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Diabetes mellitus (DM) leads to nearly 3-fold higher risk of pulmonary tuberculosis (TB), indicating an increasing challenge to public health in low-to-middle income countries. Till now, the risk factor is still uncertain. We carried out this study with the main purpose to identify the risk factors of having TB in DM patients.A hospital-based matched case-control study was conducted in Qingdao, China from March, 2016 to January, 2018. Cases were DM patients with concurrent TB (DM-TB). Each case was matched with two controls, patients with DM only of similar age, sex and DM course. Cox regression of conditional logistic analysis was used to define the risk factors for having TB in DM, and then sensitivity analysis was carried out.We identified 315 patients, including 105 cases and 210 controls. Smokers had a higher risk of having TB with a multivariable adjusted odds ratio (aOR) of 12.45 than non-smokers. Poor glycemic control (aOR=2.66), frequency of DM re-examination1 time/year (aOR=3.39), as well as TB contact history was also independently related with higher risk, while BMI ≥24 (aOR=0.42), education level ≥ college (aOR=0.11) showed a negative association.Poor glycemic control, smoking, low frequency of reexamination was associated with higher risk of having TB in DM, while overweight and obesity, high education levels showed a negative association. These findings provide clues to target DM populations prone to TB, which may be of help to halt the epidemic of TB in high burden countries.

Tuberculosis remains a major global health challenge, particularly in low-to-middle income countries such as China. At the same time, the country is facing a rapidly increasing diabetes incidence over the last 10 years. Diabetes aggravates the tuberculosis epidemic which poses a serious challenge in public health. In recent years, the high prevalence of vitamin D deficiency represents a global health problem, which is also associated with the risk of diabetes, and tuberculosis. Therefore, this review aims to provide an overall and updated understanding of the epidemiology of co-occurrence of tuberculosis and diabetes in China, and to elucidate the possible role of vitamin D deficiency. In conclusion, significant aggravation of the tuberculosis epidemic due to diabetes may exist in China for a relatively long period of time to come. Further, the double burden and its implications to public health in this country may be significantly influenced by the high prevalence of vitamin D deficiency. Bidirectional screening for tuberculosis and diabetes is recommended, and extra vitamin D may benefit especially in a situation of a heavy tuberculosis burden combined with prevalent vitamin D deficiency. Longitudinal studies to verify the role of vitamin D deficiency in the double burden, and trials on the effect of vitamin D supplementation are needed in the future.

B vitamins are enzyme cofactors that play an important role in energy metabolism. The aim of this study was to elucidate whether B vitamin administration can reduce body weight (BW) gain by improving energy metabolism-related enzyme activities in rats fed on a highfat diet. Fifty rats were randomly assigned to one of the following five groups: control group (C), including rats fed on standard rat chow; four treatment groups (HO, HI, H2, and H3), in which rats were fed on a high-fat diet. Rats in the HI group were treated daily with 100 mg/kg BW thiamine (VB1), 100 mg/kg BW riboflavin (VB2), and 250 mg/kg BW niacin (VPP); rats in the H2 group were treated daily with 100 mg/kg BW pyridoxine (VB6), 100 mg/kg BW cobalamin (VB12), and 5 mg/kg BW folate (FA); and rats in the H3 group were treated daily with all of the B vitamins administered to the HI and H2 groups. After 12 weeks, the BW gains from the initial value were 154.5±58.4 g and 159.1±53.0 g in the HI and C groups, respectively, which were significantly less than the changes in the HO group (285.2±14.8 g, P

Background: Excessive time between the first presentation of symptoms of pulmonary tuberculosis (PTB) and diagnosis contributes to ongoing transmission and increased risk of infection in the community, as well as to increased disease severity and higher mortality. People with type 2 diabetes mellitus (T2DM) have a higher risk of developing PTB. However, the effect of T2DM on delayed diagnosis of PTB is not fully understood. This study investigated the effects of hyperglycemia (diabetes and prediabetes) and other factors on PTB patient delay in a rural area of China. Methods: In the present community-based investigation, PTB patients aged ≥16years newly diagnosed at county tuberculosis dispensaries were recruited consecutively between September 2011 and December 2013. Fasting blood glucose was determined in all subjects, and a structured questionnaire was used to collect basic information. Results: Of the 2280 patients, 605 (26.5 %) had hyperglycemia. The median (interquartile range) time to seeking health care was 44 (59) days. Health care seeking was delayed in 1754 subjects, and hyperglycemia was independently associated with an increased probability (odds ratio 2.10; 95 % confidence interval 1.49-2.97) of patient delay in subjects aged ≥30years. Other factors associated with patient delay were cough, night sweats, and lack of knowledge regarding typical tuberculosis symptoms. The onset of hemoptysis was negatively correlated with patient delay. Conclusions: Patient delay appears to be a serious problem in this rural area with a high prevalence of tuberculosis. Hyperglycemia is independently associated with an increased probability of patient delay, which, in turn, may result in more serious clinical manifestations.

Summary Vitamin D deficiency (VDD) is common in tuberculosis (TB) and may be implicated in the etiology of the disease and in its clinical course. The aim of this study was to investigate the association between leptin, inflammatory markers and VD status in TB patients, stratified for presence or absence of diabetes mellitus (DM). Two hundred ninety-nine TB patients were recruited from October 2015 to August 2016. Also, 91 normal controls were included. The information including socio-demographics, dietary intake and living habits was obtained by face-to-face interview. Serum concentrations of leptin and TNF-α, CRP and IL-6 were compared between TB patients with and without severe VDD (SVDD). Pearson’s correlation was used to analyze the association between TNF-α, leptin and 25-hydroxyvitamin D (25(OH)D). A significantly higher prevalence of VDD and SVDD was observed in TB patients compared with normal controls (93.0% vs 70.3%, 65.9% vs 3.3% respectively). Concentration of leptin was significantly lower, while TNF-α higher in TB patients with SVDD compared to those without (p

Background & aims: Tuberculosis (TB) patients have a significant vitamin D deficiency (VDD) endemic, which may be closely related to the onset and progress of the disease. The comorbidity of diabetes (DM) and TB has posed an increasing challenge in recent years. However, the influence of DM on TB and the possible mechanism are still uncertain. We carried out this study to identify the nutritional status of vitamin D (VD) in TB patients in a northern city in China (latitude 36° N) and investigate the possible predictors of severe vitamin D deficiency (SVDD). Methods: A cross-sectional study including 461 active TB patients (192 with and 269 without DM) were randomly selected from Qingdao Chest Hospital from June 2015 to August 2016. We measured serum 25 hydroxyvitamin D [25(OH)D], and investigated the association between sociodemographic, dietary intake, DM, body mass index (BMI), severity of initial TB signs and symptoms (TB score) and VD status. Multivariate logistic regression analysis was used to define the possible predictors of SVDD. Results: The median serum 25(OH)D concentration was 8.50 ng/mL. Of the 461 TB patients included, 383 (83.1%) had VDD [25(OH)D < 20 ng/mL], and 217 (47.1%) had SVDD [25(OH)D < 8 ng/mL]. The variables associated with serum 25(OH)D concentrations were DM, outdoor activity level, TB score and BMI (p < 0.05). Patients with severe TB score had nearly 5 fold higher risk of having SVDD compared with those in mild subgroup [OR (95% CI) = 4.919 (2.644-9.150), p < 0.001]. Low outdoor activity level also increased the odds of SVDD, while DM and high fish consumption showed protect effects. Conclusions: Severe hypovitaminosis D is prevalent in active TB patients, and the main predictors of SVDD were severe TB score, low outdoor activity, inadequate fish consumption. Lowered serum 25(OH)D may be associated with increased risk of TB in DM.

Background/objectives: Isoflavones are present in soy foods and soy-based supplements. Despite low plasma isoflavone concentrations in the general Western population, concentrations in supplement users exceed those suggested to be beneficial for health in Asian populations, raising concerns for adverse effects. To aid risk assessment, quantification of the relation between isoflavone intake and plasma concentrations is essential. Subjects/methods: Plasma samples were collected from postmenopausal women in three placebo-controlled crossover studies with 8-week periods for supplements (two studies, ~100¿mg isoflavones/day, n=88) or 4-week periods for soy foods (one study, ~48¿mg isoflavones/day, n=15). Plasma isoflavone concentrations (daidzein, equol, genistein and glycitein) were quantified using high-performance liquid chromatography and electrochemical detection. The association between plasma concentrations and isoflavone intake, equol producer status, intake–producer interaction and background dietary intake was assessed based on the assumption of a log-linear relation. Results: Median plasma total isoflavone concentrations after the soy food and supplement interventions were respectively 2.16 and 3.47¿µmol/l for equol producers and 1.30 and 2.39¿µmol/l for non-producers. Regression analysis showed that doubling isoflavone intake increased plasma concentrations by 55–62% (±s.e. 1–2%, R2>0.87) for daidzein, genistein, equol (only for producers) and total isoflavones; for glycitein the association was weaker (15±1%, R2=0.48). Adjustments for energy, carbohydrate and fat intake did not affect these estimates. Inter-individual variation, estimated based on repeated measures in one of the studies, was 30–96%. Conclusions: Although the relation between isoflavone intake and plasma concentrations was adequately quantified, the use of isoflavone intake data for risk assessment needs caution due to large inter-individual variation in plasma concentrations.

Background: Observational studies have shown that low folate and elevated homocysteine concentrations are risk factors for vascular disease in the general population. Randomized controlled trials in vascular patients have failed to show that folic acid reduces the risk of recurrent vascular disease, whereas such trials are lacking in the general population. Objective: The objective was to determine whether folic acid supplementation reduces the progression of atherosclerosis as measured by common carotid intima-media thickness (CIMT) a validated marker of atherosclerosis and predictor of vascular disease risk. Design: A randomized, double-blind, placebo-controlled study in 819 men and postmenopausal women aged 50-70 y, free-living in the Netherlands, and with a total homocysteine concentration >= 13 mu mol/L at screening was conducted. Participants received either 800 mu g folic acid or placebo daily for 3 y. Rate of change in CIMT and arterial distensibility were the primary and secondary outcomes, respectively. Results: Compared with placebo, serum folate increased by 577% and plasma total homocysteine concentrations decreased by 26% after 3 y of folic acid supplementation. The mean (+/- SE) rate of change in CIMT was 1.9 +/- 0.9 mu m/y in the folic acid arm and 1.3 +/- 0.8 mu m/y in the placebo arm (mean difference: 0.7 mu m/y; 95% CI: -1.8, 3.1 mu m/y; P = 0.59). No difference was observed (P = 0.23) between the rates of change in distensibility in the folic acid arm (-0.53 +/- 0.06 x 10(-3) kPa(-1)) and in the placebo arm (-0.62 +/- 0.06 x 10(-3) kPa(-1)). Conclusion: Despite a considerable increase in folate concentrations and a reduction in total homocysteine concentrations, 3-y folic acid supplementation did not slow down atherosclerotic progression or arterial stiffening. This trial was registered at clinicaltrials.gov as NCT00110604. Am J Clin Nutr 2011;93:941-9.

Aging and oxidative stress may lead to enhanced cellular damage and programmed cell death. To study the association of intrinsic apoptosis with age and the effect of antioxidant supplementation on intrinsic and UV-induced apoptosis in children, young and elderly people.The study was a 2 months, double-blind, randomized trial. Three age groups were studied: children, young adults and elderly people. A total of 274 healthy subjects were allocated to a group supplemented with moderate amounts of retinol, β-carotene, α-tocopherol, ascorbic acid and selenium or placebo. Plasma oxidative stress parameters were detected and apoptosis of lymphocytes was evaluated with TUNEL staining.At baseline, percentages of intrinsic apoptosis were 13.8% and 11.1% in elderly and young people, respectively, both significantly higher than children (6.3%). A decrease of 1.7% and 2.3% in intrinsic apoptosis of lymphocytes was found in the supplemented groups of young and elderly people compared with their control groups (all p values0.001), but no significant decrease in children. Moreover, percentages UV-induced apoptosis significantly decreased by 1.4%, 1.9% and 3.1% in children, young and elderly people, respectively, compared with control groups after the trial. There were considerable increments in concentrations of plasma β-carotene, retinol, tocopherol, ascorbic acid and selenium in all three treated groups after the supplementation.Young and elderly people have a higher intrinsic apoptosis than children, which was improved by antioxidant supplementation. UV-induced damage was attenuated by the supplementation in all three age groups.

Background Weekly fish consumption has been related to a lower risk of fatal coronary heart disease (CHD) and incident stroke in populations with a low fish intake. This relation has mainly been attributed to n-3 fatty acids in fish, that is, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). It is at present unclear whether alpha-linolenic acid (ALA), a n-3 fatty acid from vegetable origin, could also be protective against cardiovascular diseases (CVDs). There is a need for food-based trials to establish the efficacy of low doses of n-3 fatty acids in CVD prevention. Objectives The aim of the study was to evaluate the effect of an additional daily intake of 400 mg of EPA + DHA and 2 g of ALA on CVD morbidity and mortality in free-living subjects with a history of myocardial infarction. Design The multicenter Alpha Omega Trial is a randomized, double-blind, placebo-controlled trial with a 2 x 2 factorial design. Between May 2002 and December 2006, we enrolled a total of 4,837 men and women aged 60 through 80 who experienced a myocardial infarction within 10 years before entering the study. Subjects were randomized to 1 of 4 margarine spreads that were enriched with EPA + DHA and/or ALA, or placebo. Compliance was monitored via tub counts and assessment of n-3 fatty acids in plasma. Subjects were observed for 40 months for the occurrence of fatal and nonfatal CVD. Results The cohort was on average 69 years old at the start of the study and comprised 22% women. Subjects had their (last) myocardial infarction approximately 4 years before enrolment. Mean body mass index was 27.7 kg/m(2), and 17% smoked. Average serum total and high-density lipoprotein cholesterol were 4.7 and 1.3 mmol/L, respectively, and 85% used statins. Mean blood pressure was 142/80 mm Hg, and most subjects were on antihypertensive medication (88%). Diabetes mellitus was reported by 17% of the subjects, and 7% reported a history of stroke. The overall mortality rate during the trial period was 23 per 1,000 person-years, with approximately 40% due to CVD. Current status Follow-up of the patients was completed in November 2009, and findings will be reported in the second part of 2010. (Am Heart J 2010; 159: 539-546. e2.)

Objectives To determine whether a large-scale physical activity intervention could affect body composition in primary school students in Beijing, China. Methods The study design was one-year cluster randomized controlled trial of physical activity intervention (20 min of daily exercise in the classroom) with an additional year of follow-up among 4 700 students aged 8-11 years at baseline. Results After the one-year intervention, BMI increased by 0.56 kg/m 2 (SD 1.15) in the intervention group and by 0.72 kg/m 2 (SD 1.20) in the control group, with a mean difference of −0.15 kg/m 2 (95% CI: −0.28 to −0.02). BMI z score decreased by −0.05 (SD 0.44) in the intervention group, but increased by 0.01 (SD 0.46) in the control group, with a mean difference of −0.07 (−0.13 to −0.01). After another year of follow up, compared to the control group, children in the intervention group had significantly lower BMI (−0.13, −0.25 to −0.01), BMI z score (−0.05, −0.10 to −0.01), fat mass (−0.27 kg, −0.53 to −0.02) and percent body fat (−0.53, −1.00 to −0.05). The intervention had a more pronounced effect on weight, height, BMI, BMI z score, and body composition among obese children than among normal weight or overweight children. Compared to the control group, the intervention group had a significantly higher percentage of children who maintained or reduced their BMI z score at year 1 ( P =0.008) and year 2 ( P =0.04). Conclusions These findings suggest that 20 min of daily moderate to vigorous physical activity during the school year is a feasible and effective way to prevent excessive gain of body weight, BMI, and body fatness in primary school students.

Background: Little is known about the effect of different types of dairy food products on the development of hypertension. Objective: The objective was to determine whether the incidence of hypertension in older Dutch subjects is associated with intake of dairy products. Design: We examined the relation between dairy intake and incident hypertension in 2245 participants of the Rotterdam Study aged >= 55 y with complete dietary and blood pressure data, who were free of hypertension at baseline (1990-1993). Blood pressure was reexamined in 1993-1995 and in 1997-1999. Hazard ratios (HRs) with 95% CIs for 2-and 6-y incidence of hypertension were obtained in quartiles of energy-adjusted dairy intake, with adjustment for age, sex, BMI, smoking, educational level, dietary factors, and intake of alcohol and total energy. Results: Risk of hypertension after 2 y of follow-up (664 incident cases) was inversely associated with dairy product intake. After adjustment for confounders, HRs (95% CIs) were 1.00, 0.82 (0.67, 1.02), 0.67 (0.54, 0.84), and 0.76 (0.61, 0.95) in consecutive quartiles of total dairy product intake (P for trend = 0.008). Corresponding HRs for low-fat dairy products were 1.00, 0.75 (0.60, 0.92), 0.77 (0.63, 0.96), and 0.69 (0.56, 0.86) (P for trend = 0.003). Analysis of specific types of dairy products showed an inverse association with milk and milk products (P for trend = 0.07) and no association with high-fat dairy or cheese (P > 0.6). After 6 y of follow-up (984 incident cases), the associations with hypertension were attenuated to risk reductions of approximate to 20% for both total and low-fat dairy products between the extreme quartiles of intake (P for trend = 0.07 and 0.09, respectively). Conclusion: Intake of low-fat dairy products may contribute to the prevention of hypertension at an older age. Am J Clin Nutr 2009; 89: 1877-83.

Objectives: To investigate the current prevalence of anemia among pregnant women in different areas of China and the association with birth weight and educational level. Methods: A total of 6,413 women aged 24–37 in the third trimester of pregnancy from five areas were randomly selected from all gravidas who gave birth in the hospitals from 1999 to 2003. Blood hemoglobin concentration (Hb) was measured by the cyanomethemoglobin method; Hb Results: The overall prevalence of anemia was 58.6%, ranging from 48.1 to 70.5% in the five areas. There was a significant difference in the prevalence of anemia between women who have mental jobs and those who have physical jobs (52.3 vs. 61.1%, p < 0.01). The prevalence of anemia depended on the level of education: with 52.9, 62.4 and 66.5%, for college, secondary school and primary education, respectively, and the difference was statistically significant (p = 0.005). Results showed that higher birth weight was associated with Hb concentrations ranging from 90 to 140 g/l, whereas lower birth weight occurred below 80 g/l and above 140 g/l Hb. Conclusions: The prevalence of anemia in Chinese pregnant women was high both in rural areas and towns. Area of residence, education level and type of job influenced the prevalence of anemia. Low maternal Hb concentrations influenced birth weight.

Aims To determine the effects of omega-3 polyunsaturated fatty acids (omega-3 PUFAs) from fish on the incidence of recurrent ventricular arrhythmia in implantable cardioverter defibrillator (ICD) patients by combining results from published trials. Methods and results We searched in the Medline, EMBASE, and Cochrane databases and performed a meta-analysis on all three available trials on fish oil and ventricular arrhythmia. Furthermore, we pooled individual data of two of these randomized, double-blind, placebo-controlled trials (Raitt et al . Fish oil supplementation and risk of ventricular tachycardia and ventricular fibrillation in patients with implantable defibrillators: a randomized controlled trial. JAMA 2005; 293: 2884–2891 and Brouwer et al . Effect of fish oil on ventricular tachyarrhythmia and death in patients with implantable cardioverter defibrillators: the Study on Omega-3 Fatty Acids and Ventricular Arrhythmia (SOFA) randomized trial. JAMA 2006; 295: 2613–2619). The main outcome was time to first confirmed ventricular fibrillation (VF) or ventricular tachycardia (VT) combined with death for the meta-analysis, and time to first spontaneous confirmed VF or VT for the pooled analysis. The meta-analysis ( n = 1148) showed no convincing protective effect of fish oil (RR 0.90; 95% CI 0.67–1.22). The hazard ratio for the subgroup of patients with coronary artery disease at baseline (0.79; 0.60–1.06) tended towards a protective effect. The pooled analysis ( n = 722) showed that time to appropriate ICD intervention was similar for fish oil and placebo treatment (log-rank P = 0.79). Conclusion These findings do not support a protective effect of omega-3 PUFAs from fish oil on cardiac arrhythmia in all patients with an ICD. Current data neither prove nor disprove a beneficial or a detrimental effect for subgroups of patients with specific underlying pathologies.

In rural China, many pregnant women in their third trimester suffer from anemia (48%) and iron deficiency (ID; 42%), often with coexisting deficiencies of retinol and riboflavin. We investigated the effect of retinol and riboflavin supplementation in addition to iron plus folic acid on anemia and subjective well-being in pregnant women. The study was a 2-mo, double-blind, randomized trial. Subjects (n = 366) with anemia [hemoglobin (Hb)

Proper risk assessment lies at the basis of proportional risk management by business organisations and government authorities. The general stages of risk assessment (i.e. risk identification, risk estimation and risk evaluation) are considered the starting point for the development of methods for risk assessment. This paper outlines the preconditions for risk assessment methods and aims to clarify the difficulties and pitfalls in the subsequent stages of risk assessment. The criteria for proper risk assessments and the challenges described here may stimulate further developments in the design of sophisticated tools for risk assessment.

Summary Background Low folate and raised homocysteine concentrations in blood are associated with poor cognitive performance in the general population. As part of the FACIT trial to assess the effect of folic acid on markers of atherosclerosis in men and women aged 50–70 years with raised plasma total homocysteine and normal serum vitamin B 12 at screening, we report here the findings for the secondary endpoint: the effect of folic acid supplementation on cognitive performance. Methods Our randomised, double blind, placebo controlled study took place between November, 1999, and December, 2004, in the Netherlands. We randomly assigned 818 participants 800 μg daily oral folic acid or placebo for 3 years. The effect on cognitive performance was measured as the difference between the two groups in the 3-year change in performance for memory, sensorimotor speed, complex speed, information processing speed, and word fluency. Analysis was by intention-to-treat. This trial is registered with clinicaltrials.gov with trial number NCT00110604. Findings Serum folate concentrations increased by 576% (95% CI 539 to 614) and plasma total homocysteine concentrations decreased by 26% (24 to 28) in participants taking folic acid compared with those taking placebo. The 3-year change in memory (difference in Z scores 0·132, 95% CI 0·032 to 0·233), information processing speed (0·087, 0·016 to 0·158) and sensorimotor speed (0·064, −0·001 to 0·129) were significantly better in the folic acid group than in the placebo group. Interpretation Folic acid supplementation for 3 years significantly improved domains of cognitive function that tend to decline with age.

In order to investigate the determinants of childhood overweight and obesity in China, the prevalence of overweight (including obesity) was compared according to different dietary and physical activity patterns and parental body weight status. A total of 6826 children aged 7–17 years from the 2002 China National Nutrition and Health Survey were included in the study. Information for dietary intake was collected using three consecutive 24-h recalls by trained interviewers. The amounts of cooking oil and condiments consumed were weighed. An interview-administered 1-year physical activity questionnaire was used to collect physical activity information. The results showed that the heavier the parental body weight, the higher the overweight prevalence in children. The prevalence ratio increased if parent(s) were overweight and/or obese, up to 12·2 if both parents were obese. Overweight children consumed significantly more dietary energy, protein and fat, but less carbohydrate than their normal weight counterparts. On average, overweight children spent 0·5 h less on moderate/vigorous activities and 2·3 h more on low intensity activities per week. The following prevalence ratios were statistically significant: walking to and from school (0·6); moderate/vigorous activities ≥ 45 min/d (0·8); low intensity physical activities >2 h/d (1·3); the consumption of ≥ 25 g/d cooking oil (1·4); ≥ 200 g/d meat and meat products consumption (1·5); ≥ 100 g/d dairy products (1·8). After adjustment for parental body weight status and socioeconomic status, only cooking oil consumption and walking to and from school remained significantly related to child overweight. In conclusion, parental weight status is an important determinant. Fat intake, low intensity activities and active transport to/from school may be suitable entry points for overweight prevention among Chinese school children.

Vascular disease and its risk factors have been associated with the age-related hearing loss. We examined the association of elevated plasma homocysteine and its determinants with hearing levels. Pure-tone air conduction thresholds in 728 individuals with sensorineural hearing loss were not associated with homocysteine, erythrocyte folate and Vitamin B6. Low concentrations of serum folate and Vitamin B12 were associated with better hearing. When folate status was below the median, 5,10-methylenetetrahydrofolate reductase (MTHFR) 677TT homozygotes had similar hearing levels to subjects with a C allele. However, when folate status was above the median, MTHFR 677TT homozygotes had on an average 5 dB (p = 0.037) and 2.6 dB (p = 0.021) lower PTA-high and PTA-low hearing thresholds, respectively, than the subjects with a 677C allele. The relationship between serum folate and hearing thresholds appeared to be dependent on MTHFR 677 genotype (CC, r = 0.13, p = 0.034; TT, r = -0.10, p = 0.291). This supports the hypothesis that a greater one-carbon moiety commitment to de novo synthesis of nucleotides and an increase in formyl-folate derivatives relative to methyl-folate derivatives is protective for hearing.

Aim: We examined whether total homocysteine, B vitamins and the 5,10-methylenetetrahydrofolate reductase (MTHFR) 677C→T polymorphism are related to common carotid intima-media thickness, a marker of atherosclerosis, and carotid distension, a marker of arterial stiffness. Methods: We used cross-sectional data from 819 individuals aged 50–70 years. B-mode ultrasound of the distal common carotid arteries was performed to determine maximum carotid intima-media thickness, mean carotid intima-media thickness and distension. Results: Carotid intima-media thickness and distension did not differ across homocysteine, serum folate, vitamin B 6 and vitamin B 12 quartiles or between MTHFR C677T genotype. Erythrocyte folate was independently associated with maximum carotid intima-media thickness (mean difference first versus third quartile, 0.03mm, 95% CI 0.004–0.06mm; first versus fourth quartile, 0.03mm, 95% CI −0.002 to 0.06mm). Further adjustment for homocysteine did not affect this association. Folate deficient subjects had greater maximum carotid intima-media thickness than those with high-normal folate concentrations (serum folate: mean difference 0.05mm, 95% CI 0.01–0.08mm; erythrocyte folate: mean difference 0.04mm, 95% CI −0.03 to 0.11mm). Conclusion: Low folate concentrations, independent of hyperhomocysteinemia, may promote atherogenesis. Our findings confirm the null association of homocysteine with carotid intima-media thickness observed in other population-based studies, suggesting that hyperhomocysteinemia does not perpetuate atherosclerosis or arterial stiffness.

n-3 Fatty acids may protect against heart disease mortality by preventing fatal arrhythmias. Underlying effects on cardiac electrophysiology may be demonstrable in the standard electrocardiogram (ECG) and provide insight into the mechanism. Therefore, we investigated the effect of dietary n-3 fatty acids on heart-rate-corrected QT interval, T-loop width, spatial QRS-T angle and spatial U-wave amplitude in patients with frequent premature ventricular complexes. Seventy-four patients received either capsules providing 1·5 g n-3 fatty acids daily or placebo for approximately 14 weeks. ECG were recorded before and after intervention. None of the ECG characteristics was significantly affected by treatment. The present results do not provide additional support for the hypothesis that n-3 fatty acids prevent cardiac arrhythmia through generic electrophysiologic effects on heart cell membranes. However, we cannot exclude effects of n-3 fatty acids on clinical relevant endpoints that are not easily detected by prior changes in the ECG.

This review examines the relationship between hyperhomocysteinemia, a risk factor for vascular disease, and carotid intima-media thickness (CIMT), a valid marker of generalized atherosclerosis and future vascular disease risk. The relationship between two important determinants of hyperhomocysteinemia in the general population-folate status and the 677C --> T methylenetetrahydrofolate reductase (MTHFR) polymorphism-and CIMT is also covered. Methods: We searched literature databases for articles examining homocysteine and CIMT published before September 2003. Results: We identified 54 studies. Observational studies generally failed to demonstrate a relationship between homocysteine and CIMT in homocystinuric, uremic, hypercholesterolemic or non-insulin-dependent diabetes mellitus patients or in subjects with insulin insensitivity. Weak associations, but usually only in certain sub-populations were found in vascular disease patients and in population-based studies. B vitamins reduce the progression of CIMT in renal transplant recipients and vascular disease patients as demonstrated by two trials. The majority of studies demonstrated increased CIMT in individuals with the MTHFR 677TT genotype. Folate status showed no relation to CIMT. Discussion: In non-patient populations, hyperhomocysteinemia is weakly associated with CIMT. The association of the 677C --> T MTHFR polymorphism with CIMT further supports this finding. Lastly, folate levels may need to reach a critically low status before an association can be found between folate and CIMT. Larger trials in various population types are needed to determine whether folate alone or in combination with Vitamins B-6 and B-12 Will slow down or even reverse atherosclerotic progression. (C) 2004 Elsevier Ireland Ltd. All rights reserved.

OBJECTIVES We aimed to study the predictive value of heart rate-corrected QT interval (QTc) for incident coronary heart disease (CHD) and cardiovascular disease (CVD) mortality in the black and white general population, and to validate various QT measurements. BACKGROUND QTc prolongation is associated with higher risk of mortality in cardiac patients and in the general population. Little is known about the association with incident CHD. No previous studies included black populations. METHODS We studied the predictive value of QTc prolongation in a prospective population study of 14,548 black and white men and women, age 45 to 64 year. QT was determined by the NOVACODE program in the digital electrocardiogram recorded at baseline. RESULTS In quintiles of QTc, cardiovascular risk profile deteriorated with longer QTc, and risk of CHD and CVD mortality increased. The high risk in the upper quintile was mostly explained by the 10% with the longest QTc. The age-, gender-, and race-adjusted hazard ratios for CVD mortality and CHD in subjects with the longest 10% relative to the other 90% of the gender-specific QTc distribution were 5.13 (95% confidence interval 3.80 to 6.94) and 2.14 (95% confidence interval 1.71 to 2.69), respectively. The increased risk was partly, but not completely, attributable to other risk factors or the presence of chronic disease. The association was stronger in black than in white subjects. Manual- and machine-coded QT intervals were highly correlated, and the method of rate correction did not affect the observed associations. CONCLUSIONS Long QTc is associated with increased risk of CHD and CVD mortality in black and white healthy men and women.

The response of plasma lipids to dietary cholesterol and fat varies among individuals. Variations in genes involved in cholesterol metabolism can be important in these interindividual differences. The rate-limiting enzyme in the conversion of cholesterol into bile acids is cholesterol 7alpha-hydroxylase (CYP7A1). We investigated the effect of the A278-C promoter polymorphism in the CYP7A1 gene on responses of plasma lipids to an increased intake in dietary cholesterol (742 +/- 114 mg/d), cafestol (57 +/- 6 mg/d), saturated fat [change of 8-9 energy percent/d (en%/d)] and trans fat (change of 10-11 en%/d) in 496 normolipidemic subjects. These responses were measured in 26 previously published dietary trials. After adjustment for the apolipoprotein E genotype effect, AA-subjects consuming a cholesterol-rich diet had a smaller increase in plasma HDL cholesterol than CC-subjects (0.00 +/- 0.02 vs. 0.17 +/- 0.04 mmol/L; P < 0.001). Upon intake of cafestol, AA-subjects had a smaller increase in plasma total cholesterol than CC-subjects (0.69 +/- 0.10 vs. 1.01 +/- 0.10 mmol/L; P = 0.028). No effects of the polymorphism were found in the saturated and trans fat interventions. In conclusion, the CYP7A1 polymorphism has a small but significant effect on the increase in plasma HDL cholesterol and plasma total cholesterol after an increased intake of dietary cholesterol and cafestol, respectively.

Exhaled breath condensate (EBC) provides a noninvasive means of sampling the lower respiratory tract. Collection of EBC might be useful in the assessment of airway oxidative stress in smokers. The aim of this study was to determine 8‐isoprostane and hydrogen peroxide levels in EBC, and, in addition, to investigate the reproducibility of these measurements. EBC samples were collected from 12 healthy male smokers at three time points within 1 week. 8‐isoprostane and H2O2 were measured in nonconcentrated EBC using immunochemical and colorimetric assays, respectively. 8‐isoprostane and H2O2 were detected in only 36 and 47% of all EBC samples, respectively. It was not possible to calculate the within-subject variation in a reliable manner since only three of the 12 smokers exhibited detectable 8‐isoprostane concentrations on all three occasions (mean 4.6 pg·mL−1; range 3.9–7.7 pg·mL−1), whereas H2O2 could not be detected on all three occasions in any of the smokers. Spiking experiments revealed a recovery of 83.5–109.5% for 8‐isoprostane and 69.9–129.0% for H2O2 in fresh EBC samples. It was concluded that levels of 8‐isoprostane and hydrogen peroxide cannot be reproducibly assessed in exhaled breath condensate from healthy smokers because of their low concentration and/or the lack of sensitivity of the available assays. L.J. Dupont is supported by a postdoctoral research fellowship from the Fonds voor Wetenschappelijk Onderzoek – Vlaanderen (Fund for Scientific Research – Flanders, Brussels, Belgium).

Flow-mediated vasodilation (FMD) of the brachial artery is used as a marker of cardiovascular disease risk. It is defined as the percentage dilation from the baseline diameter in response to a provoked increase in blood flow. The within-subject variability, crucial in the design of trials with FMD as an endpoint, appears to vary widely between studies. We assessed the analytical and within-subject variability of FMD in healthy subjects and estimated the number of subjects needed to detect various treatment effects in intervention trials and observational studies. FMD was assessed with B-mode high-resolution ultrasound (US). A total of 13 volunteers were measured on six occasions, after they had fasted overnight. Within-subject variability was assessed from all six scans per subject. Analytical variation or reading variation was assessed by reading one scan of each subject twice by one observer. The mean (+/-tSD) FMD was 5.60 +/- 2.15 FMD% of the baseline diameter. The within-subject SD was 2.8 FMD%, resulting in a coefficient of variation (CV) of 2.8/5.6 x 100% = 50.3%. The CVs for the baseline and maximum diameter were much smaller: 4.8% (SD 0.193 mm at a mean of 4.060 mm) for the baseline and 5.2% (SD 0.222 mm at a mean of 4.285 mm) for the maximum. The CV for reading variation was 34%. The number of subjects needed to detect a treatment difference of 2 FMD% with a probability of 0.05 and a power of 0.80 would be 31 in a crossover design and 62 per group in a parallel design for comparison of group changes. We conclude that the within-subject variability of FMD is large, about 50% of the mean response. This includes biologic and reading variation. Repeated measurements and repeated readings of recorded measurements are recommended to reduce variability. (C) 2003 World Federation for Ultrasound in Medicine Biology.

OBJECTIVES: To describe the registration, management and characteristics of patients with tuberculosis (TB) in north-west China, and investigate whether patients with TB were diagnosed and treated in a timely manner.STUDY DESIGN: Health-facility-based retrospective data were collected from district patient registers and case reports for all patients with TB registered from January 2009 to December 2011 in Xinjiang Uygur Autonomous Region, north-west China.METHODS: Patient characteristics and clinical data were collected from the national TB epidemic reporting system using standardized case reporting forms for diagnosis, treatment and outcome. Data were collected and entered by trained health staff in the regional TB clinics.RESULTS: In total, data for 20,396 patients with TB were collected; of these, 78.5% were farmers. The age peaks were 20-44 years and 60-74 years. Average health-seeking and diagnostic delays were 32 days and two days, respectively. More than half (54.7%) of the patients with smear-negative TB were diagnosed by chest x-ray. Moreover, 94.3% of patients with TB were treated successfully. From 2009 to 2011, the health-seeking delay decreased significantly (P

(n-3) Fatty acids may reduce the risk of sudden death by preventing life-threatening cardiac arrhythmia. A standard electrocardiogram (ECG) may be used to detect clues as to the mechanism by which (n-3) fatty acids affect the electrophysiology of the heart. An earlier study showed that (n-3) fatty acids decreased the duration of the heart-rate corrected QT interval (QTc) in dogs. However, effects of (n-3) fatty acids on the standard ECG of humans have not been reported. Therefore, we investigated the effect of (n-3) fatty acids on QTc, QRS duration, apex-to-end-T duration, T-loop morphology and spatial QRS-T angle in apparently healthy men and women aged 50 to 70 y. Subjects (n = 42/group) received either capsules providing 1.5 g (n-3) fatty acids daily or placebo for 12 wk. ECG were recorded before and after intervention. None of the ECG characteristics were affected by (n-3) fatty acids. The QTc decreased by 0.8 ms or 0.2% (95% confidence interval, -6.1 to 4.4 ms) in subjects that consumed (n-3) fatty acids compared with the placebo group. These results do not support the hypothesis that (n-3) fatty acids prevent arrhythmia through electrophysiologic effects on heart cell membranes. However, an effect on the ECG in more susceptible populations can not be excluded. -------------------------------------------------------------------------------- KEY WORDS: … (n-3) fatty acids … ventricular arrhythmias … electrocardiogram … QTc interval … electrophysiology

SummaryHomocysteine may have an effect on risk of cardiovascular disease by stimulating procoagulant factors and/or impair anti-coagulant mechanisms or fibrinolysis. However, data in humans of such effects are sparse. In this intervention study, we examined the effect of homocysteine lowering by B-vitamin supplementation on prothrombin fragments 1 and 2 (F1+2), thrombin-antithrombin complex (TAT), and fibrin degradation products (D-dimer). The study comprised 118 healthy volunteers, 50 with homocysteine > 16 µmol/L and 68 with homocysteine ≤ 16 µmol/L, who were randomized to placebo or highdose B-vitamin supplements (5 mg folic acid, 0.4 mg hydroxycobalamin, and 50 mg pyridoxine) daily for 8 weeks. Although homocysteine concentrations were 27.7% (p < 0.0001) reduced in the Bvitamin group compared to the placebo group, no effect on F1+2 and TAT concentrations was observed. A 10.4% reduction was observed for D-dimer (p = 0.08).In conclusion, it appears that in healthy subjects homocysteine reduction by B-vitamin supplementation has a modest beneficial effect on clotting activation.

B vitamins as enzyme cofactors play an important role in energy metabolism. The aim of this study was to determine whether B vitamins can affect body weight (BW) and activity of energy metabolism-related enzymes in an animal model. Fifty Wistar rats were randomly divided to 3 groups and were fed a diet containing 10% fat (LF), a diet containing 45% fat (HF), or a HF diet supplemented with B vitamins (100 mg/kg BW for both thiamine and riboflavin, 250 mg/kg niacin) (HF+B). After rats were fed for 12 weeks, HF group had significantly larger weight gain than LF group (285.2±14.8 g versus 159.1±53.0 g, P

Background The endogenous antioxidant serum bilirubin may scavenge free radical species from cigarette smoke. Smokers are expected to have lower serum bilirubin levels than never smokers, but this has never been evaluated in a random population sample of women and men. In addition, in vitro studies indicate that filter cigarette smoke might enhance bilirubin oxidation more than non-filter cigarette smoke. Methods In this paper, data were analysed from the Belgian Interuniversity Research on Nutrition and Health (BIRNH) study. We investigated the association of smoking and type of cigarettes with serum bilirubin concentrations in men and women using multiple regression models taking into account differences in baseline and smoking characteristics. Results In men, current smokers had lower crude and adjusted serum bilirubin concentrations compared with never smokers (P = 0.0001). For women, the association between smoking and serum bilirubin concentrations adjusted for age was in the same direction as for men, but did not reach statistical significance. Male former smokers had serum bilirubin concentrations in between those of current smokers and never smokers, while female former smokers had even higher (+ 0.50 μmol/l) serum bilirubin concentrations than never smokers. Male subjects smoking filter cigarettes showed a higher serum bilirubin concentration than those smoking cigarettes without a filter (adjusted difference: 0.49 μmol/l; P = 0.03). The duration of smoking was inversely and significantly related to serum bilirubin concentrations (P = 0.0003). Conclusion Smoking may lower serum bilirubin concentrations in men, especially in those smoking non-filter cigarettes. The duration of smoking is a more important determinant for serum bilirubin concentrations than the number of cigarettes smoked per day, which may indicate the cumulative negative effects of smoking on the endogenous antioxidant system. Results for females pointed in the same direction, but were less clear, possibly due to low numbers of smoking women, who were largely young and smoked mainly filter cigarettes for a shorter period of time.

The article describes the design and preliminary evaluation of a 17-week, twice-weekly, comprehensive, progressive exercise program for frail elderly adults. The main objective was to maintain or improve mobility and performance of daily activities essential for independent functioning. Strength, speed, endurance, flexibility, and coordination were trained by walking, kneeling, and chair stands, performed in the context of motor behavior such as games and daily activities. The acceptability of the exercise program was evaluated in a population of community-dwelling, frail older adults (mean age 77.6 ± 5.4 years). Eighty-one percent completed the program. Program appreciation and attendance were high. Seventy-three percent reported wanting to continue participating if possible—although most only once a week. At follow-up (1–1.5 years afterward) 30% were still participating in an exercise program. The exercise program was enjoyed and accepted by a population of frail, previously sedentary elderly adults. Widespread implementation of this program could increase physical activity among frail older adults.

24-Hour Heart Rate Variability in Shift Workers: Impact of Shift Schedule: L.G.P.M. van AMELSVOORT, et al. Department of Epidemiology, Maastricht University—Disturbance of the circadian pattern of cardiac autonomic control by working at night when the physiological system anticipates rest could explain part of the elevated cardiovascular risk in shift workers. Analysis of Heart Rate Variability (HRV) is a non-invasive tool to estimate disturbances of the cardiac autonomic control. To assess the influence of working at night on cardiac autonomic control, HRV levels were determined in shift workers. 24-h ECG recordings were made during a day on morning shift and a day on night shift. Within person differences between a morning and a night shift were calculated. Possible modification of the reported effects by the shift schedule was determined. Significantly elevated mean %LF during sleep was found on a day worked on night shift compared with a day on day shift (%LF + 3.04, P< 0.01). Type of shift schedule was found to be a significant modifier of this effect. The difference in %LF between the night and day shift for the different shift schedules apart were: + 0.88% for the workers in the fast forward rotating shift, + 3.06% for the fast backward rotating shift, + 6.15% (P< 0.001) for the medium speed backward rotating shift and + 1.18% for the shift workers without a regular shift schedule. The results suggest an increased sympathetic dominance during a night shift sleep, indicating an inferior sleep quality. Optimisation of this schedule might diminish this impact and could contribute to a reduction of the cardiovascular disease risk among shift workers. (J Occup Health 2001; 43: 32-38)

Solid fats are used in food manufacturing to provide texture and firmness to foods. Such fats are rich in either saturated or trans-fatty acids, both of which increase the risk of coronary heart disease. Epidemiological and experimental studies suggest that trans-fatty acids increase risk more than do saturates because they lower serum high density lipoprotein (HDL) cholesterol. However, there appear to be differences between saturates in their effect on HDL cholesterol. We investigated whether the consumption of a solid fat rich in lauric acid (C12:0) would result in a more favorable blood lipid profile than the consumption of a solid fat rich in trans-fatty acids. We fed 32 healthy men and women two controlled diets in a 2 x 4-wk randomized crossover design. The diets consisted of a background diet supplemented with margarines. In the trans-diet, 9.2% of energy was provided by trans-fatty acids and 12.9% by saturated fatty acids. In the Sat-diet, energy intake was 0% from trans-fatty acids and 22.9% from saturated fatty acids. Lauric acid composed one third of all saturates in the Sat-diet. Serum HDL cholesterol was 0.36 mmol/L lower at the end of the trans-diet than at the end of the Sat-diet (95% confidence interval, -0.46 to -0.26), whereas serum low density lipoprotein cholesterol and triglyceride concentrations remained stable. Serum total cholesterol was 0.31 mmol/L (95% confidence interval, -0.48 to -0.14) lower at the end of the trans-diet than at the end of the Sat-diet. Consumption of a solid fat rich in lauric acid gives a more favorable serum lipoprotein pattern than consumption of partially hydrogenated soybean oil rich in trans-fatty acids. Thus, solid fats rich in lauric acids, such as tropical fats, appear to be preferable to trans-fats in food manufacturing, where hard fats are indispensable.

objective: The endogenous antioxidant serum bilirubin may scavenge free radicals and protect against free radical-related diseases. Methods: Using the 10-year follow-up mortality data from the Belgium Inter-university Research on Nutrition and Health (BIRNH) study the association between serum bilirubin and all-cause, cardiovascular, and cancer mortality in 5460 men and 4843 women was investigated. Results: In men, with the highest (≥0.6 mg/dl) compared with the lowest serum bilirubin concentration (≤0.2 mg/dl), the adjusted relative risk (RR) was 0.73 (95% confidence interval (CI) 0.57–0.94) for all-cause and 0.42 (95% CI 0.26–0.68) for cancer mortality. The risk for cancer mortality decreased with increasing concentrations of serum bilirubin (p for trend = 0.004) especially for non-lung cancer mortality (p for trend = 0.02). The associations persisted after adjusting for smoking. In women the associations between serum bilirubin and cancer mortality were in the same direction, but did not reach statistical significance (RR = 0.76, 95% CI 0.39–1.5). No significant associations were found between serum bilirubin and cardiovascular mortality in men and women. Conclusions: In this population high serum bilirubin, however, within normal ranges, was associated with low cancer mortality, especially in men. This may be due to the antioxidant activity of bilirubin. Measurement of serum bilirubin concentrations may contribute to cancer risk estimation.

Background —Low heart rate variability (HRV) is associated with a higher risk of death in patients with heart disease and in elderly subjects and with a higher incidence of coronary heart disease (CHD) in the general population. Methods and Results —We studied the predictive value of HRV for CHD and death from several causes in a population study of 14 672 men and women without CHD, aged 45 to 65, by using the case-cohort design. At baseline, in 1987 to 1989, 2-minute rhythm strips were recorded. Time-domain measures of HRV were determined in a random sample of 900 subjects, for all subjects with incident CHD (395 subjects), and for all deaths (443 subjects) that occurred through 1993. Relative rates of incident CHD and cause-specific death in tertiles of HRV were computed with Poisson regression for the case-cohort design. Subjects with low HRV had an adverse cardiovascular risk profile and an elevated risk of incident CHD and death. The increased risk of death could not be attributed to a specific cause and could not be explained by other risk factors. Conclusions —Low HRV was associated with increased risk of CHD and death from several causes. It is hypothesized that low HRV is a marker of less favorable health.

Antioxidant vitamins (provitamins) may protect against loss of lung function over time. We studied the association between serum carotenoids (-carotene, -carotene, lycopene, -cryptoxanthin, zeaxanthin, and lutein), -tocopherol, and lung function among noninstitutionalized Dutch elderly age 65 to 85 yr (n = 528). Multiple linear regression analysis was performed with FEV1 or FVC as dependent variables and serum levels of antioxidants in quintiles as independent variables. We adjusted for age, gender, height, and pack-years of smoking. Subjects in the fifth quintile of serum -carotene had a 195 ml (95␌onfidence interval [95␌I]: 40 to 351 ml) higher and those in the fifth quintile of -carotene had a 257 ml (95␌I: 99 to 414 ml) higher FEV1 compared with subjects in the first quintile of these carotenoids. Significant (p < 0.05) positive trends were observed between -carotene, -carotene, lycopene, and FEV1 and between -carotene, -carotene, and FVC. Subjects in the highest quintile of the other carotenoids or -tocopherol did not have significantly higher FEV1 or FVC compared with subjects in the first quintile of these antioxidants. In conclusion, this study shows that from the six major serum carotenoids and -tocopherol studied, particularly -carotene, -carotene, and lycopene were positively associated with lung function in the elderly and may be considered as candidates for further investigations. Grievink L, de Waart FG, Schouten EG, Kok FJ. Serum carotenoids, -tocopherol, and lung function among Dutch elderly.

Elevated factor VII coagulant activity (FVII:C) has been associated with an increased risk of ischaemic heart disease, particularly for fatal events. Results of studies on the association between FVII:C and atherosclerosis are not consistent. FVII:C levels are influenced by several environmental factors and by genetic factors. One of the genetic factors is the −323Ins10 polymorphism in the promoter region of the factor VII gene, which is strongly related to FVII:C, and thus may be associated with ischaemic heart disease. We studied the association of this polymorphism with the severity and progression of atherosclerosis. In 511 male patients of the Regression Growth Evaluation Statin Study, the genotype for the −323Ins10 polymorphism was determined. The minimum obstruction diameter and the mean segment diameter were determined at baseline and after a 2-year follow-up period, and new lesion formation was assessed as well. Cardiovascular events were recorded. No relationship was observed between the −323Ins10 polymorphism and angiographic measures of disease progression, nor on the risk of new cardiovascular events. The results suggest that there is no association between the −323Ins10 polymorphism for factor VII and the severity or progression of coronary atherosclerosis in male patients with symptomatic coronary artery disease.

We investigated interactions between a mutation (D9N) in the lipoprotein lipase (LPL) gene and physical activity, as well as other lifestyle factors, on lipid traits in a population-based sample of Dutch men and women (n = 379). We used questionnaire information to classify physical activity, alcohol consumption, and smoking habits, while overweight was defined as a body mass index (BMI) > 25 kg/m2. Non-fasting blood samples were used for the determination of lipid traits and the D9N genotype. Fifteen subjects (4%) carried the mutation. They presented with higher levels of total cholesterol, apolipoprotein (apo) B and triglycerides compared to non-carriers. While no interactions with overweight, alcohol consumption, and smoking were found, a strong interaction between the D9N mutation and physical activity became apparent. Physically inactive D9N carriers (n = 5) had considerably higher total cholesterol (+2 mmol/l, p < or = 0.0001) and apo B levels (+63 mg/dl, p < or = 0.0001) compared to non-carriers of this mutation, whereas their high-density lipoprotein (HDL)-cholesterol concentrations were lower (-0.22 mmol/l, p < 0.05). This was not the case for physically active D9N carriers (n = 10). In conclusion, a common variant of the LPL gene (D9N) adversely affects plasma lipid and lipoprotein profiles. However, the unfavorable consequences may be counteracted by physical activity.

Background: It has been suggested that vitamin E can counteract the age-associated decline in cellular immune responsiveness (CIR). Particularly, T helper cell type 1 (Thl) activity, ie, interferon (IFN) γ-producing Thl activity and, hence, delayed-type hypersensitivity (DTH) would be enhanced by vitamin E supplementation. Objective: Our aim was to study the effects of 6 mo supplementation with 50 and 100 mg vitamin E on CIR in the elderly. Design: A double-blind, placebo-controlled trial was conducted in 161 healthy elderly subjects aged 65-80 y. CIR was measured in vivo by means of DTH skin tests and in vitro by assessing the production of interleukin (IL) 2, IFN-γ (a typical Thl cytokine), and IL-4 (a typical Th2 cytokine) by peripheral blood mononuclear cells after stimulation with phytohemagglutinin. Results: Both DTH and IL-2 production showed a trend toward increased responsiveness with increasing dose of vitamin E. However, IFN-γ production decreased whereas IL-4 production increased in the groups receiving vitamin E. Only the change in the number of positive DTH reactions was borderline significantly larger in the 100-mg vitamin E group than in the placebo group (P = 0.06, Bonferroni adjusted). Subjects receiving 100 mg vitamin E with low baseline DTH reactivity or who were physically less active had a significantly larger increase in the cumulative diameter of the skin induration resulting from the DTH test than did the placebo group (P = 0.03), although this difference was not significant after Bonferroni correction (P = 0.07). Conclusion: Possible beneficial effects of 100-mg vitamin E supplementation may be more pronounced in particular subgroups of elderly subjects.

OBJECTIVE: An elevated cardiovascular disease risk for shiftworkers has frequently been reported, however, the mechanism is still unknown. Changes in eating habits, in physical activity or metabolic factors could be involved. In this study we assessed the relationship between body mass index (BMI) as a possible indicator of changed eating habits or metabolic involvement and duration of shiftwork. DESIGN: Data from an ongoing cohort study among 377 shiftworkers and non-shiftworking controls, all starting in a new job were used. Anthropometric measurements were carried out at the start of the assignment. Job history was obtained by a questionnaire. RESULTS: A positive relationship was observed between BMI and waist to hip ratio (WHR) and duration of shiftwork experience, with an adjustment for age. The linear regression coefficients, with additional adjustments for sex, smoking status, physical activity and educational level were 0.12 kg/m2 per y in shiftwork for BMI (P

The objective of this study was to evaluate the association of factor VII with dietary factors while also considering the R/Q353 polymorphism. Nutrition is an important determinant of coagulation factor VII, which is also genetically determined by the R/Q353 polymorphism. High levels of coagulation factor VII clotting activity (FVII:C) are associated with the risk of myocardial infarction; nutrition may have an effect on these levels if people are genetically susceptible to dietary changes. FVII:C was measured in 3005 elderly subjects, and the extreme quintiles of the FVII:C distribution were selected for measurement of the R/Q353 genotype and FVII:Chr (reflects total factor VII). In these 1158 subjects, habitual diet was assessed with a semiquantitative food-frequency questionnaire. The frequency of the Q353 allele was 0.24 in the lowest and 0.09 in the highest quintile. The quintiles were combined for linear regression analyses. FVII:C was inversely associated with fiber [beta = -0.64 %pooled plasma (PP)/g, confidence interval (CI): -1.07,-0.21] and protein intake (beta = -0.16 %PP/g, CI: -0.31,-0. 01) and positively with saturated fat intake (beta = 0.19 %PP/g, CI: -0.10,0.48). FVII:Chr was inversely associated with fiber (beta = -0. 38 %PP/g, CI: -0.71,-0.05). No other associations with diet were observed. The inverse association of FVII:C with fiber was stronger in subjects with the RR genotype (beta = -0.76 %PP/g, CI: -1.23,-0. 29), than in those with the RQ/QQ genotypes (beta = -0.19 %PP/g, CI: -0.97,0.59). The same was found for FVII:Chr. The association of FVII:C with saturated fat was positive in those with the RR allele and inverse in those carrying the Q allele. These findings suggest that the strength of the association between coagulation factor VII and diet varies across the genotypes of the R/Q353 polymorphism.

Isoflavone supplements, consumed by women experiencing menopausal symptoms, are suggested to have positive effects on menopause-related adiposity and cardiovascular disease risk profile, but discussions about their safety are still ongoing.The objective was to study the effects of an 8-wk consumption of 2 different isoflavone supplements compared with placebo on whole-genome gene expression in the adipose tissue of postmenopausal women.This double-blind, randomized, placebo-controlled crossover intervention consisted of 2 substudies, one with a low-genistein (LG) supplement (56% daidzein + daidzin, 16% genistein + genistin, and 28% glycitein + glycitin) and the other with a high-genistein (HG) supplement (49% daidzein + daidzin, 41% genistein + genistin, and 10% glycitein + glycitin). Both supplements provided ∼ 100 mg isoflavones/d (aglycone equivalents). After the 8-wk isoflavone and placebo period, whole-genome arrays were performed in subcutaneous adipose tissue of postmenopausal women (n = 26 after LG, n = 31 after HG). Participants were randomized by equol-producing phenotype, and data analysis was performed per substudy for equol producers and nonproducers separately.Gene set enrichment analysis showed downregulation of expression of energy metabolism-related genes after LG supplementation (n = 24) in both equol-producing phenotypes and oppositely regulated expression for equol producers (down) and nonproducers (up) after HG supplementation (n = 31). Expression of inflammation-related genes was upregulated in equol producers but downregulated in nonproducers, independent of supplement type. Only 4.4-7.0% of the genes with significantly changed expression were estrogen responsive. Body weight, adipocyte size, and plasma lipid profile were not affected by isoflavone supplementation.Effects of isoflavones on adipose tissue gene expression were influenced by supplement composition and equol-producing phenotype, whereas estrogen-responsive effects were lacking. LG isoflavone supplementation resulted in a caloric restriction-like gene expression profile for both producer phenotypes and pointed toward a potential beneficial effect, whereas both supplements induced anti-inflammatory gene expression in equol producers. The study was registered at clinicaltrials.gov as NCT01556737.

Low heart rate variability is associated with high risk of sudden death in myocardial infarction patients. This has been attributed to unfavorable autonomic cardiac control. In the present study, the predictive value of heart rate variability for sudden death, mortality from coronary heart disease, and from all causes was investigated in the general population, using brief electrocardiographic recordings. From 1960 to 1985, 878 middle-aged Dutch men, aged 40-60 years, were followed and repeatedly examined as part of the Zutphen Study. In 1985 the remaining cohort was extended to 885 elderly men, aged 65-85 years, and followed until 1990. Heart rate variability (standard deviation of duration of normal RR intervals) was determined from the resting 12-lead electrocardiogram. The 5-year age-adjusted relative rate of total mortality of men with heart rate variability of < 20 milliseconds (msec) compared with men with heart rate variability of 20-39 msec was 2.1 (95 percent confidence interval 1.4-3.0) in middle-aged men and 1.4 (95% confidence interval 0.9-2.2) in elderly men. Death from noncoronary causes, especially cancer, contributed significantly to this elevated risk. The association of low heart rate variability with sudden death or coronary heart disease mortality was less consistent. In conclusion, in middle-aged men and probably in elderly men, low heart rate variability is predictive of mortality from all causes. This suggests that low heart rate variability is an indicator of compromised health in the general population.

Abstract Epidemiological research has shown that elevated plasma total homocysteine (tHcy) is a risk factor for atherosclerotic disease. In the present case-control study, we investigated whether fasting or postmethionine-loading tHcy was a stronger predictor of risk of severe coronary atherosclerosis. Furthermore, we studied levels of B vitamins, which are involved in homocysteine metabolism. Subjects were recruited from men and women, aged 25 to 65 years, who underwent coronary angiography between June 1992 and June 1994 in a hospital in Rotterdam, The Netherlands. Cases (n=131) were defined as those with ≥90% occlusion in one and ≥40% occlusion in a second coronary artery, while control subjects (n=88) had ≤50% occlusion in only one coronary vessel. In addition, a population-based control group free from clinical cardiovascular disease (n=101) was studied. Coronary patients were studied at least 2.5 months after angiography or other acute illness, such as myocardial infarction. After adjusting for age and sex differences between the groups, cases had 9% ( P =.01) higher geometric mean fasting and 7% ( P =.04) higher geometric mean postload tHcy than the combined control groups. Despite higher levels of tHcy for cases, their geometric mean levels of red cell folate and pyridoxal 5′-phosphate were higher than for control subjects, whereas plasma vitamin B 12 was only slightly lower in cases. The frequency distribution of tHcy values in cases was slightly shifted toward the right, across the entire range, compared with the distribution in the combined control group. This was somewhat more obvious for fasting than postload tHcy levels. The odds ratio (OR) for severe coronary atherosclerosis (case status) for each 1 SD increase in fasting tHcy (5 μmol/L) was 1.3 (95% confidence interval [CI], 1.0-1.6), similar to the OR for each 1 SD increase (12 μmol/L) in postmethionine-loading tHcy (1.3 [95 CI, 1.0-1.7]), after adjustment for sex, age, and other potential confounders. Furthermore, there was a significant linear trend of increasing fasting tHcy with increasing number of occluded arteries ( P =.01), correcting for sex, age, and other potential confounders. Our data show a positive association between plasma tHcy and risk of severe coronary atherosclerosis, of similar strength for fasting and postload tHcy levels. The data suggest that the association exists over a wide range of tHcy levels, without a clear cutoff point below which there is no increased risk.

Department of Epidemiology and Public Health, University of Wageningen, The Netherlands.The study investigates the validity of the Physical Activity Scale for the Elderly (PASE) in 21 Dutch elderly men and women. The PASE is an easily scored, brief questionnaire for elderly, suitable for large epidemiologic studies. The PASE score was compared with physical activity measured with the doubly labeled water method. The correlation coefficient of the PASE score with the residuals from the regression analysis using total energy expenditure as dependent and resting metabolic rate as independent variate was 0.58 (95% CI = 0.50-0.81). Women had greater engagement in extremely high scoring activities as housework and taking care of others, resulting in higher PASE scores than men (97.9 and 71.9). The higher scores in women were not linked to higher activity levels, which suggests that the mentioned activities may be overvalued. Sex specific correlation coefficients were 0.79 (CI = 0.32-0.95) and 0.68 (CI = 0.15-0.90) for men and women, respectively. In conclusion, the PASE proved to be a reasonable valid method to classify healthy elderly men and women into categories of physical activity. Some possible refinements were suggested, which may improve the accuracy of the PASE questionnaire.

SummaryThe elevated incidence of thrombotic disease in elderly people may be associated with an increase in PAI-1 and fibrinogen with ageing. Cross-sectional studies report an inverse relation of PAI-1 and fibrinogen with physical activity, but training studies show inconsistent results. In a controlled intervention study among elderly subjects (aged 60-80 years) we observed a moderate decrease in PAI-1 antigen (4%, -2.1 ± 2.4 ng/ml), a significant increase in t-PA activity (11%, 0.07 ± 0.04 IU/ml) and an unexpected significant increase in fibrinogen (6%, 0.18 ± 0.07 g/1) in subjects following a 6-month intensive training program as compared to controls. Reduction in PAI-1 antigen was significantly associated with a decrease in triglycerides (β = 10.3 ng/ml per 1 mM, p

Background: In heart rate variability (HRV) studies, the duration of the electrocardiographic recordings may vary between 20 seconds and 24 hours. Little is known about the reproducibility or comparability of HRV measures calculated over observation periods of different duration. Methods: To assess the reproducibility and comparability of HRV measures computed from short recordings under standardized conditions and from ambulatory 24-hour recordings, 15 healthy young males were studied on three occasions. Results: The reliability coefficient (between subject variation divided by summed between and within subject variation) for 20-second intervals was low for all measures. For 5-minute intervals in supine position, but not standing position, the reliability coefficients of the standard deviation, root of mean squared successive differences, proportion of successive differences > 50 ms, and the proportion low frequency power were about 70%. The reliability coefficients of the 24-hour HRV measures were > 80% for all measures. Short- and long-term measures of heart rate and HRV appeared to be correlated, implying that these measures result in similar ranking of subjects. Conclusions: The results indicate that HRV measures based on 24-hour monitoring during regular activities are better reproducible than short-term measures under standardized conditions. A single 5-minute recording may suffice to characterize a group of persons in a population study, but, because of considerable day-to-day variation, it is not adequate for individual characterization.