Adobe Flash Player is required to view this feature. If you are using an operating system that does not support Flash, we are working to bring you alternative formats. Original Article Effects of Diet and Exercise in Men and Postmenopausal Women with Low Levels of HDL Cholesterol and High Levels of LDL Cholesterol Marcia L. Stefanick, Ph.D., Sally Mackey, M.S., R.D., Mary Sheehan, M.S., Nancy Ellsworth, William L. Haskell, Ph.D., and Peter D. Wood, D.Sc., Ph.D. N Engl J Med 1998; 339:12-20 DOI: 10.1056/NEJM90103.

Methods We studied plasma lipoprotein levels in 180 postmenopausal women, 45 through 64 years of age, and 197 men, 30 through 64 years of age, who had low high-density lipoprotein (HDL) cholesterol levels (≤59 mg per deciliter in women and ≤44 mg per deciliter in men) and moderately elevated levels of low-density lipoprotein (LDL) cholesterol (>125 mg per deciliter but 125 mg per deciliter but. Results Dietary intake of fat and cholesterol decreased during the one-year study (P. Elevated serum levels of low-density lipoprotein (LDL) cholesterol and reduced levels of high-density lipoprotein (HDL) cholesterol are important independent risk factors for coronary heart disease. Reducing LDL cholesterol levels by means of drug therapy has been shown to reduce the incidence of coronary heart disease among men with hypercholesterolemia and dyslipidemia and also to reduce the rate of death due to coronary heart disease in patients with the disease.

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It is believed that reductions in the serum LDL cholesterol level produced by dietary therapy will have similar benefits; however, the diet recommended for reducing LDL cholesterol levels may reduce HDL cholesterol levels to a similar degree. Earlier, we demonstrated that weight loss increased HDL cholesterol levels in moderately overweight men and that physical activity prevented the lowering of HDL cholesterol levels that usually results from a low-fat diet in overweight men and women.

Subsequently, the guidelines of the National Cholesterol Education Program (NCEP) Adult Treatment Panel, emphasizing the incorporation of weight loss and physical activity into dietary therapy for cholesterol management, were published. In the present one-year, randomized, controlled study of men and postmenopausal women with low HDL cholesterol levels and elevated LDL cholesterol levels (the Diet and Exercise for Elevated Risk trial), we examined the effects of changes in diet and exercise, alone and together, on plasma lipoproteins. We hypothesized that HDL cholesterol levels would be raised by exercise but lowered by the NCEP Step 2 diet, that LDL cholesterol levels would be reduced by the diet, and that the ratio of LDL to HDL cholesterol would be most improved by combining the diet with regular exercise.

Design of the Study We used several strategies to recruit postmenopausal women 45 through 64 years of age and men 30 through 64 years of age, who had both plasma HDL cholesterol levels below 60 mg per deciliter (1.55 mmol per liter) for women and 45 mg per deciliter (1.14 mmol per liter) for men, the approximate mean for the U.S. Population, and plasma LDL cholesterol levels greater than 125 mg per deciliter (3.23 mmol per liter) but below 210 mg per deciliter (5.43 mmol per liter) for women and greater than 125 mg per deciliter but below 190 mg per deciliter (4.91 mmol per liter) for men.

Potential subjects were excluded if they reported a history of heart disease, stroke, diabetes, recent cancer, other life-threatening illness, or any condition that limited their ability to engage in moderate-intensity exercise; if they were currently using insulin or medications for heart problems, blood pressure, or high serum cholesterol levels; or if they smoked more than nine cigarettes per day or consumed more than four alcoholic drinks daily. The women who enrolled in the study agreed not to change their hormonal therapy, if any, for one year. After providing informed consent, participants had to meet criteria for fasting plasma HDL and LDL cholesterol levels, triglyceride levels (≤500 mg per deciliter [5.64 mmol per liter]), and resting blood pressure (.

Clinical Procedures At base line and after one year, subjects came to the clinic several times to provide data on physical measures, aerobic fitness, and plasma lipoprotein and glucose levels. The body-mass index was determined by measuring the weight on a standard beam balance, during two visits, and the height with a Harpenden stadiometer. The means of three measures of the following were recorded with participants standing: waist (narrowest circumference viewed from the front); abdominal girth (at the umbilicus); and hip (largest horizontal circumference around the buttocks).

Resting heart rate and systolic and diastolic blood pressure were determined in duplicate on two morning visits, as previously described. Oxygen uptake during a graded treadmill exercise test was determined every 30 seconds, with use of a previously described semiautomated metabolic-analysis system. For aerobic capacity (maximal oxygen uptake in milliliters of oxygen consumed per minute and per kilogram of body weight per minute), we used the average of the two highest values in 30-second samples recorded during the final minutes of exercise. Venous blood was collected at two morning visits, after subjects had abstained from all food and drink, except water, for 12 to 16 hours and from vigorous activity for at least 12 hours, and was mixed with 1.5 mg of EDTA per milliliter. Aliquots of plasma were stored at –80°C for later assay of apolipoproteins. During one clinic visit, subjects consumed 75 g of glucose after the collection of fasting blood samples; venous blood was collected two hours later for the assessment of glucose tolerance. Laboratory Procedures Lipoprotein values at base line and at one year are reported as the means of two fasting values.

Plasma levels of total cholesterol and triglycerides were measured by enzymatic procedures. HDL cholesterol was measured by dextran sulfate–magnesium precipitation, followed by enzymatic measurement of the non-precipitated cholesterol. Very-low-density lipoprotein (VLDL) cholesterol levels were calculated as the triglyceride level divided by 5, unless triglyceride levels exceeded 400 mg per deciliter (4.52 mmol per liter), in which case VLDL cholesterol was measured by enzymatic methods, after ultracentrifugation of serum for 18 hours. LDL cholesterol was calculated as total cholesterol minus the sum of HDL cholesterol plus VLDL cholesterol.

Values were consistently within specified limits as monitored by the Lipid Standardization Program of the Centers for Disease Control and Prevention and the National Heart, Lung, and Blood Institute. Apolipoproteins A-I and B were measured by rate immunonephelometry (Array, Beckman, Brea, Calif.). Plasma glucose was measured by National Health Laboratories, San Diego, California. Assessment of Diet At base line and at one year, the subjects completed five unannounced 24-hour dietary-recall questionnaires, in the form of computer-assisted telephone interviews, with use of two-dimensional food posters. Nutrient intake was calculated with use of Food Database software, versions 5A and 6A, and Nutrient Database software, version 2.4 (Minnesota Nutrition Data System, Nutrition Coordinating Center, University of Minnesota, Minneapolis). Data for each period represent the mean of the data from four weekday and one weekend 24-hour dietary-recall records. Statistical Analysis Analysis of variance was used as a global test for differences in the degree of change from base-line values among groups, calculated separately for each sex.

When the analysis of variance indicated significant differences between groups (P. Results The screening procedures excluded 421 of 789 women and 341 of 767 men because they had HDL cholesterol levels at or above 60 mg per deciliter or 45 mg per deciliter, respectively. An additional 111 women and 172 men did not meet the criteria for the LDL cholesterol or triglyceride level, 20 women and 11 men did not meet the criteria for blood pressure or glucose, and 35 women and 30 men chose not to continue with the screening. Of the remaining 202 women and 213 men who were eligible, 22 women and 16 men were excluded because they had positive or equivocal treadmill tests, and 180 women and 197 men therefore underwent randomization. Of these, 177 women (98 percent) and 190 men (96 percent) returned for lipid measurements at one year. Missing data for variables presented here were distributed evenly among the treatment groups; no more than three persons within a group had missing data for any given variable.

Table 1 Base-Line Values for Variables Related to Diet and Fitness in Women and Changes at One Year, According to Study Group. And Table 2 Base-Line Values for Variables Related to Diet and Fitness in Men and Changes at One Year, According to Study Group. Trey Songz Heart Attack Free Mp3 Download Nl more. Present means (±SD) for base-line values and changes in those values at one year in women and men, respectively, according to group, for dietary and fitness-related variables. Analysis of variance revealed no significant differences among the groups at base line in any variable listed in or 2. The mean age was 56.9±5.1 years for women and 47.8±8.9 for men.

For both sexes, caloric intake decreased significantly in the groups assigned to diet and diet plus exercise, as compared with the exercise group, but not as compared with the controls, and the degree of change in weight at one year did not differ significantly between the diet group and the diet-plus-exercise group. Among the women, the composition of the diet was similar to that of the NCEP Step 1 diet at base line in all groups and was not significantly changed at one year in the controls or the subjects assigned to exercise alone; both groups following the Step 2 diet significantly reduced the percentage of calories from total, saturated, and monounsaturated fat and cholesterol and achieved NCEP Step 2 goals. Among the men, the mean base-line fat intake slightly exceeded Step 1 goals in all groups, but the two groups following the diet reduced fat and cholesterol intake significantly, as compared with the controls and the exercise group, and achieved Step 2 goals, whereas the composition of the diet was unchanged in the other groups. The mean base-line body-mass index was 26.3±3.2 for the women and 27.0±2.8 for the men. For women and men, significant weight loss occurred in both diet groups, as compared with the control and exercise groups, and changes in weight did not differ significantly between the diet and diet-plus-exercise groups or between patients assigned to exercise only and controls. Mean reductions in the waist-to-hip ratio were significant among the men assigned to diet plus exercise, as compared with the controls and those assigned to exercise only, but they did not differ significantly among the other groups.

Women and men in both the exercise and the diet-plus-exercise groups had significantly increased maximal oxygen consumption as compared with the control and diet groups. Table 3 Base-Line Values for Risk Factors for Coronary Heart Disease in Women and Changes at One Year, According to Study Group. And Table 4 Base-Line Values for Risk Factors for Coronary Heart Disease in Men and Changes at One Year, According to Study Group. Present base-line values and changes at one year, according to study group, for lipoprotein levels and other risk factors for coronary heart disease in women and men, respectively. Analysis of variance revealed no significant differences among the groups for any variable at base line ( and ) or for the ratio of LDL to HDL cholesterol (3.5±0.7 for women; 4.4±0.7 for men). Significant changes in the HDL cholesterol level were not observed for either sex, nor were changes in triglyceride levels.

Total and LDL cholesterol levels were significantly reduced among both women and men in the diet-plus-exercise group, as compared with the controls, and among men in the diet-plus-exercise group, as compared with the group assigned to exercise only. There were no significant reductions in total and LDL cholesterol levels for either sex in the diet group. Changes in the ratio of total to HDL cholesterol did not differ significantly among the groups for either sex, nor did changes in the ratio of LDL to HDL cholesterol among women (P=0.39 by analysis of variance). However, the LDL:HDL cholesterol ratio was significantly reduced among the men assigned to diet plus exercise (–0.6±0.7), as compared with the controls (–0.1±1. Bajaj Chetak Service Manual. 0, P. Discussion This study extends our previous investigations of the effects of diet, exercise, and weight loss on plasma lipoprotein levels in overweight men and premenopausal women to men and postmenopausal women who are at high risk for coronary heart disease because they have low HDL cholesterol levels and moderately elevated LDL cholesterol levels. We restricted the study to persons with LDL cholesterol levels at which drug therapy is not recommended before an attempt is made to lower LDL cholesterol levels through long-term reduction of dietary fat, particularly saturated fat. We wanted to determine whether changes in the diet would further reduce HDL cholesterol levels, thereby potentially increasing, rather than decreasing, the risk of coronary heart disease, and whether the addition of aerobic exercise to the Step 2 diet would offset this adverse effect, as we previously demonstrated in a study of overweight men and premenopausal women.

In the current study, the NCEP Step 2 diet failed to reduce LDL cholesterol levels significantly in either men or women as compared with controls; when the diet was combined with aerobic exercise, however, the resulting reductions in LDL cholesterol levels were significant, with no adverse effects on HDL cholesterol. On average, both the women and men who were eligible for this study had initial dietary fat intakes that approximated those in the NCEP Step 1 diet, a fact that may have contributed to their low HDL cholesterol levels. Nonetheless, their base-line LDL cholesterol levels would prompt a physician following the NCEP guidelines to recommend dietary therapy to achieve a Step 2 diet. Our results suggest that the stepped dietary approach of the NCEP is unlikely by itself to result in substantial reductions in LDL cholesterol levels, particularly since many patients will not be provided with a dietary program as comprehensive as that used here. It is worth recognizing, however, that the NCEP guidelines stress the importance of further reductions in the dietary intake of fat and cholesterol. It may be that greater emphasis on increased consumption of certain foods, such as grains, fruits, and vegetables, would yield a different result. Concern that substantial reductions in dietary fat content (to 20 to 22 percent of calories), with a reciprocal increase in carbohydrate intake, will raise triglyceride levels or impair glucose tolerance was not supported in this trial, possibly because of weight loss in the groups that followed the Step 2 diet.

Therefore, adoption of the NCEP Step 2 diet does not appear to be associated with these risk factors in euglycemic women or men with low HDL cholesterol levels and elevated LDL cholesterol levels. Nonetheless, the recommendation of a low-fat, high-carbohydrate diet remains controversial. Most data supporting the widespread belief that lowering dietary fat and cholesterol will reduce LDL cholesterol levels are derived from observational and cross-sectional population studies and studies conducted in institutional settings or metabolic wards, rather than under conditions of clinical practice (i.e., among people living in the community who choose their own foods). Under such conditions, Hunninghake et al. Observed no change in the LDL:HDL cholesterol ratio in men and women who initially had high LDL cholesterol levels while consuming the NCEP Step 2 diet, as compared with their levels while consuming a high-fat, high-cholesterol diet, during which levels of both LDL cholesterol and HDL cholesterol were reduced. In addition, HDL cholesterol levels were lowered, along with the levels of LDL cholesterol and apolipoprotein B, in men with hypercholesterolemia when dietary fat was reduced from a base-line level of 34 to 36 percent of total calories from fat to 22 to 25 percent. In our previous controlled study of moderately overweight men and premenopausal women with a high-fat base-line diet, a weight-reducing NCEP Step 1 diet failed to reduce LDL cholesterol levels significantly in men, with or without exercise, as compared with a control group, but it did significantly reduce LDL cholesterol levels in women.

HDL cholesterol levels were significantly reduced in the women who made only dietary changes, however, as compared with those who also exercised, despite the fact that there was no greater weight loss with the addition of exercise. Among men, the addition of aerobic exercise produced greater weight loss and significant elevation of the HDL cholesterol level; this effect was not seen with diet alone. The LDL:HDL cholesterol ratio was significantly lowered, as compared with that in the control group, among the men assigned to dietary changes alone, but not among the women, whereas this ratio was lowered in both men and women assigned to diet plus exercise. In the current study of men and postmenopausal women with elevated LDL cholesterol levels and low HDL cholesterol levels at base line, a reduction of about 8 percent in dietary fat intake was achieved, as in our previous study, but the reductions in LDL cholesterol levels were not significant for either sex without the addition of exercise. Although even small reductions in LDL cholesterol levels may yield epidemiologically important reductions in the risk of coronary heart disease, these findings demonstrate the importance of an exercise program when diet alone has not adequately reduced LDL cholesterol levels.

Furthermore, the benefits of exercise in terms of the reduction in the risk of cardiovascular disease extend far beyond improvements in the lipoprotein profile, and increased physical activity is now recommended for patients at all cholesterol levels. An interesting question is how the addition of exercise enhanced the effects of diet on LDL cholesterol. The diet-plus-exercise group may have adhered more closely to the diet than the group assigned to the diet alone; however, analyses of nutrients listed in multiple 24-hour dietary-recall records showed no significant differences in mean values between the two groups that followed the diet, for either sex. Furthermore, the amount of weight loss did not differ significantly between the groups assigned to the diet, and the slightly greater weight loss among men and women in the diet-plus-exercise group could have been due to increased energy expenditure. The combination of reduced dietary fat and increased use of energy from fat through exercise may create a physiologic state that is particularly beneficial to lipid metabolism even in the absence of weight loss.

The fact that weight loss did not differ significantly between the diet group and diet-plus-exercise group suggests that the amount of exercise achieved in the diet-plus-exercise group was not great enough to increase weight loss. The absence of weight loss in the exercise group may explain why the HDL cholesterol levels were not significantly improved in these groups, since weight loss may be a crucial factor in the increases in HDL cholesterol levels observed with exercise, whether weight loss is achieved solely by caloric restriction or by increased physical activity, with no dietary change. Greater weight loss might also have produced a greater reduction in LDL cholesterol levels.

Although LDL cholesterol levels were not reduced even among men with substantial weight loss in either of our previous randomized, controlled trials, reductions in LDL cholesterol levels have been associated with weight loss in other studies. In conclusion, these data strongly support recommendations to add exercise to diet for the management of lipoprotein levels associated with a high risk of coronary heart disease. Together with our previous findings, they suggest that weight loss should be further emphasized, when appropriate, particularly in counseling men and women who have both low HDL cholesterol levels and elevated LDL cholesterol levels. Supported by a grant (HL-45733) from the National Heart, Lung, and Blood Institute. We are indebted to the participants in the trial; to Lisa Cooper, M.S., R.D., and Charlene Kirchner, R.D., for assistance with the dietary intervention; to Cathy Norbutas and Dan Williams, Ph.D., for assistance with the exercise intervention; to Annette Keochekian, M.S., R.D., for assistance with recruitment; to Sue Swope, R.N., for managing the clinic; to Beth Williams, M.D., and M. Rebecca Duran-Guarino, M.D., for medical supervision; to Adriana Krauss and Darius Jatulis, M.S., for data management; to Ann N.

Varady, M.S., and Helena C. Kraemer for statistical consultation and analyses; to Marlene Hunter and the staff of the Stanford Center for Research in Disease Prevention Biochemistry Laboratory for lipoprotein analyses; and to the members of our scientific advisory board: Steven N. Blair, P.E.D. (chair), Gail E. Butterfield, Ph.D., R.D., Stephen P. Fortmann, M.D., Richard J. Brand, Ph.D., and Eva Obarzanek, Ph.D., R.D.

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