Quality of life assessment among HIV-positive persons entering the INSIGHT Strategic Timing of AntiRetroviral Treatment (START) trial.

OBJECTIVES: With HIV treatment prolonging survival and HIV infection now managed as a chronic illness, quality of life (QOL) is important to evaluate in persons living with HIV (PLWH). We assessed at study entry the QOL of antiretroviral-naïve PLWH with CD4 counts > 500 cells/µL in the Strategic Timing of AntiRetroviral Treatment (START) clinical trial. METHODS: QOL was assessed with: (1) a visual analogue scale (VAS) for self-assessment of overall current health; (2) the Short-Form 12-Item Version 2 Health Survey(®) (SF-12V2), for which responses are summarized into eight individual QOL domains plus component summary scores for physical health [the Physical Health Component Summary (PCS)] and mental health [the Mental Health Component Summary (MCS)]. The VAS and eight domain scores were scaled from 0 to 100. Mean QOL measures were calculated overall and by demographic, clinical and behavioural factors. RESULTS: A total of 4631 participants completed the VAS and 4119 the SF-12. The mean VAS score (with standard deviation) was 80.9 ± 15.7. Mean SF-12 domain scores were lowest for vitality (66.3 ± 26.4) and mental health (68.6 ± 21.4), and highest for physical functioning (89.3 ± 23.0) and bodily pain (88.0 ± 21.4). Using multiple linear regression, PCS scores were lower (P < 0.001) for Asians, North Americans, female participants, older participants, and those with less education, longer duration of known HIV infection, alcoholism/substance dependence and body mass index ≥ 30 kg/m(2) . MCS scores were highest (P < 0.001) for Africans, South Americans and older participants, and lowest for female participants, current smokers and those with alcoholism/substance dependence. CONCLUSIONS: In this primarily healthy population, QOL was mostly favourable, emphasizing that it is important that HIV treatments do not negatively impact QOL. Self-assessed physical health summary scores were higher than mental health scores. Factors such as older age and geographical region had different effects on perceived physical and mental health.

Calcium and colorectal epithelial cell proliferation in sporadic adenoma patients: a randomized, double-blinded, placebo-controlled clinical trial.

BACKGROUND: The kinetics of colorectal epithelial cell proliferation is altered in patients at increased risk for colon cancer. Calcium administration ameliorates such proliferative changes in rodents. Findings in preliminary clinical trials have suggested similar effects in humans. PURPOSE: A randomized, double-blind, placebo-controlled, clinical trial was designed to determine whether calcium supplementation will reduce the colorectal epithelial cell proliferation rate and normalize the distribution of proliferating cells within colorectal crypts (i.e., shift the zone of proliferation from the entire crypt to the lower 60% of the crypt, which is thought to be the normal proliferative zone of the crypt) in patients with sporadic adenomas. METHODS: Sporadic adenoma patients (n = 193) were treated with placebo (n = 66), 1.0 g calcium (n = 64), or 2.0 g calcium (n = 63) daily for 6 months. Rectal mucosa biopsy specimens were obtained at base line and at 1-, 2-, and 6-month follow-up. Cell proliferation was measured by detection of S-phase-associated proliferating cell nuclear antigen by immunohistochemical methods. The cell proliferation rate, called labeling index (LI), was calculated as the proportion of labeled cells in the crypts. The deviation of the proliferative zone from the normal location in the lower 60% of the crypt was calculated as the proportion of labeled cells in the upper 40% of the crypt, called distributional index (phi h). The effects of calcium treatment on the LI and phi h were expressed as relative effects--(calcium follow-up/calcium base line)/(placebo follow-up/placebo base line). Calculations and inference testing of the relative effects were accomplished using a repeated-measures mixed model on log-transformed LI and phi h values. All statistical tests were two-sided. RESULTS: Scorable biopsy specimens were obtained on 170 patients at base line, 164 at 1 month, 161 at 2 months, and 163 at 6 months. The difference in the change in the LI between the combined calcium groups and the placebo group was insignificant, with a relative effect of calcium versus placebo of 0.97 (P = .87). However, for the phi h, the relative effect of calcium versus placebo was 0.50 (P = .05) in the combined calcium groups, 0.56 (P = .16) in the 1.0-g calcium group, and 0.44 (P = .05) in the 2.0-g calcium group. CONCLUSIONS: Calcium supplementation normalizes the distribution of proliferating cells without affecting the proliferation rate in the colorectal mucosa of sporadic adenoma patients. IMPLICATIONS: These results support further study of whether alterations in colon cell proliferative kinetics represent true intermediate steps in colon carcinogenesis that can be used to investigate the etiology and prevention of, and whether a higher calcium consumption can reduce the risk of, colon cancer.

Calcium and colorectal epithelial cell proliferation: a preliminary randomized, double-blinded, placebo-controlled clinical trial.

BACKGROUND: Colonic epithelial cell proliferation is increased in patients at high risk for colon cancer. Calcium administration has ameliorated the proliferative changes in rodents, and findings in small, uncontrolled clinical trials have suggested similar effects in humans. PURPOSE: This preliminary, double-blind, randomized clinical trial was designed 1) to investigate whether supplemental calcium will reduce colonic epithelial cell proliferation in patients with sporadic adenomas who consume a high-fat, Western-style diet; 2) to determine the sample size (number of scorable crypts per person) needed to achieve adequate statistical power; and 3) to evaluate the feasibility of full-scale clinical trials. METHODS: Twenty-one sporadic adenoma patients were treated daily with placebo or 1200 mg of supplemental calcium. To determine colonic epithelial cell proliferation, we used tritiated thymidine labeling of colon crypt epithelial cells in rectal biopsy specimens and calculated the percentage of labeled cells (labeling index [LI]). Two pathology technician "readers" independently scored each specimen, and inter-reader reliability was determined. Subjects remained on their usual diet during the study, and intake of calories, calcium, total fat, and vitamin D did not differ substantially among them. We calculated curves for statistical power to determine the number of scorable crypts needed per person for detection of a statistically significant difference (P < .05) of 1.0% in mean LI. RESULTS: The pooled baseline LI was 4.7%. In the calcium-treated group, the LI increased 0.6% (proportional increase, 12.8%); in the placebo-treated group, it decreased 0.5% (proportional decrease, 10.6%). The difference between change in the mean LI from baseline to 8 weeks' follow-up in the placebo group versus the calcium group was not statistically significant. The intraclass correlation coefficient for inter-reader reliability for the baseline LI was .66. Analyses indicated scoring eight crypts sufficient for estimates of the LI adequate for between-group comparisons, a level achieved in 81% of biopsy specimens. CONCLUSIONS: Calcium carbonate supplements delivering 1200 mg elemental calcium daily may not decrease colonic epithelial cell proliferation over an 8-week period in sporadic adenoma patients. In future trials measuring the LI, consideration should be given to ensuring adequate numbers of scorable crypts and to the impact of inadequate biopsy procedures, labeling failure, reader reliability, and participant withdrawal. Our findings support the feasibility of a full-scale clinical trial to further study the relationships among dietary calcium, colonic epithelial cell proliferation, and colorectal cancer.

Prognostic value of heart rate adjustment of exercise-induced ST segment depression in the multiple risk factor intervention trial.

OBJECTIVES: We sought to assess the effect of heart rate adjustment of ST segment depression on risk stratification for the prediction of death from coronary artery disease. BACKGROUND: Standard analysis of the ST segment response to exercise based on a fixed magnitude of horizontal or downsloping ST segment depression has demonstrated only limited diagnostic sensitivity for the detection of coronary artery disease and has variable test performance in predicting coronary artery disease mortality. Heart rate adjustment of the magnitude of ST segment depression has been proposed as an alternative approach to increase the diagnostic and prognostic accuracy of the exercise electrocardiogram (ECG). METHODS: Exercise ECGs were performed in 5,940 men from the Usual Care Group of the Multiple Risk Factor Intervention Trial at entry into the study. An abnormal ST segment response to exercise was defined according to standard criteria as > or = 100 micro V of additional horizontal or downsloping ST segment depression at peak exercise. The ST segment/heart rate index was calculated by dividing the change in ST segment depression from rest to peak exercise by the exercise-induced change in heart rate. An abnormal ST segment/heart rate index was defined as >1.60 micro V/beats per min. RESULTS: After a mean follow-up of 7 years there were 109 coronary artery disease deaths. Using a Cox proportional hazards model, a positive exercise ECG by standard criteria was not predictive of coronary mortality (age-adjusted relative risk [RR] 1.5, 95% confidence interval [CI] 0.6 to 3.6, p = 0.39). In contrast, an abnormal ST segment/heart rate index significantly increased the risk of death from coronary artery disease (age-adjusted RR 4.1, 95% CI 2.7 to 6.0, p < 0.0001). Excess risk of death was confined to the highest quintile of ST segment/heart rate index values, and within this quintile, risk was directly related to the magnitude of test abnormality. After multivariate adjustment for age, diastolic blood pressure, serum cholesterol and cigarettes smoked per day, the ST segment/heart rate index remained a significant independent predictor of coronary death (RR 3.6, 95% CI 2.4 to 5.4, p < 0.001). CONCLUSIONS: Simple heart rate adjustment of the magnitude of ST segment depression improves the prediction of death from coronary artery disease in relatively high risk, asymptomatic men. These findings strongly support the use of heart rate-adjusted indexes of ST segment depression to improve the predictive value of the exercise ECG.

Relationships of quality-of-life measures to long-term lifestyle and drug treatment in the Treatment of Mild Hypertension Study.

OBJECTIVES: To compare 5 antihypertensive drugs and placebo for changes in quality of life (QL). To assess the relationship of lifestyle factors and change in lifestyle factors to QL in participants with stage I diastolic hypertension. METHODS: The Treatment of Mild Hypertension Study (TOMHS) was a randomized, double-blind, placebo-controlled clinical trial with minimum participant follow-up of 4 years. It was conducted at 4 hypertension screening and treatment academic centers in the United States. The cohort consisted of 902 men and women with hypertension, aged 45 to 69 years, with diastolic blood pressures less than 100 mm Hg. Informed consent was obtained from each participant after the nature of the procedures had been fully explained. Sustained nutritional-hygienic intervention was administered to all participants to reduce weight, to reduce dietary sodium and alcohol intake, and to increase physical activity. Participants were randomized to take (1) acebutolol (n = 132); (2) amlodipine maleate (n = 131); (3) chlorthalidone (n = 126); (4) doxazosin mesylate (n = 134); (5) enalapril maleate (n = 135); or placebo (n = 234). Changes in 7 QL indexes were assessed based on a 35-item questionnaire: (1) general health; (2) energy or fatigue; (3) mental health; (4) general functioning; (5) satisfaction with physical abilities; (6) social functioning; and (7) social contacts. RESULTS: At baseline, higher QL was associated with older age, more physical activity, lower obesity level, male gender, non-African American race, and higher educational level. Improvements in QL were observed in all randomized groups, including the placebo group during follow-up; greater improvements were observed in the acebutolol and chlorthalidone groups and were evident throughout follow-up. The amount of weight loss, increase in physical activity, and level of attained blood pressure control during follow-up were related to greater improvements in QL. CONCLUSIONS: In patients with stage I hypertension, antihypertensive treatment with any of 5 agents used in TOMHS does not impair QL. The diuretic chlorthali-done and the cardioselective beta-blocker acebutolol appear to improve QL the most. Success with lifestyle changes affecting weight loss and increase in physical activity relate to greater improvements in QL and show that these interventions, in addition to contributing to blood pressure control, have positive effects on the general well-being of the individual.

Long-term effects on sexual function of five antihypertensive drugs and nutritional hygienic treatment in hypertensive men and women. Treatment of Mild Hypertension Study (TOMHS)

Problems with sexual function have been a long-standing concern in the treatment of hypertension and may influence the choice of treatment regimens and decisions to discontinue drugs. The Treatment of Mild Hypertension Study (TOMHS) provides an excellent opportunity for examination of sexual function and effects of treatment on sexual function in men and women with stage I diastolic hypertension because of the number of drug classes studied, the double-blind study design, and the long-term follow-up. TOMHS was a double-blind, randomized controlled trial of 902 hypertensive individuals (557 men, 345 women), aged 45 to 69 years, treated with placebo or one of five active drugs (acebutolol, amlodipine maleate, chlorthalidone, doxazosin maleate, or enalapril maleate). All participants received intensive lifestyle counseling regarding weight loss, dietary sodium reduction, alcohol reduction (for current drinkers), and increased physical activity. Sexual function was ascertained by physician interviews at baseline and annually during follow-up. At baseline, 14.4% of men and 4.9% of women reported a problems with sexual function. In men, 12.2% had problems obtaining and/or maintaining an erection; 2.0% of women reported a problem having an orgasm. Erection problems in men at baseline were positively related to age, systolic pressure, and previous antihypertensive drug use. The incidences of erection dysfunction during follow-up in men were 9.5% and 14.7% through 24 and 48 months, respectively, and were related to type of antihypertensive therapy. Participants randomized to chlorthalidone reported a significantly higher incidence of erection problems through 24 months than participants randomized to placebo (17.1% versus 8.1%, P = .025). Incidence rates through 48 months were more similar among treatment groups than at 24 months, with nonsignificant differences between the chlorthalidone and placebo groups. Incidence was lowest in the doxazosin group but was not significantly different from the placebo group. Incidence for acebutolol, amlodipine, and enalapril groups was similar to that in the placebo group. In many cases, erection dysfunction did not require withdrawal of medication. Disappearance of erection problems among men with problems at baseline was common in all groups but greatest in the doxazosin group. Incidence of reported sexual problems in women was low in all treatment groups. In conclusion, long-term incidence of erection problems in treated hypertensive men is relatively low but is higher with chlorthalidone treatment. Effects of erection dysfunction with chlorthalidone appear relatively early and are often tolerable, and new occurrences after 2 years are unlikely. The rate of reported sexual problems in hypertensive women is low and does not appear to differ by type of drug. Similar incidence rates of erection dysfunction in placebo and most active drug groups caution against routine attribution of erection problems to antihypertensive medication.

Method issues in dietary data analyses in the Multiple Risk Factor Intervention Trial.

The selection process in the Multiple Risk Factor Intervention Trial caused relations between risk factors to differ between participants who were randomly assigned into the study and the screening population. Cigarette smoking, blood pressure, and serum cholesterol were moderately inversely related to each other in the randomly assigned population whereas these relations in the unselected population were direct and small in magnitude. This problem was addressed by covariate adjustment in analyses. The selection process also created an artificially high initial mean concentration of serum cholesterol; the mean plasma concentration at the second screening was 15 mg/dL lower than at the first screening. Most of this difference is attributable to regression to the mean. To account for this problem, emphasis was placed on change in plasma cholesterol over time, calculated from the second-screening measurement. Examination of the reliability of nutrition data based on one 24-h dietary recall showed that nutrient-biochemical relations are subject to considerable regression-dilution bias. The ratios of "within" to "between" components of variability were typically between one and four. Analyses in which multiple follow-up measures were averaged are emphasized in this monograph. Men assigned to the special intervention group reported considerable reductions in total energy intake, which was not consistent with observed weight loss. The most likely explanation for this is underreporting or underconsumption the day before the recall. To partially adjust for this, nutrient data are often expressed both in absolute units and as nutrient densities.

Relation of body mass and alcohol, nutrient, fiber, and caffeine intakes to blood pressure in the special intervention and usual care groups in the Multiple Risk Factor Intervention Trial.

This chapter presents analyses of relations of dietary variables to blood pressure, systolic (SBP) and diastolic (DBP), for men in the special intervention (SI) and usual care (UC) groups in the Multiple Risk Factor Intervention Trial. For each dietary factor, analyses were done at baseline, for trial years 1-6, and for change from baseline to years 1-6. Analyses were done for all participants and for men receiving or not receiving antihypertensive drug treatment and were controlled for age, race, education, serum cholesterol, smoking, special diet status, and (for specific nutrients) body mass index and alcohol intake. Nutrient data for trial years 1-6, which are based on four or five dietary recalls per man, are more reliable than the baseline or change data, which are based on only one recall. Therefore, this summary focuses on data for trial years 1-6, for SI and UC men pooled. Regression analyses confirmed direct independent relations of body mass index, alcohol intake, sodium, and ratio of sodium to potassium to SBP and DBP, and an inverse relation of potassium to SBP and DBP. Dietary starch was directly related to SBP and DBP; dietary saturated fatty acid and cholesterol and Keys score were directly related to DBP; dietary magnesium, fiber, and caffeine were inversely related to SBP and DBP; and dietary protein, polyunsaturated fatty acids, the ratio of polyunsaturated to saturated fatty acid, and other simple carbohydrates were inversely related to DBP. Method problems, all tending to produce underestimations, are also reviewed.

Adherence to dietary recommendations in the special intervention group in the Multiple Risk Factor Intervention Trial.

This chapter presents findings on adherence to the Multiple Risk Factor Intervention Trial eating pattern by special intervention participants, on the basis of measures other than the 24-h dietary recall and blood cholesterol concentrations. These additional assessments included subjective ratings by a nutritionist, used during follow-up years 1 and 2, and a food record rating that was calculated from a 3-d food record, used during years 3-6. An additional tool used during the latter part of the trial was a checklist for evaluating degree of shortfall of the participant's diet from recommendations, level of motivation toward adherence, and factors in the social environment potentially influencing dietary behavior. Subjective ratings and food record ratings indicated that approximately 40-65% of participants were good or excellent adherers, with declines in these percentages over time. There were consistent strong relations between these ratings and change in serum cholesterol. Checklist evaluations gave similar overall findings, with about one-half to three-quarters of participants rated positively on infrequency of deviation from the eating pattern, motivation, and conducive environment. Several baseline traits predicted adherence. Adherence was better in older participants, in white than in black men, in nondrinkers, in those with fewer stressful life events, in those eating away from home less often, in less overweight men (although heavier participants exhibited greater changes in serum cholesterol, perhaps reflecting their poorer baseline diets), in those with higher serum cholesterol and diastolic blood pressure, and in nonsmokers.

Relation of dietary carbohydrates to blood lipids in the special intervention and usual care groups in the Multiple Risk Factor Intervention Trial.

This chapter explores relations between reported intake of dietary carbohydrates and measurements of plasma lipids at baseline and during trial years 1-6 of the Multiple Risk Factor Intervention Trial. With control for dietary lipids, alcohol, and other factors, total carbohydrate intake at baseline was inversely related to baseline plasma total cholesterol and high-density-lipoprotein (HDL) cholesterol; starch and other simple carbohydrates were unrelated to plasma lipids and sucrose was inversely related to HDL cholesterol. During trial years 1-6, men assigned to the special intervention group increased their intake of starch and other simple carbohydrates as they decreased their fat intake, and lowered their intakes of refined and processed sucrose. Total carbohydrate intake of these men was inversely related to total, low-density-lipoprotein (LDL), and HDL cholesterol. Starch and sucrose intakes were also inversely related to HDL cholesterol. In contrast, intake of other simple carbohydrates was directly related to HDL, and inversely related to plasma total and LDL cholesterol. For men in the highest quintile of intake of other simple carbohydrates compared with men in the lowest quintile, plasma total cholesterol was lower by 3.6 mg/dL, LDL cholesterol was lower by 4.3 mg/dL, and HDL cholesterol was higher by 1.6 mg/dL. Findings were generally similar for men in the usual care group.

Relation of dietary fiber to blood lipids in the special intervention and usual care groups in the Multiple Risk Factor Intervention Trial.

This chapter addresses relations between intake of fiber--total, soluble, and insoluble--and blood lipids in the Multiple Risk Factor Intervention Trial through use of baseline data (single measurement), averages of four to five 24-h recalls and blood lipid determinations collected during annual follow-up examinations, and change from baseline to follow-up. No significant associations were observed at baseline. Consistent highly significant inverse associations were seen in analyses of follow-up measurements. Results from change data were of intermediate strength and consistency. These variations were in all likelihood due to the low reliability of a single 24-h recall at baseline for determination of dietary intake and change in intake for individuals. From follow-up data, plasma total and low-density-lipoprotein (LDL) cholesterol concentrations were lower by approximately 5 mg/dL for men in the special intervention group in quintile 5 of total fiber intake (25 g/d) compared with men in quintile 1 (8 g/d), after adjustment for average body mass index and intake of alcohol, saturated and polyunsaturated fatty acids, and dietary cholesterol. Results were similar for men in the usual care group. There were no adverse effects on high-density-lipoprotein cholesterol, nor any consistent associations with plasma triglycerides. Thus, increasing dietary fiber can provide additional reduction in blood total and LDL cholesterol and consequent improvement in the lipid profile, over and above the beneficial effects of a fat-modified diet.

Food group and nutrient intakes at baseline in the Multiple Risk Factor Intervention Trial.

This chapter relates food and nutrient intakes at baseline to other facets of reported dietary behavior, major risk factors, and sociodemographic characteristics of men in the Multiple Risk Factor Intervention Trial. Intakes of total fat (38.4% of energy), saturated fatty acids (14.2%), and dietary cholesterol (492 mg/d) were similar to amounts seen in the first and second National Health and Nutrition Examination Surveys in the 1970s and were generally lower than findings from studies in the 1960s. There were inverse relations between total serum cholesterol and intakes of total fat, saturated and monounsaturated fatty acids, and dietary cholesterol. These paradoxical associations were largely attributable to findings in the 21% of men who reported following a special diet, indicating that use of such a diet increases with severity of hypercholesterolemia. Fat intake was directly related to number of meals per week eaten away from home, and to cigarette smoking. Patterns of food and nutrient intake were similar for men stratified by baseline blood pressure and antihypertensive treatment. Intake of total energy and percentages from various dietary fats decreased with age, as did use of sucrose and caffeine. White men consumed more dairy products than did other ethnic groups, whereas black men consumed more eggs, sugars, and sweets. Asians had the highest intake of cereal foods. Those with more education ate less high-fat meat products, more fruit, and more polyunsaturated oils, but also more high-fat dairy products and less breads and cereals; they also drank more alcohol.

Food group and macronutrient intakes, trial years 1-6, in the special intervention and usual care groups in the Multiple Risk Factor Intervention Trial.

This chapter presents changes in dietary intake reported by men in the special intervention (SI) and usual care (UC) groups from baseline through 6 y of follow-up in the Multiple Risk Factor Intervention Trial. Changes in nutrients by SI men after 1 y of following the intensive intervention program were as follows: reduced intake of total fat (from 38.4% to 34.3% of energy), saturated fatty acids (14.2% to 10.4% of energy), and cholesterol (448 to 263 mg/d), and increased intake of polyunsaturated fatty acids (from 6.4% to 8.6% of energy). These changes were maintained and did not increase through the remaining 5 y. UC men reported small changes in similar directions. Most of the change in saturated fatty acid intake by SI participants was from high-fat meat and high- and medium-fat dairy products. Reduction in dietary cholesterol was achieved primarily by substantial decreases in intake of eggs and high-fat meats. Several baseline factors were associated with amount of dietary change in SI men. Greater changes were seen in men with higher baseline serum cholesterol concentrations, in those not consuming a special diet, in nonsmokers followed by lighter smokers, in hypertensive than in non-hypertensive men, in older participants, in white than in black men, in moderate drinkers than in nondrinkers or those consuming > or = 22 drinks/wk, and in those with no "stressful life events" than in those reporting one or more life events.

Relation of changes in dietary lipids and weight, trial years 1-6, to changes in blood lipids in the special intervention and usual care groups in the Multiple Risk Factor Intervention Trial.

For men in the special intervention (SI) group of the Multiple Risk Factor Intervention Trial, the average decrease in serum total cholesterol was 16.9 mg/dL (6.7%); for men in the usual care (UC) group, the average decrease was 9.7 mg/dL (3.8%). The difference between the two groups for plasma total cholesterol was 6.2 mg/dL. Plasma low-density-lipoprotein (LDL) cholesterol decreased 10.6 mg/dL (6.6%) in SI men and 5.4 mg/dL (3.4%) in UC men. Mean weight losses were 3.0 lb (1.36 kg) and 0.1 lb (0.05 kg) for SI and UC men, respectively. Change in blood total cholesterol was directly related to baseline concentration; for men with serum total cholesterol > or = 220 mg/dL, those in the SI group decreased their total cholesterol by 7.8% (design goal: 10%) and those in the UC group by 4.8% (expected: 0%). Change in dietary lipid intake (summarized by the Keys score) for SI men was significantly related to changes in blood total cholesterol, LDL cholesterol, and triglyceride, but not to change in high-density-lipoprotein (HDL) cholesterol. Controlled for weight change, coefficients for Keys score change were smaller but remained significantly related to each blood lipid except HDL cholesterol. Weight loss was associated with favorable effects on all blood lipids. Influences of change in diet and weight on blood lipids were quantitatively less for hypertensive men for serum total cholesterol, HDL cholesterol, and triglyceride than for nonhypertensive men. Nonsmokers had greater decreases than smokers in blood total cholesterol, LDL cholesterol, and triglyceride.

Nutritional adequacy of diets reported at baseline and during trial years 1-6 by the special intervention and usual care groups in the Multiple Risk Factor Intervention Trial.

This chapter addresses whether a fat-modified diet as implemented by special intervention participants in the Multiple Risk Factor Intervention Trial affected intake of vitamins and minerals, and whether nutritional adequacy was altered by this dietary intervention. Despite likely underreporting of intake, for men in the special intervention group, most mean intakes of 15 micronutrients estimated from 24-h recalls were above established recommended dietary allowances. A few means were slightly below; lowest was zinc at 77% (from 98% at baseline) followed by calcium at 79% (from 102% at baseline). Calculated as nutrient densities (per 1000 kcal), nutrients that were below indexes of nutritional quality (the corresponding standard based on nutrient density) during follow-up, although not reduced below baseline by this measure, were vitamin D, calcium, iron (marginally), and zinc. Analyses by food groups indicated that intake of these nutrients might have been improved by greater replacement of high- and medium-fat dairy products with low-fat dairy products (for vitamin D and calcium) and of high-fat meats with low-fat meats, fish, or poultry (for iron and zinc), or (because iron was adequate) by increasing consumption of vegetables and whole-grain products. The safety of the eating pattern was further confirmed by more favorable micronutrient profiles in men who adhered best to the intervention program, as measured by degree of serum cholesterol reduction and weight loss.

Relation of smoking at baseline and during trial years 1-6 to food and nutrient intakes and weight in the special intervention and usual care groups in the Multiple Risk Factor Intervention Trial.

This chapter describes dietary composition according to cigarette smoking status at baseline and changes in smoking status during follow-up for men in the special intervention (SI) and usual care (UC) groups of the Multiple Risk Factor Intervention Trial. Five patterns of smoking behavior were defined: 1) sustained nonsmoking, 2) early (years 1-2 of the trial) sustained quitting, 3) late (years 3-6 of the trial) sustained quitting, 4) recidivism, and 5) continued smoking. SI men who quit smoking showed greater favorable changes in dietary lipid composition and micronutrient intake than did continued smokers, and these changes were in many instances as great as favorable changes made by nonsmokers. On the other hand, SI men who quit smoking gained an average of 3.8 lb (1.7 kg), in contrast with nonsmokers who lost an average of 6.4 lb (2.9 kg). The gain by SI quitters was, however, less than that by UC quitters, who gained 6.5 lb (3.0 kg). Moreover, despite weight gain, net change in high-density-lipoprotein (HDL) cholesterol for SI quitters was positive. With the associated decrease in low-density-lipoprotein (LDL) cholesterol, early SI quitters had the most improvement in ratio of LDL to HDL among all subgroups. Thus, unfavorable nutritional patterns of smokers put them at double jeopardy regarding cardiovascular and other chronic diseases; additionally, long-term risks can be improved not only by smoking cessation but also by achievement of healthier eating patterns.

Colorectal epithelial cell proliferative kinetics and risk factors for colon cancer in sporadic adenoma patients.

Colorectal epithelial cell proliferative kinetics are altered in patients at increased risk for colon cancer: proliferation rates [labeling index (LI)] are higher and there is a shift of the proliferative zone from one confined to the lower 60% of the colonic crypt to one that includes the entire crypt (higher phi(h)). To assess factors associated with LI and phi(h), we performed a cross-sectional analysis using baseline rectal mucosal biopsies from sporadic adenoma patients participating in a chemoprevention trial. Biopsies (taken without preparatory cleansing) were taken 10 cm above the level of the anus, and proliferation was assessed by detection of endogenous S-phase-associated proliferating cell nuclear antigen by immunohistochemical methods. High-quality, scorable biopsies were obtained for 115 patients, and using analysis of covariance and multiple linear regression, the LI and phi(h) were evaluated in relation to diet and other lifestyle factors, demographics, anthropometrics, family history of colon cancer, and polyp history. Statistically significant findings included the following: (a) The LI for those in the upper versus the lowest tertile of vegetable and fruit consumption was, proportionately, 35% lower (3.4% versus 5.3%; P < 0.001); for vitamin supplement users versus nonusers, it was 36% lower (3.3 versus 5.2%; P < 0.001); for recurrent versus incident polyp patients, it was 36% higher (6.2 versus 4.0%; P < 0.001); and for those with rectal polyps only versus those with colon polyps only, it was 28% higher (6.0 versus 4.3%; P = 0.05); and (b) the phi(h) for those in the upper versus the lowest tertile of sucrose consumption was, proportionately, 48% higher (7.1% versus 3.7%; P = 0.01). These results indicate that (a) colorectal epithelial cell proliferation rates are higher in recurrent adenoma patients than in incident adenoma patients and in patients with rectal adenomas only versus those with colon adenomas only, but they are lower in patients with higher intakes of vegetables and fruit and in those who take vitamin/mineral supplements, and (b) the distribution of proliferating cells is shifted toward more inclusion of the upper 40% of the crypt in patients with higher intakes of sucrose. The pattern of positive, negative, and null associations of potential risk factors with cell proliferation is similar to that commonly found with colonic neoplasms.

Plasma carotenoids as biomarkers of vegetable and fruit intake.

Higher intakes of vegetables and fruits are associated with a lower risk of certain human cancers. A biomarker of vegetable and fruit intake would be a valuable research tool. A cross-sectional study assessed the association between plasma carotenoid concentrations and intakes of vegetables and fruits. Plasma carotenoids (alpha-carotene, beta-carotene, lutein, beta-cryptoxanthin, and lycopene) were measured in 50 male and 49 female participants, aged 18-37 years, with a wide range of habitual vegetable and fruit intakes. Dietary intakes were assessed via a food frequency questionnaire. Intake of vegetables and fruits and high carotenoid foods were measured. The sum of the plasma carotenoids (excluding lycopene) was highly correlated with intake of total vegetables and fruits (r = 0.59). Of the individual plasma carotenoids, plasma alpha-carotene had the highest correlation with intakes of both total vegetables (r = 0.50) and total fruits (r = 0.58). Intakes of foods with high carotenoid contents were correlated with their corresponding plasma concentrations as follows: high beta-carotene foods (r = 0.41); high lutein foods (r = 0.46); and high lycopene foods (r = 0.11). Multiple regression analyses showed that intake of total vegetables and fruits was the most significant determinant of each plasma carotenoid except lycopene. The utility of combining the plasma carotenoids as biomarkers of vegetable and fruit intake was assessed by a stepwise regression of total vegetable and fruit intake on plasma carotenoids. Significant determinants of intake of total vegetables and fruits were alpha-carotene, beta-cryptoxanthin, lutein, and energy intake (R2 = 0.53).(ABSTRACT TRUNCATED AT 250 WORDS)

Urinary isoflavonoid and lignan excretion on a Western diet: relation to soy, vegetable, and fruit intake.

Dietary isoflavone and lignan phytoestrogens are potential chemopreventive agents. This has led to a need to monitor exposure to these compounds in human populations and to determine which components of a mixed diet contribute to the exposure. Typically, urinary isoflavonoid excretion is associated with soy consumption and that of lignans is associated with whole grains. However, other plant foods are known to contain phytoestrogen precursors. The purpose of this study was to examine the association between urinary isoflavonoid and lignan excretion and intakes of vegetables and fruits (V&F). Isoflavonoids (genistein, daidzein, O-desmethylangolensin, and equol) and lignans (enterolactone, enterodiol, and matairesinol) were measured in urine collected for 3 days from 49 male and 49 female volunteers (age, 18-37 years) reporting a wide range of habitual V&F intakes. Dietary intakes were assessed using 5-day diet records and a food frequency questionnaire. V&F groupings (total V&F, total V, total F, soyfoods, and V&F grouped by botanical families) were used to assess the relationship between V&F intake and urinary isoflavonoid and lignan excretion. Pearson correlations were performed. Intake of soyfoods was correlated significantly with urinary genistein (r = 0.40; P = 0.0001), O-desmethylangolensin (r = 0.37; P = 0.0002), daidzein (r = 034; P = 0.0007), and the sum of isoflavonoids (r = 0.39; P = 0.0001). There was no association between equol excretion and soy intake or between the isoflavonoids and any other V&F groupings. In addition, isoflavonoid excretion was correlated positively with intake of high-fat and processed meats, particularly among men who did not consume soy. This suggests that, even in the United States, on a Western diet, soyfoods are the primary contributors to isoflavone intake; however, additional "hidden sources" of soy may also contribute to exposure. In contrast, a variety of fiber-containing foods contributed to lignan excretion; the sum of the urinary lignans, enterodiol, enterolactone, and matairesinol, was associated with intake of total F (r = 0.27; P = 0.008), total V&F (r = 0.25; P = 0.01), soyfoods (r = 0.28; P = 0.006), and dietary fiber (r = 0.36; P = 0.0003). Overall, urinary phytoestrogens (isoflavonoids + lignans) were significantly higher in "high" compared with "low" V&F consumers. Compared with the "low" V&F group, the "high" group consumed diets that were, on average, higher in fiber and carbohydrate and soyfoods and lower in fat; thus, the urinary phytoestrogens may also be a useful marker of healthier dietary patterns.

Plasma carotenoids as biomarkers of vegetable intake: the University of Minnesota Cancer Prevention Research Unit Feeding Studies.

High vegetable intake has been associated with a decreased risk for various human cancers in epidemiological studies. Carotenoids are plant compounds that may both possess chemopreventive activity and be useful biomarkers of vegetable and fruit intake. Nineteen men and women were randomized into a controlled cross-over feeding study to measure the effect of vegetable intake on plasma carotenoid concentrations. Participants consumed each of 4 experimental diets for 9 days. The control diet consisted of commonly consumed foods and was essentially carotenoid free. High vegetable diets (carotenoid, cruciferous, and soy) consisted of the control diet plus carrots and spinach (carotenoid), broccoli and cauliflower (cruciferous), and tofu and FriChik (soy). Plasma carotenoid concentrations were highest on the carotenoid and cruciferous diets. When compared to the control, mean plasma alpha-carotene, beta-carotene, and lutein concentrations were 5.2, 3.3 and 2.2 times higher on the carotenoid diet, respectively (P < 0.001). Mean plasma lutein concentrations were 2.1 times higher on the cruciferous versus the control diet (P < 0.001). There were no differences between diets in plasma beta-cryptoxanthin and lycopene concentrations. These data indicate that plasma alpha-carotene, beta-carotene, and lutein may be useful biomarkers of carotenoid-rich food intake and that lutein may act as an intake biomarker of commonly consumed vegetables in the Cruciferae family. These findings should prove useful in undertaking dietary intervention trials because they suggest the feasibility of monitoring intake of some plant foods and of distinguishing among plant food groups.