Families and natural history of lipids in childhood: an 18-year follow-up study.

The natural history of total cholesterol and lipoprotein cholesterol in offspring was studied in relation to total cholesterol levels in their parents in the Epidemiological Prevention Study of Zoetermeer (EPOZ). All residents of 5 or more years who were living in two districts in the Dutch town of Zoetermeer were invited to participate in a study on indicators for chronic diseases between 1975 and 1978. In a random sample of 483 youngsters who were 5-19 years old, yearly measurements of cardiovascular risk factors were performed during a follow-up period of 18 years (average follow-up, 13.8 years). Total and subfraction cholesterol levels in offspring during follow-up were studied by tertiles of age-adjusted total cholesterol in their parents. Total and low density lipoprotein (LDL) cholesterol levels measured from childhood into young adulthood differed significantly between offspring whose fathers were in the highest total cholesterol tertile compared with those whose fathers were in the lowest tertile, amounting to 0.4 mmol/liter for total cholesterol and 0.5 mmol/liter for LDL cholesterol. Offspring differences by maternal tertiles amounted to 0.5 mmol/liter for total cholesterol and 0.6 mmol/liter for LDL cholesterol. Offspring (n = 53) with both parents in the upper cholesterol tertile had almost 1 mmol/liter higher cholesterol levels compared with offspring (n = 51) with both parents in the lowest tertile, whereas offspring (n = 48) with both parents in the middle tertile had intermediate levels. Differences remained after adjustment for sex, Quetelet index, systolic and diastolic blood pressure, and use of alcohol, cigarettes, and oral contraceptives. Offspring group differences in total and LDL cholesterol were already present in childhood and persisted into young adulthood. There was no clear relation between offspring change in cholesterol levels and parental total cholesterol levels. For high density lipoprotein cholesterol and its subfractions, no relations with parental total cholesterol levels were found. Based on the evidence of a strong positive relation between total cholesterol levels in parents and offspring levels of total and LDL cholesterol measured from childhood into young adulthood, the authors conclude that total and LDL cholesterol levels in offspring may already be characterized from young age and beyond through cholesterol levels in their parents.

Lipoproteins and apolipoproteins in the young and familial risk of coronary atherosclerosis.

The aim of this study was to assess the predictive value of lipoproteins and apolipoproteins at a young age for the development of coronary artery disease at middle and older ages. Because children of coronary artery disease patients are at high risk themselves we compared lipoprotein and apolipoprotein levels between the offspring of parents with and without coronary artery disease. We selected a group of male patients (n = 90), who had severe coronary atherosclerosis at angiography, and a reference group of male controls (n = 62), who had no coronary atherosclerosis at angiography. Lipoprotein and apolipoprotein levels were determined in 115 sons and 73 daughters of the patients with severe coronary atherosclerosis. These were compared to levels in 68 sons and 47 daughters of controls. Additionally, lipoprotein and apolipoprotein levels were compared between patients and controls as well as between their spouses. In sons of patients, lower levels of HDL3 cholesterol (-0.07 mmol/1, standard error of the mean (SEM) 0.03, P < 0.05) and apolipoprotein A2 (-5.1 mg/dl (SEM, 1.4), P < 0.0001) were found compared to sons of controls. Similar differences were observed in daughters of such patients without, however, achieving statistical significance. No significant differences between the groups of offspring were found for total cholesterol, LDL cholesterol, HDL and HDL2 cholesterol, triglycerides and apolipoproteins A-I and B. Patients had higher levels of total (group difference 0.6 mmol/1 (SEM, 0.18), P < 0.001) and LDL cholesterol (0.6 mmol/1 (SEM, 0.17), P < 0.001), triglycerides (0.6 mmol/1 (SEM, 0.16), P < 0.001) and apolipoprotein B (21.2 mg/dl (SEM, 5.1), P < 0.001), and lower HDL cholesterol (0.1 mmol/1 (SEM, 0.04), P < 0.05) than controls. Spouses of patients had higher levels of triglycerides (0.23 mmol/1 (SEM, 0.11), P < 0.05). Our findings add to the growing evidence that predictors for atherosclerotic disease can be detected relatively early in life. It is concluded that reduced levels of HDL3 cholesterol and apolipoprotein A2 may be early risk indicators for coronary atherosclerosis later in life.

[Prevalence of chronic diseases in the elderly; the ERGO study (Erasmus Rotterdam Health and the Elderly)]. / De prevalentie van chronische ziekten bij ouderen; het ERGO-onderzoek.

In the Rotterdam Study, prevalence and determinants of chronic diseases in the elderly (age > or = 55 years), were investigated in inhabitants of Ommoord, a suburb of Rotterdam. The study focused on cardiac diseases (myocardial infarction, angina pectoris, cardiovascular risk factors), glaucoma, macular degeneration, osteoporosis, osteoarthrosis and invalidity, dementia (Alzheimer's disease, vascular dementia, Parkinson's disease), epilepsy, cerebrovascular accident. The number of participants was 7983 (3105 men, 4878 women), a response of 78%. The participants were interviewed and were twice examined in an out-patient clinic. The results will be described in subsequent issues of this journal.

Elevated plasma chitotriosidase activity in various lysosomal storage disorders.

Recently a striking elevation of the activity of chitotriosidase, an endo beta-glucosaminidase distinct from lysozyme, was found in plasma from patients with Gaucher type I disease (McKusick 230800). Plasma chitotriosidase originates from activated macrophages and this elevation is secondary to the basic defect in Gaucher disease. To investigate the specificity of this phenomenon, we have investigated 24 different lysosomal storage diseases. In 11 different diseases increased chitotriosidase activity in plasma was found (in 28% of the patients). None of these diseases showed elevations as high as in Gaucher disease. Chitotriosidase was not significantly elevated in plasma from 20 different non-lysosomal enzymopathies or in plasma from patients with infectious diseases associated with hepatomegaly. The results show that marked elevation of chitotriosidase activity in plasma appears to be specific for Gaucher disease. The data further suggest that elevated levels of chitotriosidase activity in plasma from patients with unexplained diseases may be indicative for a lysosomal disorder.

Reference values for apolipoprotein A-I and apolipoprotein B in serum still depend on choice of assay techniques.

In a study with young children receiving growth hormone treatment, it was necessary to re-establish reference values for various blood components, e.g. apolipoproteins A-I and B. We find that considerable method-to-method variation still exists. We used the DuPont Dimension analyzer (D) and the Beckman Array analyzer (B) systems and a third procedure with Orion reagents and a Kone Analyzer (K). We investigated if assay results may be pooled or exchanged within our study. In 59 serum samples we measured apolipoprotein A-I and apolipoprotein B (n = 58) and calculated the orthogonal regression equations y = a(Sa) x + b(Sb). For apolipoprotein A-I the results are: (I) B = 1.165 (0.065) D - 0.193 (0.077), Syx = 0.055; with r = 0.922 and (II) K = 0.831 (0.056) D - 0.190 (0.066), Syx = 0.055; with r = 0.898. For apolipoprotein B the equations are: (III) B = 1.586 (0.137) D - 0.246 (0.100), Syx = 0.061; with r = 0.840 and (IV) K = 0.869 (0.065) D + 0.251 (0.048), Syx = 0.044; with r = 0.875. According to Passing & Bablok, the slopes and intercept values are 1.093 and -0.126; 0.848 and 0.167; 1.500 and -0.185; 0.880 and 0.249. The overall impression is the same for both regression methods: comparability had not yet been achieved by early 1993, particularly not for apolipoprotein B, and reference values differ significantly depending on the selected methodology.

Postprandial triglyceride response in young adult men and familial risk for coronary atherosclerosis.

OBJECTIVE: To determine whether an increased familial risk for coronary artery disease in young adult men is related to changes in postprandial lipoprotein metabolism. DESIGN: Cross-sectional study. SETTING: Coronary angiography departments of four central general hospitals in the Netherlands. PATIENTS: 80 sons (mean age, 24.8 years) of men with severe coronary artery disease and 55 sons (mean age, 23.2 years) of controls. MEASUREMENTS: Postprandial levels of serum triglycerides, retinyl palmitate, and total cholesterol were measured during a 12-hour period after a standardized oral lipid load. RESULTS: Both groups showed a marked increase in levels of serum triglyceride and retinyl palmitate after lipid loading, reaching a maximum 4 to 6 hours postprandially. No changes in postprandial total cholesterol levels were observed in either group. Sons of men with coronary artery disease had prolonged postprandial hypertriglyceridemia when compared with sons of controls. Significant differences in postprandial triglyceride levels were found at 8 hours (difference, 0.35 mmol/L; 95% CI, 0.07 to 0.62 mmol/L), at 10 hours (difference, 0.21 mmol/L; CI, 0.06 to 0.36 mmol/L), and at 12 hours after lipid loading (difference, 0.13 mmol/L; CI, 0.01 to 0.26 mmol/L). Levels of postprandial retinyl palmitate were also slightly, but not statistically, different (mainly after 6 hours). CONCLUSIONS: Healthy young adult sons, whose fathers have established coronary artery disease, have prolonged postprandial hypertriglyceridemia. Changes in postprandial lipoprotein metabolism appear to be associated with familial risk for coronary atherosclerosis.

Reduction of blood pressure with oral magnesium supplementation in women with mild to moderate hypertension.

In a double-blind controlled trial, 91 middle-aged and elderly women with mild to moderate hypertension who were not on antihypertensive medication were randomly assigned to treatment with magnesium aspartate-HCl (20 mmol Mg/d) or placebo for 6 mo. Magnesium aspartate-HCl in the given dose was well-tolerated and was not associated with an increased frequency of diarrhea compared with placebo. At the end of the study, systolic blood pressure had fallen by 2.7 mm Hg (95% CI -1.2, 6.7; P = 0.18) and diastolic blood pressure by 3.4 mm Hg (1.3, 5.6; P = 0.003) more in the magnesium group than in the placebo group. Blood pressure response was not associated with baseline magnesium status, as measured by dietary magnesium intake and urinary magnesium excretion. Urinary magnesium excretion in the magnesium group increased by 50% during the intervention period. No changes were seen in other biochemical indexes, including serum concentrations of total and high-density-lipoprotein cholesterol. The findings suggest that oral supplementation with magnesium aspartate-HCl may lower blood pressure in subjects with mild to moderate hypertension.

Do oral contraceptives increase blood pressure and serum total cholesterol in young women?

The effects of the use of oral contraceptives on serum lipids and blood pressure were studied among young women who participated in a longitudinal survey of risk factors for coronary heart disease (CHD) in the Netherlands. Fifty-three participants, ages 14 to 24 years, initiated oral contraceptive use during follow-up to the primary study on CHD. They continued oral contraceptive use for at least 2 subsequent years. From 53 age-matched control subjects, who did not use oral contraceptives, data were obtained for the same follow-up period. Women using oral contraceptives showed a significantly greater rise in serum total cholesterol levels than did the reference subjects (14 mg/100 ml/2 year vs 4 mg/100 ml/2 year; 95% confidence interval of the difference was 0.1 to 19.6). The increase in systolic blood pressure (4.7 mm Hg/2 year vs 2.1 mm Hg/2 year; 95% confidence interval of the difference was -1.8 to 6.9) did not differ between the groups. These findings suggest that oral contraceptive use may be associated with an enhanced rise in total cholesterol during adolescence.

Selenium status and cardiovascular risk factors in healthy Dutch subjects.

To provide further insight into the possible role of selenium in cardiovascular disease, we examined the relationship between cardiovascular risk factors, some nutritional parameters, and short- and long-term selenium status. A total of 82 healthy Dutch volunteers, 59 men and 23 women, aged 40-75 years, were studied. Means and standard deviations of selenium parameters were: plasma selenium 106.4 +/- 23.7 micrograms/L, erythrocyte selenium 0.59 +/- 0.19 microgram/g Hb, toenail selenium 0.78 +/- 0.17 ppm, and erythrocyte glutathione peroxidase activity 28.0 +/- 8.1 U/g Hb. No association was found between selenium status and gender, age, serum total-, LDL-, and HDL-cholesterol, systolic and diastolic blood pressure, alcohol intake, and body mass index. A significantly lower plasma selenium level was observed among smokers compared to nonsmokers (101.0 micrograms/L, SE = 3.9 vs 112.0 micrograms/L, SE = 3.6, p = 0.04). A significant negative association was found between erythrocyte selenium and serum levels of vitamin A and ferritin. No relevant relationship was observed between selenium status and serum fatty acid composition, vitamin E, vitamin B6, and iron. Apart from an association between smoking and short-term selenium status, we found no indications that a possible effect of selenium on cardiovascular disease may operate through the known risk factors.

Decreased selenium levels in acute myocardial infarction.

To study the association between selenium status and the risk of myocardial infarction, we compared plasma, erythrocyte, and toenail selenium levels and the activity of erythrocyte glutathione peroxidase among 84 patients with acute myocardial infarction and 84 population controls. Mean concentrations of all selenium measurements were lower in cases than controls. The differences were statistically significant, except for the plasma selenium level. A positive trend in the risk of acute myocardial infarction from high to low toenail selenium levels was observed, which persisted after adjustment for other risk factors for myocardial infarction. In contrast, erythrocyte glutathione peroxidase activity was significantly higher in cases than controls (31.3 +/- 8.4 U/g of hemoglobin and 28.0 +/- 8.1 U/g of hemoglobin, respectively). Because the toenail selenium level reflects blood levels up to one year before sampling, these findings suggest that a low selenium status was present before the infarction and, thus, may be of etiologic relevance. The higher glutathione peroxidase activity in the cases may be interpreted as a defense against increased oxidant stress either preceding or following the acute event.

Characteristics of the mitogenic activity found in the supernatant of pokeweed mitogen stimulated human mononuclear cells.

Human peripheral blood mononuclear cells were stimulated with pokeweed mitogen (PWM), washed, and cultured in fresh mitogen-free culture medium; a second set of peripheral blood mononuclear cells was used to assess the mitogenic activity of supernatants of these cultures. The effects of this stimulation resembled those of a normal PWM stimulation, including the formation of blast cells, proliferation of lymphoid cells, and immunoglobulin synthesis. Our findings led us to perform experiments to investigate the nature of this mitogenic factor. The molecular weight of the mitogenic activity was found in the region of 700 kD. Additional experiments indicated that human alpha 2-macroglobulin was not responsible for the high molecular weight of the mitogenic factor. Protein digestion or precipitation with trichloroacetic acid only partially abolished the mitogenicity of the mitogenic supernatant. Comparison of the molecular weight of the mitogenic factor with that of the PWM in culture medium showed that the mitogenic activity in the supernatants could be caused by PWM associated with a high molecular weight component.

Serum lipids in young women before, during, and after pregnancy.

The associations between pregnancy and serum lipids were investigated in a cohort of 831 Dutch women, initially aged 5-19 years. These women were examined yearly from 1975 to 1985 for an average period of six years, as part of a longitudinal survey of risk factors for coronary heart disease. During this period, 62 women became pregnant, and their serum total and high density lipoprotein (HDL) cholesterol levels were compared with those of an age-matched reference series of nonpregnant women, derived from the same cohort. Pregnant women showed higher total cholesterol levels (235 +/- 7.4 mg/100 ml) than nonpregnant women (205 +/- 2.7 mg/100 ml). Pregnant women also had higher levels of HDL cholesterol (66 +/- 2.1 mg/100 ml) than their referents (57 +/- 1.0 mg/100 ml). Total and HDL cholesterol increased with duration of pregnancy. When serum lipid levels of pregnant women were compared with the levels one year before and one year after pregnancy, it was observed that the year after pregnancy, HDL cholesterol levels dropped below pre-pregnancy concentrations. At the final examination, women who had ever been pregnant showed lower HDL cholesterol levels than those who had never been pregnant. The difference was most marked in users of oral contraceptives. These observations suggest that serum total and HDL cholesterol levels are elevated during pregnancy, probably because of hormonal changes. Furthermore, they point to a possibly lowering effect of parity on HDL cholesterol. These findings may help to explain the reported positive association between parity and the occurrence of cardiovascular diseases.

Selenium status and chronic disease mortality: Dutch epidemiological findings.

This paper summarizes Dutch epidemiological findings on the impact of a low selenium (Se) status on mortality from cardiovascular disease (CVD) and cancer. Se status parameters of Dutch subjects are compared to those from Finland and the USA, and the concept of a threshold effect for Se on disease risk is discussed. Case-control analyses of prospective data suggest that low serum Se (below 105 micrograms/l) is not clearly associated with an excess risk of CVD death (relative risk RR = 1.6, 90% confidence interval Cl = 0.9-2.9). Se cancer findings indicate a possible gender difference in risk (in males RR = 2.7, 90% Cl = 1.2-6.2; in females RR = 1.5, 90% Cl = 0.5-4.5). Larger studies, monitoring a combination of Se status parameters are recommended.

Serum selenium, vitamin antioxidants, and cardiovascular mortality: a 9-year follow-up study in the Netherlands.

The association between low serum selenium, vitamin A, and vitamin E levels and mortality from cardiovascular disease (CVD) was investigated in a case-control study nested in a 9-yr prospective study in the Netherlands. For 10,532 persons aged greater than or equal to 5 yr who participated in a 1975-1978 medical survey, serum was stored at -20 degrees C. For the 84 of 106 subjects aged 37-87 yr who died of CVD after the baseline exam, 168 cohort members alive at the end of 1983 and matched for age and gender were selected as controls. No significant associations between serum selenium. vitamin A, vitamin E, and CVD mortality were observed before and after multivariate analyses. The adjusted risk of death from CVD for subjects in the lowest selenium quintile (less than 105.0 micrograms/L) was 1.6 (95% CI, 0.8-3.2). For coronary and stroke death risk, estimates were 1.1 (95% CI, 0.5-2.6) and 3.2 (95% CI, 0.8-12.1). Our findings do not show a clear CVD risk from low selenium and vitamin levels. Although some of the risk estimates were strong, larger studies are required for definitive conclusions.

Is serum selenium a risk factor for cancer in men only?

The association of serum selenium with the subsequent risk of death from cancer was investigated in a case-control study that was nested in a prospective nine-year follow-up study in the Netherlands. In 1975-1978, 10,532 persons in the Dutch town of Zoetermeer who were aged five years or more participated in a medical survey. Serum samples were collected and stored at -20 C. For the 82 persons who died of cancer since the baseline examination, 164 cohort members still alive by the end of 1983 were selected as controls and matched for age, sex, and smoking. Cancer deaths that occurred in the first year of follow-up were excluded, leaving 69 cases for statistical analyses. The mean serum selenium level of 116.7 +/- 4.0 micrograms/liter among male cancer deaths (n = 40) was significantly different (p = 0.04) from that in the control subjects (126.4 +/- 3.1 micrograms/liter). In females, selenium levels were similar among cases and controls. The adjusted risk of death from cancer for men in the lowest quintile of serum selenium (below 100.8 micrograms/liter) was more than twice that of subjects with higher levels (relative risk = 2.7,90% confidence interval = 1.2-6.2). These data support recent findings of an increased cancer risk associated with low serum selenium levels in men but not in women.

Distributions and determinants of total and high-density lipoprotein cholesterol in Dutch children and young adults.

Serum total cholesterol and its putative determinants were measured in 5,089 subjects, ages 5-30 years, comprising 76% of the total population of two districts of the Dutch town of Zoetermeer. From this group, 596 subjects, ages 5-19 years, were randomly selected, and distributions and determinants of high-density lipoprotein (HDL) cholesterol were studied in 458 of them. The variables studied included body weight; Quetelet index; menarche; parental cholesterol; physical activity; consumption of coffee, alcohol, and tobacco; and use of oral contraceptives. Mean total cholesterol levels showed a decrease in both boys and girls between the ages of 10 and 16 years. Mean HDL cholesterol levels remained the same until the age of 17, after which they showed an increase for females and a decrease for males. Total cholesterol was associated with age, body weight (in those older than 15 years), and parental cholesterol concentrations. For HDL cholesterol, the most important determinants were gender, age, and body weight (the latter only for males 15 years and older). These findings suggest that during growth and maturation the determinants of serum cholesterol differ from those later on in life.

The effect of the diffusion medium on quantification of human IgM by radial immunodiffusion.

The results of quantification of human IgM by radial immunodiffusion (RID) are influenced by the charge of the diffusion medium and by the radio of IgM to other serum proteins. Agarose has almost no influence, while some heavily charged agars are unsuitable for RID, even after reduction of the IgM. Reference and test sera should not differ too widely in IgM levels. The interaction between charged agar and human IgM explains the subgroup phenomenon described earlier by Klein et al. (1973).