Jorma Viikari

Endothelial Dysfunction and Increased Arterial Intima-Media Thickness in Children With Type 1 Diabetes

Background—Endothelial dysfunction may play a pathophysiological role in the development of atherosclerosis in subjects with type 1 diabetes. We examined whether alterations in vascular endothelial function exist in children with type 1 diabetes and tested the hypothesis that endothelial dysfunction is associated with early structural atherosclerotic vascular changes in these children. Methods and Results—Noninvasive ultrasound was used to measure brachial artery flow-mediated dilation (FMD) responses and carotid artery intima-media thickness (IMT) in 75 children (mean age 11±2 years), 45 with type 1 diabetes (diabetes duration 4.4±2.9 years) and 30 healthy control children. Children with diabetes had lower peak FMD response (4.4±3.4% versus 8.7±3.6%, P <0.001) and increased IMT (P <0.001) compared with controls. Sixteen children with diabetes (36%) had endothelial dysfunction defined as total FMD response in the lowest decile for normal children. These children had increased carotid IMT (0.58±0.05 versus 0.54±0.04 mm, P =0.01) and higher LDL cholesterol concentration (2.63±0.76 versus 2.16±0.60 mmol/L, P =0.03) compared with diabetic children without endothelial dysfunction. Multivariate correlates of increased IMT included diabetes group (P =0.03), low FMD (P =0.03), and high LDL cholesterol (P =0.08). Conclusions—Impaired FMD response is a common manifestation in children with type 1 diabetes and is associated with increased carotid artery IMT. These data suggest that endothelial dysfunction in children with type 1 diabetes may predispose them to the development of early atherosclerosis.

Elevated Serum C-Reactive Protein Levels and Early Arterial Changes in Healthy Children

Objective—Elevated serum concentration of C-reactive protein (CRP) predicts cardiovascular events in adults. Because atherosclerosis begins in childhood, we undertook a study to determine whether changes in brachial artery endothelial function and the thickness of the carotid intima-media complex, 2 markers of early atherosclerosis, are related to CRP levels in healthy children. Methods and Results—Brachial artery flow-mediated dilatation (FMD) and carotid artery intima-media thickness (IMT) were measured with ultrasound in 79 children (aged 10.5±1.1 years). Compared with the children with CRP levels under the detection limit (<0.1 mg/L, n=40, group 1), the children with higher CRP (0.1 mg/L≤CRP≤0.7 mg/L, n=20, group 2; CRP >0.7 mg/L, n=19, group 3) had lower FMD (9.0±4.4% versus 7.8±3.3% versus 6.5±2.6%, respectively;P =0.015 for trend) and greater carotid IMT (0.45±0.03 versus 0.46±0.04 versus 0.49±0.06 mm, respectively, P =0.002 for trend). CRP level remained a statistically significant independent predictor for brachial FMD and carotid IMT in multivariate analyses. Conclusions—These data suggest that CRP affects the arteries of healthy children by disturbing endothelial function and promoting intima-media thickening. The findings support the hypothesis that CRP plays a role in the pathogenesis of early atherosclerosis.

Hepatic lipase promoter C-480T polymorphism is associated with serum lipids levels, but not subclinical atherosclerosis: the Cardiovascular Risk in Young Finns Study.

The common C‐480T polymorphism (rs1800588) of the hepatic lipase gene (LIPC) has been associated with high‐density lipoprotein (HDL) cholesterol, atherosclerosis, and coronary artery disease. In this study, we examined whether the polymorphism is associated with serum lipid and lipoprotein concentrations, as well as with subclinical atherosclerosis in Young Finns. The participants comprised 2041 men and women (aged 24–39 years) enrolled in the Cardiovascular Risk in Young Finns Study with complete data concerning the rs1800588 polymorphism and serum lipids concentration. All participants underwent an ultrasound examination for brachial artery flow‐mediated vasodilatation (FMD) and carotid artery intima‐media thickness (IMT) measurement. The marker of arterial elasticity, carotid artery compliance (CAC), was also calculated by means of ultrasound and concomitant brachial blood pressure measurements. In all subjects, serum total cholesterol (p < 0.001), HDL cholesterol (p = 0.006), apolipoprotein AI (apoAI, p < 0.001), and triglyceride (p = 0.009) concentrations increased according to rs1800588 genotype in the order CC, CT, and TT. The same order applied only to apoAI after adjustment for age, body mass index, systolic and diastolic blood pressure, smoking, alcohol consumption, physical activity, diabetes, hypertension, contraceptive hormone use in women, and concentrations of glucose, insulin and C‐reactive protein in men and women separately (p = 0.007 and p = 0.003, respectively). The polymorphism was also associated with HDL cholesterol, total cholesterol, and triglyceride levels in women (adjusted p = 0.004, p = 0.007 and 0.02, respectively), but not in men (p was not significant for all). No significant association between the rs1800588 and brachial FMD, carotid IMT, or CAC was found among the entire study population or among women or men separately, with or without adjustment for the above‐mentioned factors. The rs1800588 is associated with serum lipid and apolipoprotein concentrations, especially in women, but does not seem to be a determinant of brachial artery FMD, carotid IMT, or CAC in young healthy adults.

Effect of repeated endotoxin treatment and hypercholesterolemia on preatherosclerotic lesions in weaned pigs Part 1. Scanning and transmission electron microscopic study

Endothelial cell damage is considered to be the primary event in atherogenesis. In this study we compared the effects of mild hypercholesterolemia and repeated E. coli endotoxin infusions on the endothelial cells of the coronary arteries of the pig. We divided 24 pigs into 4 groups: I: controls on normal diet; II: normal diet and endotoxin treatment; III: fat-supplemented diet; IV: fat-supplemented diet and endotoxin treatment. The animals on a fat-supplemented diet showed the most frequent and most severe endothelial cell damage. The damage was less when this diet was combined with endotoxin treatment. Endotoxin reduced the serum total cholesterol level (P less than 0.01). The cholesterol level correlated very significantly (P less than 0.001) with endothelial damage of the coronary arteries. Mild hypercholesterolemia (s-cholesterol 5.68 mmol/l, controls 2.28 mmol/l) was thus associated with toxic effects in the endothelial cells. The E. coli endotoxin infusions did not have any cumulative effect on the lesions.