT was significantly different by gender (male 0.53 mm (± 0.045), female 0.50 mm (± 0.048); p < 0.001). Interaction was highly significant by gender (p = 0.001) with significantly increased CIMT in asthmatic vs. non-asthmatics boys (difference 0.023 mm, 95% CI 0.003; 0.043), as compared to girls.
What is Known:
• Evidence points to a significant impact of adult respiratory disease on cardiovascular health indicators as well as on endpoints.
• Inflammation is a key pathway in vascular change across the life course.
What is New:
• We observe an adverse association between physician-diagnosed asthma and carotid intima media thickness in adolescent boys.
• Albeit a limited number of asthmatic girls, we hypothesize the gender typical timing of asthma or a higher male cardiovascular vulnerability as possible explanations for the gender-specific results.
KeywordsAsthma Atherosclerosis Epidemiology Carotid intima media thickness
Body mass index
Carotid artery intima media thickness
Forced expiratory volume
Swiss Study on Air Pollution and Lung and Heart Disease In Adults
We thank Prof. Christian Schindler for his statistical support and critical input and the SAPALDIA Youth study participants for providing data and trust in our research.
Julia Dratva is the primary investigator of the SAPALDIA Youth study. She developed the study protocol and supervised the data collection, has developed the hypotheses and analytic plan presented in this paper, conducted the analyses, interpreted the data in conjunction with all authors, and was responsible for writing the first and all consecutive drafts and the submitted paper.
Seraina Caviezel was involved in the CIMT data collection and management, provided analytic support and contributed in the interpretation of the presented results in conjunction with all authors, and participated in the drafting of the manuscript.
Emmanuel Schaffner is involved in the CIMT data management, provided analytic support and contributed in the interpretation of the presented results in conjunction with all authors, and participated in the drafting of the manuscript.
Daiana Stolz was involved in the SAPALDIA Youth data collection as study center physician and pneumologist. She contributed in the interpretation of the presented results in conjunction with all authors, and participated in the drafting of the manuscript.
Thomas Rothe was involved in the SAPALDIA Youth data collection as study center physician and pneumologist. He contributed in the interpretation of the presented results in conjunction with all authors and participated in the drafting of the manuscript.
Nino Kuenzli is a longstanding member of the SAPALDIA cohort study, in which the SAPALDIA Youth study is nested. He oversaw the SAPALDIA 3 survey and the development of the SAPALDIA CIMT protocol and provided methodological support in the development of the SAPALDIA Youth study. He contributed in the interpretation of the presented results in conjunction with all authors and participated in the drafting of the manuscript.
Arno Schmidt-Trucksäss was involved in the SAPALDIA CIMT protocol development, data collection and analyses, contributed to the interpretation of results in conjunction with all authors, and participated in drafting the paper.
Elisabeth Zemp provided methodological support in the development of the SAPALDIA Youth study and contributed in the interpretation of the presented results in conjunction with all authors and participated in the drafting of the manuscript.
Nicole Probst-Hensch is the primary investigator of the SAPALDIA cohort study, in which the SAPALDIA Youth study is nested. She implemented into the SAPALDIA cohort the comorbidity framework between inflammation-related diseases. She provided methodological support in the development and data collection of the SAPALDIA Youth study and contributed in the interpretation of the presented results in conjunction with all authors, and participated in the drafting of the manuscript.
The SAPALDIA Youth study was funded by the Swiss National Science Foundation (PMPDP3_129021/1, PMPDP3_141671/1) and supported financially by the canton’s Lung League of Basel Stadt/Basel Landschaft and Graubünden and the Stiftung ehemals Bündner Heilstätten.
The SAPALDIA cohort study, from which offspring were recruited, is funded by the Swiss National Science Foundation (grant no. 33CSCO-134276/1, 33CSCO-108796, 3247BO104283, 3247BO-104288, 3247BO-104284, 3247-065896, 3100-059302, 3200-052720, 3200042532, 4026-028099). For additional information on funding bodies, please refer the homepage: www.sapaldia.ch/en/.
Compliance with ethical standards
Parents signed written informed consent for adolescent < 18 years; as of 15 years of age, adolescent were asked to provide written informed consent. The study protocol was approved by the respective cantonal Ethical Review Boards.
Conflict of interest
The authors declare that they have no conflict of interest.
- 1.Ackermann-Liebrich U, Kuna-Dibbert B, Probst-Hensch NM, Schindler C, Dietrich DF, Stutz EZ, Bayer-Oglesby L, Baum F, Brändli O, Brutsche M, Downs SH, Keidel D, Gerbase MW, Imboden M, Keller R, Knöpfli B, Künzli N, Nicod L, Pons M, Staedele P, Tschopp JM, Zellweger JP, Leuenberger P, SAPALDIA team (2005) Follow-up of the Swiss Cohort Study on Air Pollution and Lung Diseases in Adults (SAPALDIA 2) 1991-2003: methods and characterization of participants. Soz Praventivmed 50(4):245–263. https://doi.org/10.1007/s00038-005-4075-5 CrossRefPubMedPubMedCentralGoogle Scholar
- 3.Asher MI, Montefort S, Björkstén B, Lai CKW, Strachan DP, Weiland SK, Williams H (2006) Worldwide time trends in the prevalence of symptoms of asthma, allergic rhinoconjunctivitis, and eczema in childhood: ISAAC Phases One and Three repeat multicountry cross-sectional surveys. Lancet 368(9537):733–743. https://doi.org/10.1016/S0140-6736(06)69283-0 CrossRefPubMedPubMedCentralGoogle Scholar
- 4.Böhm B, Hartmann K, Buck M, Oberhoffer R (2009) Sex differences of carotid intima-media thickness in healthy children and adolescents. Atherosclerosis 206(2):458–463. https://doi.org/10.1016/j.atherosclerosis.2009.03.016 CrossRefPubMedPubMedCentralGoogle Scholar
- 5.Bohm B et al (2009) Sex differences of carotid intima-media thickness in healthy children and adolescents. Atherosclerosis 206(2):458–463. https://doi.org/10.1016/j.atherosclerosis.2009.03.016 CrossRefPubMedPubMedCentralGoogle Scholar
- 8.Corne JM, Marshall C, Smith S, Schreiber J, Sanderson G, Holgate ST, Johnston SL (2002) Frequency, severity, and duration of rhinovirus infections in asthmatic and non-asthmatic individuals: a longitudinal cohort study. Lancet 359(9309):831–834. https://doi.org/10.1016/S0140-6736(02)07953-9 CrossRefPubMedPubMedCentralGoogle Scholar
- 11.Dratva J, Probst-Hensch N, Schmidt-Trucksäss A, Caviezel S, de Groot E, Bettschart R, Saleh L, Gapoz JM, Rothe T, Schindler C, Stolz D, Turk A, Rochat T, Kuenzli N, Zemp E (2013) Atherogenesis in youth-early consequence of adolescent smoking. Atherosclerosis 230(2):304–309. https://doi.org/10.1016/j.atherosclerosis.2013.08.004 CrossRefPubMedPubMedCentralGoogle Scholar
- 13.Dratva J, Caviezel S, Schaffner E, Bettschart R, Kuenzli N, Schindler C, Schmidt-Trucksäss A, Stolz D, Zemp E, Probst-Hensch N (2015) Infectious diseases are associated with carotid intima media thickness in adolescence. Atherosclerosis 243(2):609–615. https://doi.org/10.1016/j.atherosclerosis.2015.10.021 CrossRefPubMedPubMedCentralGoogle Scholar
- 16.Elkiran O, Yilmaz E, Koc M, Kamanli A, Ustundag B, Ilhan N (2013) The association between intima media thickness, central obesity and diastolic blood pressure in obese and owerweight children: a cross-sectional school-based study. Int J Cardiol 165(3):528–532. https://doi.org/10.1016/j.ijcard.2011.09.080 CrossRefPubMedPubMedCentralGoogle Scholar
- 17.Freedman DS, Dietz WH, Tang R, Mensah GA, Bond MG, Urbina EM, Srinivasan S, Berenson GS (2004) The relation of obesity throughout life to carotid intima-media thickness in adulthood: the Bogalusa Heart Study. Int J Obes Relat Metab Disord 28(1):159–166. https://doi.org/10.1038/sj.ijo.0802515 CrossRefPubMedPubMedCentralGoogle Scholar
- 19.Grize L, Gassner M, Wuthrich B, Bringolf-Isler B, Takken-Sahli K, Sennhauser FH, Stricker T, Eigenmann PA, Braun-Fahrlander C, the Swiss Surveillance Programme on Childhood Allergy and Respiratory symptoms with respect to Air Pollution (SCARPOL) team (2006) Trends in prevalence of asthma, allergic rhinitis and atopic dermatitis in 5-7-year old Swiss children from 1992 to 2001. Allergy 61(5):556–562. https://doi.org/10.1111/j.1398-9995.2006.01030.x CrossRefPubMedPubMedCentralGoogle Scholar
- 20.Jarvisalo MJ et al (2002) Elevated serum C-reactive protein levels and early arterial changes in healthy children. Arterioscler Thromb Vasc Biol 22(8):1323–1328. https://doi.org/10.1161/01.ATV.0000024222.06463.21 CrossRefPubMedPubMedCentralGoogle Scholar
- 21.Juhola J, Magnussen CG, Berenson GS, Venn A, Burns TL, Sabin MA, Srinivasan SR, Daniels SR, Davis PH, Chen W, Kahonen M, Taittonen L, Urbina E, Viikari JSA, Dwyer T, Raitakari OT, Juonala M (2013) Combined effects of child and adult elevated blood pressure on subclinical atherosclerosis: the International Childhood Cardiovascular Cohort Consortium. Circulation 128(3):217–224. https://doi.org/10.1161/CIRCULATIONAHA.113.001614 CrossRefPubMedPubMedCentralGoogle Scholar
- 22.Kiechl S, Egger G, Mayr M, Wiedermann CJ, Bonora E, Oberhollenzer F, Muggeo M, Xu Q, Wick G, Poewe W, Willeit J (2001) Chronic infections and the risk of carotid atherosclerosis: prospective results from a large population study. Circulation 103(8):1064–1070. https://doi.org/10.1161/01.CIR.103.8.1064 CrossRefPubMedPubMedCentralGoogle Scholar
- 24.Lang AM, Konradsen J, Carlsen KH, Sachs-Olsen C, Mowinckel P, Hedlin G, Lødrup Carlsen KC (2010) Identifying problematic severe asthma in the individual child--does lung function matter? Acta Paediatr 99(3):404–410. https://doi.org/10.1111/j.1651-2227.2009.01625.x CrossRefPubMedPubMedCentralGoogle Scholar
- 25.Li S, Chen W, Srinivasan SR, Tang R, Bond MG, Berenson GS (2007) Race (black-white) and gender divergences in the relationship of childhood cardiovascular risk factors to carotid artery intima-media thickness in adulthood: the Bogalusa Heart Study. Atherosclerosis 194(2):421–425. https://doi.org/10.1016/j.atherosclerosis.2006.08.026 CrossRefPubMedPubMedCentralGoogle Scholar
- 30.Melo X, Santa-Clara H, Pimenta NM, Carrolo M, Martins SS, Minderico CS, Fernhall B, Sardinha LB (2014) Body composition phenotypes and carotid intima-media thickness in 11-13-year-old children. Eur J Pediatr 173(3):345–352. https://doi.org/10.1007/s00431-013-2164-7 CrossRefPubMedPubMedCentralGoogle Scholar
- 32.Murray CJL, Vos T, Lozano R, Naghavi M, Flaxman AD, Michaud C, Ezzati M, Shibuya K, Salomon JA, Abdalla S, Aboyans V, Abraham J, Ackerman I, Aggarwal R, Ahn SY, Ali MK, AlMazroa MA, Alvarado M, Anderson HR, Anderson LM, Andrews KG, Atkinson C, Baddour LM, Bahalim AN, Barker-Collo S, Barrero LH, Bartels DH, Basáñez MG, Baxter A, Bell ML, Benjamin EJ, Bennett D, Bernabé E, Bhalla K, Bhandari B, Bikbov B, Abdulhak AB, Birbeck G, Black JA, Blencowe H, Blore JD, Blyth F, Bolliger I, Bonaventure A, Boufous S, Bourne R, Boussinesq M, Braithwaite T, Brayne C, Bridgett L, Brooker S, Brooks P, Brugha TS, Bryan-Hancock C, Bucello C, Buchbinder R, Buckle G, Budke CM, Burch M, Burney P, Burstein R, Calabria B, Campbell B, Canter CE, Carabin H, Carapetis J, Carmona L, Cella C, Charlson F, Chen H, Cheng ATA, Chou D, Chugh SS, Coffeng LE, Colan SD, Colquhoun S, Colson KE, Condon J, Connor MD, Cooper LT, Corriere M, Cortinovis M, de Vaccaro KC, Couser W, Cowie BC, Criqui MH, Cross M, Dabhadkar KC, Dahiya M, Dahodwala N, Damsere-Derry J, Danaei G, Davis A, Leo DD, Degenhardt L, Dellavalle R, Delossantos A, Denenberg J, Derrett S, Des Jarlais DC, Dharmaratne SD, Dherani M, Diaz-Torne C, Dolk H, Dorsey ER, Driscoll T, Duber H, Ebel B, Edmond K, Elbaz A, Ali SE, Erskine H, Erwin PJ, Espindola P, Ewoigbokhan SE, Farzadfar F, Feigin V, Felson DT, Ferrari A, Ferri CP, Fèvre EM, Finucane MM, Flaxman S, Flood L, Foreman K, Forouzanfar MH, Fowkes FGR, Fransen M, Freeman MK, Gabbe BJ, Gabriel SE, Gakidou E, Ganatra HA, Garcia B, Gaspari F, Gillum RF, Gmel G, Gonzalez-Medina D, Gosselin R, Grainger R, Grant B, Groeger J, Guillemin F, Gunnell D, Gupta R, Haagsma J, Hagan H, Halasa YA, Hall W, Haring D, Haro JM, Harrison JE, Havmoeller R, Hay RJ, Higashi H, Hill C, Hoen B, Hoffman H, Hotez PJ, Hoy D, Huang JJ, Ibeanusi SE, Jacobsen KH, James SL, Jarvis D, Jasrasaria R, Jayaraman S, Johns N, Jonas JB, Karthikeyan G, Kassebaum N, Kawakami N, Keren A, Khoo JP, King CH, Knowlton LM, Kobusingye O, Koranteng A, Krishnamurthi R, Laden F, Lalloo R, Laslett LL, Lathlean T, Leasher JL, Lee YY, Leigh J, Levinson D, Lim SS, Limb E, Lin JK, Lipnick M, Lipshultz SE, Liu W, Loane M, Ohno SL, Lyons R, Mabweijano J, MacIntyre MF, Malekzadeh R, Mallinger L, Manivannan S, Marcenes W, March L, Margolis DJ, Marks GB, Marks R, Matsumori A, Matzopoulos R, Mayosi BM, McAnulty JH, McDermott MM, McGill N, McGrath J, Medina-Mora ME, Meltzer M, Memish ZA, Mensah GA, Merriman TR, Meyer AC, Miglioli V, Miller M, Miller TR, Mitchell PB, Mock C, Mocumbi AO, Moffitt TE, Mokdad AA, Monasta L, Montico M, Moradi-Lakeh M, Moran A, Morawska L, Mori R, Murdoch ME, Mwaniki MK, Naidoo K, Nair MN, Naldi L, Narayan KMV, Nelson PK, Nelson RG, Nevitt MC, Newton CR, Nolte S, Norman P, Norman R, O’Donnell M, O’Hanlon S, Olives C, Omer SB, Ortblad K, Osborne R, Ozgediz D, Page A, Pahari B, Pandian JD, Rivero AP, Patten SB, Pearce N, Padilla RP, Perez-Ruiz F, Perico N, Pesudovs K, Phillips D, Phillips MR, Pierce K, Pion S, Polanczyk GV, Polinder S, Pope CA III, Popova S, Porrini E, Pourmalek F, Prince M, Pullan RL, Ramaiah KD, Ranganathan D, Razavi H, Regan M, Rehm JT, Rein DB, Remuzzi G, Richardson K, Rivara FP, Roberts T, Robinson C, de Leòn FR, Ronfani L, Room R, Rosenfeld LC, Rushton L, Sacco RL, Saha S, Sampson U, Sanchez-Riera L, Sanman E, Schwebel DC, Scott JG, Segui-Gomez M, Shahraz S, Shepard DS, Shin H, Shivakoti R, Silberberg D, Singh D, Singh GM, Singh JA, Singleton J, Sleet DA, Sliwa K, Smith E, Smith JL, Stapelberg NJC, Steer A, Steiner T, Stolk WA, Stovner LJ, Sudfeld C, Syed S, Tamburlini G, Tavakkoli M, Taylor HR, Taylor JA, Taylor WJ, Thomas B, Thomson WM, Thurston GD, Tleyjeh IM, Tonelli M, Towbin JA, Truelsen T, Tsilimbaris MK, Ubeda C, Undurraga EA, van der Werf MJ, van Os J, Vavilala MS, Venketasubramanian N, Wang M, Wang W, Watt K, Weatherall DJ, Weinstock MA, Weintraub R, Weisskopf MG, Weissman MM, White RA, Whiteford H, Wiebe N, Wiersma ST, Wilkinson JD, Williams HC, Williams SRM, Witt E, Wolfe F, Woolf AD, Wulf S, Yeh PH, Zaidi AKM, Zheng ZJ, Zonies D, Lopez AD (2012) Disability-adjusted life years (DALYs) for 291 diseases and injuries in 21 regions, 1990–2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet 380(9859):2197–2223. https://doi.org/10.1016/S0140-6736(12)61689-4 CrossRefPubMedPubMedCentralGoogle Scholar
- 34.Onufrak S, Abramson J, Vaccarino V (2007) Adult-onset asthma is associated with increased carotid atherosclerosis among women in the Atherosclerosis Risk in Communities (ARIC) study. Atherosclerosis 195(1):129–137. https://doi.org/10.1016/j.atherosclerosis.2006.09.004 CrossRefPubMedPubMedCentralGoogle Scholar
- 37.Quanjer PH, Stanojevic S, Cole TJ, Baur X, Hall GL, Culver BH, Enright PL, Hankinson JL, Ip MSM, Zheng J, Stocks J, the ERS Global Lung Function Initiative (2012) Multi-ethnic reference values for spirometry for the 3-95-yr age range: the global lung function 2012 equations. Eur Respir J 40(6):1324–1343. https://doi.org/10.1183/09031936.00080312 CrossRefPubMedPubMedCentralGoogle Scholar
- 44.Tattersall MC, Guo M, Korcarz CE, Gepner AD, Kaufman JD, Liu KJ, Barr RG, Donohue KM, McClelland RL, Delaney JA, Stein JH (2015) Asthma predicts cardiovascular disease events: the multi-ethnic study of atherosclerosis. Arterioscler Thromb Vasc Biol 35(6):1520–1525. https://doi.org/10.1161/ATVBAHA.115.305452 CrossRefPubMedPubMedCentralGoogle Scholar
- 45.Teynor A, Caviezel S, Dratva J, Künzli N, Schmidt-Trucksäss A (2012) An automated, interactive analysis system for ultrasound sequences of the common carotid artery. Ultrasound Med Biol 38(8):1440–1450. https://doi.org/10.1016/j.ultrasmedbio.2012.03.015 CrossRefPubMedPubMedCentralGoogle Scholar
- 47.Vestbo J, Anderson JA, Brook RD, Calverley PMA, Celli BR, Crim C, Martinez F, Yates J, Newby DE (2016) Fluticasone furoate and vilanterol and survival in chronic obstructive pulmonary disease with heightened cardiovascular risk (SUMMIT): a double-blind randomised controlled trial. Lancet 387(10030):1817–1826. https://doi.org/10.1016/S0140-6736(16)30069-1 CrossRefPubMedPubMedCentralGoogle Scholar
- 48.Vink NM, Postma DS, Schouten JP, Rosmalen JGM, Boezen HM (2010) Gender differences in asthma development and remission during transition through puberty: The TRacking Adolescents’ Individual Lives Survey (TRAILS) study. J Allergy Clin Immunol 126(3):498–504.e6. https://doi.org/10.1016/j.jaci.2010.06.018 CrossRefPubMedPubMedCentralGoogle Scholar