Abstract
Introduction
Cardiovascular disease (CVD) is the leading cause of mortality and disease burden worldwide.\cite{Kassebaum2016,GBD2015MortalityandCausesofDeathCollaborators2016} Despite improvements in prevention and management, the prevalence of CVD continues to increase.\cite{WHO2014} The underlying pathology in CVD is atherosclerosis, a chronic disease process of medium to large arterial walls. Traditional risk factors for atherosclerosis, such as dyslipidaemia, hypertension, diabetes and obesity, account for only half of all CVD disease occurrence.\cite{Braunwald1997} Considerable gaps in our knowledge about the aetiology of CVD remain, and novel determinants of disease are of interest revention strategies.
Inflammation plays a significant role in the pathophysiology of atherosclerosis and the subsequent remodelling of the arterial wall.\cite{Libby2002,Libby2011,ChristopherGlass2001} Infections are a common cause of inflammation and have been associated with increased CVD risk and events in adults.\cite{Prasad2002,Zhu2001} Although the clinical complications of CVD usually occur in adulthood, atherosclerosis begins in childhood\cite{Strong1999}; this is also when infection burden is the highest.\cite{Kyu2016}
There is considerable animal and in vitro evidence suggesting that pathogens elicit an inflammatory response that causes accelerated atherosclerosis. Pathogens may directly invade arterial walls and cause local inflammation; this is pathogenmaterial found in tatherosclerotic plaques???.\cite{Melnick1994,Kaplan2006} In animals studies, infection in hypercholesterolaemic animals increased resultatherosclerosis.atherosclerosis.\cite{Fabricant1978,Moazed1999}
Previous studies have shown a significant association between severe infection burden childhoodand adult CVD risk and events.\cite{Qanitha2016,Burgner2015,Burgner2015a,Burgner2015b}. Ultrasound measurement of children's arteries has been used to investigate the association between childhood infection burden and childhood vascular characteristics, however the results have been inconclusive.\cite{Dratva2015,Evelein2015}
We report findings using longitudinal data from the WHISTLER (WHeezing-Illnesses-STudy-LEidsche-Rijn) cohort to investigate the association between childhood infection burden and childhood vascular characteristics using general practitioner-diagnosed infections. We used non-invasive measures of carotid intima-media thickness (CIMT) and carotid distensibility that are associated with traditional cardiovascular risk factors in childhood.\cite{Aggoun2000}
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