E. Matti Nuutinen

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.

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.

Blood Pressure in Children, Adolescents and Young Adults

The question of whether blood pressure is one of the main risk factors for cardiovascular diseases in childhood has been evaluated in a Study of Cardiovascular Risk in Young Finns. In the second follow-up study, carried out in 1986, blood pressure was successfully measured in 2500 individuals aged nine to 24 years using a random zero sphygmomanometer. The mean systolic blood pressure in girls rose from 102 mmHg (95th percentile 119 mmHg) at age nine to 116 mmHg (138 mmHg) at age 24 and that in boys from 102 mmHg (95th percentile 121 mmHg) to 128 mmHg (148 mmHg). Diastolic blood pressure was more often measurable using Korotkoffs 5th than the 4th phase. The values observed were similar to those reported by the Second Task Force on Blood Pressure Control in Children, but owing to differences in the methods used to measure blood pressure it cannot be reliably concluded that the blood pressures were similar in the two series. Even in childhood blood pressure measurement is important, and since it changes wit...

THE GLUTAMATE DEHYDROGENASE SYSTEM AND THE REDOX STATE OF MITOCHONDRIAL FREE NICOTINAMIDE ADENINE DINUCLEOTIDE IN MYOCARDIUM

Knowledge of the redox state of the free NAD’/ NADH couple in the mitochondria is essential in assessing the state of mitochondrial terminal oxidations. This is particularly important because the principal level of regulation of cellular respiration in intact tissues such as the heart is still in dispute. The myocardial mitochondrial free NAD’/NADH ratio has, in a few instances, been estimated from the ratio of [2-oxoglutarate] [N&‘]/[glutamate] in the tissue, assuming that the glutamate dehydrogenase reaction is in equilibrium in myocardium [l-3]. The usefulness of the NADlinked glutamate dehydrogenase reaction in heart muscle has not found general acceptance, and its systematic validation is lacking. In the liver, the p-hydroxyburyrate dehydrogenase and glutamate dehydrogenase reactions are apparently in near equilibrium [4], but in the heart the activity of the former enzyme is l/2, and that of the latter l/3 of that found in the liver [4]. For these reasons and because the metabolic capacity of the heart for ketone bodies is high and their intracellular concentrations are low, it was pointed out [2] that calculations of the mitochondrial free NAD’/NADH ratios in heart tissue must be tempered with reservations. These experiments on isolated perfused rat hearts and suspensions of isolated heart mitochondria indicate that the glutamate dehydrogenase reaction can be used as an indicator of the redox state of the mitochondrial free NAD’ pool which is in equilibrium with the mitochondrial high fluorescence flavoprotein. Validation of this indicator metabolite method is especially important because the data obtained

Regional Differences in Apolipoprotein E Polymorphism in Finland

Apolipoprotein E (apoE) polymorphism is a genetic determinant of plasma lipid levels and of coronary heart disease risk. We determined apoE phenotypes and plasma lipid levels in 1564 subjects aged three to 18 years, living in five geographical areas of Finland in 1980. ApoE phenotyping was performed directly from plasma by isoelectric focusing and immunoblotting. The serum concentrations of total cholesterol, low density lipoprotein cholesterol and apolipoprotein B varied with apoE phenotype, and there were increases in all three variables (all P less than 0.001) of the order of E2/2 less than E3/2 less than E4/2 less than E3/3 less than E4/3 less than E4/4. These differences were present in all five areas. The mean levels of high density lipoprotein cholesterol, apolipoprotein A-I and triglyceride in the subjects did not differ between the apoE phenotypes or between their areas of residence. The apoE phenotype dependency of serum total and LDL cholesterol remained significant in all five areas during the six year follow-up from 1980 to 1986, when the mean level of serum total cholesterol fell by 5.8% in east (P less than 0.05) and by 4.4% in west Finland (P less than 0.05); the fall was steeper (P less than 0.01) in the east than the west. In all subjects, particularly those in west Finland, the size of the falls of serum total and LDL cholesterol concentrations depended on the apoE phenotype in the order of E3/2 less than E3/3 less than E4/3, but this effect was not seen in the east.(ABSTRACT TRUNCATED AT 250 WORDS)

The effect of cholinergic agonists on coronary flow rate and oxygen consumption in isolated perfused rat heart

The metabolic and circulatory consequences of activation of the muscarinic receptor(s) were investigated by local administration of acetylcholine and its three analogues (bethanechol, carbachol and methacholine) into beating and KCl-arrested perfused rat hearts. Acetylcholine and the three other choline esters caused vasoconstriction in both types of preparations and this vasoconstriction was accompanied by a decrease in oxygen consumption. In most cases the dose-response curves were biphasic and changes in coronary flow paralleled those in oxygen consumption. Both phenomena were abolished by administration of atropine and either removal of calcium or infusion of verapamil but were unaffected by addition of the adrenergic alpha-blocker, prazosin, and the adrenergic beta-blocker, propranolol. Infusions of low concentrations of the cholinergic agonists were accompanied by increases in the myocardial phosphorylation state ratio [( ATP]free/[ADP]free[Pi]) which correlated with the simultaneous decreases in oxygen consumption and coronary flow. It is suggested that muscarinic receptors responsible for vasoconstriction in perfused rat heart are located not only on coronary vessels but also on the cardiac muscle cells. Activation of the former receptors induces vasoconstriction by direct action on the vascular smooth muscle while activation of the latter receptors induces vasoconstriction indirectly by decreasing cardiac work and increasing the myocardial [ATP]free/[ADP]free[Pi] ratio. The results also show that stimulation of muscarinic receptor(s) and the consequent metabolic and vasoregulatory responses are coupled to calcium movements.

Two cases of large placental chorioangioma with fetal and neonatal complications

Two cases of infants born from pregnancies complicated by large placental chorioangiomas causing congestive heart failure in the neonate as the main complication are presented. Chorioangiomas may be diagnosed early in pregnancy by ultrasound examination. Since both their maternal and their neonatal complications may indicate premature termination of the pregnancy or be conducive to premature birth, repeated ultrasound examinations, including fetal echocardiography, are suggested in order to optimize the timing of the delivery.

Dependence of cellular metabolism and local oxygen delivery on oxygen tension.

It is recognized that the survival of nearly all mammalian cells is dependent on the availability of an adequate supply of oxygen. An elaborate and highly regulated vascular system is responsible for maintaining the proper oxygen tension at each region of the body, with some areas (such as the kidney) being higher than others (such as the liver). Thus the vascular system must not only deliver O2 at the rate it is being consumed by the tissue but also maintain the characteristic local oxygen tension. Studies on the oxygen dependence of pulmonary flow have indicated that the control sites are predominantly precapillary, residing particularly in the arterial and arteriolar vessel walls (Marshall and Marshall, 1983). The situation in skeletal muscle is more complex. Gorczynski and Duling (1978) observed the effect of electrical stimulation of small isolated groups of striated muscle cells in hamster cremaster muscle on arteriolar diameter and reported that arteriolar dilation preceded the decrease in local oxygen tension. The steady state amount of dilation, however, correlated with the steady state decrease in local oxygen tension.

The Oxygen Dependence of Mitochondrial Oxidative Phosphorylation and Its Role in Regulation of Coronary Blood Flow

The oxygen dependence of mitochondrial oxidative phosphorylation measured in isolated cells of cardiac and non-cardiac origin are affected by the metabolic state of the cells. The contribution of oxygen diffusion to the measured P50 value in resting cells is small. In cardiac myocytes, and possibly in the other cells as well, this contribution may become significant near maximal levels of respiration. The influence of cellular energy metabolism on the oxygen dependence of respiration in cardiac myocytes suggests strongly that mitochondrial oxidative phosphorylation in these cells is an oxygen sensor for adjusting coronary vascular tone during normal cardiac function.

Blood pressure in children, adolescents and young adults

The question of whether blood pressure is one of the main risk factors for cardiovascular diseases in childhood has been evaluated in a Study of Cardiovascular Risk in Young Finns. In the second follow-up study, carried out in 1986, blood pressure was successfully measured in 2500 individuals aged nine to 24 years using a random zero sphygmomanometer. The mean systolic blood pressure in girls rose from 102 mmHg (95th percentile 119 mmHg) at age nine to 116 mmHg (138 mmHg) at age 24 and that in boys from 102 mmHg (95th percentile 121 mmHg) to 128 mmHg (148 mmHg). Diastolic blood pressure was more often measurable using Korotkoffs 5th than the 4th phase. The values observed were similar to those reported by the Second Task Force on Blood Pressure Control in Children, but owing to differences in the methods used to measure blood pressure it cannot be reliably concluded that the blood pressures were similar in the two series. Even in childhood blood pressure measurement is important, and since it changes with the physical size of the child, observations should be compared with normal values such as those reported here. No data are yet available to suggest that children with blood pressure values in the high normal range would benefit from interventions. Thus normal blood pressure value curves should be applied with caution when assessing children.