Arlene W. Caggiula

The Effects of Dietary Protein Restriction and Blood-Pressure Control on the Progression of Chronic Renal Disease

Background Restricting protein intake and controlling hypertension delay the progression of renal disease in animals. We tested these interventions in 840 patients with various chronic renal diseases. Methods In study 1, 585 patients with glomerular filtration rates of 25 to 55 ml per minute per 1.73 m2 of body-surface area were randomly assigned to a usual-protein diet or a low-protein diet (1.3 or 0.58 g of protein per kilogram of body weight per day) and to a usual- or a low-blood-pressure group (mean arterial pressure, 107 or 92 mm Hg). In study 2, 255 patients with glomerular filtration rates of 13 to 24 ml per minute per 1.73 m2 were randomly assigned to the low-protein diet (0.58 g per kilogram per day) or a very-low-protein diet (0.28 g per kilogram per day) with a keto acid-amino acid supplement, and a usual- or a low-blood-pressure group (same values as those in study 1). An 18-to-45-month follow-up was planned, with monthly evaluations of the patients. Results The mean follow-up was 2.2 years. ...

Menopause and risk factors for coronary heart disease

Abstract Postmenopausal women are believed to have a higher risk of coronary artery disease than premenopausal women. In this study, we prospectively determined changes in coronary risk factors that were attributable to natural menopause in 541 healthy, initially premenopausal women 42 to 50 years of age. After approximately 2 1/2 years, 69 women had spontaneously stopped menstruating for at least 12 months, and 32 women had stopped natural menstruation and received hormone-replacement therapy for a period of at least 12 months. An equal number of age-matched premenopausal women in the study group served as controls. In women who had a natural menopause and did not receive hormone-replacement therapy, serum levels of high-density lipoprotein (HDL) cholesterol declined as compared with those of premenopausal controls (-0.09 vs. 0.00 mmol per liter; P = 0.01), and levels of lowdensity lipoprotein (LDL) cholesterol increased (+0.31 vs. +0.14 mmol per liter; P = 0.04). In menopausal women who received hormone...

Effects of dietary protein restriction on the progression of advanced renal disease in the Modification of Diet in Renal Disease Study.

Patients with advanced renal disease randomized to the very low-protein diet group in the Modification of Diet in Renal Disease (MDRD) Study had a marginally (P = 0.066) slower mean glomerular filtration rate (GFR) decline compared with patients randomized to the low-protein diet group. The objective of these secondary analyses was to determine the relationship between achieved, in addition to prescribed, dietary protein intake and the progression of advanced renal disease. A randomized controlled trial was conducted in patients with chronic renal diseases of diverse etiology. The average follow-up was 2.2 years. Fifteen university hospital outpatient nephrology practices participated in the study, which comprised 255 patients aged 18 to 70 years with a baseline GFR 13 to 24 mL/min/1.73 m2 who participated in MDRD Study B. Patients with diabetes requiring insulin were excluded. The patients were given a low-protein (0.58 g/kg/d) or very low-protein (0.28 g/kg/d) diet supplemented with keto acids-amino acids (0.28 g/kg/d). Outcomes were measured by comparisons of protein intake from food or from food and supplement between randomized groups, and correlations of protein intake with rate of decline in GFR and time to renal failure or death. Comparison of the randomized groups showed that total protein intake from food and supplement was lower (P < 0.001) among patients randomized to the very low-protein diet (0.66 g/kg/d) compared with protein intake from food only in patients randomized to the low-protein diet (0.73 g/kg/d). In correlational analyses, we combined patients assigned to both diets and controlled for baseline factors associated with a faster progression of renal disease. A 0.2 g/kg/d lower achieved total protein intake (including food and supplement) was associated with a 1.15 mL/min/yr slower mean decline in GFR (P = 0.011), equivalent to 29% of the mean GFR decline. After adjusting for achieved total protein intake, no independent effect of prescription of the keto acid-amino acid supplement to slow the GFR decline could be detected. If the GFR decline is extrapolated until renal failure, a patient with a 29% reduction in the rate of GFR decline would experience a 41% prolongation in the time to renal failure. Additional analyses confirmed a longer time to renal failure in patients with lower total protein intake. In conclusion, these secondary analyses of the MDRD Study suggest that a lower protein intake, but not the keto acid-amino acid supplement, retards the progression of advanced renal disease. In patients with GFR less than 25 mL/min/1.73 m2, we suggest a prescribed dietary protein intake of 0.6 g/kg/d.

The multiple risk factor intervention trial (MRFIT). IV. Intervention on blood lipids

Abstract The results are presented for the first 4 years of the Multiple Risk Factor Intervention Trial (MRFIT) nutrition intervention program. Study participants were at high risk (upper 10–15%) for Coronary Heart Disease (CHD). The Special Intervention (SI) group reached and sustained the goals of an eating pattern originally designed to limit cholesterol intake to less than 300 mg/day, with less than 10% of calories as saturated fat and not more than 10% as polyunsaturated fat. By the end of the first year, mean serum total cholesterol had fallen by 6.3% from the mean initial value of 254 mg/dl. The magnitude of the decrease became slightly greater in the ensuing years, reaching 7.4% by the fourth annual visit. Substantially larger decreases in mean serum cholesterol level were observed in the subgroups with the highest baseline level, greatest weight loss, in those who did not smoke, and in those who had normal blood pressure on entry. The changes in cholesterol level were accompanied by parallel changes in mean plasma LDL cholesterol, which also fell by 6.6% over the 4 years, but mean HDL cholesterol was not substantially altered. Comparison with earlier population data suggests that the overall responses to the MRFIT eating pattern were limited by the apparent fact that participants had already made self-initiated changes toward the fatcontrolled dietary pattern before they entered the study.

Relationship to Blood Pressure of Combinations of Dietary Macronutrients Findings of the Multiple Risk Factor Intervention Trial (MRFIT)

BACKGROUND Elevated blood pressure remains a widespread major impediment to health. Obesity and specific dietary factors such as high salt and alcohol intake and low potassium intake adversely affect blood pressure. It is a reasonable hypothesis that additional dietary constituents, particularly macronutrients, may also influence blood pressure. METHODS AND RESULTS Participants were 11,342 middle-aged men from the Multiple Risk Factor Intervention Trial (MRFIT). Data from repeat 24-hour dietary recalls (four to five per person) and blood pressure measurements at six annual visits were used to assess relationships, singly and in combination, of dietary macronutrients to blood pressure, adjusted for multiple possible confounders (demographic, dietary, and biomedical). Multiple linear regression was used to assess diet-blood pressure relations in two MRFIT treatment groups (special intervention and usual care), with adjustment for confounders, pooling of coefficients from the two groups (weighted by inverse of variance), and correction of coefficients for regression-dilution bias. In multivariate regression models, dietary cholesterol (milligrams per 1000 kilocalories), saturated fatty acids (percent of kilocalories), and starch (percent of kilocalories) were positively related to blood pressure; protein and the ratio of dietary polyunsaturated to saturated fatty acids were inversely related to blood pressure. These macronutrient-blood pressure findings were obtained in analyses that controlled for body mass, dietary sodium and ratio of sodium to potassium, and alcohol intake, each positively related to blood pressure, and intake of potassium and caffeine, both inversely related to blood pressure. CONCLUSIONS These data support the concept that multiple dietary factors influence blood pressure; hence, broad improvements in nutrition can be important in preventing and controlling high-normal and high blood pressure.

Effects of antihypertensive therapy on plasma lipids and lipoproteins in the multiple risk factor intervention trial

The Multiple Risk Factor Intervention Trial was a randomized clinical trial that studied the efficacy of multiple risk factor reduction in lowering coronary heart disease mortality in high-risk men. Nutrition counseling based on a fat-modified eating pattern resulted in a significant reduction of total cholesterol and low-density lipoprotein cholesterol. However, based on further analysis not involving comparisons of randomized groups, the reduction in total cholesterol appeared to be blunted by the effects of the antihypertensive medication utilized in the stepped-care therapy in this study. The use of diuretics was associated with an increase in triglycerides and a lesser decrease in total plasma cholesterol when compared with non-diuretic users. The use of diuretic therapy was also associated with a slight decrease in high-density lipoprotein cholesterol, when compared with changes in those not receiving diuretic therapy. The combination of diuretics plus propranolol was related to a substantial decrease in high-density lipoprotein cholesterol in both the Special Intervention and Usual Care participants. The changes in lipoproteins for men receiving diuretic therapy are probably influenced substantially by nutritional factors, especially weight change. Concomitant nutritional changes must be considered when analyzing the short- and long-term effects of therapy with diuretics or other antihypertensive drugs on lipoprotein metabolism.

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.

Effects of dietary fat and fatty acids on coronary artery disease risk and total and lipoprotein cholesterol concentrations: epidemiologic studies.

Because of their large sample sizes, epidemiologic studies can provide important data on the relation between diet, specifically dietary fat and fatty acids, and lipid and lipoprotein concentrations as well as the incidence of coronary artery disease. Although correlation coefficients vary widely (from 0.84 to 0.01) and are frequently low between dietary variables and coronary artery disease or lipids and lipoprotein fractions in the studies reviewed here, intakes of saturated fatty acids and dietary cholesterol are generally positively correlated with blood cholesterol in men and women. Associations between other fatty acids are less consistent and may be related to the considerable differences in these studies in dietary methodologies used, databases used for analyses, and homogeneity of intakes within populations. Relatively few data are available for women, cultural minorities within the United States, or young or elderly populations. However, the trends observed in the United States, ie, lower rates of coronary artery disease as well as lower reported intakes of both total and saturated fats, support the relations observed in the epidemiologic studies.

Plasma testosterone, high density lipoprotein cholesterol and other lipoprotein fractions

High density lipoprotein (HDL) cholesterol levels are strongly related to risk of heart attack. Identification of determinants of high density lipoprotein cholesterol may provide important information concerning the cause of heart disease. The relation between one possible determinant, testosterone, and high density lipoprotein cholesterol and other lipoprotein fractions was evaluated in 247 middle-aged men. The results indicate that testosterone levels (both free and total) were positively correlated with high density lipoprotein cholesterol (r = +0.24, p less than 0.01) and negatively correlated with triglycerides and very low density lipoprotein cholesterol. The association between testosterone and high density lipoprotein cholesterol could not be explained by intake of alcohol, obesity, age, smoking or physical activity. Furthermore, the relation of testosterone to HDL cholesterol was independent of the relation of testosterone to very low density lipoprotein (VLDL) cholesterol or triglycerides.

Low-fat diet practices of older women: prevalence and implications for dietary assessment.

OBJECTIVE To evaluate the importance of information on low-fat diet practices and consumption of reduced-fat foods for accurate assessment of energy and fat intakes using a semiquantitative food frequency questionnaire (FFQ). SUBJECTS Subjects were 7,419 women, aged 50 to 79 years, who filled out an FFQ as part of eligibility screening for a diet modification component and/or a hormone replacement trial in a multicenter study of chronic disease prevention in postmenopausal women (Womens Health Initiative). STATISTICAL ANALYSIS For 26 FFQ questions, we recoded the low-fat diet choices of participants to a high-fat counterpart and recalculated energy and fat intakes. We then determined the decrease in energy and nutrient estimates attributable to adding low-fat options to the FFQ. RESULTS Low-fat diet practices were widespread in this population. For example, 69% of respondents rarely or never ate skin on chicken, 76% rarely or never ate fat on meat, 36% usually drank nonfat milk, 52% usually ate low-fat or fat-free mayonnaise, 59% ate low-fat chips/snacks, and 42% ate nonfat cheese. These low-fat choices had substantial effects on energy and nutrient estimates. Absolute decreases (and mean percentage decreases) for energy and nutrient measures attributable to adding low-fat diet options to the FFQ were 196 kcal (11.4%) energy, 9 percentage points in percentage energy from fat (22.3%), 23.2 g fat (29.0%), and 9.6 g saturated fat (32.5%). Black and Hispanic women and women of lower socioeconomic status reported significantly fewer low-fat diet practices than white women and women of higher socioeconomic status. CONCLUSION Failure to collect information on low-fat diet practices with an FFQ will result in an upward bias in estimates of energy and fat intake, and the amount of error will vary by the personal characteristics of respondents.