Medicine & Science in Sports & Exercise:
CLINICAL SCIENCES: Clinically Relevant
Physical activity and the presence and extent of calcified coronary atherosclerosis
TAYLOR, ALLEN J.; WATKINS, TAMMY; BELL, DEBBIE; CARROW, JON; BINDEMAN, JODY; SCHERR, DIANE; FEUERSTEIN, IRWIN; WONG, HENRY; BHATTARAI, SAROJ; VAITKUS, MARK; O’MALLEY, PATRICK G.
Cardiology, General Internal Medicine, and Radiology Services, Walter Reed Army Medical Center, Washington, DC; Uniformed Services University of the Health Sciences, Bethesda MD; and Armed Forces Physical Fitness Research Institute, Carlisle, PA
Submitted for publication January 2001.
Accepted for publication May 2001.
TAYLOR, A. J., T. WATKINS, D. BELL, J. CARROW, J. BINDEMAN, D. SCHERR, I. FEUERSTEIN, H. WONG, S. BHATTARAI, M. VAITKUS, and P. G. O’MALLEY. Physical activity and the presence and extent of calcified coronary atherosclerosis. Med. Sci. Sports Exerc., Vol. 34, No. 2, pp. 228–233, 2002.
Purpose: Regular physical activity leads to a more favorable cardiovascular risk factor profile and a lower risk of developing incident coronary heart disease (CHD). These correlations suggest that higher levels of physical activity should also attenuate the presence and extent of coronary atherosclerosis.
Methods: Physical activity was measured using the Baecke Physical Activity Index in 630 consecutive asymptomatic men and women ages 39–45 without known heart disease. The degree of physical activity was compared with the cardiovascular risk factor profile and the presence and extent of subclinical atherosclerosis measured using electron beam computed tomography.
Results: Sports-related physical activity was associated with lower body mass index (r = −0.11;P = 0.001), higher high-density lipoprotein (HDL) cholesterol (r = 0.13;P = 0.003) and less glucose resistance as assessed by fasting serum insulin levels (r = −0.16;P = 0.001). Leisure-time and work-related physical activity were unrelated to any coronary risk variables. Calcified subclinical atherosclerosis was unrelated to all physical activity dimensions. Comparing the most sedentary (lowest quartile) and most active (highest quartile) patients, the prevalence of coronary calcium (17.0% vs 18.5%;P = 0.92) and mean coronary calcium scores (8 ± 31 vs 5 ± 15;P = 0.87) were similar. In a multivariate model controlling for standard cardiovascular risk factors and physical activity level, only low-density lipoprotein (LDL) cholesterol was associated with the presence of coronary calcium.
Conclusion: Physical activity, particularly high-intensity exercise in sports-related activities, promotes a healthy cardiovascular risk profile, including lower body mass index and insulin resistance, but is unrelated to coronary calcification. This suggests that the risk reduction associated with physical activity is mediated by factors other than retarding the development of calcified atherosclerosis.
Aerobic physical exercise favorably modifies multiple cardiovascular risk factors, including blood pressure, lipoproteins (particularly high-density lipoprotein (HDL) and triglycerides), fibrinogen, body mass index, and insulin resistance (2,7,9,14,15,19,30). As a result of these and other influences, such as normalization of endothelial function (11), an active lifestyle, including regular physical activity or good cardiorespiratory fitness, is associated with a 30–50% reduction in coronary heart disease (CHD) (7,16–18,27,28,31). It is not known whether the reduction in CHD seen in more active individuals is a result of alteration in the atherothrombotic potential of existing atherosclerosis or whether there are effects (direct or indirect) of physical activity on the development of atherosclerosis. Previous cross-sectional data (7,13) suggest that adjustment for differences in coronary risk variables between active and sedentary individuals attenuates, but does not negate, the effect of exercise on CHD. Furthermore, regular physical activity is inversely related to prevalent, undiagnosed CHD (30) and to the extent of angiographic coronary artery disease and noncalcified atherosclerosis detected in the common carotid artery (8). The Kuopio Ischemic Heart Disease Risk Factor (13) study recently demonstrated that high levels of cardiorespiratory fitness are associated with a slower progression of early atherosclerosis in the carotid artery. In an effort to further clarify the link between physical activity and reductions in CHD mortality, and to extend these data to calcified atherosclerosis measured using electron beam computed tomography, we compared the relationships between physical activity, the cardiovascular risk factor profile, and the presence and extent of subclinical calcified coronary atherosclerosis in a screening population of middle-aged men and women.
The methods and demographic characteristics (21) of participants in the Prospective Army Coronary Calcium Project have been previously described (29). Briefly, all active duty Army personnel, ages 39–45 yr old and stationed within the National Capital Area of the Walter Reed Health Care System, were screened for the study at the time of a periodic, Army-mandated physical examination. Patients with a history of CHD or who indicated a history of angina pectoris were ineligible. Between October 26, 1998, and November 4, 1999, 705 eligible patients were screened, and 630 provided written informed consent to undergo electron beam computed tomography (EBCT) in addition to the required physical examination procedures. Those personnel who did not consent to the study (N = 75) were similar to participants with respect to age, gender, education, and cardiovascular risk factors (diabetes mellitus, total cholesterol, and smoking status).
Each participant provided details of their medical history, including a history of hypertension, diabetes mellitus, hypercholesterolemia, and a family history of cardiovascular disease. Smoking was self-reported as current, recent (within 6 months) or remote (>6 months) use of any inhaled tobacco products. Subjects who reported infrequent use of cigars were classified as nonsmokers based its limited relationship with adverse cardiovascular outcomes (12). Resting blood pressure was measured using an automated sphygmomanometer and was recorded as the average of three seated measurements taken 5 min apart. Hypertension was defined as either a systolic blood pressure of >135 mm Hg, a diastolic blood pressure of >85 mm Hg, or a history of hypertension (treated or untreated). After a 12-h fast, subjects donated blood for the measurement of serum glucose, glycosylated hemoglobin, insulin, homocysteine (using a fluorescent polarization immunoassay), lipoprotein(a), fibrinogen (using an immunoprecipitin assay), and serum lipid concentrations (total cholesterol, low-density lipoprotein (LDL), HDL, and triglycerides). LDL cholesterol was measured using a direct assay. Height, weight, and waist circumference were measured, and body mass index (BMI) was calculated as weight·height−2 (kg·m−2). The predicted 5-yr risk of developing manifest CHD was calculated using measured risk factor variables based upon the regression equations from the Framingham Study.
Electron beam computed tomography.
Coronary artery calcification (CAC) was assessed with concurrent EBCT using an Imatron C-150LXP scanner. Images were obtained using a 40- to 50-slice (3-mm thickness) protocol with image acquisition gated to 70–80% of the electrocardiographic RR interval while respirations were held. Scans were interpreted in a blinded manner by an experienced radiologist (IMF) using the Agatston scoring method (1). Scans with at least four contiguous pixels with >130 Hounsfield units of CAC (CAC score > 0) were considered to be positive for CAC. A total CAC score was determined from the sum of the individual scores of the four major epicardial coronary arteries.
Physical activity questionnaire.
Physical activity was quantified using the Baecke physical activity questionnaire (3). The Baecke questionnaire is self-reporting and consists of 16 questions, providing 3 semicontinuous indices of physical activity: work index (WI), sport index (SI), and leisure index (LI). These three indices are summed to provide a composite Physical Activity Index (PI). This questionnaire provides a valid and reliable assessment of the frequency and intensity of physical activity and is appropriate for use in middle-aged populations. Short- to long-term test-retest correlations are excellent (23,24). The instrument has shown modest correlation with other measures of physical activity (24) and is predictive for incident CHD mortality (7). Because the Baecke index incorporates the frequency, intensity, and duration of activity, it is a particularly good instrument to measure the correlation with cardiovascular risk variables that appear to be most tightly correlated with frequent, intense physical activity (3,19).
The relationship between physical activity and cardiovascular risk factors was evaluated by comparing physical activity scores with continuous risk factor variables using bivariate correlations. Subjects were also grouped by gender and quartile of physical activity scores for comparisons with categorical variables using the χ2 test. Risk factor comparisons between groups of patients with and without CAC using a threshold value of any detectable coronary calcium (CAC score > 0) were performed. The relationship between physical activity, cardiovascular risk factors, and the presence of CAC was assessed using stepwise logistic regression analysis. Physical activity scores and cardiovascular risk factor variables with a univariate relationship (P ≤ 0.05) to CAC were entered into the model. The relationships between the Framingham risk index and the Baecke physical activity index (test variables) and the presence of any CAC (state variable) were analyzed using the area under receiver operator characteristic curve. All analyses were performed using SPSS for Windows (v 10.05, Chicago IL). Data are presented as mean ± SD. A two-tailed P-value ≤ 0.05 was considered significant.
Demographic and cardiovascular risk factor variables for the 630 participants are shown in Table 1. The study included 515 men and 115 women. Based upon the Framingham Risk Index (FRI), the 5-yr predicted CHD risk of the study group was relatively low (1.6 ± 1.2%). Coronary artery calcification was present in 20.6% of men and 4.3% of women. The mean CAC scores were 11 ± 53 and 3 ± 25, respectively. Physical activity scores were normally distributed within the study group. The mean physical activity scores were as follows: physical activity 7.9 ± 1.4, work index 2.2 ± 0.6, leisure index 2.7 ± 0.6, and sports index 3.0 ± 0.8. These are comparable to physical activity scores derived from other, middle-aged populations (6,7,24). There was a modest correlation (r = 0.32;P = 0.001) between the SI and peak oxygen consumption during exercise stress testing (N = 110).
Correlation of physical activity with cardiovascular risk variables.
Correlations between the individual components of the Baecke physical activity scores and cardiovascular risk factor variables are shown in Table 2. Body mass index and serum insulin were inversely correlated with both the overall physical activity index and the sports index. Positive correlations were found between the sports index and systolic blood pressure, and the work index and glycosylated hemoglobin. There were no significant correlations observed for any of the physical activity indices and serum lipoprotein levels.
Men had significantly higher sports index scores than women (3.0 ± 0.8 vs 2.7 ± 0.9;P < 0.001). In men, there were inverse correlations observed for increased sports index scores and body mass index, waist girth, and serum insulin levels (Table 3). HDL-C was directly correlated with sports index scores. With the exception of HDL (no correlation), these same associations were stronger for women than for men (Table 3). For men, a sports activity score in the highest quartile was associated with a more favorable cardiovascular risk factor profile, including lower waist girth, lower diastolic blood pressure, lower LDL-C and triglycerides, higher HDL-C, and lower serum insulin levels. (Table 4)
The mean Baecke activity scores were similar in male subjects with and without CAC (Table 5). Men in the upper quartile of sports activity also had a similar prevalence of CAC compared with men in the lower three quartiles (21.2 vs 20.4%;P = 0.88). The extent of CAC (log-transformed CAC score) was unrelated to any of the physical activity indices (bivariate correlation coefficients −0.037 to 0.33;P = NS for all comparisons). A logistic model for the prediction of the presence of any CAC in men, including the variables LDL, HDL, BMI, insulin, and the Baecke SI found that LDL was the only variable significantly related to CAC (OR 1.009 per mg·dL−1 increment in LDL;P = 0.029). Coronary artery calcification was uncommon (prevalence 4.2%) in women and was also unrelated to Baecke physical activity scores. ROC curve analysis demonstrated a significant relationship between the Framingham risk index and coronary calcification (area under the curve 0.67 ± 0.03; 95% CI 0.61–0.72;P < 0.001). The Baecke physical activity index was unrelated to coronary calcification (area under the curve 0.51 ± 0.03; 95% CI 0.45–0.57;P = 0.77). (Fig. 1)
Maximal oxygen consumption (V̇O2max) and CAC were measured in 95 men. Coronary artery calcification tended to be less common (8 of 32, 25%) and severe (mean CAC score 6 ± 20) in subjects within the highest tertile of V̇O2max values versus the lower two tertiles (21/63, 33.3%, and mean CAC score 16 ± 54), but the differences were not significant (P = 0.40, and P = 0.3).
Numerous studies have demonstrated an association between a lifestyle, including frequent moderate to vigorous physical activity and a reduced incidence of CHD. The benefits of exercise have been documented in both men and women, and can exceed a 50% lower risk of CHD. In this study, despite the relationships between predominately sports-related physical activity and a less atherogenic cardiovascular risk factor profile, physical activity was unrelated to the presence and extent of calcified subclinical atherosclerosis.
Part of the reduction in CHD risk associated with exercise is produced by favorable effects on cardiovascular risk factors. This can be summarized as a favorable effect on the insulin-resistant phenotype, including the specific components of obesity (2,9,14,19), blood pressure (2,17,19,30), fibrinogen (15,17), HDL cholesterol (2,9,14,19,30), small dense LDL cholesterol (9), diabetes mellitus, and insulin resistance (14,30). Our data confirms these benefits within a relatively healthy, middle-aged population, including reductions in blood pressure, fibrinogen, serum insulin levels, obesity, and increased HDL cholesterol.
Despite the favorable associations between physical activity and risk factors that promote the development of coronary atherosclerosis, we did not find a relationship between physical activity and the presence or extent of calcified subclinical atherosclerosis. This is in direct contrast to prior cross-sectional studies demonstrating that physical activity is associated with prevalent, subclinical CHD (30), to angiographic coronary artery disease, and to the extent (8) and progression of noncalcified atherosclerosis detected in the common carotid artery. Furthermore, a high level of leisure time physical activity has been shown to delay coronary atherosclerosis progression (10).
Prior studies have established that coronary artery calcification, a validated surrogate for the presence and extent of coronary atherosclerosis (25), is related to multiple cardiovascular risk factors (32). In particular, LDL cholesterol is one of the most important variables related to the presence (29) and progression (5,26) of coronary calcium. In contrast, a relationship between LDL cholesterol and physical activity has not been consistently demonstrated by these observational and cross-sectional studies (2,9) or in randomized trials (33). This suggests that exercise may exert a differential effect on the presence and extent of calcified versus noncalcified atherosclerosis, in part mediated through its limited effect on LDL cholesterol.
Both physical activity (7,16–18,27,28,31) and coronary artery calcification (22) have important relationships to incident CHD. Thus, the failure of this study to find a relationship between physical activity and coronary artery calcification is unexpected. There are several possible explanations for this. First, adjustment for the effects of exercise on cardiovascular risk variables attenuates, but does not abolish, its relationship with incident CHD (7,27). Factors other than effects on atherosclerosis, such as the correction of endothelial dysfunction (11), are likely contributors. Additional support for this is found in data demonstrating that only current, regular exercise is protective against ischemic heart disease (31). Thus, there is no latency to the effects of exercise, as might be expected if exercise primarily acted to retard the development of atherosclerosis. Second, the benefits of physical activity may be mediated through the stabilization of noncalcified atherosclerotic plaques. Indeed, calcification is most commonly found in stable plaques versus those that contribute to acute coronary syndromes (20). Calcification is also more commonly found in healed plaque ruptures (4). These clinical-anatomic associations suggest that coronary calcification is a surrogate for the extent of plaques prone to cause acute coronary events and for patients prone to plaque rupture events. Third, the relationships with subclinical atherosclerosis for measures of physical activity versus direct measures of cardiorespiratory fitness may vary. For example, the Kupio Ischemic Heart Disease Risk study (13) found a relationship between V̇O2max and carotid intima media thickness. However, this same study could not demonstrate a similar relationship between a leisure time physical activity questionnaire and carotid intima media thickness. In contrast, the Atherosclerosis Risk in Communities study (8) did find a relationship between the Baecke physical activity index, as utilized in this study, and carotid intima media thickness. Lastly, the strength of the relationships between coronary risk factors and both physical activity and coronary atherosclerosis (including coronary artery calcification) are, although significant, modest. A significant proportion of the variance of atherosclerosis remains unexplained, and therefore it is not surprising that only a minority of the variance in coronary artery calcification is explained by coronary risk factors.
This study assessed physical activity and coronary calcification in a cross-sectional manner. Longitudinal data are needed to definitively exclude an effect of physical activity on calcified atherosclerosis. However, individuals tend to maintain relatively stable exercise habits (31), and the Baecke questionnaire has demonstrated reproducibility over time (23).
Obesity and diabetes mellitus are growing problems within the spectrum of coronary disease risk. Physical activity has a strong, inverse correlation with body mass index (2,9,14,19) and insulin resistance (14,30). Thus, the promotion of regular physical exercise achieves greater importance to lower the cardiovascular risk attributed to these risk factors. Our data from a middle-aged, relatively active cohort confirm these correlations and suggest caution is required when using anatomic screening tests acting as a “litmus test” in the evaluation and treatment of coronary risk factors. EBCT is a controversial test promulgated on its ability to detect patients at risk for CHD and to motivate behavioral change. However, because of the absence of a relationship between coronary calcification and physical activity, physical activity is an important cardiovascular risk variable that should not be overlooked in a patient with low, age-adjusted levels of coronary calcium. Sedentary lifestyle patterns should be discouraged in light of clear relationships seen in this and other studies between physical inactivity, obesity, insulin resistance, and CHD risk (8).
Physical activity, particularly high-intensity exercise in sports-related activities, promotes a healthy cardiovascular risk profile, including lower body mass index and insulin resistance but is unrelated to coronary calcification. This suggests that the risk reduction associated with physical activity is mediated by factors other than retarding the development of calcified atherosclerosis. Simple clinical advice for adherence to AHA recommendations for physical activity is prudent for the maintenance of ideal body weight and an optimal cardiovascular risk factor profile, although it may not affect calcified atherosclerosis.
This study was funded by Walter Reed Army Medical Center.
This work was presented in part at the 50th Scientific Session of the American College of Cardiology, Orlando FL, March 2001.
The opinions or assertions herein are the private views of the authors and are not to be construed as reflecting the views of the Department of the Army or the Department of Defense.
Conflict of interest: None of the authors of this manuscript has a financial interest in this work. The results of this study do not constitute endorsement of any product by the authors or ACSM.
Address for correspondence: Allen J. Taylor, M.D., LTC MC USA, Director, Cardiovascular Research, Cardiology Service, Walter Reed Army Medical Center, 6900 Georgia Ave., NW, Building 2, Room 4A, Washington DC, 20307-5001; E-mail: firstname.lastname@example.org.
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