Determinants of Mortality from Cardiovascular Disease in the Slums of Nairobi, Kenya.

Background: Cardiovascular diseases (CVD) comprise eighty percent of non-communicable disease (NCD) burden in low- and middle-income countries and are increasingly impacting the poor inequitably. Traditional and socioeconomic factors were analyzed for their association with CVD mortality over 10 years of baseline assessment in an urban slum of Nairobi, Kenya. Methods and results: A 2008 survey on CVD risk factors was linked to cause of death data collected between 2008 and 2018. Cox proportional hazards on relative risk of dying from CVD over a 10-year period following the assessment of cardiovascular disease risk factors were computed. Population attributable fraction (PAF) of incident CVD death was estimated for key risk factors. In total, 4,290 individuals, 44.0% female, mean age 48.4 years in 2008 were included in the analysis. Diabetes and hypertension were 7.8% and 24.9% respectively in 2008. Of 385 deaths recorded between 2008 and 2018, 101 (26%) were caused by CVD. Age (hazard ratio (HR) 1.11; 95% confidence interval (CI) 1.03-1.20, p = 0.005) and hypertension (HR 2.19, 95% CI 1.44-3.33, p <0.001) were positively associated with CVD mortality. Primary school education and higher (HR 0.57, 95% CI 0.33-0.99, p = 0.044) and formal employment (HR 0.22, 95% CI 0.06-0.75, p = 0.015) were negatively associated with CVD mortality. Controlling hypertension would avert 27% (95% CI 9%-42%, p = 0.004) CVD deaths, while if every member of the community attained primary school education and unemployment was eradicated, 39% (95% CI 5% - 60%, p = 0.026), and 17% (95% CI 5%-27%, p = 0.030) of CVD deaths, would be averted respectively. Conclusions: A holistic approach in addressing socioeconomic factors in the broader context of social determinants of health at the policy, population and individual level will enhance prevention and treatment-adherence for CVD in underserved settings.

Short-Term Daily Intake of Polydextrose Fiber Does Not Shorten Intestinal Transit Time in Constipated Adults: A Randomized Controlled Trial.

Chronic constipation (CC) remains a common gastrointestinal (GI) disorder that conveys a substantial healthcare burden. Expert guidelines recommend increasing fiber intake, yet the clinical evidence to support this needs strengthening for specific fibers. The aim was to evaluate changes in intestinal transit time and GI symptoms in CC patients who consumed polydextrose. In a randomized, double-blind, placebo-controlled trial, 128 adults with CC received 8 g or 12 g polydextrose, or placebo, daily for 4 weeks. Transit time, as primary outcome, was assessed by radiopaque marker distribution after 2-weeks intervention. Bowel habits, GI symptoms and quality of life (QOL) were assessed by questionnaire, including the Patient-Assessment of Constipation (PAC) Symptoms (SYM), and PAC-QOL. Following 2-weeks intervention, no reduction was seen in transit time in any group and following 2- or 4-weeks intervention, no improvements were seen in stool frequency or consistency in any group. After 2-weeks intervention with 8 g/day polydextrose an improvement was seen in the PAC-SYM rectal score (p = 0.041). After 4-weeks intervention both rectal (p = 0.049) and stool (p = 0.029) scores improved while improvement in the QOL satisfaction score did not reach significance (p = 0.071). Overall, the results suggest that 2-weeks consumption of 8 or 12 g/day polydextrose does not significantly improve physiological measures of gut function in CC adults. Longer term consumption may improve clinical measures, but further studies will be required to substantiate this.

Antenatal coffee and tea consumption and the effect on birth outcome and hypertensive pregnancy disorders.

BACKGROUND AND OBJECTIVE: Coffee and tea are commonly consumed during pregnancy. While several of their components, like caffeine, have strong pharmacological effects, the effect on the unborn fetus remains unclear. Caffeine intake has been associated with abortion, preterm birth and fetal growth restriction, but a general consensus on caffeine restriction is still lacking. We aimed to investigate antenatal coffee, tea and caffeine consumption and the effect on birth weight and length, gestational age at birth and hypertensive disorders in pregnancy. METHODS: A total of 936 healthy pregnancies from the WHISTLER birth cohort with data on coffee and tea consumption were included. Maternal and child characteristics as well as antenatal coffee and tea consumption were obtained through postpartum questionnaires. Reported consumption was validated using available preconceptional data. Caffeine intake was calculated from coffee and tea consumption. Linear and logistic regression was used to assess the association with birth outcome and hypertensive disorders. RESULTS: After adjustment for smoking and maternal age, a daily consumption of more than 300mg of caffeine compared to less than 100mg of caffeine was significantly associated with an increased gestational age (linear regression coefficient = 2.00 days, 95%CI = 0.12-4.21, P = 0.03). Tea consumption was significantly related to a higher risk of pregnancy induced hypertension (OR = 1.13, 95%CI = 1.04-1.23, P = 0.004). No associations concerning coffee consumption or birth weight and birth length were observed. CONCLUSIONS: Daily caffeine consumption of more than 300mg is possibly associated with an increase in gestational age at birth. A possible relation between high tea consumption and increased risk for pregnancy induced hypertension warrants further research. For most outcomes, we found no significant associations with coffee or tea intake.

Uterine Tonus Assessment by Midwives versus Patient self-assessment in the active management of the third stage of labor (UTAMP): study protocol for a randomized controlled trial.

BACKGROUND: Postpartum hemorrhage (PPH) is the leading cause of maternal mortality worldwide and accounts for one third of maternal deaths in low-income and middle-income countries. PPH can be prevented by active management of the third stage of labor (AMTSL), a series of steps recommended by the World Health Organization to be performed by skilled birth attendants (SBAs). Task shifting in the AMTSL step of uterotonic drugs administration to community health workers, traditional birth attendants and self-administration has been investigated as a strategy to increase access to quality obstetric care considering persistent SBA and facility-based delivery shortages. The aim of this study is to assess task shifting in the final step of AMTSL and compare uterine tonus assessment by a SBA to self-assessment. METHODS AND DESIGN: The study is an individual-level two-arm non-inferiority randomized controlled trial (RCT). A total of 800 women will be recruited in Korle Bu Teaching Hospital in Accra, Ghana. Adult women in labor at term with an expected vaginal delivery who received antenatal instructions for self-assessment of uterine tonus will be eligible for inclusion. Women with an increased risk for PPH will be excluded. Women will be randomized to uterine tone assessment by a skilled birth attendant (midwife) or uterine tone self-assessment (with the safety back-up of a midwife present in case of PPH or uterine atony). Postpartum blood loss will be measured through weighing of disposable mats. The main study endpoints are PPH (≥500 ml blood loss), severe PPH (≥1000 ml blood loss), mean blood loss, and routine maternal and neonatal outcomes. Participants and caregivers will not be blinded given the nature of the intervention. DISCUSSION: A reduction of PPH-related maternal mortality requires full implementation of AMTSL. Task shifting of uterine tone assessment may contribute to increased AMTSL implementation in (clinical) settings where SBAs capacity is constrained. TRIAL REGISTRATION: Clinicaltrials.gov: NCT02223806 , registration August 2014. PACTR: PACTR201402000736158 , registration July 2014. University of Ghana, Medical School Ethical and Protocol Review Committee: MS-Et/M.8-P4.1/2014-2015.

The evening versus morning polypill utilization study: the TEMPUS rationale and design.

BACKGROUND AND RATIONALE: In clinical practice, blood pressure (BP)-lowering agents are generally prescribed for use in the morning, whereas (short-acting) statins are recommended for use in the evening. There is evidence that the reduction in LDL cholesterol (LDL-c) achieved with short-acting statins is superior when taken in the evening and reported improvement in BP control when aspirin and BP-lowering agents are taken in the evening. However, it is unclear whether the additional reduction in LDL-c and BP is offset by a reduction in adherence, given that taking medication in the evening may be less typical or convenient. There is therefore uncertainty concerning the best timing of administration of a cardiovascular combination pill such as the polypill. AIM: The aim of TEMPUS (NCT01506505), a prospective randomized open blinded endpoint (PROBE) crossover trial, is to evaluate whether there is a difference in LDL-c levels or 24-hour ambulatory BP in individuals at increased risk of cardiovascular disease when the cardiovascular polypill is taken in the evening compared to the morning. An additional aim is to assess the effect of the polypill on LDL-c and BP compared to the administration of separate pills of identically dosed components of the polypill. METHODS: In total 75 participants with established cardiovascular disease or an intermediate to high risk for cardiovascular disease are randomly allocated to the sequence of three different treatments of 6-8 weeks: (1) the cardiovascular polypill (aspirin 75 mg, simvastatin 40 mg, lisinopril 10 mg, and hydrochlorothiazide 12.5 mg) in the evening; (2) the polypill in the morning; and (3) the use of the identically dosed agents in separate pills taken at different time points during the day. The primary endpoint is the difference in LDL-c and mean 24-hour ambulatory systolic BP. Secondary outcomes are the difference in relative risk reduction, biochemistry, platelet function and pulse wave analysis, participants' adherence, and acceptability. CONCLUSIONS: TEMPUS will evaluate the effect of timing of the administration of a cardiovascular polypill on LDL-c and BP measurements in patients with an intermediate or high risk for cardiovascular disease.

Effect of 3 y of folic acid supplementation on the progression of carotid intima-media thickness and carotid arterial stiffness in older adults.

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 µmol/L at screening was conducted. Participants received either 800 µg 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 µm/y in the folic acid arm and 1.3 ± 0.8 µm/y in the placebo arm (mean difference: 0.7 µm/y; 95% CI: -1.8, 3.1 µm/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 × 10(-3) kPa(-1)) and in the placebo arm (-0.62 ± 0.06 × 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.

Tea and coffee consumption and cardiovascular morbidity and mortality.

OBJECTIVE: To examine the associations of coffee and tea consumption with risk of morbidity and mortality of stroke and coronary heart disease (CHD) and with all-cause mortality. METHODS AND RESULTS: Coffee and tea consumption were assessed with a validated food-frequency questionnaire, and 37 514 participants were observed for 13 years for the occurrence of cardiovascular morbidity and mortality. A U-shaped association between coffee and CHD was found, with the lowest hazard ratio (HR [95% CI]) for 2.1 to 3.0 cups per day (0.79 [0.65 to 0.96]; P(trend)=0.01). Tea was inversely associated with CHD, with the lowest HR (95% CI) for more than 6.0 cups per day (0.64 [0.46 to 0.90]; P(trend)=0.02). No associations between tea or coffee and stroke were found (P(trend)=0.63 and P(trend)=0.32, respectively). Although not significant, coffee slightly reduced the risk for CHD mortality (HR, 0.64; 95% CI, 0.37 to 1.11; P(trend)=0.12) for 3.1 to 6.0 cups per day. A U-shaped association between tea and CHD mortality was observed, with an HR of 0.55 (95% CI, 0.31 to 0.97; P(trend)=0.03) for 3.1 to 6.0 cups per day. Neither coffee nor tea was associated with stroke (P(trend)=0.22 and P(trend)=0.74, respectively) and all-cause mortality (P(trend)=0.33 and P(trend)=0.43, respectively). CONCLUSIONS: High tea consumption is associated with a reduced risk of CHD mortality. Our results suggest a slight risk reduction for CHD mortality with moderate coffee consumption and strengthen the evidence on the lower risk of CHD with coffee and tea consumption.

Coffee, decaffeinated coffee, and tea consumption in relation to incident type 2 diabetes mellitus: a systematic review with meta-analysis.

BACKGROUND: Coffee consumption has been reported to be inversely associated with risk of type 2 diabetes mellitus. Similar associations have also been reported for decaffeinated coffee and tea. We report herein the findings of meta-analyses for the association between coffee, decaffeinated coffee, and tea consumption with risk of diabetes. METHODS: Relevant studies were identified through search engines using a combined text word and MeSH (Medical Subject Headings) search strategy. Prospective studies that reported an estimate of the association between coffee, decaffeinated coffee, or tea with incident diabetes between 1966 and July 2009. RESULTS: Data from 18 studies with information on 457 922 participants reported on the association between coffee consumption and diabetes. Six (N = 225 516) and 7 studies (N = 286 701) also reported estimates of the association between decaffeinated coffee and tea with diabetes, respectively. We found an inverse log-linear relationship between coffee consumption and subsequent risk of diabetes such that every additional cup of coffee consumed in a day was associated with a 7% reduction in the excess risk of diabetes relative risk, 0.93 [95% confidence interval, 0.91-0.95]) after adjustment for potential confounders. CONCLUSIONS: Owing to the presence of small-study bias, our results may represent an overestimate of the true magnitude of the association. Similar significant and inverse associations were observed with decaffeinated coffee and tea and risk of incident diabetes. High intakes of coffee, decaffeinated coffee, and tea are associated with reduced risk of diabetes. The putative protective effects of these beverages warrant further investigation in randomized trials.

Routine follow-up after pacemaker implantation: frequency, pacemaker programming and professionals in charge.

AIMS: To describe current evidence of the frequency, contents, and involved professionals of the routine follow-up visits in patients who have received a pacemaker (PM). METHODS AND RESULTS: The multicentre FOLLOWPACE study prospectively collected data during implantation and follow-up of 1526 patients who received a PM for the first time. A total of 4914 follow-up visits were studied. Mean follow-up was 394 days with a mean of 3.2 visits per patient. At all follow-up visits, the battery condition was tested in >93%, the stimulation threshold in >91%, and sensing in >87%. The pacemaker parameters as stimulation and sensing thresholds, lead impedances, and percentages of pacing remained stable over time, but these values did depend on the lead location, lead fixation, and pulse duration. The majority of PM (re-)programming was performed during implantation and/or shortly before hospital discharge (50%). PM re-programming during follow-up was most frequently performed by the PM technician alone (95%). CONCLUSION: Crucial PM parameters are regularly checked. Re-programming of PM parameters declined during the first year after PM implantation. The majority of PM checks were carried out by the PM technician, indicating the major influence of the allied professional on the quality and safety of the pacing therapy.

Effect of testosterone supplementation on functional mobility, cognition, and other parameters in older men: a randomized controlled trial.

CONTEXT: Serum testosterone levels decline significantly with aging. Testosterone supplementation to older men might beneficially affect the aging processes. OBJECTIVE: To investigate the effect of testosterone supplementation on functional mobility, cognitive function, bone mineral density, body composition, plasma lipids, quality of life, and safety parameters in older men with low normal testosterone levels. DESIGN, SETTING, AND PARTICIPANTS: Double-blind, randomized, placebo-controlled trial of 237 healthy men between the ages of 60 and 80 years with a testosterone level lower than 13.7 nmol/L conducted from January 2004 to April 2005 at a university medical center in the Netherlands. INTERVENTION: Participants were randomly assigned to receive 80 mg of testosterone undecenoate or a matching placebo twice daily for 6 months. MAIN OUTCOME MEASURES: Functional mobility (Stanford Health Assessment Questionnaire, timed get up and go test, isometric handgrip strength, isometric leg extensor strength), cognitive function (8 different cognitive instruments), bone mineral density of the hip and lumbar spine (dual-energy x-ray absorptiometry scanning), body composition (total body dual-energy x-ray absorptiometry and abdominal ultrasound of fat mass), metabolic risk factors (fasting plasma lipids, glucose, and insulin), quality of life (Short-Form Health 36 Survey and the Questions on Life Satisfaction Modules), and safety parameters (serum prostate-specific antigen level, ultrasonographic prostate volume, International Prostate Symptom score, serum levels of creatinine, aspartate aminotransferase, alanine aminotransferase, gamma-glutamyltransferase, hemoglobin, and hematocrit). RESULTS: A total of 207 men completed the study. During the study, lean body mass increased and fat mass decreased in the testosterone group compared with the placebo group but these factors were not accompanied by an increase of functional mobility or muscle strength. Cognitive function and bone mineral density did not change. Insulin sensitivity improved but high-density lipoprotein cholesterol decreased; by the end of the study, 47.8% in the testosterone group vs 35.5% in the placebo group had the metabolic syndrome (P = .07). Quality-of-life measures were no different except for one hormone-related quality-of-life measure that improved. No negative effects on prostate safety were detected. CONCLUSION: Testosterone supplementation during 6 months to older men with a low normal testosterone concentration did not affect functional status or cognition but increased lean body mass and had mixed metabolic effects. TRIAL REGISTRATION: isrctn.org Identifier: ISRCTN23688581.

Dietary phytoestrogen intake and cognitive function in older women.

BACKGROUND: Aging is associated with a decline in cognitive function; we explored the possible influence of dietary phytoestrogens on this decline. METHODS: We conducted a cross-sectional study in 301 Dutch women aged 60-75 years. Dietary isoflavone and lignan intake was assessed with a food-frequency questionnaire covering habitual diet in the year preceding enrolment. The endpoints were cognitive function measured in three domains: memory, processing capacity and speed, and executive function. Data were analyzed using linear regression models, after adjusting for confounders. RESULTS: No association between dietary isoflavone intake and cognitive function was found. High lignan intake was associated with a better performance in processing capacity and speed, and in executive function (p for trend over quartiles =.01 and.02, respectively). CONCLUSIONS: This finding calls for further research to elucidate the relatively underexplored role of lignans within the range of phytoestrogens.

Coffee intake and incidence of hypertension.

BACKGROUND: The long-term longitudinal evidence for a relation between coffee intake and hypertension is relatively scarce. OBJECTIVE: The objective was to assess whether coffee intake is associated with the incidence of hypertension. DESIGN: This study was conducted on a cohort of 2985 men and 3383 women who had a baseline visit and follow-up visits after 6 and 11 y. Baseline coffee intake was ascertained with questionnaires and categorized into 0, >0-3, >3-6, and >6 cups/d. Hypertension was defined as a mean systolic blood pressure (SBP) >or=140 mm Hg over both follow-up measurements, a mean diastolic blood pressure (DBP) >or=90 mm Hg over both follow-up measurements, or the use of antihypertensive medication at any follow-up measurement. RESULTS: Coffee abstainers at baseline had a lower risk of hypertension than did those with a coffee intake of >0-3 cups/d [odds ratio (OR): 0.54; 95% CI: 0.31, 0.92]. Women who drank >6 cups/d had a lower risk than did women who drank >0-3 cups/d (OR: 0.67; 95% CI: 0.46, 0.98). Subjects aged >or=39 y at baseline had 0.35 mm Hg (95% CI: -0.59, -0.11 mm Hg) lower SBP per cup intake/d and 0.11 mm Hg lower DBP (95% CI: -0.26, 0.03 mm Hg) than did those aged <39 y at baseline, although the difference in DBP was not statistically significant. CONCLUSIONS: Coffee abstinence is associated with a lower hypertension risk than is low coffee consumption. An inverse U-shaped relation between coffee intake and risk of hypertension was observed in the women.

Association of endogenous sex hormone with C-reactive protein levels in middle-aged and elderly men.

BACKGROUND: In women, postmenopausal oestrogen supplementation increases levels of systemic markers of inflammation, which are important predictors of coronary heart disease (CHD) risk. Whether endogenous sex hormone levels in men are also related to systemic subclinical inflammation is still unknown. OBJECTIVE: We tested the hypothesis that higher endogenous sex hormones levels within the physiological range may be associated with systemic subclinical inflammation. METHODS: Circulating sex hormone and high-sensitivity C-reactive protein (hs-CRP) levels were determined in 400 apparently healthy men aged between 40 and 80 years. We used multivariate linear regression analysis with the various sex hormones as determinant, and natural log hs-CRP as outcome. RESULTS: Higher levels of total as well as bioavailable oestradiol (E2) were associated with increased natural log hs-CRP levels, which remained statistically significant after adjustment for age and cardiovascular risk factors. Natural log hs-CRP was 0.26 mg/l higher [95% confidence interval (CI) -0.02 to 0.54] in the fourth than in the first quartile of total E2; the P-value for linear trend was 0.05. For bioavailable E2, the difference in natural log hs-CRP between the fourth and the first quartile was 0.30 mg/l (95% CI 0.03-0.56; P-value for linear trend 0.04). After adjustment for age and cardiovascular risk factors, physiological levels of total (TT) or bioavailable testosterone or dehydroepiandrosterone sulfate (DHEAS) were not associated with hs-CRP. CONCLUSION: Endogenous total and bioavailable E2 levels are significantly associated with CRP among middle-aged and elder men.

Depression and cardiovascular mortality: a role for n-3 fatty acids?

BACKGROUND: Recent studies indicate that depression plays an important role in the occurrence of cardiovascular diseases (CVDs). The underlying mechanisms are not well understood. OBJECTIVE: We investigated whether dietary intake of the n-3 fatty acids (FAs) eicosapentaenic acid and docosahexaenoic acid could explain the relation between depressive symptoms and cardiovascular mortality. DESIGN: The Zutphen Elderly Study is a prospective cohort study conducted in the Netherlands. Depressive symptoms were measured in 1990 with the Zung Self-rating Depression Scale in 332 men aged 70-90 y and free from CVD and diabetes. Dietary factors were assessed with a cross-check dietary history method in 1990. Mortality data were collected between 1990 and 2000. Logistic and Cox regression analyses were performed, with adjustment for demographics and CVD risk factors. RESULTS: Compared with a low intake (x: 21 mg/d), a high intake (x: 407 mg/d) of n-3 FAs was associated with fewer depressive symptoms [odds ratio: 0.46; 95% CI: 0.22, 0.95; P for trend = 0.04] at baseline and no significant reduced risk of 10-y CVD mortality [hazard ratio (HR): 0.88; 95% CI: 0.51, 1.50]. The adjusted HR for an increase in depressive symptoms with 1 SD for CVD mortality was 1.28 (95% CI: 1.03, 1.57) and did not change after additional adjustment for the intake of n-3 FAs. CONCLUSION: An average intake of approximately 400 mg n-3 FA/d may reduce the risk of depression. Our results, however, do not support the hypothesis that the intake of n-3 FAs explains the relation between depression and CVD.

Double blind randomized placebo-controlled trial on the effects of testosterone supplementation in elderly men with moderate to low testosterone levels: design and baseline characteristics [ISRCTN23688581].

In ageing men testosterone levels decline, while cognitive function, muscle and bone mass, sexual hair growth, libido and sexual activity decline and the risk of cardiovascular diseases increase. We set up a double-blind, randomized placebo-controlled trial to investigate the effects of testosterone supplementation on functional mobility, quality of life, body composition, cognitive function, vascular function and risk factors, and bone mineral density in older hypogonadal men. We recruited 237 men with serum testosterone levels below 13.7 nmol/L and ages 60-80 years. They were randomized to either four capsules of 40 mg testosterone undecanoate (TU) or placebo daily for 26 weeks. Primary endpoints are functional mobility and quality of life. Secondary endpoints are body composition, cognitive function, aortic stiffness and cardiovascular risk factors and bone mineral density. Effects on prostate, liver and hematological parameters will be studied with respect to safety. Measure of effect will be the difference in change from baseline visit to final visit between TU and placebo. We will study whether the effect of TU differs across subgroups of baseline waist girth (< 100 cm vs. > or = 100 cm; testosterone level (< 12 versus > or = 12 nmol/L), age (< median versus > or = median), and level of outcome under study (< median versus > or = median). At baseline, mean age, BMI and testosterone levels were 67 years, 27 kg/m2 and 10.72 nmol/L, respectively.

Effects of dehydroepiandrosterone and atamestane supplementation on frailty in elderly men.

BACKGROUND: It has been suggested that the age-related decline of androgens in men plays a distinct role in the development of several aspects of frailty. Therefore, hormone replacement might improve the course of frailty by increasing lean body mass and muscle strength, decreasing fat mass, and improving the subjective quality of life. OBJECTIVE: The objective of the study was to assess whether hormone replacement with dehydroepiandrosterone (DHEA) and/or atamestane might improve the course of frailty. DESIGN: This was a double-blind, randomized, controlled trial. SETTING: The study was conducted in the general community. PARTICIPANTS: Participants included 100 nonhospitalized, nondiseased, independently living men, aged 70 yr and over with low scores on strength tests. Seventeen participants did not complete the trial. INTERVENTION: Subjects were randomly assigned to one of four intervention arms: atamestane (100 mg/d) and placebo, DHEA (50 mg/d) and placebo, a combination of atamestane (100 mg/d) and DHEA (50 mg/d), or two placebo tablets for 36 wk. MAIN OUTCOME MEASURES: Physical frailty was measured by means of a specific test battery, including isometric grip strength, leg extensor power, and physical performance. RESULTS: The randomization was successful, and 83 (83%) men completed the intervention. There were no differences between the treatment arms and placebo group in any of the outcome measurements after intervention. CONCLUSIONS: The results of this double-blind, randomized trial do not support the hypothesis that hormone replacement with DHEA and/or atamestane might improve the course of frailty.

Higher dietary intake of lignans is associated with better cognitive performance in postmenopausal women.

Data on the relation between phytoestrogens and cognitive function are still sparse. The purpose of this study was to examine the relation between the dietary intake of phytoestrogens and cognitive function in healthy postmenopausal women consuming a Western diet. We conducted a community-based survey among 394 postmenopausal women. Isoflavone and lignan intake was calculated from a validated FFQ. Cognitive function was evaluated using the Mini-Mental State Examination (MMSE). Data were analyzed using logistic regression with intact cognitive function defined as a score >/= 26 as the outcome variable. After adjustment for confounders, increasing dietary lignans intake was associated with better performance on the MMSE [OR and (95%CI): 1.49 (0.94-2.38)]. Results were most pronounced in women who were 20-30 y postmenopausal [2.02 (1.11-3.71)]. Isoflavone intake was not related to cognitive function. From our results we conclude that higher dietary intake of lignans is associated with better cognitive function in postmenopausal women.

Blood pressure response to chronic intake of coffee and caffeine: a meta-analysis of randomized controlled trials.

PURPOSE: Coffee is a widely consumed beverage and small health effects of substances in coffee may have large public health consequences. It has been suggested that caffeine in coffee increases the risk of hypertension. We performed a meta-analysis of randomized controlled trials of coffee or caffeine and blood pressure (BP). DATA IDENTIFICATION: BP trials of coffee or caffeine published between January 1966 and January 2003 were identified through literature databases and manual search. STUDY SELECTION: A total of 16 studies with a randomized, controlled design and at least 7 days of intervention was selected, comprising 25 strata and 1010 subjects. DATA EXTRACTION: Two persons independently obtained data on sample size, type and duration of intervention, changes in BP and heart rate (HR), and subjects' characteristics for each trial. Meta-analysis was performed using a random-effects model. RESULTS: A significant rise of 2.04 mmHg [95% confidence interval (CI), 1.10-2.99] in systolic BP and 0.73 mmHg (95% CI, 0.14-1.31) in diastolic BP was found after pooling of coffee and caffeine trials. When coffee trials (n = 18, median intake: 725 ml/day) and caffeine trials (n = 7, median dose: 410 mg/day) were analysed separately, BP elevations appeared to be larger for caffeine [systolic: 4.16 mmHg (2.13-6.20); diastolic: 2.41 mmHg (0.98-3.84)] than for coffee [systolic: 1.22 mmHg (0.52-1.92) and diastolic: 0.49 mmHg (-0.06-1.04)]. Effects on HR were negligible. CONCLUSIONS: Regular caffeine intake increases BP. When ingested through coffee, however, the blood pressure effect of caffeine is small.

Prospective study on usual dietary phytoestrogen intake and cardiovascular disease risk in Western women.

BACKGROUND: Phytoestrogens have been suggested to lower cardiovascular disease risk, but existing research focused on non-Western high intake levels and on risk factors. We investigated whether habitual low phytoestrogen intake is associated with manifest cardiovascular disease risk. METHODS AND RESULTS: Between 1993 and 1997, 16,165 women 49 to 70 years old and free from cardiovascular disease were enrolled in the Dutch Prospect-EPIC cohort (European Prospective study Into Cancer and nutrition) and followed up for a median period of 75 months. At enrollment, women filled in questionnaires on chronic disease risk factors and nutrition. Intake of phytoestrogens was estimated using the food frequency questionnaire covering regular dietary intake of 178 food items in the year before enrollment. Cox regression analysis was used to estimate hazard ratios of cardiovascular disease for quartiles of phytoestrogen intake adjusted for age at intake, body mass index, smoking, physical activity, hypertension, hypercholesterolemia, use of hormone replacement therapy, menopausal status, and intake of total energy, total fiber, vegetables, fruit, and alcohol. In total, 372 women experienced a coronary event (CHD) (International Classification of Diseases, Ninth Revision, Clinical Modification [ICD-9], 410 to 414, 427.5) and 147 women a cerebrovascular event (CVD) (ICD-9, 430 to 438) during follow-up. Overall, neither isoflavones nor lignans were associated with decreased cardiovascular disease risk. When stratifying for ever versus never smokers, CHD risk decreased with increasing lignan intake for ever smokers. CONCLUSIONS: Our results do not support the presence of a protective effect of higher intake of phytoestrogens in low doses on cardiovascular disease risk, although a small risk reduction with higher lignan intake cannot be excluded for smokers.

A randomized, placebo-controlled trial on the effects of soy protein containing isoflavones on quality of life in postmenopausal women.

OBJECTIVE: Postmenopausal estrogen decline is implicated in several age-related physical and psychological changes in women, including decreases in perceived quality of life (QoL). A number of trials with hormone therapy showed beneficial effects of the intervention on parameters of quality of life. However, because of known or suspected serious side-effects of conventional hormone therapy there is a need for alternatives. DESIGN: We conducted a double-blind randomized placebo-controlled trial with soy protein, containing 52 mg genistein, 41 mg daidzein, and 6 mg glycitein (aglycone weights), or milk protein (placebo) daily for 1 year. For this trial, we recruited 202 postmenopausal women aged 60 to 75 years. RESULTS: At baseline and at final visit, participants filled in the Short Form of 36 questions (SF-36), the Questionnaire on Life Satisfaction Modules (QLS(M)), and the Geriatric Depression Scale (GDS). For the placebo group scores on all dimensions of the SF-36 and the QLS(M) decreased during the intervention year, except for the dimension "role limitations caused by physical problems." The soy group showed increases on two dimensions of the SF-36 ("social functioning" and "role limitations caused by physical problems") and on one dimension of the QLS(M). There were however no statistically significant differences in changes of scores between the two intervention groups. For the GDS similarly, no significant differences were found between the groups. CONCLUSIONS: In conclusion, the findings in this randomized trial do not support the presence of a marked effect of soy protein substitution on quality of life (health status, life satisfaction, and depression) in elderly postmenopausal women.