Connecting the dots between breast cancer, obesity and alcohol consumption in middle-aged women: ecological and case control studies.

BACKGROUND: Breast cancer (BC) incidence in Australian women aged 45 to 64 years ('middle-aged') has tripled in the past 50 years, along with increasing alcohol consumption and obesity in middle-age women. Alcohol and obesity have been individually associated with BC but little is known about how these factors might interact. Chronic psychological stress has been associated with, but not causally linked to, BC. Here, alcohol could represent the 'missing link' - reflecting self-medication. Using an exploratory cross-sectional design, we investigated inter-correlations of alcohol intake and overweight/obesity and their association with BC incidence in middle-aged women. We also explored the role of stress and various lifestyle factors in these relationships. METHODS: We analysed population data on BC incidence, alcohol consumption, overweight/obesity, and psychological stress. A case control study was conducted using an online survey. Cases (n = 80) were diagnosed with BC and controls (n = 235) were women in the same age range with no BC history. Participants reported lifestyle data (including alcohol consumption, weight history) over consecutive 10-year life periods. Data were analysed using a range of bivariate and multivariate techniques including correlation matrices, multivariate binomial regressions and multilevel logistic regression. RESULTS: Ecological inter-correlations were found between BC and alcohol consumption and between BC and obesity but not between other variables in the matrix. Strong pairwise correlations were found between stress and alcohol and between stress and obesity. BMI tended to be higher in cases relative to controls across reported life history. Alcohol consumption was not associated with case-control status. Few correlations were found between lifestyle factors and stress, although smoking and alcohol consumption were correlated in some periods. Obesity occurring during the ages of 31 to 40 years emerged as an independent predictor of BC (OR 3.5 95% CI: 1.3-9.4). CONCLUSIONS: This study provides ecological evidence correlating obesity and alcohol consumption with BC incidence. Case-control findings suggest lifetime BMI may be important with particular risk associated with obesity prior to 40 years of age. Stress was ecologically linked to alcohol and obesity but not to BC incidence and was differentially correlated with alcohol and smoking among cases and controls. Our findings support prevention efforts targeting weight in women below 40 years of age and, potentially, lifelong alcohol consumption to reduce BC risk in middle-aged women.

Effects of dietary carbohydrate on 1,5-anhydroglucitol in a population without diabetes: results from the OmniCarb trial.

AIMS: To determine the effects of dietary changes in amount and type of carbohydrate on 1,5-anhydroglucitol levels. METHODS: We conducted an ancillary study to a completed, randomized clinical trial in overweight and obese adults without diabetes (N=159). Using a crossover design, participants were fed each one of four diets in turn for 5 weeks, with 2-week washout periods inbetween. The four diets were: high glycaemic index (≥65) with high proportion of carbohydrate (58% kcal) (GC); low glycaemic index (GI≤45) with low proportion of carbohydrate (40% kcal) (gc); low glycaemic index with high proportion of carbohydrate (gC); and high glycaemic index with low proportion of carbohydrate (Gc). Plasma 1,5-anhydroglucitol levels were measured at baseline and after each feeding period. RESULTS: At baseline, participants had a mean age of 53 years (53% women, 52% non-Hispanic black, 50% obese). Their mean fasting glucose and 1,5-anhydroglucitol levels were 97 mg/dl (5.4 mmol/l) and 18.6 µg/mL (113.3 µmol/l), respectively. Compared with baseline, each of the four diets reduced 1,5-anhydroglucitol by a range of -2.4 to -3.7 µg/mL (-14.6 to -22.5 µmol/l); all P <0.001). Reducing either glycaemic index or proportion of carbohydrate lowered 1,5-anhydroglucitol levels. These effects were additive, such that reducing both glycaemic index and proportion of carbohydrates decreased 1,5-anhydroglucitol by -1.31 µg/mL [95% CI: -1.63, -0.99; P<0.001 or -8.0 (-9.9, -6.0) µmol/l]. Furthermore, these effects were confirmed in a subgroup of participants with 12-h glucose monitoring and no documented hyperglycaemia (fasting glucose <160 mg/dl or 8.9 mmol/l). CONCLUSIONS: Both type and amount of dietary carbohydrate affect 1,5-anhydroglucitol plasma concentrations in adults without diabetes. This finding contradicts the long-standing notion that 1,5-anhydroglucitol remains at constant concentrations in the blood in the absence of hyperglycaemic excursions. (Clinical trials registry number: NCT00051350).

Mechanisms for the near-UV photodissociation of CH3I on D2O/Cu(110).

The system of CH3I adsorbed on submonolayer, monolayer, and multilayer thin films of D2O on Cu(110) has been studied by measuring the time of flight (TOF) distributions of the desorbing CH3 fragments after photodissociation using linearly polarized λ = 248 nm light. For multilayer D2O films (2-120 ML), the photodissociation is dominated by neutral photodissociation via the "A-band" absorption of CH3I. The polarization and angle dependent variation in the observed TOF spectra of the CH3 photofragments find that dissociation is largely via the (3)Q0 excited state, but that also a contribution via the (1)Q1 excitation can be identified. The photodissociation results also indicate that the CH3I adsorbed on D2O forms close-packed islands at submonolayer coverages, with a mixture of C-I bond axis orientations. For monolayer and submonolayer quantities of D2O we have observed a contribution to CH3I photodissociation via dissociative electron attachment (DEA) by photoelectrons. The observed DEA is consistent with delocalized photoelectrons from the substrate causing the observed dissociation- we do not find evidence for an enhanced DEA mechanism via the temporary solvation of photoelectrons in localized states of the D2O ice.

The effects of dietary patterns on plasma renin activity: results from the Dietary Approaches to Stop Hypertension trial.

A diet rich in fruits, vegetables and low-fat dairy products, and reduced in saturated fat, total fat and cholesterol (the 'DASH' diet) significantly lowers blood pressure (BP). Previous studies have documented that certain therapies that lower BP increase plasma renin activity (PRA). Using data from the Dietary Approaches to Stop Hypertension (DASH) trial, we assessed the effects of dietary patterns on PRA and determined the relationship of change in PRA with change in BP on each diet. After eating a control diet for 3 weeks, participants were then randomized to receive for 8 weeks: the control diet, a diet rich in fruits and vegetables (F/V), or the DASH diet. Baseline and follow-up levels of PRA were available in 381 participants. Compared with the control diet, the DASH diet increased PRA by 0.37 ng ml(-1) h(-1) (P=0.01). In multivariable linear regression analyses, there was an inverse association of PRA change with systolic BP change on the control diet (slope=-0.35, P=0.001), but PRA did not differ by BP change on the F/V diet (slope=-0.002, P=0.98) or DASH diet (slope=-0.08, P=0.32). These data suggest that a blunted counter-regulatory response of the renin-angiotensin system is associated with the BP-lowering effect of the F/V and DASH diets.

Systematics of early and middle Miocene Old World monkeys.

New information about the early cercopithecoids Prohylobates tandyi (Wadi Moghra, Egypt) and Prohylobates sp. indet. (Buluk and Nabwal, Kenya) is presented. Comparisons are made among all major collections of Early and Middle Miocene catarrhine monkeys, and a systematic revision of the early Old World monkeys is provided. Previous work involving the systematics of early Old World monkeys (Victoriapithecidae; Cercopithecoidea) has been hampered by a number of factors, including the poor preservation of Prohylobates material from North Africa and lack of comparable anatomical parts across collections. However, it is now shown that basal cercopithecoid species from both northern and eastern Africa can be distinguished from one another on the basis of degree of lower molar bilophodonty, relative lower molar size, occlusal details, symphyseal construction, and mandibular shape. Results of particular interest include: 1) the first identification of features that unambiguously define Prohylobates relative to Victoriapithecus; 2) confirmation that P. tandyi is incompletely bilophodont; and 3) recognition of additional victoriapithecid species.

Markers and risk factors for HCV, HBV and HIV in a network of injecting drug users in Melbourne, Australia.

BACKGROUND AND AIMS: Current injecting drug users (IDU) in major street drug markets within greater Melbourne were recruited to a longitudinal study on blood borne viruses. Here we investigated risk factors for hepatitis C virus (HCV), hepatitis B virus (HBV) and HIV infection in these IDU at the time of their recruitment. METHODS: Three hundred and eighty-two IDU completed detailed questionnaires on their drug use and risk behaviours, and provided blood samples for serology testing. These data were analysed using univariate and multivariate techniques. RESULTS: The overall prevalence of exposure to HCV, HBV and HIV was estimated at 70%, 34% and <1%, respectively. Independent predictors of HCV exposure were history of imprisonment (RR 1.34, 95% CI 1.19-1.52), use of someone else's needle or syringe (RR 1.23, 95% CI 1.07-1.42), >7.6years length of time injecting (RR 1.21, 95% CI 1.07-1.37), and originating from Vietnam (RR 1.12, 95% CI 1.07-1.18). Independent predictors of HBV exposure were HCV exposure (RR 2.15, 95% CI 1.35-3.43), >7.6years length of time injecting (RR 1.57, 95% CI 1.17-2.13) and originating from outside Australia (RR 1.60, 95% CI 1.22-2.10). Neither prison- nor community-applied tattoos predicted HCV or HBV exposure. Up to 31% of IDU who injected for 1year or less were HCV antibody positive, as were 53% of those who injected for 2years or less. CONCLUSIONS: Ongoing engagement with young IDU, through the provision of harm reduction education and resources, is critical if we are to address blood borne viral infections and other health and social harms associated with injecting drug use.

Correlates of N-terminal prohormone brain natriuretic peptides in African Americans with hypertensive chronic kidney disease: the African American Study of Kidney Disease and Hypertension.

BACKGROUND/AIMS: The N-amino-terminal fragment of the prohormone B-type natriuretic peptide (NT-proBNP) is a marker of cardiac stress and elevated levels are indicative of heart failure. Few correlates of NT-proBNP levels have been identified in persons with moderate chronic kidney disease (CKD), and data from those without heart failure and from African Americans are especially limited. METHODS: The African American Study of Kidney Disease and Hypertension (AASK) enrolled nondiabetic African Americans with hypertensive kidney disease (glomerular filtration rate [GFR] = 20-65 ml/min/1.73 m(2)) and no evidence of clinical heart failure. NT-proBNP was measured in 982 AASK participants. RESULTS: In unadjusted analyses, GFR (r = -0.39; p < 0.001), hematocrit (r = -0.21; p < 0.001) and body mass index (BMI; r = -0.07; p = 0.04) were inversely correlated, and systolic blood pressure (r = 0.30; p < 0.001) and log UPCR (r = 0.32; p < 0.001) were positively correlated with log NT-proBNP levels. After adjustment for potential confounders, lower GFR and hematocrit and higher systolic blood pressure and protein:creatinine ratio remained significantly associated with higher NT-proBNP. CONCLUSION: Lower GFR and hematocrit, and higher urinary protein excretion may be associated with volume expansion in CKD. These results suggest that these processes are associated with increased NT-proBNP in CKD and may play a role in the development of heart failure.

The addition of ground wheat straw as a fiber source in the gestation diet of sows and the effect on sow and litter performance for three successive parities.

A regional experiment was conducted at 8 experiment stations, with a total of 320 sows initially, to evaluate the efficacy of adding 13.35% ground wheat straw to a corn-soybean meal gestation diet for 3 successive gestation-lactation (reproductive) cycles compared with sows fed a control diet without straw. A total of 708 litters were farrowed over 3 reproductive cycles. The basal gestation diet intake averaged 1.95 kg daily for both treatments, plus 0.30 kg of straw daily for sows fed the diet containing ground wheat straw (total intake of 2.25 kg/d). During lactation, all sows on both gestation treatments were fed ad libitum the standard lactation diet used at each station. Response criteria were sow farrowing and rebreeding percentages, culling factors and culling rate, weaning-to-estrus interval, sow BW and backfat measurements at several time points, and litter size and total litter weight at birth and weaning. Averaged over 3 reproductive cycles, sows fed the diet containing wheat straw farrowed and weaned 0.51 more pigs per litter (P

Varicella infection--evidence for peak activity in summer months.

This study aimed to identify seasonal variations in the presentation of primary varicella infection in susceptible patients in Victoria (a temperate region in south-east Australia) by analysing Victorian hospital admissions data and medical locum service data from the years preceding the introduction of a universally offered vaccination, complemented by available surveillance data from the neighbouring state, of South Australia. Contrary to the conventional assumption, which is based on observations in temperate regions elsewhere in the world, we found no consistent evidence of seasonal peaks during late winter and early spring for varicella infection in Victoria. This finding may have implications for prevention in temperate regions elsewhere in the world wherever estimations of local seasonal trends have been based on international experiences.

One year follow-up of overweight and obese hypertensive adults following intensive lifestyle therapy.

OBJECTIVE: To examine the long-term effect on weight maintenance and dietary habits of participants in a clinical trial for weight loss. SETTING: Community-based residents living in Maryland. PARTICIPANTS: Forty-four hypertensive, overweight adults who participated in a randomized clinical trial of weight loss. Participants were randomized to an intensive 'lifestyle' intervention or a 'monitoring' group. MAIN OUTCOME MEASURES: Weight, self-reported current intake of fat and fruit/fibre and self-reported barriers to maintain weight loss were assessed 1 year after the completion of the Diet, Exercise and Weight-loss Intervention Trial (DEW-IT) trial. ANALYSIS: t-tests were used to compare groups for differences in continuous variables and chi-square tests were used to compare groups for categorical variables. RESULTS: Fourty-two of the 44 DEW-IT subjects participated in the follow-up study. Overall, 55% (12/19) of the lifestyle intervention group remained at or below their baseline weight at 1 year, compared with 48% (11/23) of the monitoring group (P = 0.32). However, during that year, 95% (18/19) of the lifestyle intervention group and 52% (12/23) of the monitoring group gained weight from the end of the study. Both groups reported similar intake of fruits/vegetables (servings day(-1)), dietary fibre (g day(-1)) and fat (g day(-1)). CONCLUSIONS AND IMPLICATIONS: The majority of participants who lost weight during the trial regained weight during the course of 1 year. A successful intensive 2-month programme of lifestyle modification (DEW-IT) was ineffective for long-term maintenance of weight loss.

From disorder to order in marching locusts.

Recent models from theoretical physics have predicted that mass-migrating animal groups may share group-level properties, irrespective of the type of animals in the group. One key prediction is that as the density of animals in the group increases, a rapid transition occurs from disordered movement of individuals within the group to highly aligned collective motion. Understanding such a transition is crucial to the control of mobile swarming insect pests such as the desert locust. We confirmed the prediction of a rapid transition from disordered to ordered movement and identified a critical density for the onset of coordinated marching in locust nymphs. We also demonstrated a dynamic instability in motion at densities typical of locusts in the field, in which groups can switch direction without external perturbation, potentially facilitating the rapid transfer of directional information.

The prevalence of HCV antibody in South Australian prisoners.

OBJECTIVES: The study was aimed at identifying the hepatitis C virus (HCV)-antibody status of prisoners incarcerated in South Australia in order to develop an HCV prevalence estimate for the whole prison system. METHODS: The health records of persons incarcerated within eight prisons (accommodating approximately 93% of the jurisdiction's adult incarcerated population) were audited for evidence of HCV infection, age, sex, Indigenous status (Australian Aboriginal or Torres Strait Islander) and date of entry to prison. These data were analysed using both univariate and multivariate techniques. RESULTS: Among 1347 prisoners (1254 males and 93 females), 30.2% were HCV-antibody positive. After excluding those with no history of testing, HCV-antibody prevalence rose to 41.3% (males 39.8%, females 66.1%). HCV-antibody positivity was significantly associated with age, sex and Indigenous status in both univariate and multivariate analyses. CONCLUSIONS: Consistent with the literature, the prevalence of HCV infection in the SA prison system appears to be extremely high. This study suggests that HCV prevention efforts in prison settings should be considered as an important priority.

Broiler responsiveness (Ross x 708) to diets varying in amino acid density.

Sex-separate male and female broilers (2,592 broilers; Ross x 708) were placed in 144 floor pens (12 replications per treatment) and fed diets containing high (H) and moderate (M) amino acid density from 1 to 55 d of age. Diets were formulated using ileal digestible amino acid ratios to Lys. Six dietary treatment combinations (MMMMM, HMMMM, HHMMM, HHHMM, HHHHM, and HHHHH) were implemented in 5 diet phases (1 to 5, 6 to 14, 15 to 35, 36 to 45, and 46 to 55 d of age). Male birds were heavier (P < or = 0.05) and had lower (P < or = 0.05) feed conversion, abdominal fat, and breast yield than female birds. Birds fed H diets in the first 3 phases had optimal (P < or = 0.05) BW and feed conversion (d 35, and 45), but optimal (P < or = 0.05) feed conversion at d 55 warranted H diets in all phases. Breast meat (d 35) and carcass (d 55) relative to BW were highest (P < or = 0.05) in birds fed H diets in the first 3 phases; however, differences in 55 d breast meat yield did not occur. Results indicate that amino acid needs of Ross x 708 broilers are most critical from 1 to 35 d of age. Predicted economic margins were advantageous in birds fed H diets resulting in dollar 0.12 and dollar 0.05/bird more income over feed costs at 35 and 55 d, respectively, in comparison with birds fed M diets.

The impact of angiotensin II receptor blockade and the DASH diet on markers of endogenous fibrinolysis.

Hypertension is associated with impaired fibrinolysis. Both angiotensin receptor blockers (ARB) and the DASH (Dietary Approaches to Stop Hypertension) diet effectively lower blood pressure in hypertensive patients. Some evidence suggests that treatment with ARBs could increase fibrinolysis, however, data is conflicting. The impact of the DASH diet on fibrinolytic parameters is not known. Fifty-five hypertensive participants (35 African-American, 20 white) were randomly assigned to receive 8 weeks of either a control diet or the DASH diet. The diets did not differ in sodium content (approximately 3 g/day). Within each diet, individuals were randomly assigned to receive losartan or placebo for 4 weeks in double-blind, cross-over fashion. Tissue plasminogen activator (t-PA) antigen, t-PA activity, plasminogen activator inhibitor-1 (PAI-1) activity and plasma renin activity (PRA) were measured at the end of a 2-week run-in period on the control diet and after each treatment period. The DASH diet did not affect markers of fibrinolysis. Losartan significantly lowered t-PA antigen levels (-1.8 ng/mL, P = 0.045), but had no effect on t-PA or PAI-1 activities. This effect was more pronounced in whites (-4.1 ng/mL (P = 0.003)) compared with African-Americans (-0.3 ng/mL (P = 0.7), P-interaction = 0.03). Results were not materially affected by adjustment for basline values or changes in blood pressure. This study demonstrates that losartan reduces t-PA antigen levels in white, but not African-American hypertensive individuals. In contrast, the DASH diet had no significant effect on markers of fibrinolysis in whites or African-Americans.

Intercenter variance in clinical trials of head trauma--experience of the National Acute Brain Injury Study: Hypothermia.

OBJECT: In a recently conducted trial of hypothermia in patients with severe brain injury, differences were found in the effects of hypothermia treatment among various centers. This analysis explores the reasons for such differences. METHODS: The authors reviewed data obtained in 392 patients treated for severe brain injury. Prerandomization variables, critical physiological variables, treatment variables, and accrual methodologies were investigated among various centers. Hypothermia was found to be detrimental in patients older than the age of 45 years, beneficial in patients younger than 45 years of age in whom hypothermia was present on admission, and without effect in those in whom normothermia was documented on admission. Marginally significant differences (p < 0.054) in the intercenter outcomes of hypothermia-treated patients were likely the result of wide differences in the percentage of patients older than 45 years of age and in the percentage of patients in whom hypothermia was present on admission among centers. The trial sensitivity was likely diminished by significant differences in the incidence of mean arterial blood pressure (MABP) less than 70 mm Hg (p < 0.001) and cerebral perfusion pressure (CPP) less than 50 mm Hg (p < 0.05) but not intracranial pressure (ICP) greater than 25 mm Hg (not significant) among patients in the various centers. Hours of vasopressor usage (p < 0.03) and morphine dose (p < 0.001) and the percentage of dehydrated patients varied significantly among centers (p < 0.001). The participation of small centers increased intercenter variance and diminished the quality of data. CONCLUSIONS: For Phase III clinical trials we recommend: 1) a detailed protocol specifying fluid and MABP, ICP, and CPP management: 2) continuous monitoring of protocol compliance; 3) a run-in period for new centers to test accrual and protocol adherence; and 4) inclusion of only centers in which patients are regularly randomized.

Vancomycin-resistant enterococci colonization in patients at seven hemodialysis centers.

BACKGROUND: Vancomycin-resistant enterococci (VRE) are increasing in prevalence at many institutions, and are often reported in dialysis patients. We studied the prevalence of and risk factors for VRE at seven outpatient hemodialysis centers (three in Baltimore, MD, USA, and four in Richmond, VA, USA). METHODS: Rectal or stool cultures were performed on consenting hemodialysis patients during December 1997 to April 1998. Consenting patients were recultured during May to July 1998 (median 120 days later). Clinical and laboratory data and functional status (1 to 10 scale: 1, normal function; 9, home attendant, not totally disabled; 10, disabled, living at home) were recorded. RESULTS: Of 478 cultures performed, 20 (4.2%) were positive for VRE. Among the seven centers, the prevalence of VRE-positive cultures varied from 1.0 to 7.9%. Independently significant risk factors for a VRE-positive culture were a functional score of 9 to 10 (odds ratio 6.9, P < 0.001), antimicrobial receipt within 90 days before culture (odds ratio 6.1, P < 0.001), and a history of injection drug use (odds ratio 5.4, P = 0.004). CONCLUSIONS: VRE-colonized patients were present at all seven participating centers, suggesting that careful infection-control precautions should be used at all centers to limit transmission. In agreement with previous studies, VRE colonization was more frequent in patients who had received antimicrobial agents recently, underscoring the importance of judicious antimicrobial use in limiting selection for this potential pathogen.

Quality of life in HCV-infection: lack of association with ALT levels.

OBJECTIVES: To examine the impact of HCV infection in an Australian clinic population and identify the relationships between morbidity, psychosocial variables and one clinical indicator of HCV activity, alanine aminotransferase (ALT). METHOD: Ninety-five untreated HCV-infected patients (21-69 years) in infectious and liver diseases clinics who were all positive for HCV-RNA and had no significant comorbidities or coinfections completed a survey containing the Short Form 36 (SF36), as well as the six-item Social Support Questionnaire (SSQ6), demographic items and questions concerning respondents' perceptions of their mode and duration of infection. Nine volunteers from this group participated in semi-structured qualitative interviews aimed at exploring the social impact of HCV status. These data were compared with serum ALT levels. SF36 scores were compared to population norms and according to participant variables. RESULTS: Mean SF36 scores were significantly lower, across all modalities, than population norms. SF36 scores differed significantly according to age, sex, mode of infection, alcohol and methadone use, and satisfaction with social support. They did not differ significantly according to perceived or actual ALT level or pattern of ALT activity. Worry about ALT was prevalent (>50%) and this was independent of perceived ALT level. CONCLUSIONS AND IMPLICATIONS: HCV-infection is associated with significantly reduced quality of life and includes the perception of substantial social discrimination. ALT levels are of limited usefulness in ascertainment of a person's sense of wellbeing and quality of life in HCV-infection. Increased support and information for affected individuals and measures aimed at countering social discrimination are important recommendations of the current study.

Relationship between systemic markers of inflammation and serum beta-carotene levels.

BACKGROUND: Low serum levels of beta-carotene have been associated with increased risk of cancer and cardiovascular disease. However, in clinical trials, supplementation of the diet with beta-carotene either had no benefit or caused harm. This pattern of findings raises the possibility that confounding by other factors might explain the association between serum beta-carotene level and disease risk. METHODS: We used data from 14 470 current smokers, ex-smokers, and never smokers aged 18 years or older who participated in the Third National Health and Nutrition Examination Survey to assess the relationship between serum beta-carotene and markers of inflammation (C-reactive protein and white blood cell count). RESULTS: After adjustment for beta-carotene intake and other factors, geometric mean levels of serum beta-carotene for individuals with undetectable (< 0.22 mg/dL), mildly elevated (0.22-0.99 mg/dL), and clinically elevated (> or =1.0 mg/dL) C-reactive protein levels were 18.0, 16.1, and 13.6 microg/dL, respectively, in never smokers; 18.1, 15.7, and 13.9 microg/dL in ex-smokers; and 11.3, 10.2, and 9.4 microg/dL in current smokers (P< .001 for all). In corresponding analyses, white blood cell count was also inversely related to serum beta-carotene concentration (P< .05 for all). CONCLUSIONS: The strong and inverse association of serum beta-carotene level with C-reactive protein level and white blood cell count suggests that the relationship between serum beta-carotene concentration and disease risk might be confounded by inflammation. More broadly, for beta-carotene and likely other nutrients, it seems unwise to interpret biomarker data as prima facie evidence of dietary intake without a more complete understanding of the physiologic processes that affect nutrient levels.

Effects on blood lipids of a blood pressure-lowering diet: the Dietary Approaches to Stop Hypertension (DASH) Trial.

BACKGROUND: Effects of diet on blood lipids are best known in white men, and effects of type of carbohydrate on triacylglycerol concentrations are not well defined. OBJECTIVE: Our goal was to determine the effects of diet on plasma lipids, focusing on subgroups by sex, race, and baseline lipid concentrations. DESIGN: This was a randomized controlled outpatient feeding trial conducted in 4 field centers. The subjects were 436 participants of the Dietary Approaches to Stop Hypertension (DASH) Trial [mean age: 44.6 y; 60% African American; baseline total cholesterol: < or = 6.7 mmol/L (< or = 260 mg/dL)]. The intervention consisted of 8 wk of a control diet, a diet increased in fruit and vegetables, or a diet increased in fruit, vegetables, and low-fat dairy products and reduced in saturated fat, total fat, and cholesterol (DASH diet), during which time subjects remained weight stable. The main outcome measures were fasting total cholesterol, LDL cholesterol, HDL cholesterol, and triacylglycerol. RESULTS: Relative to the control diet, the DASH diet resulted in lower total (-0.35 mmol/L, or -13.7 mg/dL), LDL- (-0.28 mmol/L, or -10.7 mg/dL), and HDL- (-0.09 mmol/L, or -3.7 mg/dL) cholesterol concentrations (all P < 0.0001), without significant effects on triacylglycerol. The net reductions in total and LDL cholesterol in men were greater than those in women by 0.27 mmol/L, or 10.3 mg/dL (P = 0.052), and by 0.29 mmol/L, or 11.2 mg/dL (P < 0.02), respectively. Changes in lipids did not differ significantly by race or baseline lipid concentrations, except for HDL, which decreased more in participants with higher baseline HDL-cholesterol concentrations than in those with lower baseline HDL-cholesterol concentrations. The fruit and vegetable diet produced few significant lipid changes. CONCLUSIONS: The DASH diet is likely to reduce coronary heart disease risk. The possible opposing effect on coronary heart disease risk of HDL reduction needs further study.

Effect of ramipril vs amlodipine on renal outcomes in hypertensive nephrosclerosis: a randomized controlled trial.

CONTEXT: Incidence of end-stage renal disease due to hypertension has increased in recent decades, but the optimal strategy for treatment of hypertension to prevent renal failure is unknown, especially among African Americans. OBJECTIVE: To compare the effects of an angiotensin-converting enzyme (ACE) inhibitor (ramipril), a dihydropyridine calcium channel blocker (amlodipine), and a beta-blocker (metoprolol) on hypertensive renal disease progression. DESIGN, SETTING, AND PARTICIPANTS: Interim analysis of a randomized, double-blind, 3 x 2 factorial trial conducted in 1094 African Americans aged 18 to 70 years with hypertensive renal disease (glomerular filtration rate [GFR] of 20-65 mL/min per 1.73 m(2)) enrolled between February 1995 and September 1998. This report compares the ramipril and amlodipine groups following discontinuation of the amlodipine intervention in September 2000. INTERVENTIONS: Participants were randomly assigned to receive amlodipine, 5 to 10 mg/d (n = 217), ramipril, 2.5 to 10 mg/d (n = 436), or metoprolol, 50 to 200 mg/d (n = 441), with other agents added to achieve 1 of 2 blood pressure goals. MAIN OUTCOME MEASURES: The primary outcome measure was the rate of change in GFR; the main secondary outcome was a composite index of the clinical end points of reduction in GFR of more than 50% or 25 mL/min per 1.73 m(2), end-stage renal disease, or death. RESULTS: Among participants with a urinary protein to creatinine ratio of >0.22 (corresponding approximately to proteinuria of more than 300 mg/d), the ramipril group had a 36% (2.02 [SE, 0.74] mL/min per 1.73 m(2)/y) slower mean decline in GFR over 3 years (P =.006) and a 48% reduced risk of the clinical end points vs the amlodipine group (95% confidence interval [CI], 20%-66%). In the entire cohort, there was no significant difference in mean GFR decline from baseline to 3 years between treatment groups (P =.38). However, compared with the amlodipine group, after adjustment for baseline covariates the ramipril group had a 38% reduced risk of clinical end points (95% CI, 13%-56%), a 36% slower mean decline in GFR after 3 months (P =.002), and less proteinuria (P<.001). CONCLUSION: Ramipril, compared with amlodipine, retards renal disease progression in patients with hypertensive renal disease and proteinuria and may offer benefit to patients without proteinuria.