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Several studies have reported that elevated plasma levels of total homocysteine (tHcy) are related to an increased risk of cardiovascular disease. Only a few studies have looked at the effect of cysteine, another amino thiol, on cardiovascular disease risk. Therefore, in the present case-control study we compared plasma total cysteine (tCys) levels and plasma tHcy levels among subjects with severe coronary atherosclerosis (cases, n=131), subjects without severe coronary atherosclerosis (coronary controls, n=88) and healthy subjects (population-based controls, n=101). Cases were defined as those havingor =90% occlusion in one andor =40% occlusion in a second coronary artery, while coronary controls had a maximum of 50% occlusion in only one coronary artery. Both males and females, aged 26--64 years were studied. We have previously reported that plasma tHcy is an independent risk factor for coronary atherosclerosis in this study population. In the present analysis, we found that cases had statistically significant higher mean plasma tCys levels than coronary controls and population-based controls (295.8+/-40.2, 279.0+/-35.5 and 282.6+/-32.4 micromol/l, respectively). The odds ratio (OR) of coronary atherosclerosis for the upper tertile of tCys compared with the bottom tertile was 2.5 (95% confidence interval (CI), 1.4--4.3). However, the association between tCys and coronary atherosclerosis was confounded to a great extent by risk factors (OR, 1.0; 95% CI, 0.5--2.0). The multivariate adjusted OR of coronary atherosclerosis per 1 S.D. increase in plasma tCys was 1.0 (95% CI, 0.8--1.3). The corresponding OR per 1 S.D. increase in plasma tHcy was 1.4 (95% CI, 1.1--1.8). We conclude that plasma tCys, unlike plasma tHcy, is not an independent risk factor for atherosclerosis.

Objective: Several studies suggest that a fatty meal impairs flow-mediated vasodilation (FMD), a measur9e of endothelial function. We tested whether the impairment was greater for trans fats than for saturated fats. We did this because we previously showed that replacement of saturated fats by trans fats in a controlled diet decreased FMD after 4 weeks. Design: We fed 21 healthy men two different test meals with 0.9-1.0 g fat/kg body weight in random order: one rich in saturated fatty acids (Sat), mainly from palm kernel fat, and one rich in trans fatty acids (Trans) from partially hydrogenated soy bean oil. The study was performed in our metabolic ward. We had complete data for both diets of 21 men. Results: FMD increased from a fasting value of 2.3±2.0 percent of the baseline diameter to 3.0±1.7 percent after the Sat test meal (95 percent I for change -0.33, 1.70) and from 2.7±2.3 to 3.1±2.0 percent after the Trans test meal (95 percent I for change -0.57, 1.29). The increase after the Sat meal was 0.22 (-1.18-1.61) FMD igher than after the Trans meal. Serum triacylglycerols increased by 0.46±0.36 mmol/l after the Sat test meal and by 0.68±0.59 mmol/l after the Trans test meal; a difference of 0.23 (0.07, 0.39) mmol/l. Serum HDL-cholesterol was hardly affected by the test meals. The activity of serum paraoxonase, an esterase bound to HDL, increased slightly after the two test meals but the difference between meals was not significant. Conclusion: FMD was not impaired and not different after test meals with saturated or trans fatty acids. Thus, differences in long-term effects of these fats are not caused by differences in acute effects on the vascular wall

To investigate the relationship between parental history of myocardial infarction (MI), lipid traits and gene polymorphisms involved in lipid metabolism, we examined Dutch men and women, who were selected from a large population-based study. Subjects whose father (n=112), mother (n=115) or both parents (n=115) suffered from a premature MI presented with significantly higher apolipoprotein B (apo B) levels than subjects without a parental history (n=114). Genetic analyses revealed that the apo E4 isoform and the D9N mutation of lipoprotein lipase (LPL) were more frequent among subjects with a parental history (P< or =0.05). A similar trend was found for the LPL N291S mutation. In contrast, the LPL S447X mutation and polymorphisms at the cholesteryl ester transfer protein (TaqIB) and apo CIII (SstI) loci proved to be noninformative. Body mass index and lifestyle could not explain differences in apo B levels between parental history groups. In contrast, the apo E polymorphism and the LPL D9N mutation accounted for some, but not all, of the higher apo B levels in subjects with a parental history. Therefore, other genetic or lifestyle-related factors must be responsible for the increased levels of apo B in individuals with a family history of myocardial infarction.

Item does not contain fulltext BACKGROUND: Although beta-carotene has shown inverse associations with chronic diseases involving free radical damage in observational epidemiological studies less attention has been paid to five other major carotenoids also showing antioxidant activity in vitro. METHODS: We studied the associations between 7.2-year mortality and serum levels of six carotenoids, and alpha-tocopherol, measured in stored serum, sampled in 1991/1992 during a health survey among 638 independently living elderly subjects aged 65-85 years. Proportional hazards regression was used to estimate hazard ratios of all-cause mortality for the lowest tertiles of serum vitamins with the highest tertiles, adjusting for possible confounding effects. RESULTS: During a follow-up period of 7.2 years 171 elderly died. The adjusted hazard ratios for all-cause mortality for the lowest tertiles of vitamins compared with the highest tertiles were between 1.02 and 1.73. The strongest increase in mortality risk was seen for beta-cryptoxanthin (1.52, 95% CI : 1.00, 2.32), lutein (1.56, 95% CI : 1.05, 2.31) and zeaxanthin (1.32, 95% CI : 0.89, 1.97) and their sum (oxygenated carotenoids: 1.73, 95% CI : 1.12, 2.67). Tests for trend were significant (P < 0.05) for all-cause mortality risk and serum levels of total carotenoids, oxygenated carotenoids and beta-cryptoxanthin. CONCLUSIONS: Our findings suggest that serum levels of individual carotenoids, particularly the oxygenated species are inversely associated with all-cause mortality and should be considered as candidates for further investigations.

To examine the effects of 17-wk physical exercise and enriched foods on cellular immune response (CIR) in frail elderly. METHODS: A total of 112 independently living, frail elderly men and women (mean age 79.2 /- 5.9) received: twice weekly comprehensive, moderate intensity, progressive group exercise (group A, N = 26); daily enriched foods (group B, N = 31); both (group C, N = 29); or neither (group D, N = 26). Exercises focused on skills training. Foods were enriched with micronutrients with a high prevalence of deficiency in older people (at 25-100% the RDA). A social program and identical regular foods were offered as a control. CIR was measured by delayed-type hypersensitivity skin test response (DTH) against seven recall antigens expressed as the total number of positive responses and sum of diameters of all positive responses. RESULTS: No independent or interactive effect of enriched foods was observed. Therefore, exercise (groups A C) was compared with no exercise (groups B D). Nonexercising subjects showed an average decline of 0.5 responses compared with an unchanged responsiveness among exercising subjects (difference = 0.5, 95% CI: 0.04-0.89, P = 0.03 adjusted for baseline DTH, activity level, and micronutrient status). Nonexercising subjects had a larger decline in the sum of diameters of all positive responses than exercising subjects but the difference did not reach significance (adjusted difference = 2.1 mm, 95% CI:-1.0-4.8). CONCLUSION: Exercise may prevent or slow the age-related decline in immune response. Micronutrient enriched foods showed no effect. As infectious diseases can have debilitating or even fatal consequences for the elderly, prevention of the age-related decline in CIR could significantly improve their quality of life.

Objectives: Analysis of HRV has been suggested as a way to study the effects of work-related stresses on cardiovascular autonomic regulation. The aim of this study was to evaluate the use of HRV in the investigation of work-related stressors. Methods: Cross-sectional data from an ongoing cohort study were used to analyse the relationship of the potential workplace stressors of job-strain, noise and shift work, with HRV. Mean HRV values during sleep and work were calculated in 135 24-h EKG recordings. Results: Shift workers displayed significantly decreased SDNNi levels during sleep, compared with those of the daytime workers (adjusted least square mean values: 69.3 and 85.8 ms, respectively, P

Aim of this study was to compare three different working definitions for selecting a frail elderly population. Frailty was defined as inactivity combined with (1) low energy intake (n = 29), (2) weight loss (n = 26), or (3) low body mass index (n = 26). In the Zutphen Elderly Study (n = 450; age 69-89 years) differences in health, functioning, and diet in 1990 and functional decline and mortality in the following 3 years between "frail" and "nonfrail" participants, according to the working definitions, were studied using logistic regression analysis. Differences according to the inactivity/weight loss criterium were more pronounced than according to the other two criteria. Inactivity/weight loss was associated with lower subjective health and performance and more diseases and disabilities in 1990. Three-year relative risks of mortality (odds ratio [OR]: 4.1, 1.8-9.4) and functional decline (OR: 5.2, 1.04-25.8 for disabilities, OR: 3.7, 0.8-16.2 for performance) were higher as well. Inactivity in combination with weight loss seems a practicable working definition for selecting a frail elderly population.

We examined the relation between total serum cholesterol decline and depression in the postpartum period in a prospective study of 266 Dutch women, who were followed until 34 weeks after delivery. The decline in serum cholesterol between week 32 of pregnancy and week 10 postpartum was similar for women who became depressed (n = 63) in the subsequent period and women who did not (difference, 0.10 mmol/l; 95% confidence interval [CI] -0.16 to 0.37). Adjusting for age, multiparity, education level, smoking status, concurrent illness, and social support, the odds ratio of depression was 1.4 (95% CI, 0.64 to 2.9) for women in the highest tertile of serum cholesterol decline and 0.61 (95% CI, 0.28 to 1.3) for women in the intermediate tertile, as compared with women in the lowest tertile. Our results do not support the hypothesis that rapid serum cholesterol decline increases risk of depression in the postpartum period.

Background: Activated factor VII (FVIIa) is a very potent coagulant and may be a key determinant of the outcome of a cardiovascular event. The main determinants of FVIIa are the R353Q polymorphism and dietary fat intake, which may have an interactive effect. Objective: The objective was to investigate whether the response of FVIIa to a fat-rich breakfast varies across genotypes of the R353Q polymorphism. Design: Ninety-one apparently healthy elderly women (>60 y of age), 56 with the RR genotype and 35 with the RQ or QQ genotype, participated in a randomized, controlled crossover study. Subjects received 5 breakfasts, each on a separate day: 1 low-fat control breakfast and 4 high-fat test breakfasts. Blood samples were taken for measurement of FVIIa at 0800 before each breakfast (fasting) and at 1300 and 1500. Results: The mean (±SD) fasting FVIIa concentration was 93.3 ± 26.7 U/L in women with the RR genotype, 49.3 ± 19.1 U/L in those with the RQ genotype and 39.5 ± 17.2 U/L in those with the QQ genotype. The mean absolute response to all 4 test breakfasts was 37.0 U/L in those with the RR genotype and 16.1 U/L in those carrying the Q allele (P < 0.001 for difference). Likewise, the FVIIa response relative to fasting FVIIa was significantly higher in women homozygous for the R allele. Conclusion: This observation may indicate a considerable difference in cardiovascular risk between genotype groups as a result of an increase in FVIIa after a fat-rich diet.

In order to assess whether heart rate-adjusted QT duration (QTc) is reduced by physical activity in an elderly population, a randomized, controlled intervention study of the effect of a 6-month intensive training program on QTc was undertaken. The participants were 229 healthy men and women, aged 60-80 years. The subjects of the intervention group trained three to four times a week at a work load of about 70% of their maximum capacity for 6 months, while the control subjects maintained their habitual activities. The main outcome measures were change in QTc and resting heart rate. For women, the mean QTc interval (ms) of the intervention group changed by -6.7 (SE 2.8) versus 0.6 (SE 2.4) in the control group (P = .05), while for men, the change in the intervention group subjects was -2.7 (SE 2.2) versus 0.4 (SE 3.1) in the control subjects (P = .39). Also, resting heart rate (beats/ min) changed in intervention group women by -4.6 (SE 1.7) as against -0.06 (SE 1.1) in the control subjects (P = .02), and in intervention group men it changed by -3.2 (SE 1.2) versus -0.9 (SE 1.5) in the control subjects (P = .25). These data indicate that regular physical activity favorably affects QTc in elderly women. A similar, but not significant, trend was observed in men. The beneficial shift in QTc may be caused by a more favorable autonomic balance through increased parasympathetic activity. The reduced resting heart rate in subjects of the intervention group supports this view. Although the reduction was relatively small, it may represent a favorable effect on cardiovascular risk.

Abstract —A fat-rich meal increases activated factor VII (FVIIa), but it is not clear whether this increase depends on the fatty acid composition of the meal. Therefore, we studied the FVIIa response to fat-rich meals with different fatty acid composition in a randomized controlled crossover trial and investigated whether this response is mediated by an increase in serum triglycerides. Elderly women (> 60 years, n=91) received on separate days four different fat-rich breakfasts (50 energy percent [en%] of fat) and a control breakfast (1.5 en% fat; crossover). The fat-rich breakfasts differed in fatty acid composition: one rich in palmitic acid (21.7 g), one in stearic acid (18.6 g), and the other two in linoleic and linolenic acid−one with a ratio 3:1 (12.5/3.9 g) and the other with a ratio of 15:1 (18.8/1.2 g). At 8 am before the breakfast (fasting) and at 1 and 3 pm, blood samples were taken, in which FVIIa and serum triglycerides were measured. FVIIa response to the fat-rich meals ranged from 11.6 mU/mL (95% confidence interval: 8.3,14.9) on the stearic meal to 15.9 mU/mL (12.0,19.8) on the linoleic/linolenic 15:1 meal at 1 pm and from 14.9 mU/mL (10.6,19.2) to 21.1 mU/mL (16.6,25.6) for the same meals at 3 pm . The responses did not differ between the fat-rich meals. After the control breakfast, FVIIa decreased, with 6.3 mU/mL (3.9,8.7) at 1 pm and 8.7 mU/mL (6.3,11.1) at 3 pm . The triglyceride response was lower after both linoleic/linolenic rich breakfasts compared with the palmitic and stearic breakfast ( P

Prolongation of heart rate-adjusted QT length (corrected QT interval [QTc]) is associated with elevated risk of coronary heart disease and sudden death. This may have to do with autonomic cardiac control. Because insulin is known to stimulate sympathetic activity, we studied the association of insulin level and glucose tolerance with QTc. In 1990, 383 elderly men 70–89 years of age without previous myocardial infarctions or known diabetes had a 12-lead electrocardiogram recorded and glucose tolerance determined in the frame of an ongoing follow-up study. QTc was significantly associated with fasting glucose, insulin, and C-peptide and glucose levels 60 and 120 min after an oral glucose load. For fasting C-peptide and the area under the glucose curve (AUGC), this association could not be explained by the concomitant occurrence of other risk factors of coronary heart disease. Furthermore, fasting C-peptide and the AUGC were independently additive predictors of QTc duration. The difference in QTc between men in the extreme quintiles of both variables was 22 ms. QTc prolongation seems to be part of the insulin resistance syndrome. The association may be explained by increased sympathetic activity induced by high insulin levels. An additional explanation could be an effect of high insulin, impaired glucose utilization, or both on membrane activity of myocardial cells.

The Cardiac Infarction Injury Score (CIIS), based on electrocardiographic characteristics, was developed as a measure to determine the presence of myocardial infarctions. In the present study the association of the CIIS with coronary morbidity and mortality was investigated among middle-aged and elderly men. A cohort of 877 men, born between 1900 and 1919, was followed and repeatedly examined from 1960 onwards. In 1985 the remaining cohort was extended to 836 elderly men from the same birth cohort, and followed until 1990. In both middle-aged and elderly men with high CIIS the prevalence of (silent) previous myocardial infarction and the occurrence of ST-T abnormalities were increased. Five-year relative risks of men with CIIS 20 or more relative to men with CIIS5 were 2.2 (95% confidence interval: 1.2-4.1) for angina pectoris, 2.4 (1.4-4.0) for myocardial infarction and 5.8 (3.4-9.9) for coronary heart disease death. Thus, the CIIS is associated with risk of coronary heart disease in apparently healthy middle-aged as well as elderly men.

Objectives. This study evaluated the predictive value of T wave amplitude and ST segment level on lead I for angina pectoris, a first myocardial infarction, sudden death and coronary heart disease death in middle-aged and elderly men. Background. Certain ST-T wave characteristics may reflect favorable autonomic cardiac control. Slight ST segment elevation has been reported to indicate a low risk of coronary heart disease mortality. Methods. A total of 876 men, born between 1900 and 1920, participated in periodic medical examinations and were followed up with respect to morbidity and mortality from 1960 to 1985. In 1985, the remaining cohort was extended to 836 elderly men from the same birth cohort who were followed up until 1990. Relative risks in categories of T wave amplitude and ST segment level were estimated by survival analysis. Results. Both middle-aged and elderly men with T wave amplitudes ≥0.15 mV had a lower risk of myocardial infarction, coronary heart disease death and sudden death than men with T wave amplitudes 0.05 to 0.15 mV. The adjusted relative risk of coronary heart disease death was 0.5 (95% confidence interval [CI] 0.2 to 1.0); in men with T wave amplitude ≤0.05 mV, relative risk was 2.0 (95% CI 1.3 to 3.1). Slight ST segment elevation was also associated with decreased risk: relative risk 0.5 (95% CI 0.3 to 1.0) compared with the isoelectric ST segment level. In men with ST segment depression, relative risk was 2.2 (95% CI 1.4 to 3.4). The associations of T wave amplitude and ST segment level were independent of each other. Conclusions. In addition to the elevated risk of coronary heart disease that is associated with ST-T wave abnormalities, we observed that normal variations in repolarization characteristics are predictive of future heart disease.

BACKGROUND Heart-rate-adjusted QT-interval (QTc) is prognostic of sudden death in myocardial infarction patients. So far, population studies have yielded conflicting results on the predictive value of QTc for coronary heart disease morbidity and mortality. Therefore, we investigated this in a longitudinal study of middle-aged and elderly men. METHODS AND RESULTS From 1960 to 1985, 877 middle-aged men were followed and repeatedly examined in the Zutphen Study. In 1985 the remaining cohort was extended to 835 elderly men from the same birth cohort and followed until 1990. Men with prolonged QTc (420 ms1/2 or more) had a higher risk of myocardial infarction and coronary heart disease death relative to men with QTc less than 385 ms1/2. Age-adjusted coronary heart disease mortality rate ratios were 4.3 (95% confidence interval, 1.3 to 13.8) in middle-aged men and 3.3 (95% confidence interval, 1.0 to 11.6) in elderly men. These associations could not be attributed to prevalent heart disease and were independent of other cardiovascular risk factors. CONCLUSIONS These results indicate that within the normal range of QTc in the general population, men with long QTc are at higher risk for coronary heart disease. Because QTc is easily determined, it may provide a valuable contribution to risk stratification.

Combinations of dietary factors were studied in relation to breast-cancer occurrence among 133 breast cancer cases and 289 population controls in The Netherlands. Dietary factors were classified according to their possible mechanism of action, i.e., relating either to the intestinal microflora (total fat, fiber, fermented milk products) or to the anti-oxidant hypothesis (beta-carotene, selenium and polyunsaturated fatty acids). From 6 interactions evaluated, the combination of high fiber intake and high intake of fermented milk products was the only one suggesting synergistic protection (age- and-fat-adjusted OR for interaction = 0.48, 95% confidence interval (CI) = 0.21-1.13). In order to estimate the extent to which the above dietary factors together might be related to breast cancer, subjects with a supposedly favorable dietary pattern (low fat intake, high fiber intake, high intake of fermented milk products; high intake of beta-carotene and selenium, low intake of polyunsaturated fatty acids) were compared with subjects with an unfavorable dietary pattern. This resulted in an age-adjusted odds ratio of 0.40 (95% CI = 0.14-1.15), which was largely attributable to the combination of low intake of fat and high intake of fermented milk products and fiber (age-adjusted OR = 0.33, 95% CI = 0.15-0.73). The other factors did not appreciably affect the odds ratio. These analyses show in a quantitative way that a dietary pattern which combines low intake of fat and high intake of fiber and fermented milk products might provide substantial protection against breast cancer. Chemicals/CAS: beta Carotene, 7235-40-7; Calcium, Dietary; Carotenoids, 36-88-4; Dietary Fats, Unsaturated; Selenium, 7782-49-2

To study the association between dietary fiber, beta-carotene and breast cancer, the average daily intake of these dietary components was compared among 133 incident breast cancer cases and 238 population controls. Average daily intake of cereal products, fruit and vegetables was also studied. A statistically significant lower energy-adjusted intake of dietary fiber was observed in cases than in controls (mean +/- SD: 25.4 +/- 6.7 g vs. 27.7 +/- 7.4 g, 95% confidence interval (CI) of the age-adjusted difference = -3.8, -0.8). Intake of beta-carotene was similar for cases and controls. The multivariate adjusted odds ratio (OR) of breast cancer among women in the highest quartile of intake of cereal products, as compared to those in the lowest quartile, was 0.42 (95% CI = 0.19-0.92) and the trend was statistically significant (p = 0.03). The corresponding OR for intake of dietary fiber was 0.55 (95% CI = 0.26-1.17) but the trend was not significant. The OR for the highest quartile of intake of beta-carotene, fruit, vegetables, and all vegetable products combined was less than unity, but there was no significant inverse trend. These results suggest that a high intake of cereal products, especially those rich in fiber, may be inversely related to incidence of breast cancer.

In 460 apparently healthy Dutch elderly, aged 65–79 years, serum uric acid correlates were studied by linear regression analyses, for men and women separately. Diuretic therapy, total serum cholesterol (women only) and creatinine clearance (in bivariate analysis only) were significantly associated with serum uric acid level. Positive associations of serum uric acid with body weight, body mass index, body fatness (men) and lean body mass (men) were observed, with and without adjustment for diuretic therapy, creatinine clearance and age. Serum uric acid levels, whether adjusted or not for these variables and for body mass index, were positively associated with alcohol intake (men) and consumption of meat and fish (women), and inversely with consumption of bread, margarine and milk products (women). These results indicate that limited medication with diuretics, weight control and restriction of alcohol use may help to prevent hyperuricemia in the elderly.

Background: Age-related hearing loss is a common chronic condition of elderly persons. Low folate status has been associated with poor hearing. Objective: To determine whether folic acid supplementation slows age-related hearing loss. Design: Double-blind, randomized, placebo-controlled trial conducted from September 2000 to December 2004. Setting: The Netherlands. Participants: 728 older men and women recruited from municipal and blood bank registries with plasma total homocysteine concentrations 13 mu mol/L or greater serum and vitamin B-12 concentrations 200 pmol/L or greater at screening, and no middle ear dysfunction, unilateral hearing loss, or pathologic ear conditions unrelated to aging. Intervention: Daily oral folic acid (800 mu g) or placebo supplementation for 3 years. Measurements: 3-year change in hearing thresholds, assessed as the average of the pure-tone air conduction thresholds of both ears of the low (0.5-kHz, 1-kHz, and 2-kHz) and high (4-kHz, 6-kHz, and 8-kHz) frequencies. Results: Initial median hearing thresholds were 11.7 dB (interquartile range, 7.5 to 17.5 dB) for low frequencies and 34.2 dB (interquartile range, 22.5 to 50.0 dB) for high frequencies. Sixteen participants (2%) were lost to follow-up. After 3 years, thresholds of the low frequencies increased by 1.0 dB (95% CI, 0.6 to 1.4 dB) in the folic acid group and by 1.7 dB (CI, 1.3 to 2.1 dB) in the placebo group (difference, -0.7 dB [CI, -1.2 to -0.1 dB]; P = 0.020). Folic acid supplementation did not affect the decline in hearing high frequencies. Limitations: The strict criterion for participation on the basis of serum homocysteine concentrations limits extrapolation to the general population. Folic acid fortification of food was prohibited in the Netherlands during the study, so baseline folate levels in participants were about half of those found in the U. S. population. Conclusions: Folic acid supplementation slowed the decline in hearing of the speech frequencies associated with aging in a population from a country without folic acid fortification of food. The effect requires confirmation, especially in populations from countries with folic acid fortification programs.

Background Humans and animals show a certain consistency in the response of their serum lipids to fat-modified diets. This may indicate a genetic basis underlying this response. Coffee oil might be used as a model substance to investigate which genes determine differences in the serum lipid response. Before carrying out such studies our objective was to investigate to what extent the effect of coffee oil on serum lipid concentrations is reproducible within subjects. Methods The serum lipid response of 32 healthy volunteers was measured twice in separate five-week periods in which coffee oil was administered (69 mg cafestol / day). Results Total cholesterol levels increased by 24% in period 1 (range:0;52%) and 18% in period 2 (1;48%), LDL cholesterol by 29 % (-9;71%) and 20% (-12;57%), triglycerides by 66% (16;175%) and 58% (-13;202%), and HDL cholesterol did not change significantly: The range of the HDL response was -19;25% in period 1 and -20;33% in period 2. The correlation between the two responses was 0.20 (95%CI -0.16, 0.51) for total cholesterol, 0.16 (95%CI -0.20, 0.48) for LDL, 0.67 (95%CI 0.42, 0.83) for HDL, and 0.77 (95%CI 0.56, 0.88) for triglycerides. Conclusions The responses of total and LDL cholesterol to coffee oil were poorly reproducible within subjects. The responses of HDL and triglycerides, however, appeared to be highly reproducible. Therefore, investigating the genetic sources of the variation in the serum-lipid response to coffee oil is more promising for HDL and triglycerides.

To elucidate the role of modifiable factors and the apolipoprotein E polymorphism in explaining lipid profiles reflecting low, average and high risk for coronary heart disease, we selected subjects from a large population-based study. Subjects with low total cholesterol (TC) (< 15th percentile) and high HDL-cholesterol levels (> 85th percentile) were randomly selected (n = 99) and represent subjects with a low risk lipid profile. Additionally, 95 subjects with total and HDL-cholesterol levels in the 15% around the population-median (median risk lipid profile) and 100 subjects with high TC (> 85th percentile) and low HDL-cholesterol levels (< 15th percentile) (high risk lipid profile) were selected. Compared with E3/3 subjects, the likelihood for a low risk lipid profile was considerably higher (odds ratio 14.3; 2.6-79) in female, but not in male E2-carriers (1.5; 0.3-6.7). Smoking and alcohol consumption were independently associated with a low risk lipid profile in both genders, physical inactivity only in women. The odds ratio for a high risk lipid profile was elevated in male E4-carriers (4.9; 1.1-23) only. In addition to the E4 isoform, smoking and physical inactivity, overweight was the main determinant for a high risk lipid profile (odds ratio 16.8; 3.4-82). Male overweight E4-carriers had a 50 times higher likelihood of a high risk lipid profile than E3/3 men of normal weight. In women, only overweight was independently associated with a high risk lipid profile. Our results suggest that both modifiable factors and the apolipoprotein E polymorphism contribute to a lipid profile, reflecting low, average and high risk for coronary heart disease, but effects may be gender-specific.

SummaryWe examined the diurnal pattern in Plasminogen Activator Inhibitor-type 1 (PAI-1) activity and Plasminogen activator (t-PA) in relation to the 4G/5G-polymorphism in the promoter of the PAI-1 gene. The analyses were performed in the Arnhem Elderly Study, a populationbased study of 598 elderly. A single blood sample was drawn and the time of blood sampling was recorded (between 8 a. m. and 5.30 p. m.). Plasma PAI-1 activity was strongly associated with time of blood sampling, showing the highest values in the early morning. The diurnal pattern was clearly present in the 4G/4G (n = 184) and 4G/5G (n = 275) genotypes, but not in the 5G/5G-genotype (n = 139). T-PA antigen showed a weak diurnal variation, which did not differ across the variants of the 4G/5G-polymorphism. Our findings raise the hypothesis that 5G-homozygotic persons may be relatively protected from diurnal variation in the occurrence of coronary events.

The association between serum total cholesterol and cancer mortality was investigated in a 28-year follow-up study of 3,091 Dutch civil servants aged 40-65 years and their spouses. After adjustment for age, body mass index, and smoking, an inverse association between serum total cholesterol and all-cancer mortality was observed in men during the first 15 years of follow-up, excluding the first 2 years: The multivariate rate ratio of those in the lowest cholesterol quintile compared with those in the highest quintile was 2.1 (95% confidence interval (Cl) 1.1-4.0); this association was accounted for mainly by gastrointestinal cancers (RR = 4.2, 95% Cl 1.4-12.9). For follow-up years 16-28, the multivariate rate ratio for all-cancer mortality was 0.8 (95% Cl 0.5-1.40. In women, no consistent association between serum total cholesterol and cancer was observed. After the first 5 years of follow-up were excluded, the significant inverse association in men still persisted. These results suggest that in this study population, low serum cholesterol seems not to be attributable to undetected cancer, but might be a risk factor for cancer mortality in men.

SummaryThe habitual level of PAI-1 is influenced by many factors, of which obesity and insulin resistance are the most important. It is possible to reduce plasma PAI-1 by changes in life style, e.g. weight reduction and physical activity. Data on potential interactions between environmental and metabolic variables on one hand, and the 4G/5G-polymorphism on the other hand, are still scarce. It becomes more and more clear that PAI-1 may possibly not be a major (causal) factor in cardiovascular disease, but its role in inflammation deserves further attention. In the presence of the 4G-allele not only the PAI-1 response was more pronounced, but also the response of other acute-phase reactants, which implies that the increases of these reactants are secondary to the increase in PAI-1. A myocardial infarction also provokes an acute phase response. It can thus be hypothesized that the 4G-allele might exacerbate tissue injury during the acute phase after a myocardial infarction, and thereby negatively affect the prognosis.

Purpose: Heart rate variability (HRV), a characteristic that is potentially increased by physical activity, has been associated with incidence of cardiac events and total mortality. Since the incidence of cardiac events among older people is high and their physical activity levels and HRV are generally low, it is important to investigate whether regular physical activity can modify HRV in this age group. The purpose of the study was to investigate the effect of regular physical activity on HRV in older men and women. Methods: In a randomized controlled trial, the effect of six months' training on HRV was investigated in a group of 51 older men and women (67.0 ± 5.1 yr). The training group gathered three times per week for 45 min supervised training. Results: At the end of the intervention period, HRV was higher primarily during the day. During daytime, the SD of all normal intervals (+ 6%) as well as the low frequency component (+ 15%) and the very low frequency component (+ 10%) of HRV were significantly increased (P < 0.05) as compared with the control group. Effects of training were most pronounced in subjects inactive in sports at baseline. Conclusion: This study demonstrates that regular physical activity increases HRV (specifically in the very low and low frequency components) in older subjects. Hence, in older subjects, physical training may be an effective means to modify positively a factor that is associated with increased incidence of cardiac events.