Erkki Pesonen

Atherosclerosis precursors in Finnish children and adolescents. I. General description of the cross-sectional study of 1980, and an account of the children's and families' state of health.

ABSTRACT. The paper describes the general outline of a multicentre study on the risk factors of coronary heart disease (CHD) and their determinants in children of various ages in different parts of Finland. The study was a cross‐sectional one, and was carried out in 1980 in five university cities of Finland with medical schools and in 12 rural communities in their vicinity. The randomized sample included an equal number of boys and girls, aged 3, 6, 9, 12, 15, and 18 years, and an equal number of urban and rural population in each area. The total sample size was 4,320 subjects, and of these 3,596 participated (83.1 %). The families received before the medical examination of the child, questionnaires on the Socioeconomic background, the childs general health and development, the parents’and grandparents’health status, and the childs food and exercise habits. At the physical examination also a fasting blood sample (lipids, insulin, trace elements) was taken, a bundle of hair was cut for trace element analysis, and a 48‐hour recall on food intake was obtained from every second subject.

Endothelial Dysfunction After Repeated Chlamydia pneumoniae Infection in Apolipoprotein E–Knockout Mice

BackgroundArterial 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 repeated Chlamydia pneumoniae inoculation. Methods and ResultsForty-eight apoE-KO mice, 8 weeks old, were inoculated intranasally with C 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 of NG-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 and P <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. ConclusionsC pneumoniae impairs 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 of C pneumoniae infection in atherosclerosis development.

Serum Insulin and Other Cardiovascular Risk Indicators in Children, Adolescents and Young Adults

We wanted to determine the levels of fasting serum insulin during growth, the tracking of serum insulin, and the correlation of serum insulin with other coronary heart disease risk indicators in children and young adults. In 1986 2433 subjects, aged nine to 24 were studied, and insulin data were available from the same population in 1980 and 1983. Serum insulin levels showed a peak during puberty in both sexes and the decline in insulin continued after the age of 21. Tracking of serum insulin was only moderate, especially in females and young boys. Serum insulin correlated positively with body mass index, concentrations of serum triglycerides, and blood pressure, and inversely with the concentration of high density lipoprotein cholesterol. High triglycerides, high systolic blood pressure, and low level of high density lipoprotein cholesterol clustered among subjects within the highest insulin quartile. Our results suggest that the insulin resistance phenomenon, caused mainly by obesity and leading to unfavourable levels of other coronary heart disease risk indicators, is already developing in children and young adults. This suggests that preventing obesity in early life is important.

Acute infections in children are accompanied by oxidative modification of LDL and decrease of HDL cholesterol, and are followed by thickening of carotid intima-media.

BACKGROUND 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. METHODS 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). RESULTS 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). CONCLUSION 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.

Serum Lipids and Lipoproteins in Children, Adolescents and Young Adults in 1980–1986

A multicentre study on atherosclerosis precursors in young Finns aged three to 18 years was started in 1980 (3596 subjects) serum lipid concentrations (cholesterol, HDL (high density lipoprotein) cholesterol and triglycerides) were determined (n = 3554) and the apolipoproteins A-I and B measured (n = 1355). Two follow-up studies were carried out in 1983 (n = 2851) and 1986 (n = 2489), when HDL-subfractions (HDL-2-cholesterol and HDL-3-cholesterol) were also determined. Apolipoproteins A-I and B were measured again in 1986 (n = 1202). Serum total cholesterol concentration has fallen by about 1% annually during the 1980s from 5.07 mmol/l (1980) to 4.79 mmol/l (1986) in 9- to 18-year old children and adolescents. Mean values of serum triglycerides have slightly increased during the follow-up from 0.79 mmol/l to 0.84 mmol/l, respectively. In children and young adults (3-24 years) the mean cholesterol concentration was highest at the age of six and lowest during puberty. Concentrations of serum cholesterol, LDL (low density lipoprotein) cholesterol apoprotein B and triglycerides were higher in eastern than in western Finland in 1980 and 1983, but these differences were smaller in 1986, with the exception of serum triglycerides. Both in 1983 and in 1986 HDL-2-cholesterol was lower in the west than in the east, whereas HDL-3-cholesterol was higher in the former. The favourable changes in lipid levels should be reflected in future morbidity and mortality rates from coronary heart disease in Finland.

Early protein oxidation in the neonatal lung is related to development of chronic lung disease

Free radical‐mediated oxidation of proteins may impair their function and cause cellular damage. We studied pulmonary protein oxidation and its association with the development of chronic lung disease in 61 newborn infants (mean gestational age 31.1 ± 4.0, range 24‐41 weeks) requiring intensive care with oxygen therapy. Protein oxidation was quantified as protein carbonylation in tracheal aspirates recovered daily during the first week of life. Mean carbonyl concentration was 3.5 ± 1.6 μmol/mg protein. Negative correlations existed between protein carbonylation during days 2‐4 and gestational age (day 2: r= ‐0.37, p= 0.01; day 3: r= ‐0.48, p= 0.001; and day 4: r= ‐0.33, p= 0.03). Patients who developed bronchopulmonary dysplasia showed significantly higher protein carbonylation on days 1‐6 (all p < 0.05). In multiple regression analysis explaining bronchopulmonary dysplasia, using gestational age, inspired oxygen on days 1‐3 and protein carbonylation on day 3 as independent variables, only protein carbonylation remained significant. We conclude that immaturity is the most important factor explaining free radical‐mediated pulmonary protein oxidation in newborn infants and that oxidation of proteins is related to the development of chronic lung disease.

Atherosclerosis precursors in Finnish children and adolescents. IV. Serum lipids in newborns, children and adolescents

ABSTRACT. A multicentre study on atherosclerosis precursors in Finnish children and adolescents was carried out in five urban and 12 rural areas in the autumn of 1980 and spring of 1981. Serum lipids, i.e. cholesterol (TC), HDL‐cholesterol (HDL‐C) and triglyceride (TG) concentrations were determined and LDL‐cholesterol (LDL‐C) was calculated in 630 newborns and 3,596 children aged 3, 6, 9, 12, 15 and 18 years. In the newborns the mean serum TC concentration was 1.50 mmol/l, and the ratio of HDL‐C to TC was 0.44. Newborn boys had lower mean TC, HDL‐C and LDL‐C values than the girls. In 3 to 18‐year‐old children the mean TC, LDL‐C and HDL‐C concentrations were 4.83 mmol/l, 3.09 mmol/l and 1.38 mmol/l, respectively. During puberty, TC mean values decreased, more so in boys. The serum levels of HDL‐C also decreased, especially in boys, and after passing puberty boys had lower mean HDL‐C levels than girls (1.26 vs. 1.39 mmol/l, p

Myocardial function in children and adolescents after therapy with anthracyclines and chest irradiation

Cardiotoxicity is a potential adverse effect of anthracycline (A) therapy. Radiotherapy (XRT) may also cause a variety of cardiac complications. The purpose of the present study was to evaluate these cardiac side-effects in children and adolescents treated for cancer. We assessed the cardiac status of 91 patients, divided into three groups: Group A (n = 53) had anthracyclines at a mean cumulative dose of 410 mg/m2, group A+XRT (n = 26) had both chest irradiation (XRT) and A (mean 360 mg/m2), and group XRT (n = 12) had XRT alone. The patients differed from the controls in both systolic and diastolic indices of myocardial function. In echocardiography, the left ventricular (LV) contractility was abnormal in 32% in group A, in 50% in group A+XRT, and in 8% in group XRT. In radionuclide cineangiography, the LV ejection fraction was subnormal in 19% in group A, in 24% in group A+XRT, and in 1 patient in group XRT. A higher cumulative dose of A predicted decreased contractility. Treatment with A and/or XRT often leads to cardiotoxicity. Although in most cases this cardiotoxicity seems to be mild and subclinical, the long-term clinical sequelae merit further evaluation.

Computer-based detection and analysis of heart sound and murmur.

To develop a digital algorithm that detects first and second heart sounds, defines the systole and diastole, and characterises the systolic murmur. Heart sounds were recorded in 300 children with a cardiac murmur, using an electronic stethoscope. A Digital algorithm was developed for detection of first and second heart sounds. R-waves and T-waves in the electrocardiography were used as references for detection. The sound signal analysis was carried out using the short-time Fourier transform. The first heart sound detection rate, with reference to the R-wave, was 100% within 0.05–0.2R-R interval. The second heart sound detection rate between the end of the T-wave and the 0.6R-R interval was 97%. The systolic and diastolic phases of the cardiac cycle could be identified. Because of the overlap between heart sounds and murmur a systolic segment between the first and second heart sounds (20–70%) was selected for murmur analysis. The maximum intensity of the systolic murmur, its average frequency, and the mean spectral power were quantified. The frequency at the point with the highest sound intensity in the spectrum and its time from the first heart sound, the highest frequency, and frequency range were also determined. This method will serve as the foundation for computer-based detection of heart sounds and the characterisation of cardiac murmurs.

Echocardiographic study of the morphology and growth of the aortic arch in the human fetus. Observations related to the prenatal diagnosis of coarctation.

BackgroundIn a study of normal and abnormal growth of the aorta before birth, high-resolution echocardiographic imaging of the aortic arch in 92 normal fetuses aged 16–38 weeks was used to establish normal values for aortic arch dimensions at varying gestational ages. Methods and ResultsFrom long-axis views of the aortic arch, the internal diameter of the aortic root, ascending aorta, transverse aortic arch, aortic isthmus, proximal descending thoracic aorta, and left common carotid artery were measured. Correlation coefficients for the diameter of each aortic arch segment when related to gestational age varied from r=0.87 to r=0.94 (p<0.001 for each), and growth curves were derived from the third and 97th percentiles around each linear regression analysis. In most of the fetuses, there was progressive tapering of the aortic arch, with the smallest diameter being at the isthmus. The ratio of the transverse aorta, isthmus, descending aorta, and aortic root to the ascending aorta remained relatively constant with gestational age, with mean values of 0.94, 0.81, 0.96, and 1.13, respectively. In five fetuses in whom a prenatal diagnosis of aortic coarctation was confirmed postnatally, transverse aortic and isthmic measurements fell on or below the third percentile for gestational age from the above data. In each case, the ratio of left common carotid artery to transverse aorta was ≥0.73 compared with ≤0.62 for the 92 normal fetuses (mean ratios, 0.77±0.05 [SD] for coarctation versus 0.48±0.08 for normal fetuses; p ≤0.001). ConclusionsUse of normal growth curves for the developing aortic arch should facilitate the prenatal diagnosis of left heart and aortic arch abnormalities, particularly aortic coarctation, which until recently has been a difficult prenatal diagnosis to make with certainty.