Associations between diet and cardiometabolic risk among Yup'ik Alaska Native people using food frequency questionnaire dietary patterns.

BACKGROUND AND AIMS: In previous analyses, we identified three dietary patterns from food frequency questionnaire data among a sample of Yup'ik Alaska Native people living in Southwest Alaska: a "subsistence foods" dietary pattern and two market-based dietary patterns "processed foods" and "fruits and vegetables". In this analysis, we aimed to characterize the association between the dietary patterns and cardiometabolic (CM) risk factors (lipids, blood pressure, glucose, adiposity). METHODS AND RESULTS: We used multilevel linear regression to estimate the mean of each CM risk factor, comparing participants in the 4th to the 1st quartile of each dietary pattern (n = 637). Models were adjusted for age, sex, past smoking, current smoking, and physical activity. Mean log triglyceride levels were significantly higher among participants in the 4th compared to the 1st quartile of the processed foods dietary pattern (ß = 0.11). Mean HbA1c percent was significantly lower (ß = -0.08) and mean diastolic blood pressure (DBP) mm Hg was significantly higher (ß = 2.87) among participants in the 4th compared to the 1st quartile of the fruits and vegetables dietary pattern. Finally, mean log triglyceride levels and mean DBP mm Hg were significantly lower among participants in the 4th compared to the 1st quartile of the subsistence foods dietary pattern (ß = -0.10 and ß = -3.99 respectively). CONCLUSIONS: We found increased CM risk, as reflected by increased triglycerides, associated with eating a greater frequency of processed foods, and reduced CM risk, as reflected by lower triglycerides and DBP, associated with eating a greater frequency of subsistence foods.

Assessing change in diet-intervention research.

In nutrition-intervention research, it is important to consider the sensitivity of dietary assessment instruments to the changes in nutrient intake or dietary behavior under study. This presentation describes a measure called "responsiveness," an index of an instrument's sensitivity to change. Illustrations of this measure are from two randomized dietary-intervention trials that targeted reductions in fat intake: the Women's Health Trial (WHT), a trial to test whether fat reduction would reduce the risk of breast cancer, and the Eating Patterns Study (EPS), a trial to evaluate a self-help booklet to promote dietary change. In the WHT, a 4-d diet record (FDDR) was only slightly more responsive to dietary change than was a food-frequency questionnaire (FFQ). In the EPS, a fat-related diet-habits questionnaire was most responsive, followed by an FDDR and an FFQ. These data suggest that short, inexpensive measures such as FFQs or questionnaires that assess dietary habits can be as responsive as multiple-day diet records. More research is needed on the relative responsiveness of dietary assessment tools. Intervention studies should include at least two types of dietary assessment tools and the relative validity, reliability, and responsiveness of these tools should be reported as part of the study outcome.

The controversy over homocysteine and cardiovascular risk.

Elevated plasma total homocysteine (tHcy) is a risk factor for occlusive cardiovascular disease (CVD). This concept is based on the observations of premature vascular disease in patients with homocystinuria, the relation between tHcy and both clinical CVD as well as preclinical atherosclerotic disease, the relation between tHcy in children and CVD in their parents or relatives, and reduction in CVD or surrogate endpoints after tHcy-lowering intervention with B vitamins. Plausible mechanisms include the in vivo interference with nitric oxide-dependent reactive vasodilatation. Some observations have raised questions about tHcy as a risk factor. 1) Some prospective studies showed a weak relation or no relation between tHcy and CVD. 2) Several traditional risk factors are associated with tHcy and may confound the relation between tHcy and CVD. 3) tHcy is related to renal function, and hyperhomocysteinemia may reflect early nephrosclerosis. 4) The C677T transition of the methylenetetrahydrofolate reductase gene causes a moderate increase in tHcy but no or only minor increased CVD risk. However, the strength of some of these arguments can be questioned because there is increasing evidence that tHcy is a proximate risk factor provoking the acute event, it strongly interacts with traditional risk factors, and it may predict CVD or death in patients with chronic renal failure. Furthermore, the studies of the C677T polymorphism lack statistical power, and the TT genotype may even modulate CVD risk independently of homocysteine. Thus, only placebo-controlled intervention studies with tHcy-lowering B vitamins and clinical endpoints can provide additional valid arguments for the debate over whether tHcy is a causal CVD risk factor.

Differential effects of phosphatidylinositol-3/Akt-kinase inhibition on apoptotic sensitization to cytokines in LNCaP and PCc-3 prostate cancer cells.

Alterations in phosphatidylinositol 3'-kinase (PI3'-kinase) and Akt activation frequently occur in prostate cancer and may disrupt apoptotic induction by such cytokines as tumor necrosis factor (TNF) and TNF-related apoptosis-inducing ligand (TRAIL). To examine the role of PI3' phosphorylation in the cellular response to cytokines, two prostate cancer cell lines with constitutively activated PI3'-kinase cascades (LNCaP and PC-3) were examined for direct sensitivity to cytokines. TNF or TRAIL alone failed to activate apoptosis in either LNCaP or PC-3 cells, and drug-mediated inhibition of the PI3k/Akt cascade caused only minimal activation of apoptosis in either cell line. Suppression of PI3'-kinase/Akt signaling markedly enhanced the apoptotic activity of both TNF and TRAIL in LNCaP cells but not in PC-3 cells. Adenovirus-mediated PTEN/MMAC1 expression in LNCaP cells reduced Akt activation, activated apoptosis, and sensitized cells to TNF but not to TRAIL. Together, these results suggest that PI3'-kinase signaling inhibits both TNF-mediated and TRAIL-mediated apoptosis but may represent one of several apoptotic resistance mechanisms that inhibit cytokine-mediated killing of prostate cancer cells.

Application of a behavioral approach to measuring dietary change: the fat- and fiber-related diet behavior questionnaire.

This study reports the validity, reliability, and responsiveness of a 33-item fat- and fiber-related behavior questionnaire (FFB) and describes how this instrument provides insight into the process of adopting healthy diets. Data are from the Eating Patterns Study, a randomized clinical trial of a physician-delivered, self-help intervention to reduce fat and increase fiber intake. Intervention (n = 850) and control participants (n = 945) completed both a food frequency questionnaire and the FFB at baseline and at 3 and 12 months postintervention. Validity, as assessed by correlation of the FFB with the food frequency questionnaire at baseline, was 0.53 for fat (fat scale with percentage energy from fat) and 0.50 for fiber (fiber scale with fiber g/1000 kcal; both P < 0.001). Reliability, as assessed by the intraclass correlation in controls across all three time points, was 0.77 for the fat scale and 0.74 for the fiber scale (both P < 0.001). The largest changes in fat-related behavior were in avoiding fat as a flavoring and in using specially manufactured low-fat foods, and the largest changes in fiber-related behavior were in substituting high-fiber versions of common foods. Overall, the FFB was a reasonably valid and reliable measure of dietary intake, which provided insight into the behavioral effects of the dietary intervention.

Colorectal adenomas and the C677T MTHFR polymorphism: evidence for gene-environment interaction?

5,10-Methylene-tetrahydrofolate reductase (MTHFR), an enzyme in folate metabolism, may play a role in the etiology of colorectal adenomas via effects on DNA methylation and nucleotide synthesis. We investigated the association between a common polymorphism (C677T, reduced MTHFR activity) and colorectal adenomas within the Minnesota CPRU case-control study. Cases (n = 527) were diagnosed with colonoscopically confirmed adenomas; controls (n = 645) were derived from the same gastroenterology practice and were polyp free at colonoscopy. Dietary intakes were obtained from a self-administered food-frequency questionnaire prior to colonoscopy. Age- and sex-adjusted odds ratios (ORs) and 95% confidence intervals for the MTHFR genotype were 0.9 (0.7-1.2; CT versus CC wild-type) and 0.8 (0.6-1.3; TT versus CC). The associations between dietary intakes of folate, vitamin B12, vitamin B6, or methionine and risk of adenomas showed consistent patterns dependent upon MTHFR genotype. Individuals with the TT genotype and intakes of any of these nutrients in the lowest tertile were at elevated risk for adenomas (about 2-3-fold when compared with TT genotype with high intakes). These trends were more pronounced among individuals over age 60, resulting in a 3-6-fold increase for low intakes of folate, B12, and B6. An increased risk with increasing alcohol consumption was observed only among those with the CC genotype (P-trend = 0.005); among those with the TT genotype, those with moderate alcohol consumption were at lowest risk (P for interaction P = 0.02). In conclusion, nutrients involved in the MTHFR metabolic pathway may modify the relationship between the MTHFR C677T polymorphism and colorectal adenomas. Low intakes of folate, vitamin B12, and vitamin B6 increase risk among those (particularly the elderly) with the MTHFR TT genotype.

Lack of association between the C677T MTHFR polymorphism and colorectal hyperplastic polyps.

Colorectal hyperplastic polyps are benign lesions that share many risk factors with colorectal adenomas and cancers. Low folate intakes are associated with an increased risk of colon cancer. The enzyme 5,10-methylene-tetrahydrofolate reductase (MTHFR) may be linked to DNA methylation and nucleotide synthesis and thus play a role in the etiology of colorectal neoplasia. We investigated an association between the common MTHFR polymorphism (C677T) and colorectal hyperplastic polyps within the Minnesota Cancer Prevention Research Unit case-control study. Cases (n = 200) were diagnosed with colonoscopically confirmed hyperplastic polyps; controls (n = 645) were derived from the same gastroenterology practice and were polyp-free at colonoscopy. Dietary intakes were estimated from a self-administered food-frequency questionnaire prior to colonoscopy. Multivariate adjusted odds ratios (ORs) and 95% confidence intervals for MTHFR status were 0.8 (0.6-1.2; CT versus CC wild-type) and 0.9 (0.5-1.6; TT versus CC). In subgroup analyses stratified on dietary intakes of folate, vitamin B12, vitamin B6, or methionine, those with the TT genotype and either low intakes of folate or vitamin B6 were at increased risk relative to those with normal or high vitamin intake. However, most 95% confidence intervals included 1.0, and no consistent trends were observed. In contrast to our findings on colorectal adenomas, increasing alcohol consumption was associated with an elevated risk of colorectal hyperplastic polyps, regardless of genotype. The MTHFR (C677T) variant genotype does not appear to be related to risk of colorectal hyperplastic polyps, and there is no convincing evidence that MTHFR shows a different relation to risk, dependent on dietary intakes of nutrients related to its pathway.

Risk factors for synchronous primary endometrial and ovarian cancers.

PURPOSE: The incidence of synchronous primary endometrial and ovarian cancer is 2- to 10-fold higher than that expected based on the incidence of each cancer alone. We sought to evaluate reasons for this in a case-control study. METHODS: We combined data on a maternal history of cancer and reproductive and menstrual factors from 56 women with synchronous multiple primary disease who had participated in three population-based studies of gynecologic cancer. For comparison, we analyzed the same information from 280 women with endometrial cancer alone, 280 with ovarian cancer alone, and 280 without a history of either cancer. RESULTS: The reduced risk of multiple primary disease associated with high parity (2 or more births vs 0: OR = 0.37, 95% Cl, 0.19-76) and long-term use of oral contraceptives (12 or more months vs none: OR = 0.60, 95% Cl, 0.24-1.5) tended to be more pronounced than that associated with endometrial cancer alone or with ovarian cancer alone. CONCLUSIONS: Though limited by relatively small numbers, our results suggest that the presence of some common etiologies is a basis for the unusually high co-occurrence of endometrial and ovarian cancers.

Maternal physical activity in pregnancy and infant size for gestational age.

PURPOSE: To estimate the effect of several types of maternal physical activity in pregnancy on size for gestational age and length of gestation. METHODS: Telephone interviews, birth certificates, and medical records provided data on physical activity and other factors for a random sample of 291 Colorado residents. Backward polychotomous logistic regression modeling yielded estimates of the odds ratios for size for gestational age (appropriate versus small or large) and length of gestation (term versus pre-term or post-term) in relation to second and third trimester maternal physical activity. RESULTS: Performance of any moderate or vigorous physical activity for two hours per week or more in any month was associated with a decreased risk of large infant size for gestational age (LGA; odds ratio = 0.3, 95% confidence interval = 0.2, 0.7), but had no significant effect on risk of small infant size for gestational age (SGA; odds ratio (OR) = 0.8, 95% confidence interval (CI) = 0.3, 2.3). Length of gestation was not affected by prenatal physical activity. CONCLUSIONS: These results suggest that prenatal physical activity may decrease risk of LGA, as might be expected given its salutary effects on glucose tolerance.

Is nitrate in the drinking water associated with the risk of cancer in the urban UK?

Several studies have suggested that nitrate levels in drinking water may be linked with stomach cancer. Recent investigations of this hypothesis in rural areas of the UK, where nitrate levels can be high, have been inconclusive. The present study examined mortality data for the years 1969-1973 in 253 urban areas in relation to treated water nitrate levels. Variations in socioeconomic status and urban area size were taken into account. Drinking water nitrate levels were negatively associated with mortality from stomach cancer even when the analysis was restricted to urban areas with nitrate levels above the EEC guide. There was no evidence of a positive association between nitrate in the drinking water and the risk of stomach cancer in the urban areas of the UK, an important finding for the British water industry.

The relationship between water quality and health in the London area.

In a retrospective study of the relationship between reuse of water and hazards to health, the mortality experience from different causes, principally cancer, was examined for 29 boroughs and districts in the London area for the period 1968 to 1974. Information concerning the source of water supply to each borough was obtained both for the current situation, and historically back to 1926. Socioeconomic characteristics of the boroughs were extracted from 1971 census data. Differential mortality experiences for each sex were analysed using the standardised mortality ratio for ages 25 to 74. Most of the causes of death examined were associated with one or more of the socioeconomic characteristics of the boroughs. These socioeconomic characteristics accounted for the statistical associations between water reuse and mortality for each cause studied, except male stomach cancer, where a weak residual association remained. This association disappeared when variation in the size of boroughs was taken into account.

Cancer mortality and type of water source: findings from a study in the UK.

The age-adjusted, sex-specific mortality rates from certain cancers of the digestive system were analysed by type of water source supplied to 238 urban areas in England, Wales and Scotland using weighted multiple regression. Of the types of water source, the per cent supplied from upland rivers best described the pattern in cancer mortality for each cancer site and each sex. After adjustment was made for a number of socioeconomic factors, the regression coefficient for the percentage of upland river supply remained statistically significant only for female stomach cancer and female intestinal cancer. The association with intestinal cancer could equally well be explained by some other factor with a strong north-west/south-east geographical distribution. The association found for female stomach cancer could not be accounted for by a geographical trend, but suggests a small effect, equivalent to a relative risk of only 1.11. This is an unexpected finding and must be considered a hypothesis, to be tested further by studies conducted by other researchers, in different locations, preferably on individuals.

Factors influencing demand for primary medical care in women aged 20-44 years: a preliminary report.

This paper reports on a study designed to relate certain social and psychological variables to demand for medical care in a random sample of female patients aged between 20 and 44 years, in a National Health Service General Practice in the United Kingdom. Women selected for study completed questionnaires on anxiety and on their social characteristics. They also completed a health diary for four weeks, and over 12 months their demand for general practitioner care was recorded. This paper summarizes some of the literature on the subject of utilization behaviour, describes the objectives and methodology, and gives some preliminary results suggesting associations between anxiety, perception of symptoms and demand for primary care.

Interpreting excess mortality in a prevention trial for older adults.

BACKGROUND: In a randomized trial evaluating preventive services for older adults excess mortality was observed in the treatment group. We examined four explanations: unbalance of baseline characteristics, unintended effects of the intervention, consequence of an autonomy intervention (including increased number of living wills in the treatment group), and chance. We focus here on the effects of the autonomy intervention. METHODS: Preparation of living wills in the treatment and control groups was compared both at baseline and follow-up. A linear predictor of mortality was used to identify participants at high risk of dying. Charts of these 200 participants were reviewed for evidence of serious medical events and resuscitation decisions. Rates of life-sustaining treatment were compared between treatment and controls using logistic regression. RESULTS: More living wills (65%) were noted for the treatment group than control group (47%) at follow-up. Thirty-six per cent of participants were identified as having a serious medical event; of these, participants in the treatment group were over twice as likely not to receive life-sustaining treatment. CONCLUSIONS: Advance directives contributed to excess deaths, indicating the success of the autonomy intervention.

Risk of endometrial cancer in relation to use of low-dose, unopposed estrogens.

OBJECTIVE: To determine whether a low dosage (0.3 mg/day) of unopposed conjugated estrogens can be used without incurring an elevated risk of endometrial cancer. METHODS: In this case-control study, cases (n = 484) consisted of women diagnosed with endometrial cancer between 1985 and 1991 in three counties in Western Washington. Controls (n = 780) were identified using random digit dialing within the same three counties. Subjects were interviewed in person to obtain basic demographic and medical history information, as well as specific information about hormone use. RESULTS: Eighteen cases and eight controls had taken 0.3 mg/day of unopposed conjugated estrogens and no other dose or preparation of estrogens (risk relative to that of women who had not taken postmenopausal hormones = 5.4, 95% confidence interval [CI] 2.3, 13.0). The risk was particularly high in women whose use of this dose was both current and of more than 8 years' duration (odds ratio = 9.2, 95% CI 2.9, 29.0). The elevation in risk in users of 0.3 mg/day was similar in size to that associated with the daily unopposed use of 0.625 mg of conjugated estrogens. CONCLUSION: The results suggest that a dosage of 0.3 mg per day of unopposed conjugated estrogens is associated with an increased risk of endometrial cancer.

Lactose metabolism and time to pregnancy.

OBJECTIVE: To investigate whether, in the absence of galactosemia, relatively high intestinal lactase activity or low activity of an enzyme involved in galactose catabolism reduces fertility, as it does in the presence of galactosemia. DESIGN: Retrospective cohort study. SETTING: Healthy women selected from the community. PATIENTS: Fifty-three married women. INTERVENTION: Urinary galactose after an oral lactose challenge (a measure of intestinal lactase activity), erythrocyte galactose-1-phosphate uridyltransferase (transferase) activity, and transferase polymorphisms by isoelectric focusing. MAIN OUTCOME MEASURE: Pregnancy rate (number of pregnancies divided by number of months at risk) in the 12 months after stopping use of birth control to become pregnant. RESULTS: Relatively high urinary galactose was not related to a decreased rate of pregnancy during the first 12 months (> or = 24.6 compared with < or = 14.3 mg: relative risk [RR] = 1.9; 95% confidence interval [CI] = 0.86 to 4.0). Relatively high transferase activity was not related to an increased rate of pregnancy (> or = 19.5 compared with < or = 17.2 mumol/h per g hemoglobin: RR = 1.1; 95% CI = 0.56 to 2.4). Low-activity transferase polymorphisms were not related to a decreased rate (RR = 1.2; 95% CI = 0.58 to 2.5). CONCLUSION: Our study does not support the hypothesis that the biologic variation in galactose metabolism that exists in the general population influences infertility.

The mode of inheritance of blood pressure levels.

In a sample of 465 families living in a suburb of north-west London the systolic and diastolic blood pressure consistently showed a greater correlation for sib/sib (0.16 to 0.28) than for parent/offspring (0.07 to 0.18); this pattern is consistent with the hypothesis of a dominance component in the inheritance of blood pressure assuming there is no difference in the interaction between environment and genes in people of different ages. This assumption was examined by studying the sib/sib correlation according to the age gap between sibs; for diastolic blood pressure this remained almost the same but for systolic blood pressure the correlation tended to diminish as the age gap increased. A dominance component in the inheritance of blood pressure levels could explain the sort of results we have found in this study. However, we cannot ignore the fact that similar results could be obtained if the contribution of the environment within the same generation of relatives differs from that of the environment shared by all relatives.

Which measure of adolescent psychiatric disorder--diagnosis, number of symptoms, or adaptive functioning--best predicts adverse young adult outcomes?

OBJECTIVE: To test the ability of psychiatric diagnosis, symptom count, and adaptive functioning in adolescence to predict failure to complete secondary school and criminal involvement in young adulthood. DESIGN: Community-based cohort study. SETTING: Two counties in upstate New York, USA. PARTICIPANTS: 181 adolescents interviewed in 1983 and 1985-86 who were randomly selected in 1975 from a probability area sampling of representative families with 1-10 year old children. MAIN RESULTS: Compared with adolescents without psychiatric disorders, adolescents with depressive, anxiety, disruptive, and substance abuse disorders were 2.86-9.21 times more likely to fail to complete secondary school. Compared with adolescents without disruptive disorders, adolescents with disruptive disorders were 4.04 (1.96-8.32) times more likely to get in trouble with police during young adulthood. The positive predictive value of each measure of adolescent psychiatric disorder for school non-completion was higher in the lowest SES stratum and for young adult criminal involvement was higher for boys. Combining knowledge of symptom counts, age, gender, and social class in a logistic regression model yielded 89% sensitivity and 87% specificity for predicting future school non-completion at the p >or= 0.13 cut off. The optimal cut off value in a model incorporating knowledge of disruptive symptoms and demographic characteristics yielded 75% sensitivity and 76% specificity for predicting future criminal involvement. CONCLUSIONS: Screening children and adolescents for psychiatric disorders can identify those at high risk of adverse young adult outcomes. Future school and community adjustment can be predicted as easily and accurately on the basis of a simple count of psychiatric symptoms as by applying more complex diagnostic algorithms. Screening youth for psychiatric symptoms in neighbourhood, school, or primary care settings is a logical first step for early intervention to promote increased school completion and decreased criminal activity in young adulthood.

Dietary vitamin C and bone mineral density in postmenopausal women in Washington State, USA.

STUDY OBJECTIVE: To examine the relationship between dietary vitamin C and hip bone mineral density (BMD) in postmenopausal women. DESIGN: This was a cross sectional study using retrospective diet and vitamin supplement data. SETTING: The Seattle area of Washington State. PARTICIPANTS: Screenees for a clinical trial of a drug to prevent osteoporotic fractures; 1892 women aged 55-80 years who had hip bone densitometry and osteoporosis risk factor information. MAIN RESULTS: Mean energy adjusted dietary intake of vitamin C was 113 mg/day; including supplement use, mean intake was 407 mg/day. There were no differences in BMD according to diet-only vitamin C intake or combined dietary and supplemental vitamin C intake. Longer duration of vitamin C supplement use was associated with higher BMD in women who had not used oestrogen replacement therapy (trend p = 0.02) and among women aged 55-64 years (trend p = 0.01). Women aged 55-64 years who used vitamin C supplements for > or = 10 years had a higher BMD than non-users aged 55-64 years (multivariate adjusted mean BMD 0.699 (0.017) g/cm2 versus 0.655 (0.007) g/cm2, p = 0.02). Benefits were not evident in older age groups or in women who had used oestrogen in the past. Frequent intake of foods rich in vitamin C was not associated with BMD. CONCLUSION: There was no evidence that vitamin C from the diet was associated with BMD, although long term use of vitamin C supplements was associated with a higher BMD in the early postmenopausal years and among never users of oestrogen.

Cost and outcomes of Medicare reimbursement for HMO preventive services.

Medicare beneficiaries enrolled in a health maintenance organization (HMO) were randomized to a preventive services benefit package for 2 years or to usual care. At 24- and 48-month follow-ups, the treatment group had completed more advance directives, participated in more exercise, and consumed less dietary fat than the control group. Unexpectedly, more deaths occurred in the treatment group. Surviving treatment-group enrollees reported higher satisfaction with health, less decline in self-rated health status, and fewer depressive symptoms than surviving control participants. Despite these changes, the intervention did not yield lower cost per quality-adjusted life year in this historically prevention-oriented HMO.