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.

Effect of carvedilol, lisinopril and their combination on vascular and cardiac health in patients with borderline blood pressure: the DETECT Study.

Antihypertensive therapy is aimed at improving vascular and cardiac health, as well as lowering blood pressure (BP). The benefit of such drugs in untreated patients with borderline BP has not been demonstrated. Subjects with BPs ≥130 mm Hg systolic or ≥85 mm Hg diastolic and at least one additional risk factor were randomly assigned to treatment with carvedilol, lisinopril, their combination or placebo. Cardiovascular health was assessed by a disease score (DS), which combines the following tests of cardiovascular function and structure: resting BP, large- and small-artery elasticity (SAE), BP response to exercise, retinal vasculature analysis, electrocardiogram, carotid intima-medial thickness, left ventricular mass, microalbuminuria and N-terminal pro B-type natriuretic peptide. DS was assessed at baseline, after 3 and 9 months of therapy and 1 month after discontinuation of therapy. All active treatment groups displayed a sustained reduction in BP during 9 months of treatment, with the greatest reduction in the cardvedilol+lisinopril group. DS and SAE improved in all the treatment groups but the changes were of borderline significance and exhibited no evidence for progressive improvement from 3 months (functional) to 9 months (structural). All changes were reversed within 1 month after discontinuation of therapy. We conclude that 9 months of treatment with carvedilol, lisinopril or their combination produce a sustained and well-tolerated functional improvement but not a structural improvement, perhaps because of a lack of the nitric oxide-enhancing effects of other agents that inhibit structural changes in the vasculature.

Skin and soft tissue infections among HIV-infected persons in the late combination antiretroviral therapy era.

Skin and soft tissue infections (SSTIs) occur at higher rates among HIV-infected persons, but current trends and risk factors are largely undefined. We evaluated SSTIs among a prospective cohort of HIV-infected persons during the late combination antiretroviral therapy (cART) era (2006-2010). Of the 1918 HIV-infected persons evaluated, 379 (20%) developed an SSTI during a median of 3.7 years of follow-up; of these, 118 (31%) developed at least one recurrent SSTI. The incidence rate of SSTIs was 101 (95% confidence interval [CI] 93-109) cases per 1000 person-years, and rates did not significantly change during the study period. Compared with not receiving cART and having an HIV RNA level >1000 copies/mL, patients receiving cART with an HIV RNA level <1000 copies/mL had a reduced risk of an SSTI (hazard ratio 0.64, 95% CI 0.48-0.86, P < 0.01). In summary, initial and recurrent SSTIs are common among HIV-infected persons, and HIV control is associated with a lower risk of SSTIs.

Independent risk for cardiovascular disease predicted by modified continuous score electrocardiographic criteria for 6-year incidence and regression of left ventricular hypertrophy among clinically disease free men: 16-year follow-up for the multiple risk factor intervention trial.

Risk prediction for electrocardiographic (ECG) left ventricular hypertrophy related criteria, used in clinical trials, and epidemiologic studies of clinically healthy people, has depended in the past on dichotomous classification of ECG LVH criteria. Recent analyses have shown that more sensitive methods of LVH ECG classification without loss of specificity are needed to improve on dichotomous classification. This was done by relating six year incident significant change in continuous score criteria of ECG LVH to the 16 year (10 year post trial) coronary heart disease (CHD) and cardiovascular disease (CVD) mortality among 12,866 men, free of clinical disease, aged 35 to 57 years at baseline in the Multiple Risk Factor Intervention Trial. It was found that significant change in continuous ECG LVH criteria was a stronger independent predictor of future CHD and CVD mortality than was use of dichotomous classification of the same criteria. It was also demonstrated that increase in continuous ECG LVH indexes, below previous dichotomous thresholds independently (of standard CVD risk factors, including increase in obesity-indicated by an increase in adult BMI) predicted excess CHD and CVD mortality and that combinations of continuous indices increases the specificity and relative risk in clinically disease-free middle-aged men.

Obtaining event status at the close of the Treatment of Mild Hypertension Study: methods and implication for other trials.

The Treatment of Mild Hypertension Trial was a randomized, double-blind clinical trial conducted from 1986 to 1992 comparing the efficacy of six antihypertensive treatment regimens in 902 participants with stage I hypertension. To satisfy a secondary objective of the study, follow-up information on mortality and cardiovascular morbidity was collected. For this objective the aim was to ascertain the vital and cardiovascular event status as of the last day of the trial. This was accomplished by inviting each participant to attend a closeout visit shortly after the closeout date. In addition to serving as verification of vital status, this visit allowed data collection on nonfatal events that occurred between the last clinic visit and the closeout date. During this visit the patient was unblinded to study medication and given a medical summary of their participation during the trial, as well as a bottle of open-label medication. The advantages of a closeout visit are discussed along with a call for studies to provide clearer definitions of lost to follow-up and censoring times used in life-table analyses, especially when the primary event includes both fatal and nonfatal events. Control Clin Trials 2001;22:56-61

Effect of calcium supplementation on serum cholesterol and blood pressure. A randomized, double-blind, placebo-controlled, clinical trial.

OBJECTIVE: To test the effect of daily supplemental calcium on serum total and high-density lipoprotein cholesterol (HDL-C) levels and blood pressure in adults. DESIGN: Randomized, double-blind, placebo-controlled clinical trial; adjunct study to a trial of calcium and colon cell proliferation in patients with sporadic adenoma. SETTING: Outpatient clinic. PATIENTS: A total of 193 men and women, aged 30 to 74 years. INTERVENTION: Treatment with 1.0 and 2.0 g/d of elemental calcium vs placebo over a 4-month period for cholesterol determinations and 6 months for blood pressure. MAIN OUTCOME MEASURES: Serum total cholesterol and HDL-C levels, systolic and diastolic blood pressure. RESULTS: Because there were no apparent differences in responses between the 1.0-g and 2.0-g calcium groups, their data were combined and compared with those of the placebo group. Among all participants, the mean total cholesterol level dropped 0.07 mmol/L (2.9 mg/dL) (1.3%) (P = .43) more, and the mean HDL-C level dropped 0.01 mmol/L (0.4 mg/dL) (1.1%) (P = .71) less in the calcium group than in the placebo group. Among participants without a history of hypercholesterolemia, the mean total cholesterol level dropped 0.18 mmol/L (6.8 mg/dL) (3.3%) (P = .10) and the HDL-C level dropped 0.02 mmol/L (0.6 mg/dL) (1.5%) (P = .61) more in the calcium group than in the placebo group. Among all participants, there was no apparent change in blood pressure until 6 months, when the mean systolic blood pressure dropped 0.8 mm Hg (0.6%) (P = .85) and the mean diastolic blood pressure dropped 0.4 mm Hg (0.5%) (P = .80) more in the calcium group than in the placebo group. CONCLUSIONS: There were no substantial or statistically significant effects of calcium supplementation on total cholesterol or HDL-C levels or on blood pressure. There was a suggestion (not statistically significant) of a 0.07 to 0.18 mmol/L (3-7 mg/dL) or 2% to 4% drop in the total cholesterol level, a finding similar to that reported in other studies, which indicates the need for further study.

Urinary sodium and potassium profile of blacks and whites in relation to education in two different geographic urban areas. TOMHS Research Group. Treatment of Mild Hypertension Study.

The high Na/low K environment of modern society is related to the genesis of hypertension and stroke. There is prior evidence of racial, geographical, and social class differences in Na and K intake and blood pressure. Baseline data from the Treatment of Mild Hypertension Study (TOMHS) was used to assess urinary Na and K excretion profiles by race, clinic geographic area, and education. Participants were adult black and white hypertensive patients from the Birmingham, Alabama, and Chicago, Illinois, area. Level of education was categorized as: less than college graduate and college graduate or more. Two overnight urine samples were collected and analyzed for Na and K at entry from 154 blacks and 281 whites. The urinary Na:K ratio was significantly higher in both blacks (5.1 v 3.8, P < .001) and whites (4.1 v 3.4, P < .005) in Birmingham compared with Chicago. This was primarily due to the lower excretion of urinary K in blacks (12.8 v 16.9 mmol/8 h, P < .01) and whites (14.0 v 16.5 mmol/8 h, P < .01). The highest urinary Na:K ratio was observed in blacks in Birmingham with lower education level; urinary Na excretion was high in blacks with a lower education level in both cities. No such differences were seen in whites. Although TOMHS was not population-based, these findings suggest the possibility that potassium intake among persons with stage 1 hypertension is related to geographic area in both blacks and whites, and sodium intake is inversely related to education level in blacks.

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.

Rationale and design for the Controlled ONset Verapamil INvestigation of Cardiovascular Endpoints (CONVINCE) Trial.

The Controlled ONset Verapamil INvestigation of Cardiovascular Endpoints (CONVINCE) Trial is a randomized, prospective, double-blind, parallel-group, two-arm, actively controlled, multicenter, international 5-year clinical trial involving 15,000 patients. CONVINCE will compare the incidence of fatal or nonfatal myocardial infarction (MI), fatal or nonfatal stroke, or cardiovascular-disease-related death in two antihypertensive treatment regimens. One treatment arm begins with controlled onset-extended release (COER)-verapamil, which has its major antihypertensive effect 6-12 hours after administration. The other arm (standard of care (SOC)) begins with either hydrochlorothiazide (HCTZ) or atenolol, one of which is preselected by the investigator for an individual patient prior to randomization. Secondary objectives include comparisons of the regimens for each of the components of the primary endpoint (separately), death or hospitalization related to cardiovascular disease, efficacy in lowering blood pressure to goal, primary events occurring between 6 am and noon, all-cause mortality, withdrawals from blinded therapy, cancer, and hospitalizations due to bleeding. Patients may be enrolled if they are hypertensive and at least 55 years of age and have an established second risk factor for cardiovascular disease. Initial medications include COER-verapamil (180 mg/d), HCTZ (12.5 mg/d), or atenolol (50 mg/d). Initial doses are doubled if blood pressure (BP) does not reach goal (systolic BP < 140 mm and diastolic BP < 90 mm Hg). If BP is not controlled by the higher dose of the initial medication, HCTZ is added to COER-verapamil, or the SOC choice not initially selected is added in the SOC arm. An ACE-inhibitor is recommended (although nearly any open-label medication is allowed) as the third step for patients whose BP is not adequately controlled or who have a contraindication to one of the two SOC medications. Patients take two sets of tablets daily, one in the morning and one in the evening. Although most patients switch from an established antihypertensive medication to randomized treatment, untreated patients with stages I-III hypertension (SBP between 140 and 190 or DBP between 90 and 110 mm Hg) are eligible. Outcomes are monitored by an independent Data and Safety Monitoring Board. Enrollment began during the third quarter of 1996, and follow-up is to be completed in the third quarter of 2002.

Heart rate adjustment of exercise-induced ST-segment depression identifies men who benefit from a risk factor reduction program.

BACKGROUND: Whether subjects identified as being at increased risk of coronary heart disease (CHD) death by heart rate adjustment of exercise-induced ST-segment depression will benefit from therapy aimed at reducing risk factors has not been examined. METHODS AND RESULTS: Exercise ECGs were performed in 11,880 men from the Usual Care (UC) and Special Intervention (SI) groups of the Multiple Risk Factor Intervention Trial. UC men were referred to customary sources of care in the community; SI men received counseling on smoking cessation and dietary reduction of cholesterol, and stepped-care therapy for hypertension. An abnormal ST-segment response to exercise was defined according to standard criteria as > or = 100 microV of additional horizontal or downsloping ST-segment depression and by an ST-segment/heart rate (ST/HR) index >1.60 microV/bpm. After 7 years of follow-up, CHD mortality was significantly lower in SI than UC men with an abnormal ST/HR index (2.4%, 19/786 versus 5.3%, 39/729, P=.005) but was comparable in SI and UC men with a normal ST/HR index (1.6%, 84/5154 versus 1.3%, 70/5211, P=NS). Risk reduction in SI men with an abnormal ST/HR index was independent of age and other cardiac risk factors. In contrast, there was no significant difference in CHD death rate between the smaller groups of SI and UC men with an abnormal test by standard criteria (3.6%, 7/192 versus 2.7%, 5/186, P=NS). CONCLUSIONS: An abnormal ST/HR index identifies men in whom therapy aimed at reducing CHD risk factors reduces the risk of CHD death by 61%. These findings support the application of heart rate adjustment of ST depression for screening of asymptomatic subjects at increased risk of CHD to identify those who will benefit most from risk factor-reduction programs.

Higher education and income are related to a better Na:K ratio in blacks: baseline results of the Treatment of Mild Hypertension Study (TOMHS) data.

In the United States, blacks have higher rates of hypertension than whites. A possible contributing factor to this higher rate of hypertension could be dietary differences between blacks and whites relating to sodium and potassium intake, which in turn could be related to socioeconomic differences between blacks and whites. Baseline data from the Treatment of Mild Hypertension Study (TOMHS) was used to assess differences in the urinary excretion of sodium and potassium, and the Na:K ratio between black and white participants, and also to explore the relationship of socioeconomic status (SES) and urinary electrolyte excretion within each ethnic group. Participants were men and women ages 45 to 69 with stage I diastolic hypertension (DBP < or = 99 mm Hg). Level of education and annual household income were used as indicators of SES. Two overnight urine samples were collected and analyzed for Na and K at entry on 172 black and 710 white participants. Blacks had a significantly higher mean Na:K ratio than whites, 4.3 v 3.6 (P < .001). This was primarily due to higher urinary Na excretion in blacks than whites, 57.8 v 52.7 mmol/8 h (P = .05). Analysis by education and income level showed that higher levels of urinary Na and Na:K in blacks than whites was restricted to those with lower education and income levels. For higher education and income levels, blacks had slightly lower levels of urinary Na and Na:K than whites. Correspondingly, education and income levels were related to urinary Na and Na:K in blacks but not in whites. This suggests that lower SES blacks could benefit from interventions to reduce dietary Na and increase dietary K, which would decrease their urinary Na:K ratio and may make them less prone to developing hypertension.

Prognostic associations of Minnesota Code serial electrocardiographic change classification with coronary heart disease mortality in the Multiple Risk Factor Intervention Trial.

A central requirement for epidemiologic studies and clinical trials is a bias-free, objective determination of cardiac incidence rates between comparison groups. Epidemiologic studies and clinical trials frequently use changes in the Minnesota Code to document incident ischemic events. An electrocardiographic (ECG) classification system was developed to document significant ECG pattern change using objective comparison rules for side-by-side annual ECG comparison. Previously, we showed that major evolving Q waves were strongly and independently associated with total and coronary disease mortality. Using baseline-to-annual ECG comparisons in the Multiple Risk Factor Intervention Trial, we evaluated major evolving Q waves, minor evolving Q waves combined with major evolving ST-T waves and major evolving ST-T waves alone for their prognostic associations with coronary, cardiovascular, and total mortality during 16 years of follow-up. The 16-year coronary mortality rate in men with evolving minor Q waves plus evolving ST-T waves had an average adjusted relative risk of 4, equivalent to that of a major evolving Q wave. These risk ratios held whether a clinical infarction had occurred. Silent evolving ST-T waves without Q-wave change had an average adjusted relative coronary mortality risk of 1.6. Serial comparison methodology documents additional incident ischemic ECG events beyond the traditional major Minnesota Q-code change used in older epidemiologic studies. The procedure is standardized, quantitative, and repeatable. It is applicable for any study, present or past, that used Minnesota coding. The method is also well suited for incorporation in computer analysis programs.

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.

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.

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.

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.