Endothelial Dysfunction in Childhood Infection

Updated:Aug 27,2014
Pub Date:Friday, June 24, 2005
Authors:Hugh Allen, MD  
Article: Endothelial Dysfunction in Childhood Infection


  1. Charakida M; Donald AE; Terese M; Leary S; Halcox JP; Ness A; Davey Smith G; Golding J; Friberg P; Klein NJ; Deanfield JE; ALSPAC (Avon Longitudinal Study of Parents and Children) Study Team,  Endothelial dysfunction in childhood infection,  Circulation,  111 (13) 1660-5. View in PubMed
  2. Napoli C; Pignalosa O; de Nigris F; Sica V,  Childhood infection and endothelial dysfunction: a potential link in atherosclerosis?[comment].,  Circulation,  111 (13) 1568-70. View in PubMed

Clinical Question

Charakida et al. report findings from the Avon Longitudinal Study of Parents and Children (ALSPAC), where they evaluated the effects of mild infections such as upper respiratory infections (cough, sore throat, fever, cold, or gastroenteritis) on a measure of endothelial function, brachial artery reactivity. Their ultimate concern is the role of infection on endothelial dysfunction. Is this a stimulus for pathogenesis of early atherosclerosis?


The study population started with over 15,000 women who lived in three health authorities near Bristol, UK, and were pregnant sometime between April, 1991 and December, 1992. A population of their 14,062 liveborn children has been followed prospectively. From this group, a study population of 600 children aged 10 years was used to compare the presence of recent infection with brachial arterial reactivity. They did not have asthma and were not taking antibiotics or antiinflammatories. Questionnaire responses regarding recent infections that were determined by clinical symptoms allowed development of three subgroups: (1) acute infection (AI) at the time of study; (2) improving from infection in the previous 2 weeks, but well at study (convalescent group); and (3) no recent illness (controls).

Brachial arterial reactivity—flow mediated dilation (FMD)—was tested by high-resolution ultrasound. Patients rested 10 min before the study, and the room was temperature controlled. No comment regarding hydration status was made. A blood pressure cuff was inflated on the forearm at 200 mm Hg and was kept inflated for 5 min, then deflated. For the next 5 min, the brachial artery was scanned and Doppler flows were recorded. Increase in flow after cuff release was compared to baseline flow measurements. For details, see the text.

Subsequently, 135 AI patients and 150 random controls were invited to be reevaluated to determine long-term effects of infection on reactivity.

301 of 600 had either an acute illness or were recovering from one. FMD was lowest in those with acute infection. Those who were convalescent had higher flows but were not at the level seen in controls. At follow-up, the FMDs in all three groups were statistically similar.

They conclude that acute minor infections are associated with impairment in endothelial function, which improves after recovering from the illness. Although not significant, some children never reached normal 1 year later. "This raises the possibility that infection may contribute to mechanisms relevant to the development of arteriosclerosis."

Napoli, in an accompanying editorial, appropriately raises questions about the clinical meaning of brachial arterial reactivity when compared with coronary or peripheral circulation. Others have pointed out that the brachial reactivity test may vary with the state of patient hydration, or even the menstrual cycle. He correctly cautions that other endothelial function tests, such as plasma markers, should be evaluated. He also raises the concern that various infectious agents may have differing effects on the endothelium. What is the impact of genetic factors? He cautions that more prospective studies are needed before conclusions can be drawn.

Clinical Implication/Application

This is a provocative and important study that raises the possibility that acute infections in childhood may be associated—or causative—with later development of arteriosclerosis. More prospective studies of careful nature are needed before such conclusions can be made, but the authors have done a service to us by raising and studying the question. This will be a very important area to follow.

-- The opinions expressed in this commentary are not necessarily those of the editors or of the American Heart Association. -- 

AHA Scientific Journals

AHA Scientific Journals