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Biomedical subjects

J C Seidell

Publications and source records attributed to J C Seidell.

At least 109 records · Page 6Linked to original sources

Smoking and relative body weight: an international perspective from the WHO MONICA Project.

STUDY OBJECTIVE: To investigate the magnitude and consistency of the associations between smoking and body mass index (BMI) in different populations. DESIGN: A cross sectional study. SETTING AND PARTICIPANTS: About 69,000 men and women aged 35-64 years from 42 populations participating in the first WHO MONICA survey in the early and mid 1980s. MAIN RESULTS: Compared to never smokers, regular smokers had significantly (p < 0.05) lower median BMI in 20 (men) and 30 (women) out of 42 populations (range -2.9 to 0.5 kg/m2). There was no population in which smokers had a significantly higher BMI than never smokers. Among men, the association between leanness and smoking was less apparent in populations with relatively low proportions of regular smokers and high proportions of ex-smokers. Ex-smokers had significantly higher BMI than never smokers in 10 of the male populations but in women no consistent pattern was observed. Adjustment for socioeconomic status did not affect these results. CONCLUSIONS: Although in most populations the association between smoking and BMI is similar, the magnitude of this association may be affected by the proportions of smokers and ex-smokers in these populations.

Adult↗

Common C-to-T substitution at position -480 of the hepatic lipase promoter associated with a lowered lipase activity in coronary artery disease patients.

We studied the molecular basis of low hepatic lipase (HL) activity in normolipidemic male patients with angiographically documented coronary artery disease (CAD). In 18 subjects with a lowered HL activity (< 225 mU/mL), all nine exons of the HL gene and part of the promoter region (nucleotides -524 to +7) were sequenced. No structural mutations in the coding part of the HL gene were found, but 50% of the subjects showed a C-to-T substitution at nucleotide -480. Screening for the base substitution in 782 patients yielded an allele frequency of 0.213 (297 heterozygotes, 18 homozygotes). In a group of 316 nonsymptomatic control subjects, the allele frequency was 0.189, which is significantly less than in the CAD patients (P = .035). In the CAD patients, the C-to-T substitution was associated with a lowered lipase activity (heterozygotes -15%, homozygotes -20%). The patients were divided into quartiles on the basis of HL activity. Sixty percent (allele frequency 0.32) of the patients in the lowest quartile (HL activity < 306 mU/mL) had the gene variant against 27% (allele frequency 0.14) in the highest quartile (HL activity > 466 mU/mL). In the noncarriers, but not in the carriers, HL activity was related with plasma insulin, being increased at higher insulin concentration. Homozygous carriers had a significantly higher HDL cholesterol level-than noncarriers (1.13 +/- 0.28 mmol/L versus 0.92 +/- 0.22 mmol/L, P < .02). Our results show that a C-to-T substitution at -480 of the HL promoter is associated with a lowered HL activity. The base substitution, or a closely linked gene variation, may contribute to the variation in HL activity and affect plasma lipoprotein metabolism.

Alleles↗

Heterogeneity at the CETP gene locus. Influence on plasma CETP concentrations and HDL cholesterol levels.

This study was designed to investigate the association(s) between heterogeneity at the cholesteryl ester transfer protein (CETP) gene locus, CETP plasma concentrations, and HDL cholesterol levels. Healthy men with the lowest, median, and highest deciles of HDL cholesterol were selected from a large population database. We accounted for factors that are known to influence HDL cholesterol levels, such as smoking, exercise, body mass index, alcohol consumption, and blood pressure. Plasma CETP concentrations were measured, and we determined the allele frequency distribution of six CETP DNA polymorphisms. The group with low HDL cholesterol exhibited a significant increase in CETP concentration compared with both the median and high HDL cholesterol groups, whereas CETP concentrations did not differ among the groups with median and high HDL cholesterol. The allele frequency distributions of the TaqIB (intron 1), Msp I (intron 8), and Rsa I (exon 14) polymorphisms differed significantly between the groups with low and high HDL cholesterol. Further analysis revealed that the Msp I polymorphism had a 1.5-fold larger impact on CETP concentration than the TaqIB polymorphism and a fivefold larger impact than the Rsa I polymorphism. In conclusion, we demonstrated that heterogeneity at the CETP gene locus is correlated with CETP plasma concentrations and HDL cholesterol levels. More specifically, our data indicate the presence of a strong association between common variants of the CETP gene, high plasma CETP concentrations, and consequently hypoalphalipoproteinemia in healthy white men.

Carrier Proteins↗

Ser447stop mutation in lipoprotein lipase is associated with elevated HDL cholesterol levels in normolipidemic males.

This report describes the association between a frequent mutation in the lipoprotein lipase (LPL) gene and HDL cholesterol levels. It concerns a previously described defect that predicts a premature truncation of the LPL protein (447stop). We determined the frequency of this mutation in three groups of healthy men with low-, middle-, and upper-decile HDL cholesterol. The number of carriers of the 447stop allele was significantly greater in the high HDL group than in either the groups with normal HDL (P = .017) or low HDL (P < .0001). Additional functional assessment of this mutation did not reveal distinct differences between wild-type LPL and the LPL447stop protein. In conclusion, we have shown that the 447stop mutation is associated with increased HDL cholesterol in healthy Dutch males, although the underlying mechanism remains to be elucidated. Because HDL cholesterol is strongly inversely related with CAD, this genotype might be of potential benefit to its carriers.

Adult↗

Reversal of the sex difference in serum leptin levels upon cross-sex hormone administration in transsexuals.

Women have higher circulating leptin levels than men. This sex difference is not simply explained by differences in the amount of body fat and is possibly influenced by their different sex steroid milieus. This prompted us to study prospectively the effects of cross-sex steroid hormones on serum leptin levels in 17 male to female transsexuals and 15 female to male transsexuals. Male to female transsexuals were treated with 100 micrograms ethinyl estradiol and 100 mg cyproterone acetate (antiandrogen) daily, and female to male transsexuals received testosterone esters (250 mg/2 weeks, im). Before and after 4 and 12 months of cross-sex hormone treatment, serum leptin levels and measures of body fatness were assessed. Before treatment, female subjects had higher serum leptin levels than male subjects independently of the amount of body fat (P < 0.01). Cross-sex hormone administration induced a reversal of the sex difference in serum leptin levels. Estrogen treatment in combination with antiandrogens in male subjects increased median serum leptin levels from 1.9 ng/mL before treatment to 4.8 ng/mL after 4 months and 5.5 ng/mL after 12 months of treatment (P < 0.0001). Testosterone administration in female subjects decreased median serum leptin levels from 5.6 to 2.6 ng/mL after 4 months and to 2.5 ng/mL after 12 months (P < 0.0001). Analysis of covariance revealed that the changes in serum leptin levels were independent of changes in body fatness in both groups (P < 0.01). In conclusion, these results indicate that sex steroid hormones, in particular testosterone, play an important role in the regulation of serum leptin levels. The prevailing sex steroid milieu, not genetic sex, is a significant determinant of the sex difference in serum leptin levels.

Adipose Tissue↗

Long-term testosterone administration increases visceral fat in female to male transsexuals.

The amount of intraabdominal (visceral) fat is an important determinant of disturbances in lipid and glucose metabolism. Cross-sectional studies in women have found associations between high androgen levels and visceral fat accumulation. The causal relation between these phenomena is unknown. We, therefore, studied prospectively the effect of testosterone administration on body fat distribution in 10 young, nonobese, female to male transsexuals undergoing sex reassignment. Before, after 1 yr, and after 3 yr of testosterone administration, magnetic resonance images were obtained at the level of the abdomen, hip, and thigh to quantify both sc and visceral fat depots. After 1 yr of testosterone administration, sc fat depots at all levels showed significant reductions compared to baseline measurements. The mean visceral fat area did not change significantly, but subjects who gained weight in the first year after testosterone administration showed an increase in visceral fat. After 3 yr of testosterone administration, sc fat depots were no longer significantly lower compared to pretreatment measurements, but the mean visceral fat depot had increased significantly by 13 cm2 (95% confidence interval, 4-22 cm2), a relative increase of 47% (95% confidence interval, 8-91%) from baseline. The increase in visceral fat was most pronounced in those subjects who had gained weight. We conclude that long term testosterone administration in young, nonobese, female subjects increases the amount of visceral fat. In addition, an increase in weight in this hyperandrogenic state leads to a preferential storage of fat in the visceral depot.

Abdomen↗

Overweight, underweight, and mortality. A prospective study of 48,287 men and women.

BACKGROUND: The relative contributions of a low and high body mass index (BMI [weight in kilograms divided by height in meters squared]) to all-cause and cause-specific mortality are still controversial. OBJECTIVE: To examine mortality rates in relation to BMI in a prospective cohort study of 48,287 Dutch men and women aged 30 to 54 years at baseline from 1974 to 1980. METHODS: During an average 12-year follow-up, 1319 deaths occurred. Relative risks (RRs) were calculated from the Cox proportional hazard model by using a BMI between 18.5 and 24.9 kg/m2 as the reference category. RESULTS: All-cause mortality was significantly increased in obese men (BMI, > or = 30 kg/m2; RR, 1.5; 95% confidence interval [CI], 1.1-2.0) and in underweight men (BMI, < 18.5 kg/m2; RR, 2.6; 95% CI, 1.8-3.9) but not in women. The increased risk in underweight men could be attributed to deaths within the first 5 years of follow-up and to lung cancer mortality among smokers. Coronary heart disease (CHD) mortality was about 3-fold higher among obese men and women. About 21% and 28% of CHD mortality in men and women, respectively, could be attributed to being overweight (BMI, > or = 25 kg/m2). The RR (but not the absolute risk) for CHD among obese men was still significant after adjustment for the presence of smoking, hypertension, hypercholesterolemia, and diabetes mellitus at baseline, and it was more pronounced for CHD among nonsmokers than among smokers (RR, 7.1; 95% CI, 2.3-21.7; and RR, 2.7; 95% CI, 1.5-4.7, respectively). CONCLUSIONS: Total mortality was increased in obese and underweight men but not in women. The increased mortality in overweight men was mainly attributable to CHD and, in underweight men, to early mortality and especially lung cancer mortality among smokers.

Adult↗

Waist circumference as a screening tool for cardiovascular risk factors: evaluation of receiver operating characteristics (ROC).

UNLABELLED: To evaluate the receiver operating characteristics (ROC) to determine the cutoffs of waist circumference as a potential population directed screening tool for hypercholesterolaemia (> or = 6.5 mmol/L), low high density lipoprotein cholesterol (< 0.9 mmol/L), and hypertension (treated and/or systolic > or = 160 and/or diastolic blood pressure > or = 95 mmHg), in 2183 men and 2698 women aged 20 to 59 years selected at random from Dutch civil registries. MAIN OUTCOME MEASURES: Height, weight, body mass index (BMI), waist circumference, total plasma cholesterol and high density lipoprotein cholesterol concentrations, and blood pressure. RESULTS: ROC curves showed that sensitivity equalled specificity at waist circumferences between 93-95 cm in men and 81-84 cm in women for identifying individual risk factors, and 92 cm in men and 81 cm in women for identifying those with at least one risk factor. Sensitivity and specificity were equal at levels between 61% to 69% for identifying individual risk factors, with positive predictions (56.8% in men and 37.8% in women) within 2% of those using previously defined 'Action Level 1' of waist circumference 94 cm in men and 80 cm in women (58.8% in men and 37.4% in women). Risk prediction by anthropometric methods was relatively low: ROC areas for identifying each risk factor by waist varied from 55% to 60%, and reached about 65% for identifying at least one risk factor. Height accounted for less than 0.3% of variance in waist circumference. Using BMI at 25 kg/m2 gave similar prediction to waist, but its combination with waist did not improve predictive values. CONCLUSIONS: Measurement of waist circumference 'Action Level 1' at 94 cm (37 inches) in men and 80 cm (32 inches) in women could be adopted as a simpler valid alternative to BMI for health promotion, to alert those at risk of cardiovascular disease, and as a guide to risk avoidance by self-weight management.

Adult↗

Autoantibodies against MDA-LDL in subjects with severe and minor atherosclerosis and healthy population controls.

Autoantibodies against oxidized low-density lipoprotein (LDL) have been reported to be associated with atherosclerosis. However, data are not consistent. We compared the titres of autoantibodies to malondialdehyde-modified LDL in three groups, a case group with angiographically documented severe coronary stenosis (> 80% stenosis in at least 1 vessel, n = 47), a hospital control group with minor stenosis on the coronary angiography (< 50% stenosis in all three major vessels, n = 47) and a healthy population control group with no history of coronary heart disease (n = 49). Age ranged from 26 to 68 years. Subjects were frequency-matched for gender distribution and storage time of the blood samples. No relevant differences in autoantibody titre between case and control groups were found. The mean autoantibody titres (+/- S.D.) were 1.44 +/- 1.82, 1.46 +/- 1.40 and 1.62 +/- 1.95 for cases, hospital controls and population controls, respectively. No correlations were found between autoantibody titre and age, number of cigarettes smoked and LDL or total cholesterol. Autoantibody titres were correlated with body mass index (r = 0.2) and high-density lipoprotein (HDL) (r = -0.2). Odds ratios (OR) were calculated by tertiles of autoantibody titres for the hospital control group and the population control group, respectively. Age-adjusted OR (95% confidence interval) for medium and high compared to low autoantibody titre were 0.76 (0.27-2.14) and 1.09 (0.39-2.95) for the comparison between cases and hospital controls and 1.09 (0.39-3.07) and 0.90 (0.32-2.56) for the comparison between cases and population controls. Adjustment for gender, body mass index, smoking habits and HDL yielded essentially the same results. This study does not support an association between autoantibody titres to oxidized LDL and the extent of coronary stenosis.

Adult↗

Obesity and fat distribution in relation to hot flashes in Dutch women from the DOM-project.

The authors studied obesity and fat distribution in relation to the occurrence of hot flashes in a population-based study comprising 2904 women aged 40-44 and 569 women aged 54-69 presenting for mammographic screening (the DOM-project). Women aged 40-44 in the upper tertiles of Quetelet's index and waist/hip ratio reported hot flashes significantly more often than women in the respective lower tertiles. These associations were independent of each other and independent of age. After adjustment for age, waist/hip ratio and menopausal status, the odds ratio comparing the upper tertile of Quetelet's index to the lower tertile was 1.70 (95% confidence interval, 1.30-2.21). After adjustment for age, Quetelet's index and menopausal status, the odds ratio comparing the upper tertile of waist/hip ratio to the lower tertile was 1.37 (95% CI, 1.05-1.78). In women aged 54-69 no significant associations between Quetelet's index and complaints of hot flashes were observed. Women in the upper tertile of waist/hip ratio reported hot flashes more often than women in the lower tertile, but this result was not significant (OR 1.38; 95% CI, 0.87-2.22).

Adult↗

Plasma factor VII and its relation to adipose tissue fatty acids and other atherogenic risk factors in healthy men.

In this study the authors examined the relationships of plasma factor VII (F-VII) to adipose tissue fatty acid composition, as an objective index of the habitual dietary fat intake, as well as to a number of other atherogenic risk factors in 60 healthy male volunteers (aged 38 years). Significant positive correlations were found between plasma F-VII [measured as antigen (F-VIIAg) and coagulant activity, using bovine thromboplastin (F-VIIbt)] and body mass index (BMI), waist-thigh girth ratio (WTR), cigarette smoking and plasma triglyceride concentration. After adjustment for BMI, only plasma triglycerides remained positively correlated with F-VII (r = 0 center dot 27, P = 0 center dot 03, and r = 0 center dot 29, P < 0 center dot 01, for F-VIIbt and F-VIIAg respectively). A significant positive relation was found between F-VII and the total proportion of fatty acid as monounsaturated fatty acid (r = 0 center dot 26, P < 0 center dot 05, for F-VIIAg), whereas inverse relations were found between F-VII, the total proportion of fatty acid as polyunsaturated fatty acid (r = -0 center dot 26 and r = -0 center dot 25, P < 0 center dot 05, for F-VIIbt and F-VIIAg respectively), polyunsaturated-saturated fat ratio (r = -0 center dot 25, P < 0 center dot 05, for F-VIIbt) and, more significantly, between F-VII and adipose-tissue alpha-linolenic acid (r = -0 center dot 29, P < 0 center dot 01, for F-VIIbt and r = -0 center dot 49, P < 0 center dot 001, for F-VIIAg). All these correlations remained significant after matching for BMI. In a multiple linear regression analysis, only adipose tissue alpha-linolenic acid was a negative and independent predictor of F-VIIAg (P = 0 center dot 004) and, at borderline significance, of F-VIIbt (P = 0 center dot 061) when allowance was made for BMI, WTR, smoking and plasma triglycerides. In conclusion, this study shows significant relations between F-VII and adipose tissue fatty acid composition in healthy male individuals; it supports the possibility that adipose tissue poly-unsaturated fatty acids, derived from dietary intake, play a role in the relation between F-VII and coronary heart disease (CHD), thus suggesting that high dietary polyunsaturated fatty acid intake (especially alpha-linolenic acid) may reduce the risk for CHD by an improvement of a number of risk factors, including a lowering of plasma F-VII (both activity and antigen).

Adipose Tissue↗

The white blood cell count: its relationship to plasma insulin and other cardiovascular risk factors in healthy male individuals.

OBJECTIVES: To evaluate the relationships of total and differential white blood cell (WBC) count to the components of the so-called insulin resistance syndrome. SUBJECTS AND DESIGN: The study population consisted of a random sample of 90 38-year-old healthy men with normal glucose tolerance. INTERVENTIONS: A 75 g oral glucose tolerance test was performed in all participants. MAIN OUTCOME MEASURES: Total and differential WBC count, lipids, blood pressure, plasma glucose, C-peptide and insulin (at fasting and 2 h after glucose load). RESULTS: Total WBC count correlated consistently with plasma 2-h glucose (r = 0.38; P < 0.001), fasting and 2-h postload insulin (r = 0.26 and r = 0.33; P < 0.01-0.001, respectively) and C-peptide (r = 0.28 and r = 0.32; P < 0.01-0.001) concentrations. Smokers had significantly higher total leukocytes (P < 0.01), neutrophils and lymphocytes than nonsmokers. Furthermore, total WBC count correlated positively with body mass index, blood pressure, plasma triglycerides, fibrinogen, and negatively with HDL cholesterol concentration. As differential WBC count, most variables correlated essentially to neutrophils and/or lymphocytes, whereas plasma insulin and C-peptide concentrations correlated essentially to lymphocytes and monocytes, but not to neutrophils. In a multiple linear regression analysis, only 2-h plasma glucose (P < 0.01) and fibrinogen (P < 0.05) were positive predictors of total WBC count after adjusting for all potentially confounding variables. CONCLUSIONS: The results indicate that increased, albeit normal, WBC count associates with the cluster of metabolic and haemodynamic disorders typical of the insulin resistance syndrome, and suggest that increased WBC count may be yet another component of this syndrome.

Adult↗

Do dietary and supplementary intakes of antioxidants differ with smoking status?

BACKGROUND: Differences in dietary and supplementary intake of antioxidants were determine between different categories of smokers and never-smokers. METHODS: Data from a large, cross-sectional, population-based study were used. Subjects (n = 4244) were divided into five smoking categories according to the number of cigarettes smoked per day. Differences in intake of antioxidants or frequency of supplement use were assessed using multiple linear regression analysis and multiple logistic regression analysis, adjusting for potential confounders such as age, body mass index, education level, alcohol intake, and total energy intake. RESULTS: Men who smoked > 20 cigarettes/day had significantly lower intakes of beta-carotene and especially ascorbic acid compared to those who never smoked, resulting from an almost 60% lower fruit intake. Moderate and heavy smoking women also had lower ascorbic acid and fruit intake but differences were not as large as in men. A higher percentage of female heavy smokers compared with never-smokers consumed vitamin C (21.1% versus 14.1%), vitamin E (5.6% versus 1.8%), and multivitamin supplements (18.5% versus 12.2%). Among men only the moderate smokers differed significantly from never-smokers in supplement intake, in the sense that male moderate smokers had a higher percentage of multivitamin use (15.3% versus 12.2%) compared to never-smokers. CONCLUSIONS: Male heavy smokers not only have a lower dietary antioxidant intake than never-smokers, but additionally seem to use supplementation relatively infrequently.

Adult↗

Waist circumference action levels in the identification of cardiovascular risk factors: prevalence study in a random sample.

OBJECTIVE: To determine the frequency of cardiovascular risk factors in people categorised by previously defined "action levels" of waist circumference. DESIGN: Prevalence study in a random population sample. SETTING: Netherlands. SUBJECTS: 2183 men and 2698 women aged 20-59 years selected at random from the civil registry of Amsterdam and Maastricht. MAIN OUTCOME MEASURES: Waist circumference, waist to hip ratio, body mass index (weight (kg)/height (m2)), total plasma cholesterol concentration, high density lipoprotein cholesterol concentration, blood pressure, age, and lifestyle. RESULTS: A waist circumference exceeding 94 cm in men and 80 cm in women correctly identified subjects with body mass index of > or = 25 and waist to hip ratios > or = 0.95 in men and > or = 0.80 in women with a sensitivity and specificity of > or = 96%. Men and women with at least one cardiovascular risk factor (total cholesterol > or = 6.5 mmol/l, high density lipoprotein cholesterol < or = 0.9 mmol/l, systolic blood pressure > or = 160 mm Hg, diastolic blood pressure > or = 95 mm Hg) were identified with sensitivities of 57% and 67% and specificities of 72% and 62% respectively. Compared with those with waist measurements below action levels, age and lifestyle adjusted odds ratios for having at least one risk factor were 2.2 (95% confidence interval 1.8 to 2.8) in men with a waist measurement of 94-102 cm and 1.6 (1.3 to 2.1) in women with a waist measurement of 80-88 cm. In men and women with larger waist measurements these age and lifestyle adjusted odds ratios were 4.6 (3.5 to 6.0) and 2.6 (2.0 to 3.2) respectively. CONCLUSIONS: Larger waist circumference identifies people at increased cardiovascular risks.

Adult↗

Obesity in Europe.

Obesity, defined as a body mass index > 30 kg/m2 is relatively common in Europe, particularly among women, and especially in Southern and Eastern European countries. Among men the distribution of body mass index values is surprisingly similar in most countries of Europe. Educational level is strongly inversely associated with the prevalence of obesity. Although differences in body mass index cannot entirely explain the large variation in risk factors and mortality from coronary heart disease, it can be shown that within populations an increased body mass index is associated with less favorable risk patterns. More research is needed to elucidate the reasons for the large variation in the prevalence of obesity among European women and to the health risks associated with obesity in different European countries.

Adult↗

Obesity and subcutaneous fat patterning in relation to survival of postmenopausal breast cancer patients participating in the DOM-project.

The effect of obesity and fat distribution on survival of breast cancer patients was studied prospectively in 241 women with a natural menopause who participated in a breast cancer screening project, the DOM-project in Utrecht, The Netherlands. Mean follow-up time was 9.1 years and endpoint of interest was death from breast cancer. Fat distribution was assessed by contrasting groups of subscapular and triceps skinfold thickness. No significant differences in survival time between more obese (Quetelet's index > or = 26 kg/m2) and leaner (Quetelet's index < 26 kg/m2) patients or between patients with central fat distribution and patients with peripheral fat distribution were observed. Analyses were stratified by axillary node status, estrogen receptor status, and way of detection (by first screening or afterwards). Results of the stratified analyses were suggestive of a modifying effect of these factors. The absence of an association between obesity and survival time might be explained by two counteracting mechanisms. On the one hand obesity might be related to impaired survival, due to a tumor growth promoting effect of extra-ovarian estrogens. On the other hand obesity might be related to improved survival in a screened population, because obese patients profit more from screening by earlier detection of tumors than leaner counterparts.

Adipose Tissue↗

Body fat distribution in relation to breast cancer in women participating in the DOM-project.

The association between body fat distribution and breast cancer risk was studied in 5923 pre- and 3568 post-menopausal women, participating in a breast cancer screening project (the DOM-project in Utrecht, the Netherlands). Cases were fifty six premenopausal women and thirty eight postmenopausal women with breast cancer detected at screening or afterwards. Controls were women participating in the breast cancer screening project without breast cancer. Waist- and hip circumferences, height and weight were measured at screening, before diagnosis of breast cancer. In postmenopausal women the estimated relative risk of women in the upper tertile of waist/hip ratio compared with women in the lower tertile was 1.89 (95% CI 0.80-4.48), (test for trend p = 0.11). The estimated relative risk of women in the upper tertile of waist circumference compared with women in the lower tertile was 2.86 (95% CI 1.12-7.32), (test for trend p = 0.08). The association between waist circumference and breast cancer was stronger than the association between any of the other anthropometric variables and breast cancer. In premenopausal women the association between fat distribution and breast cancer was equivocal.

Abdomen↗