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The Journals of Gerontology Series A: Biological Sciences and Medical Sciences 55:M342-M349 (2000)
© 2000 The Gerontological Society of America

Cardiovascular Fitness, Body Composition, and Lipoprotein Lipid Metabolism in Older Men

Andrew P. Goldberga,b, M. Janette Busby-Whiteheadc, Leslie I. Katzela,b, Ronald M. Kraussd, Marilyn Lumpkina,b and James M. Hagberga,b,e

a Division of Gerontology, Department of Medicine, University of Maryland School of Medicine
b Geriatrics Service/GRECC, Baltimore Veterans Administration Maryland Health Care System
c Division of Gerontology and Geriatrics, Department of Medicine, Johns Hopkins University School of Medicine, Bayview Medical Center, Baltimore, Maryland.
d Ernest Orlando Lawrence Berkeley National Laboratory, University of California, Berkeley
e Center on Aging, University of Maryland, College Park

Andrew P. Goldberg, GRECC (BT/18/GR), Baltimore VA Medical Center, 10 N. Greene St., Baltimore, MD 21201 E-mail: apgoldbe{at}umaryland.edu.

Decision Editor: William B. Ershler, MD


   Abstract
Top
 Abstract
Methods
 Results
 Discussion
 References
 
Background. Lipoprotein lipids in older individuals are affected by family history of coronary artery disease (CAD), obesity, diet, and physical activity habits.

Methods. The relationship of obesity and physical fitness (O2max) to lipoprotein lipids and postheparin lipases was examined in a cross-sectional study of 12 lean (LS) and 26 obese (OS) sedentary men and 18 master athletes (MAs) aged 65 ± 1 years (mean ± SE). The men were healthy, had no family history of CAD, and were weight stable on AHA diets at the time of study.

Results. O2max was similar in LS and OS men but higher in the MAs. The OS men had a higher percentage of body fat (%BF), waist circumference, and waist:hip ratio (WHR) than the MA and LS men, but MA and LS men differed only in waist circumference. Total and LDL-C levels were comparable, but HDL-C, HDL2-C, and %HDL2b subspecies were higher in MAs than in OS and LS men, and in LS than in OS men. Triglyceride (TG) was similar in MAs and LS men but higher in OS men. Across groups, two multiple regression analyses models (O2max, %BF, and WHR or waist circumference) showed that %BF and O2max independently predicted HDL-C and HDL2, whereas WHR predicted TG more strongly than waist circumference Postheparin lipoprotein lipase activity (LPL) was comparable among groups and correlated independently with O2max. Total postheparin lipolytic activity (PHLA), hepatic lipase activity (HL), and HL:PHLA ratio were similar in MAs and LS men but higher in OS men. In both multiple regression analysis models, only %BF predicted HL activity and the HL:PHLA ratio. The HL:PHLA ratio independently predicted HDL-C, HDL2-C, %HDL2b, %HDL3 subspecies, and the cholesterol:HDL-C ratio, whereas LPL activity predicted TG.

Conclusions. Increased fitness and reduced total and abdominal fatness in MAs are associated with lower HL and higher LPL activities, which may mediate their higher HDL-C and lower TG levels relative to their sedentary peers.

THERE are wide variations in plasma lipoprotein lipid levels among older individuals. Although some of these differences may reflect diversity in primary aging processes, secondary processes including chronic disease, body composition, and cardiovascular fitness (O2max) undoubtedly also affect lipoprotein lipid levels. Numerous studies in older individuals show that O2max and total and regional body composition are closely and probably causally related to plasma lipoprotein levels (1)(2)(3)(4)(5). The development of abdominal obesity often occurs with aging and has adverse effects on lipoprotein lipids that increase risk for coronary artery disease (CAD) (6)(7)(8). These alterations in lipoprotein lipids that occur with advancing age predispose older people to atherosclerosis and its complications (9)(10).

Cross-sectional studies have shown that higher levels of O2max and reduced percentage of body fat (%BF) in older athletes are associated with lower triglyceride (TG) and low density lipoprotein cholesterol (LDL-C) levels and elevated high density lipoprotein cholesterol (HDL-C) levels, compared with their sedentary peers (3)(5)(11)(12). However, these studies did not report measures of total or regional body fat, nor did they consider the effects of diet, family history of CAD, or the presence of CAD and other diseases that could affect lipoprotein lipid profiles in older persons. Furthermore, none of these studies examined the relationship of O2max and body composition to lipoprotein lipase (LPL) and hepatic lipase (HL), enzymes regulating the formation of the HDL2 subspecies from TG-rich lipoproteins and the clearance of TG and HDL from plasma (13)(14). The cross-sectional examination of the relationship of HDL and TG to the activity of LPL and HL in a group of healthy sedentary and endurance-trained older men across a wide spectrum of O2max and body fatness levels may provide insight into the relationship of plasma lipoproteins to physical fitness and body composition in older men.

This study was designed to test the hypothesis that the more favorable, cardioprotective lipid profiles of older athletes would be related to the lower HL and higher LPL activities that are associated with their higher O2max and lower total and abdominal fat compared with their sedentary peers. The hypothesis was examined in a cross-sectional study of the independent effects of O2max, %BF, waist circumference, and waist:hip ratio (WHR) on postheparin HL and LPL activities and lipoprotein lipids in older endurance-trained athletes and in lean and obese sedentary men of comparable age.


   Methods
Top
 Abstract
 Methods
Results
 Discussion
 References
 
Subjects and Screening Tests
Endurance-trained and sedentary men aged 50–79 years were recruited by telephone and media advertisements. All subjects provided written informed consent as approved by the Institutional Review Boards of the University of Maryland, Baltimore School of Medicine and the Johns Hopkins–Bayview Medical Center to participate in the study. Before enrollment, subjects completed medical, dietary, and physical activity history questionnaires. Nonsmoking, healthy men who were not on medications underwent a physical examination and a screening blood chemistry profile. Those with renal or hematologic disorders, liver disease, diabetes mellitus by oral glucose tolerance test (15), or hyperlipidemia defined as total cholesterol or TG > 250 mg/dl or LDL-C > 165 mg/dl (16) were excluded from the study. All subjects completed a maximal treadmill exercise test according to the Bruce protocol (17), with ECG, blood pressure, and heart rate monitoring to screen for CAD. Subjects continued the exercise until they reached subjective exhaustion unless significant arrhythmias or signs or symptoms of CAD occurred. O2 was measured continuously during this test (2).

Maximal exercise testing with thallium-201 scanning using single photon emission computed tomography (SPECT) was performed in all subjects to exclude those with asymptomatic CAD (18). Thallium-201 was injected intravenously 1 minute prior to exercise cessation. Tomographic reconstruction was performed to improve image quality and reduce artifacts related to cardiac motion (19). Thallium scans were read by a nuclear cardiologist blinded to the patient's history, and quantitative profile analyses confirmed the results of visual interpretation (18).

The O2max test started on a level treadmill at a speed eliciting approximately 70% of the peak VO2 achieved during the subject's screening maximal treadmill exercise test. The treadmill grade was increased to 4% after 2 minutes and continued to increase by 2% every minute thereafter until the subject became exhausted or the cardiovascular responses contraindicated further exercise. ECG, heart rate, and blood pressure were monitored prior to, during, and following exercise. O2 and CO2 were also measured during this test (2), and if standard criteria for a true O2max were not achieved (11), additional O2max tests were done.

All subjects included in the study had normal exercise ECG responses (<0.1 mV ST segment depression) during both maximal treadmill exercise tests, a negative thallium maximal exercise test, a negative family history for premature CAD (myocardial infarction prior to age 60), and no history of CAD, pulmonary, or metabolic disease (2).

Body composition was determined by underwater weighing using a stainless steel tank and a load cell interfaced to a computerized system with customized software as described previously (2). Fat-free mass (FFM) was calculated from body weight and %BF. WHR was calculated from the minimal waist circumference divided by the maximal gluteal circumference (2). Body mass index (BMI) was calculated as weight divided by the square of the height (kg/m2).

Based on their O2max and %BF, subjects were categorized into one of three groups: master athletes (MAs; O2max > 40 [ml/kg]/min, body fat < 20%), lean sedentary men (LS; O2max < 40 [ml/kg] /min, body fat < 20%), and obese sedentary men (OS; O2max < 35 [ml/kg]/min, body fat > 25%). None of the sedentary men had any recent history of regular exercise training. The 18 MA men trained 6 ± 1 days per week (mean ± SE) (range 3.5–6.5 d/wk) and competed at local races; three were competitive at the national level. Seven of the MAs had competed in middle- or long-distance running when they were young, though none had distinguished themselves at the national level. Five other MAs had been involved in team sports such as baseball, football, and basketball in high school. Six MAs had not been athletes in their youth. When studied, the MAs had been training continuously for 15 ± 2 years; none had been training continuously since youth. All ran as their primary form of training, averaging 57 ± 7 km per week (range 24–145 km/wk). Seven, who were triathletes, swam an average of 6 ± 2 km per week (range 3–11 km/wk) and cycled 81 ± 15 km per week (range 24–113 km/wk).

Dietary Stabilization
Following screening tests, food records were reviewed and found to differ in composition among the groups. To control the confounding effects of dietary composition on lipoprotein lipids (20)(21), subjects were instructed by research dietitians for 3 months to ensure compliance with an American Heart Association (AHA) Step I Diet (22) consisting of 50%–55% carbohydrates, 30%–35% fat, and 300–400 mg of cholesterol with a polyunsaturated:saturated fat ratio of 0.6–0.8. Subjects were weight stable and compliant for >1 month based on food records prior to metabolic testing. No subject consumed more than two alcoholic beverages (12 oz. beer, 5 oz. wine) per day; most consumed only one alcoholic beverage daily during the study. All subjects were given calculated General Clinical Research Center (GCRC)–prepared weight-maintaining meals meeting AHA Step I criteria for 3 days prior to the drawing of blood samples on 3 separate days for lipid analyses. Subjects were weight stable (±0.25 kg) during this period or else the diet was continued and testing postponed until weight stabilization criteria were met.

Plasma Lipoprotein Lipid Profile
Blood samples were drawn on 3 separate days in the supine position after a 12-hour overnight fast. On the last of these days, 2280 U/m2 heparin was injected intravenously immediately after sampling for lipids, and 10 ml of blood was collected into chilled EDTA tubes, iced, and spun at 4°C. Three plasma aliquots were frozen at -70°C for analysis of lipase activities. Blood samples from MAs were drawn 24–36 hours after their last bout of exercise. Samples were drawn into chilled EDTA tubes and spun immediately at 4°C; plasma was separated for lipid analysis within 72 hours. Enzymatic measurements of plasma cholesterol and TG levels were performed on an Abbott (North Chicago, IL) ABA 200 series bichromatic analyzer. HDL-C was measured in the supernatant after precipitation of apoprotein-B containing lipoproteins with dextran sulfate. The HDL3-C subspecies was measured following a second precipitation of HDL2-C subspecies from the supernatant (23). HDL2-C levels were calculated by subtracting HDL3-C levels from the total HDL-C level. LDL-C was calculated by the Friedewald equation (24). All lipid results are the average from three blood samples drawn over a period of 7–10 days while the subject was weight stable on the GCRC prepared diet.

The size distribution of the HDL-C subspecies was measured on one of the plasma samples by using gradient gel electrophoresis on polyacrylamide gradient gels (Pharmacia Co., Piscataway, NJ) (25). The gels were stained for protein using Coomassie Brilliant Blue R 250 (Bio-Rad, Richmond, CA) and scanned at 596 nm with a model RFT densitometer (Transdyne Corp., Ann Arbor, MI) interfaced with a PDP8/E minicomputer (Digital Equipment Corp., Maynard, MA). The optical density of HDL protein was plotted as the relative mobility of HDL protein from the origin compared with that of bovine serum albumin. Five HDL subspecies were separated using these methods and quantified as the areas of HDL protein in the reference interval calculated as a percentage of the total area of the entire HDL scan (25).

Postheparin lipolytic enzyme activities were measured as total postheparin plasma lipase activity (PHLA), and LPL and HL activities, as described previously (8). The accuracy of the measurement of HL activity after protamine inhibition of LPL activity in postheparin plasma and the calculation of LPL as the difference between the total PHLA and HL activity in these samples were validated in a subset of the assays using the same antibody to human HL as previously (8) to measure LPL activity directly in postheparin plasma. The interassay coefficient of variation for the postheparin lipase assay was 7% for total PHLA, 9% for LPL, and 8% for HL activity. The addition of antiHL antibody and protamine to control plasma inhibited >97% of the total PHLA. Lipase activities are expressed in (µmol FFA/ml)/h (where FFA is free fatty acids).

Statistics
All data were analyzed using a commercial statistical software package (26) and are presented as mean ± SE. Differences were considered statistically significant at p < .05. Normal distribution for parametric analyses was achieved by log10 conversion of plasma TG, HDL-C, and HDL2-C levels, %HDL2, %HDL3, and cholesterol:HDL-C ratio and taking the square root of the LPL activity. The statistical significance of differences among groups was determined by ANOVA with post hoc testing using Tukey's range test. Pearson product moment correlations were calculated to determine bivariate relationships in the entire study population. Forward selection procedures starting with the variable with the highest bivariate r value were used to multiple stepwise regression analyses to assess multivariate relationships in models containing O2max/FFM, %BF, and either WHR or waist circumference as independent variables.


   Results
Top
 Abstract
 Methods
 Results
Discussion
 References
 
Subject Characteristics
All three groups (Table 1 ) were of similar ages. The MAs and LS men differed in their waist circumference but had similar body weight, BMI, %BF, and WHR values, all of which were significantly lower than those of the OS men. There were no differences in FFM among the three groups of subjects.


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  		Table 1. Characteristics of the Three Groups of Subjects

 
The MAs had substantially higher O2max values than both LS and OS men whether expressed in L/min or after normalizing for body weight or FFM. The OS and LS men had similar O2max values when expressed in L/min or (ml/kg FFM)/min; O2max was lower in OS than in LS men only when normalized for body weight, due to their greater body fat. Therefore, O2max is normalized per kg FFM in all further analyses.

Plasma Lipoprotein Lipid Profiles
The MAs and LS men had lower TG levels than the OS men, but plasma total cholesterol and LDL-C levels were comparable in all three groups (Table 2 ). HDL-C levels in MAs were 30% and 50% higher than in LS and OS men, respectively, and plasma HDL-C levels were 18% higher in LS than in OS men. The total cholesterol:HDL-C ratio in MAs was 22% and 33% lower than in LS and OS men, respectively, and was also 15% lower in LS than in OS men.


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  		Table 2. Plasma Lipoprotein Lipid Levels of the Three Subject Groups

 
The HDL2-C levels of the MAs were 83% and 450% higher than those of the LS and OS men, respectively. The %HDL2b subspecies was 35% and 94% higher in MAs than in LS and OS men, respectively (Table 3 ). The %HDL3a, %HDL3b, and %HDL3c subspecies were lowest in MAs, intermediate in LS men, and highest in OS men, but only the differences in %HDL3 between MAs and OS men reached statistical significance.


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  		Table 3. Plasma %HDL2 and %HDL3 Subspecies of the Three Groups of Subjects

 
Relationships Among Body Composition, O2max, and Plasma Lipoprotein Lipid Levels
When the data in the three groups were combined (Table 4 and Table 5 ), virtually all lipoprotein lipid levels that were statistically different among the groups were significantly related to O2max/FFM, %BF, waist circumference, and WHR. However, there were significant interrelationships between %BF and O2max/FFM - - - Therefore, multiple regression analyses were performed using models that included O2max/ FFM, %BF, and either waist circumference or WHR to determine the independent predictors of plasma lipoprotein lipid levels. In all analyses, the correlation coefficients were higher in the model that included WHR than in the model that included waist circumference. These analyses indicated that 45% of the variance in plasma TG levels was related to WHR (compared with 39% for waist circumference), with no other variables contributing significantly to the further estimation of TG levels. On the other hand, HDL-C levels were independently related to O2max (Table 5 and Fig. 1). WHR predicted 52% of the variance in the plasma cholesterol:HDL-C ratio, compared with 38% by waist circumference. The %HDL2b subspecies levels correlated independently with %BF (Table 5 and Fig. 2), but there was no correlation between the %HDL2a subspecies and these variables. The %HDL3a correlated independently only with %BF ; the %HDL3b subspecies correlated independently with %BF and O2max; and the %HDL3c subspecies correlated independently with WHR, but the independent correlation coefficient with waist circumference was lower .


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  		Table 4. Correlations Between Plasma Lipoprotein Lipid Levels and O2max, %BF, Waist, and WHR in All Subjects

 

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  		Table 5. Results of Multiple Regression Analyses for Plasma Lipoprotein Lipid Variables as a Function of O2max, %BF, and WHR

 


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  		Figure 1. Determinants of HDL-C in MAs and sedentary older men. Histogram shows the independent relationship of plasma HDL-C levels with O2max as determined by multiple regression analysis. The multivariate r2 when these two variables are combined is .54 (p < .0001). Bars are only included for data within the ranges of the present subject population.

 


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  		Figure 2. Determinants of HDL2b subspecies in MAs and sedentary older men. Histogram shows the relationship of %HDL2b with %BF The multivariate r2 when these two variables are combined is .45 (p < .0001). Bars are included only for data within the ranges of the present subject population.

 
Postheparin Lipase Activity Levels
The MAs had significantly lower total PHLA than the OS men, whereas PHLA levels in the LS men were intermediate between the MA and OS groups (Table 6 ). Postheparin LPL activities were comparable in all three groups. Postheparin HL activities did not differ between MAs and LS men but were significantly lower in both of these groups than in the OS men. Hence, the HL:PHLA ratio was significantly higher in the OS men than in the MAs and LS men.


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  		Table 6. Plasma Lipase Levels of the Three Subject Groups

 
Relationships Among Subject Characteristics, Lipases, and Lipoprotein Lipids
Postheparin HL activity was significantly related in bivariate analyses to O2max, %BF, waist circumference, and WHR (Table 7 ). Stepwise multiple regression analyses showed that postheparin HL activity was independently related only to %BF , with O2max, waist circumference, and WHR not adding significantly. In bivariate analyses, postheparin LPL activity was significantly related to O2max and waist circumference but not to %BF or WHR. In both models, multiple regression analyses indicated that LPL activity was independently related only to O2max with no significant contribution from %BF, WHR, or waist circumference in either model. The HL:PHLA ratio was significantly related to O2max, %BF, waist circumference, and WHR. In multiple regression analyses, only %BF independently predicted the HL:PHLA ratio , with no significant contribution from the other variables.


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  		Table 7. Correlations of Subject Characteristics and Plasma Lipoprotein Lipid Levels with Postheparin Lipase Activities in All Subjects

 
The plasma lipoprotein lipid variables that differed among the groups, including HDL-C and HDL2-C levels, and %HDL2b and all %HDL3 subspecies had stronger correlations with postheparin HL and the HL:PHLA ratio, whereas plasma TG correlated strongest with postheparin LPL activity. Multiple regression analyses demonstrated that HL and the HL:PHLA ratio were the only independent predictors of plasma HDL-C and the cholesterol:HDL-C ratio whereas LPL activity correlated independently with plasma TG .


   Discussion
Top
 Abstract
 Methods
 Results
 Discussion
References
 
The principal finding of this study is that the plasma lipoprotein lipid profile, specifically the components of HDL associated with risk for CAD, are independently associated with both increased cardiovascular fitness and reduced total and abdominal body fatness in older men. This conclusion is based on cross-sectional comparisons of plasma lipoprotein lipid levels between groups of older men of comparable body composition but different levels of cardiovascular fitness (MAs and LS men) and in older men with similar O2max levels but different body composition (LS and OS men). The results show that the activity of HL and the HL:PHLA ratio are higher in the OS men and correlate directly with %BF, WHR, and waist circumference, whereas the postheparin LPL is directly related to O2max. Furthermore, abdominal obesity and higher HL activity are associated with lower HDL and HDL2 subspecies levels, whereas reduced O2max and lower LPL are associated with higher TG levels. Collectively, these cross-sectional findings support our hypothesis that lifestyle habits that increase cardiovascular fitness and reduce total and abdominal body fat in older men affect postheparin HL and LPL activities to mediate changes in the metabolism of HDL-C and TG that reduce lipoprotein lipid risk factors for CAD.

Several cross-sectional studies show that middle-aged and older endurance-trained athletes have higher plasma HDL-C levels and lower cholesterol:HDL-C ratios than their age-matched sedentary peers (3)(11)(12). Northcote and coworkers (12) and Williams and coworkers (3) also reported that middle-aged and older runners have higher plasma HDL2-C levels than sedentary individuals of similar age. However, the middle-aged and older athletes in those studies had both a higher O2max and a lower %BF than did their sedentary peers. In addition, body fat distribution (WHR) was not measured, and there was no attempt to control dietary factors that could contribute to the differences in plasma lipoprotein lipids among the subjects. In the present study, the differences in plasma lipoprotein lipid profiles and postheparin LPL and HL activity among the subjects were related to O2max and total and abdominal fatness independent of the following: (a) disease, because no subjects were on medications and all were rigorously screened for metabolic, CAD, and other diseases, as well as a family history of premature CAD; (b) the effects of diet, because subjects were weight stable on an AHA Step I diet for >1 month before the study; and (c) the acute effect of exercise, because lipid studies were performed in the MAs at 24–36 hours after their last exercise session.

Plasma HDL-C levels were lower and cholesterol:HDL-C ratios were higher in these MAs than in the older athletes we studied previously (11). The lower HDL-C levels and smaller differences in lipoprotein lipids between MAs and sedentary subjects in this study compared with our previous report may be related to the somewhat higher body fat (14% vs 11%) and lower O2max (48 vs 53 [ml/kg]/min) of these MAs. The smaller differences in lipoprotein lipids in these MAs may also be related to their less rigorous training (running 57 vs. 90 km/wk), even though they had been training somewhat longer (15 vs. 11 years). Although adherence to the AHA low-fat, high-carbohydrate diet—known to lower total cholesterol, LDL-C, and HDL-C levels (20)(21)(27)(28)(29)—may also have affected the HDL-C levels in these subjects, the diet was carefully controlled to the same extent to minimize the effects of differences in diet composition among the groups on lipoprotein metabolism. However, it is possible that the AHA Step I diet affected lipoprotein metabolism and levels to a different degree among the three groups. This should be considered in the interpretation of our findings, because several studies show consistent reductions in HDL-C, with variable effects on TG, cholesterol, and LDL-C that may be related to the prediet lipid concentrations, gender, and the degree of obesity of the study subjects (20)(28)(29)(30). The lipid and lipoprotein responses to a low-fat, high-carbohydrate diet also may depend on the apolipoprotein APO-E and A-IV genotype (20), LDL particle size and density (30), and other gene–diet and environmental interactions that affect CAD risk (31). Individuals with the APO E3/4 or the APO A-IV 1,2 allele seem to have a greater LDL reduction on AHA Step I diets compared with subjects with the APO E3/3 or APO A-IV 1,1 polymorphism (20), whereas subjects with smaller, dense LDLs respond more favorably than those with larger, more buoyant LDL particles (29). The degree of insulin resistance of the study subjects also may affect the lipid response to diet; it is possible that sedentary, more obese insulin-resistant men with the worst lipoprotein lipid profiles prior to the AHA Step I diet may benefit most from the reduction in dietary fat. Thus, by controlling diet in this study, we may have produced an additional perturbation on lipid and glucose metabolism that could affect the lipoprotein lipid profiles of the three groups by different degrees. Further study of the effects of genes and environmental factors on glucose and lipid metabolic responses to diet is an important area of investigation for the prevention of CAD (32)(33).

The differences in lipoprotein lipids and postheparin plasma lipase activities, and the significant bivariate and multivariate correlations between lipoprotein lipids and physical characteristics of the study groups suggest that both cardiovascular fitness and body composition play independent roles in determining plasma HDL-C and TG levels in healthy older men. From these data, one can calculate the relative contributions of "fitness and fatness" to differences in HDL-C for the average study participant with a O2max of 44 (ml/kg FFM)/min, %BF of 20%, and WHR of 0.93 from the multiple regression models. If this average individual had a O2max one standard deviation below the mean of the entire population (35 vs. 44 [ml/kg FFM]/min), the model indicates that his plasma HDL-C level would be 0.93 mmol/L or 36 mg/dl, as opposed to 1.03 mmol/L or 40 mg/dl (see Fig. 1), and his %HDL2b subspecies would be 18% as opposed to 21% (see Fig. 2). On the other hand, if his %BF were one standard deviation higher than the average for the population (29% vs 20%), the models indicate that his plasma HDL-C level would be 0.95 mmol/L or 37 mg/dl, compared with 1.03 mmol/L or 40 mg/dl (Fig. 1), and his %HDL2b subspecies would be 16%, compared with 21% (Fig. 2). Collectively, these analyses clearly indicate that O2max and total and abdominal body fat contribute independently and substantially to plasma HDL-C and %HDL2b subspecies levels in older men.

The lower postheparin HL activity in the MAs was related to their leanness and was associated with higher total HDL-C, HDL2-C, and HDL2b subspecies, whereas LPL activity correlated directly with O2max and was associated with lower plasma TG levels in the MAs, compared with the sedentary (LS and OS) men. The stronger correlation between HDL-C, HDL2-C, and HDL2b with postheparin HL rather than LPL activity suggests that the catabolism and not the formation of HDL-C (13)(14) is the major factor regulating HDL-C levels in healthy older men. The elevated HDL and HDL2 subspecies and lower HL activity observed in these MAs are compatible with the metabolic adaptations observed in younger persons in response to exercise training (1)(34)(35). Williams and coworkers (3) reported that middle-aged runners had 40% lower HL and higher LPL activity than sedentary peers having a slightly higher BMI. The MAs in the present study had roughly 25% and 40% lower HL activity than their lean and obese sedentary peers, respectively. However, LPL activity did not differ among the groups in the present study. This may be related to the effects of the low-fat, high-carbohydrate diet that was imposed on the subjects, which reduces HDL-C (27). The cross-sectional nature of this study prevents more definitive conclusions, but other investigators have reported that lower HDL-C levels in obese sedentary subjects are associated with either high HL or low LPL activity (14)(34)(36), and the converse in endurance-trained athletes and other individuals, where high HDL-C levels are associated with low HL and normal or high LPL activity (3)(14)(37).

Collectively, these results show that increased O2max and reduced total and abdominal body fat in older endurance-trained athletes compared with sedentary older subjects result in marked increases in the cardioprotective HDL-C and its HDL2 subspecies. This finding has major public health implications for the prevention of CAD with aging, since higher HDL-C levels are associated with reduced CAD risk in epidemiologic and case-control studies (38)(39)(40)(41). Thus, a reduction in CAD risk may be possible through exercise and weight loss in the elderly by raising HDL-C and its cardioprotective and HDL2 subspecies. Longitudinal studies are needed to determine the validity of these cross-sectional findings and the potential for interventions that modify physical activity and dietary habits to reduce lipoprotein and other risk factors for CAD in obese sedentary older persons.


   Acknowledgments
 
This article is dedicated to the memory of Mrs. Marilyn Lumpkin, who died in August 1996. M. Janette Busby-Whitehead, MD, is currently at Program on Aging, University of North Carolina, Chapel Hill.

This research was supported by NIA Grant RO1-AG07660 and the Johns Hopkins Academic Teaching Nursing Award PO1-AG04402; a grant from the American Federation for Aging Research; NIA Clinical Investigator Awards KO8-AG00383, KO8-AG00497, KO7-AG00608, and T32-AG00219; General Clinical Research Center MO1-RR02719; the Maryland Affiliate of the American Heart Association; NIH-NHLBI Program Project HL-18574; a grant from the National Dairy Promotion and Research Board of the National Dairy Council; and a US Department of Energy Contract No. DE-ACO3-76SF00098 to Ernest Orlando Lawrence Berkeley National Laboratory.

We are indebted to the subjects for their participation and to the nursing staff, laboratory technicians, dietitians, exercise physiologists, and biostatisticians for their assistance in the conduct of this research. We are grateful to our administrative staff for typing the manuscript and assistance with graphics.

Received March 22, 1999

Accepted October 26, 1999


   References
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 Abstract
 Methods
 Results
 Discussion
 References
 

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