Atherosclerosis begins early in life. Infections might contribute to the pathogenesis of atherosclerosis. In this study, we investigated whether acute infections in children could alter the carotid wall morphology and the lipid profile. Mean carotid intima-media thickness (IMT) was measured by high-resolution ultrasound in 28 hospitalised children (mean age: 5+/-2 years), who fulfilled the diagnostic criteria of acute infections (body temperature, >38 degrees C; C-reactive protein, >15mg/ml, and clinical), and in 20 age- and gender-matched controls. Antibodies against oxidised low-density lipoprotein (anti-oxLDL antibodies), as well as total and high-density lipoprotein cholesterol (HDL-C) were analysed in all children. The infection group was investigated both during the acute illness and 3 months after clinical recovery (post-infection). During the acute illness, the infection group had elevated anti-oxLDL antibodies and decreased HDL-C, as compared to those obtained at 3 months and in controls (p<0.05). These changes in the infection group were followed, at 3 months, by thickening of carotid intima-media. Those who received antibiotics during their acute illness had less carotid thickening than those who were not treated with antibiotics (p<0.05). Acute infections in children seem to be accompanied by enhanced oxidative modification of LDL and by decrease in HDL-C. These lipid changes may be followed by thickening of carotid artery intima-media. These findings suggest that, in childhood, acute infections could be associated with increased risk of atherosclerosis, and warrant further studies on this topic.

Background—Arterial relaxation is largely regulated by endothelial nitric oxide (NO). Its diminished activity has been associated with incipient atherosclerosis. We investigated the endothelium-dependent relaxation of aorta in apolipoprotein E–knockout (apoE-KO) mice exposed to single or repeatedChlamydia pneumoniaeinoculation.Methods and Results—Forty-eight apoE-KO mice, 8 weeks old, were inoculated intranasally withC pneumoniae(n=24) or saline (n=24) every 2 weeks over a 6-week period. Twenty mice (10 infected and 10 controls) were killed at 2 weeks and 6 weeks, respectively, after the first inoculation. The smooth muscle tone of aortic rings was measured in vitro at both time points. The norepinephrine-precontracted thoracic aortic rings were successively exposed to methacholine in the absence and presence ofN^G-nitro-l-arginine methyl ester (L-NAME) and diclofenac. The methacholine-induced relaxation was attenuated in the infected mice at 6 weeks in both the absence and presence of L-NAME (P<0.05 andP<0.01, respectively). When administered together with L-NAME, diclofenac enhanced the relaxation of the L-NAME–pretreated aortas in infected mice at 2 weeks (P<0.05) but not in noninfected mice. The relaxation response from infected mice tended to differ in the same manner at 6 weeks (P<0.1). No intimal thickening was detected at either time point.Conclusions—C pneumoniaeimpairs arterial endothelial function, and the NO pathway is principally involved. Cyclooxygenase-dependent vasoconstricting products may also account for the infection-induced impaired relaxation. These findings further support the role ofC pneumoniaeinfection in atherosclerosis development.

Low birthweight has been linked to increased cardiovascular risk in adulthood. We evaluated the effect on cardiovascular outcome of intrauterine growth restriction (IUGR) with abnormal fetal blood flow in children born very preterm. Blood pressure, cardiac function and size, diameters, distensibility, and stiffness of the abdominal aorta, carotid, and popliteal arteries, and endothelial function were assessed non-invasively in 7-year-old children (n = 32) born very preterm with IUGR, with birthweight (median, range) 650 g (395–976 g) and gestational age 27 weeks (24–29 weeks). In addition, intima-media thickness was measured in the carotid artery. Controls were matched for gender and age and had birthweight appropriate-for-gestational-age (AGA). The study included 32 preterm-AGA children with birthweight 1010 g (660–1790) g and 32 term-AGA children with birthweight 3530 g (3000–4390) g. Preterm-IUGR children had lower microvascular response to acetylcholine, lower aortic stiffness, and higher distensibility compared with the preterm-AGA group (p = 0.019, p = 0.001, and p < 0.001, respectively) and lower carotid intima-media thickness compared with the term-AGA group (p = 0.047). The highest aortic β and lowest distensibility were found in the preterm-AGA group. Height-adjusted systolic blood pressure was higher in the preterm groups than in the term-AGA group (p = 0.018). Cardiac function and size did not differ between the groups. IUGR and preterm birth appear to be associated with structural changes in the arterial wall, whereas preterm birth seems to be associated with higher blood pressure. Using conventional echocardiography, we observed no effect of IUGR on cardiac size and function.

Background. Several clinical studies have suggested possible increase in cardiovascular risk during and in the first weeks after an acute inflammatory disease. Using influenza vaccine as inflammatory stimulus, we investigated whether arterial endothelial dysfunction could persist beyond the inflammatory state, and whether amplified oxidative modification of low‐density lipoprotein (LDL) accompanies this vascular disturbance. Methods and subjects. The brachial artery responses to hyperemia (flow‐mediated dilatation (FMD), and to sublingual glyceryl trinitrate (GTN), and the carotid intima‐media thickness were assessed by external ultrasound in eight healthy male volunteers (age 17–30 y) before, and 2 and 14 days after intramuscular administration of influenza vaccine. Plasma levels of high‐sensitivity C‐reactive protein (CRP), fibrinogen, cyclic guanosine monophosphate (cGMP), and antibodies against oxidized LDL (oxLDL) were measured at each time point. Data are means±standard errors of the mean (SEM). Results. Influenza vaccination caused a slight elevation in CRP (from 0.5±0.1 at baseline, to 2±0.6 mg/L, P = 0.01) and fibrinogen (from 2.3±0.1 to 2.7±0.1 g/L, P = 0.01) at 2 days, which completely resolved at 14 days (CRP: 0.6±0.2 mg/L, P = 0.9, and fibrinogen: 2.3±0.1 g/L, P = 0.8 versus baseline). OxLDL antibody levels rose significantly at 2 days (from 1±0.1 at baseline to 2±0.4, P = 0.04), and remained elevated at 14 days (1.7±0.3, P = 0.1 versus baseline). FMD of the brachial artery decreased at 2 days (from 8.3±1.2% at baseline, to 5.4±1%, P = 0.05) with a further decrease at 14 days (4.9±0.8%, P = 0.03 versus baseline). The dilatory responses to GTN and the carotid IMT remained unchanged throughout the study period (P>0.5). Conclusion. Abnormalities in arterial function and LDL oxidation may persist for at least 2 weeks after a slight inflammatory reaction induced by influenza vaccination. These could explain in part the earlier reported increase in cardiovascular risk during the first weeks after an acute inflammatory disorder.