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Dose-response: variation with age, sex, and health status

WILMORE, JACK H.

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Medicine and Science in Sports and Exercise: June 2001 - Volume 33 - Issue 6 - p S622-S634
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Abstract

It has become widely accepted that a physically active lifestyle promotes good health and reduces the risk of chronic disease and disability (6,13,36,37). It is less clear as to what levels of activity are necessary to optimize these benefits. In 1995, the Centers for Disease Control and Prevention in collaboration with the American College of Sports Medicine (ACSM) introduced a radical change in how we view the dose of exercise necessary for health promotion and disease prevention (37). A panel of experts reviewed the pertinent physiological, epidemiological, and clinical evidence and came up with the following concise public health message: “Every U.S. adult should accumulate 30 min or more of moderate-intensity physical activity on most, preferably all, days of the week”(37). The scientific basis for this new statement had been clearly established by Dr. William L. Haskell, in the 1993 ACSM Wolffe Lecture published in 1994 (21). Many clinicians, researchers, and the lay public had previously subscribed to the believe that a substantially higher dose of exercise was necessary in order to obtain the health-related benefits, and the ACSM Position Stand on “The Recommended Quantity and Quality of Exercise for Developing and Maintaining Cardiorespiratory and Muscular Fitness in Healthy Adults”(1) was used to support their beliefs. Although there is not a large database to support this new statement, it was adopted by the NIH (36) and the Surgeon General (6). The new statement, however, is not without its critics (54), and many scientists are presently engaged in researching the benefits of cumulative brief bouts of lower intensity exercise.

With this as background, the present article investigates the dose-response relationship and its variation with age, sex, and health status. Since this symposium explores many outcome variables, it was not practical to conduct an analysis of each of these variables with respect to age, sex, and health status. Therefore, a decision was made to focus on blood pressure, including systolic (SBP) and diastolic blood pressure (DBP), and blood lipids and lipoproteins, specifically triglycerides (TG) and HDL-cholesterol (HDL-C).

METHODS

An attempt was made to review every article that had been published on the changes in blood pressure and lipids and lipoproteins consequent to exercise training as specifically related to age, sex, and health status. It was immediately evident that a strategy had to be developed to limit the scope of this review. With this in mind, studies were selected by priority as follows: 1) studies specifically investigating the influence of age, sex, or health status on the training response; 2) studies investigating a specific age (adolescents, adults, older adults), sex (male or female), and health status (diseased or healthy); and 3) in areas where there were too many studies (i.e., studies on blood pressure and/or lipid and lipoprotein changes in adults, or studies on a diseased population), reliance was placed on detailed reviews and meta-analyses.

Attempts were made to locate randomized controlled trials when available, but this was not always possible. Many of the studies included in this review were not truly randomized, and some were strictly observational studies. However, several of the nonrandomized, observational trials with no control groups were tightly controlled, using repeated measures of the outcome variables both before and after the exercise training period, and included large numbers of subjects. A MEDLINE search was conducted for all training studies in which either or both blood pressure and blood lipids and lipoproteins were the outcome variables. The database extended from January, 1966 through August 2000. The reference list from each article obtained in the MEDLINE search was then screened for additional studies. Review articles concerning the responses of blood pressure and blood lipids and lipoproteins to exercise training were also obtained and their reference lists were also screened for additional studies. In several cases where the identified article was not clear on whether comparisons were conducted across age groups or for males versus females, authors were contacted directly to obtain the missing information. This review attempts to determine if age, sex, or health status affects the response to a given dose of exercise on each of the selected outcome variables.

RESULTS

The results of this review are presented in two sections: Blood Pressure and Blood Lipids and Lipoproteins. They are presented in table format, with Tables 1–3 dealing with the influence of age, sex, and health status, respectively, on the effect of exercise training on changes in blood pressure. Tables 4–6 address the influence of age, sex, and health status, respectively, on the effect of exercise training on changes in blood lipids and lipoproteins. Age was divided into the following categories: children and adolescents, young and middle-aged adults, and older and elderly adults. Sex was divided into male and female, and health status was divided into hypertensive versus normotensive for blood pressure, and no known coronary artery disease versus myocardial infarction (MI) for lipids and lipoproteins. There were several exceptions to these categories, but the rationale for including these exceptions will be provided.

Table 1
Table 1:
Effect of age on the magnitude of change in resting blood pressure consequent to exercise training.
Table 1
Table 1:
Continued
Table 2
Table 2:
Effect of sex on the magnitude of change in resting blood pressure consequent to exercise training.
Table 3
Table 3:
Effect of health status (hypertensive vs normotensive) on the magnitude of change in resting blood pressure consequent to exercise training.
Table 4
Table 4:
Effect of age on the magnitude of change in triglycerides and HDL-cholesterol consequent to exercise training.
Table 4
Table 4:
Continued
Table 5
Table 5:
Effect of sex on the magnitude of change in triglycerides and HDL-cholesterol consequent to exercise training.
Table 5
Table 5:
Continued
Table 5
Table 5:
Continued
Table 6
Table 6:
Effect of health status (CVD vs no CVD) on the magnitude of change in triglycerides and HDL-cholesterol consequent to exercise training.

Each table consists of five columns: study (author, year, and reference number) and country of origin; study design and subject population; training program details; results of the study; and comments on important aspects of the study. In the results column, attempts were made to define the effectiveness of the training program. Most of the studies presented in Tables 1–6 used aerobic endurance training as their mode of training. In most cases, authors provided the average increase in maximal oxygen uptake (O2max), whereas others provided increases in some measure of physical working capacity. For those studies using resistance training, average increases in strength are included when provided by the authors.

Blood Pressure

Effect of age.

Table 1 presents the available data on the blood pressure response to exercise training as affected by age. First, not all studies have demonstrated significant decreases in either or both SBP and DBP with training, but those studies reporting no change are in the minority. Furthermore, they appear across all groups. For the majority of studies where blood pressure decreases were reported consequent to training, the magnitude of change appears to be comparable across age groups. Unfortunately, only two studies actually compared age groups (33,55), one reporting no changes in blood pressure in either the younger or older groups (33) and the other reporting only small changes in the younger and older groups (55). Overall, it appears that there is an equivalent decrease in both SBP and DBP across age groups, which is in agreement with a recent review by Fagard (9). The magnitude of decrease varies, but would generally be in the range of 3–8 mm Hg for SBP and 2–6 mm Hg for DBP (Evidence Category B).

Effect of sex.

Table 2 presents the available data on the blood pressure response to exercise training as affected by sex. Several of the studies reported no decreases in either or both SBP and DBP, but most reported decreases. In those studies reporting decreases, there appears to be a slightly greater response in boys and men when compared with girls and women, in agreement with the conclusion of Kelley (27), who had conducted a meta-analysis of a total of 10 training studies on women. The magnitude of decrease in blood pressure in boys and men was similar to that reported for age in the previous paragraph, whereas women were, on average, 1–3 mm Hg lower in their response (Evidence Category C).

Effect of health status.

Table 3 presents the available data on the blood pressure response to exercise training as affected by health status. Although one study found no change in SBP or DBP after training (15) and another found the blood pressure decreases to be less in adolescent hypertensives compared with normotensives (20), most of the studies showed a greater decrease in both SBP and DBP in hypertensives when compared with normotensives. Fagard and Tipton’s review chapter (10), which included a meta-analysis of all studies conducted before 1994, estimated that SBP/DBP decreases in normotensives were approximately −3/−3 mm Hg compared with −6/−7 mm Hg in borderline hypertensives and −10/−8 in hypertensives. Subsequent individual studies would support these estimates, although one meta-analysis did not support a difference by health status (19) (Evidence Category B).

Blood Lipids and Lipoproteins

Effect of age.

Table 4 presents the available data on the blood lipid and lipoprotein responses to exercise training as affected by age. Not all studies reported significant favorable changes in either or both TG and HDL-C with training. However, the majority of the studies did report significant changes. In those studies where direct comparisons were made across age groups, no significant differences in responses were reported. Thus, age does not appear to affect the response to training. The magnitude of change in TG and HDL-C was quite variable, with the HDL-C changes generally being small on average (i.e., <3 mg·dL-1) (Evidence Category B).

Effect of sex.

Table 5 presents the available data on the blood lipid and lipoprotein responses to exercise training as affected by sex. Although not all studies reported favorable changes in TG and HDL-C, the majority did. There was not a consistent pattern of response differentiating males and females. Although a number of studies reported no difference in response between males and females when there was a significant change, about an equal number reported more favorable changes in HDL-C in males, with only one study showing a more favorable change in females. With TG, where there were differences in response between males and females, the studies were split, with three showing a greater decrease for females and three showing a greater decrease for males. Many of the studies reported the ratio of total cholesterol (TC) to HDL-C (TC/HDL-C ratio), and there were no apparent consistent differences between men and women in their improvement in this ratio (i.e., decreased TC/HDL-C ratio) (Evidence Category B).

Effect of health status.

Table 6 presents the available data on the blood lipid and lipoprotein responses to exercise training as affected by health status. For this analysis, because of the large number of training studies on post-MI patients and the lack of training studies comparing post-MI patients with healthy, age-matched controls, the data from three meta-analysis studies are presented. From these studies, it appears that somewhat larger decreases in TG and increases in HDL-C occur in the post-MI patient population, which is likely related to their higher pretraining levels for TG and lower levels for HDL-C (Evidence Category B).

DISCUSSION

It is important to recognize that there are a number of factors that influence the training response results of those studies that have been presented in this review, in both the areas of blood pressure and blood lipids and lipoproteins. In both areas, it appears that greater changes are possible for those subjects starting with a less favorable profile, i.e., higher SBP and DBP, higher TG, and lower HDL-C. This has been a major finding of most reviews and meta-analyses. Since men typically have higher SBP, DBP, and TG, and lower HDL-C when compared with women, men would be expected to have a greater change in these variables with training, which was, for the most part, the conclusion of this article. However, this was not the case with age, where very few studies supported differences across age in response to training for blood pressure and for blood lipids and lipoproteins, even though older individuals tend to have more unfavorable profiles.

Another confounding variable is body size. It has been well established that blood pressure is a function of body size in children and animals, and is likely a factor in full-grown adults. Yet, blood pressure is generally reported as an absolute value, without adjusting for body size. Thus, men are likely to have higher blood pressure values solely on the basis of their larger body size on average. How this might affect the response to training is less clear. Another variable that can affect the results of training studies is plasma volume. Blood lipid and lipoprotein values are reported as concentrations, yet few studies have adjusted for the changes in plasma volume, both acute and chronic, that occur in response to training.

Future research in this area should focus on developing research designs that actually investigate the influence of age, sex, and health status on the blood pressure and blood lipid and lipoprotein responses to exercise training. Subjects should be randomized into exercise and control groups by age, sex, or health status depending on the purpose of the study. Furthermore, power analyses should be conducted to ensure an adequate number of subjects in each group, and repeat measures should be taken both before and after training to increase the accuracy of measurement for the outcome variables. Few studies that have been reported in this review met all of these criteria. The changes in these variables have typically been small. Furthermore, in the HERITAGE Family Study, intraclass correlations for repeat measures of resting SBP and DBP before training ranged from 0.76 to 0.85, technical errors were 5.1 mm Hg or less, and coefficients of variation were less than 7%(45). This emphasizes the importance of having repeat measures in order to determine small differences between subgroups where the magnitude of change is small.

In summary, it is concluded that age has little or no influence on the changes in blood pressure or in blood lipids and lipoproteins (TG and HDL-C) in response to exercise training. When looking at sex, females appear to have an attenuated response to exercise training compared with males with respect to SBP, DBP, and HDL-C, but the data for TG are equivocal. Finally, there appears to be more favorable changes in resting SBP and DBP, TG, and HDL-C in unhealthy subjects (hypertensive and post-MI patients) when compared with healthy subjects.

Address for correspondence: Jack H. Wilmore, Department of Health and Kinesiology, Texas A&M University, TAMU 4243, Read Building 158, College Station, TX 77843-4243; E-mail: jwilmore@tamu.edu.

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Keywords:

EXERCISE TRAINING; RESTING SYSTOLIC AND DIASTOLIC BLOOD PRESSURE; RESTING TRIGLYCERIDES AND HDL-C; HYPERTENSIVES VERSUS NORMOTENSIVES; POST-MI VERSUS HEALTHY

© 2001 Lippincott Williams & Wilkins, Inc.