Larry W. Gibbons

Low Cardiorespiratory Fitness and Physical Inactivity as Predictors of Mortality in Men with Type 2 Diabetes

Exercise has become a standard therapy for patients with type 2 diabetes (1). Regular exercise improves conventional clinical risk factors, cardiorespiratory fitness, and components of the insulin resistance syndrome (2-6). However, it is unclear whether physical activity improves the prognosis of patients with diabetes. No data are available on the association of physical activity or cardiorespiratory fitness with mortality in patients with diabetes. The overall benefit of exercise for these patients is unclear, and some experts are concerned that macrovascular and microvascular complications may be worsened by an exercise program (1, 7). Some consider exercise only as a supplement to diet therapy (8). Studies have shown repeatedly that low cardiorespiratory fitness and physical inactivity are directly associated with cardiovascular disease and all-cause mortality (9-14), and our preliminary study with a small number of end points suggested that this association might persist across plasma glucose levels (15). In the current study, we evaluated the prospective association of cardiorespiratory fitness and physical inactivity with mortality in men who have type 2 diabetes. Methods The material presented in this report was derived from the Aerobics Center Longitudinal Study (ACLS), a prospective observational study of patients examined at The Cooper Clinic in Dallas, Texas. The study was reviewed and approved annually by the institutional review board at The Cooper Institute. Additional details of study methods and study group characteristics of this cohort have been published elsewhere (12, 13). Patients Participants were men with type 2 diabetes who completed a baseline medical evaluation at The Cooper Clinic in Dallas, Texas, during 1970 to 1993. These men came to The Cooper Clinic for a medical examination and health counseling. Many were sent by their employers for these services, some were referred by their personal physicians, and others were self-referred. More than 92% of the patients are white, and most are employed in executive or professional occupations; more than 75% are college graduates. Study participants come from middle and upper socioeconomic strata, but they are similar to other well-characterized study group-based cohorts in terms of blood pressure, cholesterol level, body weight, and cardiorespiratory fitness (6, 16, 17). We excluded men taking insulin and those with a history of cancer at baseline. Clinical Examination The baseline evaluation was performed after participants gave informed written consent for the baseline medical examination and registration in the follow-up study. Examinations followed an overnight fast of at least 12 hours and included personal and family health histories, a questionnaire on demographic characteristics and health habits, a physical examination, a maximal exercise test on a treadmill, anthropometry, electrocardiography, blood chemistry analyses, and blood pressure measurement. Technicians who followed a standard manual of operations administered all procedures. Questionnaire Patients completed an extensive self-report of personal and family medical diseases and conditions. Each clinic physician examines only four or five patients per day and thus has time for thorough additional probing of items on the self-reported questionnaire. This complete review of the patients medical history and the subsequent physical examination are strengths of the ACLS and provide a more thorough evaluation of baseline health status than is possible in many epidemiologic studies. The questionnaire also featured items on health habits, including current smoking status and smoking history and whether the participant was currently dieting to lose weight or following any other special dietary plan. Physical activity pattern was ascertained by self-report on the questionnaire. An extensive list of leisure-time physical activities was presented, and participants indicated activities in which they had participated in the 3 months before the examination. In later study years, they gave additional details on the number of times per week and the duration of exercise sessions. Laboratory Evaluations Cardiorespiratory fitness was assessed by using a maximal exercise test that followed a modified version of Balke and Wares protocol (18). Briefly, the test began with the participant walking on a horizontal treadmill at 88 m/min. After the first minute, the elevation increased to 2%, and it further increased 1% each minute up to 25 minutes. For the few patients who were still able to continue, the elevation was held constant after 25 minutes and the speed increased to 5.4 m/min until the participant reached volitional fatigue. Exercise test performance with this protocol correlates highly with measured maximal oxygen uptake (r=0.92) (19). Serum samples were analyzed by using automated techniques in a laboratory that participates in and meets the quality control standards of the Centers for Disease Control and Prevention Lipid Standardization Program. Blood pressure was measured by auscultatory methods with a mercury sphygmomanometer according to American Heart Association guidelines (20). The lowest of three blood pressure measurements at the clinic examination was recorded as the baseline blood pressure. Height and weight were measured by using a standard beam-balance scale and stadiometer, and body mass index was calculated. Type 2 Diabetes Diabetes was defined according to criteria of the American Diabetes Association: fasting plasma glucose level of 7.0 mmol/L or greater ( 126 mg/dL) (21). Three hundred seventy patients who did not meet this criterion but who gave a history of physician-diagnosed diabetes were considered to have diabetes. Patients were classified as having known diabetes or unknown diabetes according to their diabetes status before the baseline Cooper Clinic examination. Definition of Exposure Variables The principal exposure variables used in our analyses were cardiorespiratory fitness and self-reported physical activity. These exposures were determined at the baseline examination. Cardiorespiratory Fitness We categorized total time from the maximal exercise test into frequency distributions for specific age groups (30 to 39, 40 to 49, 50 to 59, and 60 years). The least fit 20% of the participants in each age group were classified as low fit, the next 40% of the distribution as moderately fit, and the highest 40% as high fit. We have used these cut-points to define fitness in previous studies (12, 13), and they are based on our entire cohort rather than on diabetic patients only. We selected these cut-points before undertaking the current analysis. Cardiorespiratory fitness is expressed as maximal metabolic units (METs) attained during the exercise test. The METs are calculated as the working metabolic rate divided by the resting metabolic rate, and 1 MET is equivalent to an oxygen uptake of 3.5 mL1 kg 1. Physical Activity Patients who reported walking, jogging, or participating in aerobic exercise programs in the 3 months before the examination were classified as active, regardless of the frequency and duration of exercise. Otherwise, patients were classified as inactive. In our cohort, more than 76% of men who reported being active at baseline still reported being active at the second visit after more than 1 year. In comparison, only 34% of men who reported being inactive at baseline reported being active at the second examination (P<0.001). Self-reported physical activity status in our cohort is correlated with maximal exercise test performance (6, 22). Baseline or Parental Cardiovascular Disease We defined baseline cardiovascular disease as a personal history of heart attack, stroke, or a revascularization procedure; an abnormal resting or exercise electrocardiogram; or the highest heart rate during exercise testing that was less than 85% of the age-predicted maximal heart rate ([220 age in years] 0.85). Men who reported a history of cardiovascular disease in either parent were classified as having parental cardiovascular disease. Conventional Cardiovascular Disease Risk Factors We assigned men to risk strata for conventional cardiovascular disease risk factors on the basis of recent recommendations (23). We defined high blood pressure as systolic blood pressure of 140 mm Hg or more, diastolic blood pressure of 90 mm Hg or more, or a history of physician-diagnosed hypertension. We classified participants with a total cholesterol level of 6.2 mmol/L (240 mg/dL) or more as having high cholesterol, those with self-reported current smoking as current smokers, those with a self-reported parental history of myocardial infarction or stroke as having a history of parental cardiovascular disease, those with a body mass index less than 25.0 kg/m2 as normal weight, and those with a body mass index of 25.0 kg/m2 or more as overweight. Statistical Analysis Our primary outcome measure was all-cause mortality. We used the National Death Index to identify decedents in the ACLS. The National Death Index has been shown to be an effective, accurate means of ascertaining deaths in the general population, with a sensitivity of about 96% and a specificity of 100% (24). We obtained official death certificates from states in which there were ACLS decedents, and we had the certificates coded by a nosologist according to the International Classification of Diseases, Ninth Revision. Only the underlying cause of death was used in analyses for this report. Data were analyzed by using the SAS statistical package (SAS Institute, Inc., Cary, North Carolina). The analyses assumed that physical activity and fitness were essentially unchanged during the study period. We used survival curves to estimate survival function against time and log [log (survival time)] to check the proportional hazards model assumption. Log [log (survival function)] estimates were approximately parallel across exposure g

The Association between Cardiorespiratory Fitness and Impaired Fasting Glucose and Type 2 Diabetes Mellitus in Men

Type 2 diabetes is a common disease in industrialized countries. It is a major cause of cardiovascular disease and all-cause mortality (1-6), and its prevalence has increased continuously over the past few decades (1). The American Diabetes Association currently defines impaired fasting glucose as a fasting plasma glucose level from 6.1 to 6.9 mmol/L (110 to 125 mg/dL) and type 2 diabetes as a fasting plasma glucose level of 7.0 mmol/L (126 mg/dL) or more (1). Data from several prospective studies show an inverse association between physical activity and diabetes (7-13). However, these studies are limited by the use of self-reporting of physical activity and presence of type 2 diabetes (7-12). Self-reporting of physical activity tends to be imprecise, and type 2 diabetes is undiagnosed in about 50% of the prevalent cases (14). This leads to misclassification on both exposure and outcome measures (15). These limitations may result in underestimation of the true association between sedentary habits and risk for type 2 diabetes. Impaired fasting glucose is a strong predictor of type 2 diabetes, cardiovascular disease, and other diabetic complications (6, 16-18). The underlying cause of impaired fasting glucose is unknown, and no prospective study of the association between physical activity and impaired fasting glucose has been published. We examined the relation of cardiorespiratory fitness, objectively determined by a maximal exercise test on a treadmill, to the incidence of impaired fasting glucose and type 2 diabetes. Cases of impaired fasting glucose and diabetes at baseline and follow-up were determined by using the American Diabetes Associations current guidelines (1). Methods Patients In our population-based prospective study, we included 8633 men 30 to 79 years of age at baseline (mean, 43.5 years) who completed at least two medical evaluations at the Cooper Clinic in Dallas, Texas, from 1970 to 1995. Patients come to the Cooper Clinic for preventive medical examinations and health promotion counseling. Many are sent by their employers for these services, some are referred by their personal physicians, and others are self-referred. More than 97% of the patients are white, and most are employed in executive or professional occupations. More than 75% are college graduates. Although study participants came from middle and upper socioeconomic strata, they were similar to other well-characterized population-based cohorts in terms of blood pressure, cholesterol level, body weight, and cardiorespiratory fitness (19). The study was reviewed and approved annually by the institutional review board at the Cooper Institute for Aerobics Research. Additional details of the study methods and population characteristics of the cohort have been published elsewhere (20, 21). Because clinical or subclinical heart disease and other conditions associated with type 2 diabetes may alter the level of physical activity and thus cardiorespiratory fitness, we excluded men with an abnormal resting or exercise electrocardiogram or a history of heart attack, stroke, or cancer at the baseline clinical examination (n=2350). The baseline evaluation was performed after participants gave written informed consent for the initial medical examination and registration in the follow-up study. Examinations were done after patients had fasted for at least 12 hours and included personal and family health histories, a questionnaire on demographic characteristics and health habits, a physical examination, an exercise test, anthropometric measurement, electrocardiography, blood chemistry analyses, and blood pressure measurement. Technicians who followed a standard manual of operations administered all procedures. Impaired fasting glucose and type 2 diabetes were diagnosed according to American Diabetes Association criteria that define impaired fasting glucose as a fasting plasma glucose level of 6.1 to 6.9 mmol/L (110 mg/dL to 125 mg/dL) and diabetes as a fasting plasma glucose level of 7.0 mmol/L (126 mg/dL) or more (1). Patients who did not meet these criteria but who reported a history of diabetes or current therapy with oral antidiabetic agents or insulin were also considered to have diabetes. We excluded patients who had diabetes at baseline according to any of these criteria (n=377). Cardiorespiratory fitness was assessed with a maximal exercise test that followed a modified Balke protocol (22). Details of treadmill speed and elevation have been described elsewhere (20, 21). Briefly, the test began with the patient walking on a horizontal treadmill at 88 m/min. After the first minute, the elevation increased to 2%; the elevation then increased 1% each minute up to 25 minutes. For the few patients who were still able to continue, the elevation was held constant after 25 minutes and the speed was increased by 5.4 m/min until the patient reached volitional fatigue. Use of this protocol for the exercise test correlates highly (r=0.92) with measured maximal oxygen uptake (23). All patients in our study achieved at least 85% of their age-predicted maximal heart rate; average maximal heart rates ( SD) in each age group were 186 11 beats/min for patients 30 to 39 years of age, 179 12 beats/min for those 40 to 49 years of age, 172 13 beats/min for those 50 to 59 years of age, and 162 17 beats/min for those 60 years of age or older. Average maximal heart rates in each age group exceeded the age-predicted rate (220 beats/min age in years), which indicates that the exercise test can be considered maximal performance. We defined level of fitness by total time on the treadmill at the baseline examination, as in our previous studies (20, 21). Treadmill times were placed in frequency distributions for specific age groups (30 to 39, 40 to 49, 50 to 59, or 60 or more years of age). The least fit 20% of the participants in each age group were classified as low fitness, the next 40% as moderate fitness, and the remaining 40% as high fitness. The respective cut-points for total treadmill time in the low-, moderate-, and high-fitness groups were 945 seconds or less, 946 to 1259 seconds, and 1260 seconds or more for patients 30 to 39 years of age; 849 seconds or less, 850 to 1020 seconds, and 1021 seconds or more for patients 40 to 49 years of age; 750 seconds or less, 751 to 1035 seconds, and 1036 seconds or more for patients 50 to 59 years of age; and 644 seconds or less, 645 to 953 seconds, and 954 seconds or more for patients 60 years of age or older. These cut-points at the 20th and 60th percentiles to define fitness levels were used in previous studies (20, 21) and were selected before analysis for our investigation. However, we calculated these cut-points with patients in the current study, from which unhealthy persons were excluded. Therefore, they differ somewhat from the cut-points derived from the entire cohort of the Aerobics Center Longitudinal Study (21). For some analyses, such as the models that included change in fitness from baseline to follow-up, cardiorespiratory fitness was expressed as maximal metabolic units (metabolic equivalents [METs], calculated as the working metabolic rate/resting metabolic rate; 1 MET is equivalent to an oxygen uptake of 3.5 mL1 kg1) achieved on the exercise test. In other analyses, time on the treadmill was used as a continuous variable. Serum samples were analyzed by using automated techniques in a laboratory that participates in the Centers for Disease Control and Prevention Lipid Standardization Program. Blood pressure was measured by using auscultatory methods with a mercury sphygmomanometer. We defined high blood pressure as systolic blood pressure of at least 140 mm Hg, diastolic blood pressure of at least 90 mm Hg, or a history of hypertension. Height and weight were measured with a standard physicians scale and stadiometer, and body mass index was calculated as weight in kg/height in m2. Waist circumference was measured with a standard anthropometric tape. Statistical Analysis We used SAS statistical software for data analyses (24). The incidence of impaired fasting glucose was calculated for men with normal fasting glucose at baseline, and the incidence of diabetes was based on data from all 8633 patients. For analyses with impaired fasting glucose as the outcome, we excluded 1122 men who had impaired fasting glucose at baseline and an additional 69 men who had normal fasting plasma glucose at baseline but developed diabetes during follow-up. Rates of impaired fasting glucose or diabetes were calculated by dividing the number of incident cases during the study period by the number of person-years over the same period. We defined the study period as the interval between the baseline examination and the last follow-up visit. We used logistic regression to estimate the association between dependent variables and independent variables after adjustment for possible confounding factors. We used general linear models to study the cross-sectional association of fitness level and parental history of diabetes (24, 25). To account for the possible cohort effect of baseline year, we examined the relation between incident cases and baseline year and found no association. We used tests for ordinal linear trend to evaluate the possible relation of higher treadmill time with risk for impaired fasting glucose or diabetes after dividing the sample into the three fitness groups. All P values are two-sided, and those less than 0.05 were considered statistically significant. Role of the Funding Source The funding agencies did not participate in the collection, analysis, or interpretation of data presented in this report or in the decision to submit the manuscript for publication. Results During an average follow-up of 6.1 4.8 years (range, 1 to 24.8 years) that included 52 588 person-years, 593 men developed impaired fasting glucose and 149 developed diabetes. Of the men with incident diabetes, 139 (93%) were not aware of their

Influences of cardiorespiratory fitness levels and other predictors on cardiovascular disease mortality in men

PURPOSE This investigation quantifies the relation between cardiorespiratory fitness levels and cardiovascular disease (CVD) mortality within strata of other CVD predictors. METHODS Participants included 25,341 male Cooper Clinic patients who underwent a maximal graded exercise test. CVD death rates were determined for low (least fit one-fifth), moderate (next two-fifths), and high (top two-fifths) cardiorespiratory fitness categories by strata of smoking habit, blood cholesterol level, resting blood pressure, and health status. There were 226 cardiovascular deaths during 211,996 man-years of follow-up. RESULTS For individuals with none of the major CVD predictors (smoking, elevated resting systolic blood pressure, elevated blood cholesterol), there was a strong inverse relation (P = 0.001) between fitness level and CVD mortality. An inverse relation between CVD mortality and fitness level was seen within strata of cholesterol levels and health status. No evidence of a trend (P = 0.60) for decreased mortality was seen across fitness levels for individuals with elevated systolic blood pressure; however, a strong inverse gradient (P < 0.001) was seen across fitness levels for individuals with normal systolic blood pressure. There was a tendency for association between high levels of fitness and decreased CVD mortality in smokers compared with low and moderately fit smokers (P < 0.076). There was no significant association between level of fitness and CVD mortality for individuals with multiple (two or more) predictors (P = 0.325). Approximately 20% of the 226 CVD deaths in the population studied were attributed to low fitness level. CONCLUSIONS Moderate and high levels of cardiorespiratory fitness seem to provide some protection from CVD mortality, even in the presence of well established CVD predictors.

Maximal exercise test as a predictor of risk for mortality from coronary heart disease in asymptomatic men

Exercise testing in asymptomatic persons has been criticized for failing to accurately predict those at risk for coronary heart disease (CHD). Previous studies on asymptomatic subjects, however, may not have been large enough or long enough to provide reliable outcome measures. This study examines the ability of a maximal exercise test to predict death from CHD and death from any cause in a population of asymptomatic men. This is a prospective longitudinal study performed between 1970 and 1989, with an average follow-up of 8.4 years. The subjects are 25,927 healthy men, 20 to 82 years of age at baseline (mean 42.9 years) who were free of cardiovascular disease and who were evaluated in a preventive medicine clinic. The main outcome measures are CHD mortality and all-cause mortality. During follow-up there were 612 deaths from all causes and 158 deaths from CHD. The sensitivity of an abnormal exercise test to predict coronary death was 61%. The age-adjusted relative risk of an abnormal exercise test for CHD death was 21 (6.9 to 63.3) in those with no risk factors, 27 (10.7 to 68.8) in those with 1 risk factor, 54 (21.5 to 133.7) in those with 2 risk factors, and 80 (30.0 to 212. 5) in those with >/=3 factors. A maximal exercise test performed in asymptomatic men free of cardiovascular disease does appear to be a worthwhile tool in predicting future risk of CHD death. An abnormal exercise test is a more powerful predictor of risk in those with than without conventional risk factors.

Usefulness of Cardiorespiratory Fitness as a Predictor of All-Cause and Cardiovascular Disease Mortality in Men With Systemic Hypertension

There is an inverse gradient of mortality across levels of cardiorespiratory fitness in healthy adults; however, the association of fitness to mortality in persons with comorbidities such as hypertension is not fully understood. This study quantifies the relation of cardiorespiratory fitness to all-cause mortality and cardiovascular disease (CVD) mortality in hypertensive men. In this observational cohort study, we calculated death rates for low, moderate, and high fitness categories in normotensive (n = 15,726) and hypertensive (n = 3,184) men, and in men without a history of hypertension but with elevated blood pressure (BP) (systolic BP > or = 140 or diastolic BP > or = 90 mm Hg) at baseline (n = 3,257). The participants were 22,167 men (average age 42.6 +/- 9.2 years [mean +/- SD]) who underwent a medical examination that included a maximal exercise test during 1970 to 1993, with mortality follow-up to December 31, 1994. We identified 628 deaths (188 from CVD) during 224,173 man-years of observation. There was an inverse linear trend across fitness groups for all-cause and CVD mortality. The relative risk (95% confidence interval [CI]), using the low fitness group as reference, for all-cause mortality in hypertensive men was 0.45 (95% CI 0.31 to 0.65) and 0.42 (95% CI 0.27 to 0.66) for moderate and high fitness groups, respectively, and in men with elevated BP, 0.49 (95% CI 0.34 to 0.70) and 0.44 (95% CI 0.29 to 0.68) for moderate and high fitness groups, respectively. The pattern of results was similar for CVD mortality. There was an inverse linear relation between fitness and death rate for all-cause mortality in both the uncontrolled and controlled hypertensive groups. This study provides evidence that moderate to high levels of cardiorespiratory fitness provide protection against all-cause and CVD mortality in hypertensive men and men without a history of hypertension but with elevated BP at examination.

The prevalence of side effects with regular and sustained-release nicotinic acid

PURPOSE To document the prevalence and nature of the side effects that occur with the use of regular and sustained-release nicotinic acid in everyday clinical practice. PATIENTS AND METHODS One hundred and ten patients seen in a private medical clinic who were given 133 separate trials of nicotinic acid during a 5-year period. The occurrence of side effects, particularly those severe enough to warrant discontinuing the drug, were carefully monitored. RESULTS Forty-three percent of individuals given regular nicotinic acid and 42% of those given sustained-release nicotinic acid were forced to discontinue the medication because of side effects; some of these side effects necessitating discontinuing nicotinic acid did not occur until the patient had been taking the drug for 1 or 2 years. CONCLUSION Nicotinic acid in both regular and sustained-release forms is a powerful drug when used in doses needed to treat lipid disorders and causes disturbing side effects a very high percentage of the time. No one should use nicotinic acid in these doses without continued careful supervision of a physician.

Association of a Favorable Cardiovascular Health Profile With the Presence of Coronary Artery Calcification

Background—To examine the association between the American Heart Association’s 7 metrics of ideal cardiovascular health (ICH) and the presence of subclinical coronary atherosclerosis as assessed by coronary artery calcification (CAC) using electron-beam computed tomography. Methods and Results—This study is a cross-sectional analysis of data obtained on 3121 male and female patients evaluated at the Cooper Clinic in Dallas, Texas, between 1997 and 2007. We included men aged ≥45 and women aged ≥55 without known cardiovascular disease and for whom information on all ICH metrics and a CAC score were available. Patients were grouped into 3 categories according to their number of ICH metrics: favorable (4–7 ICH metrics), intermediate (3 metrics), and unfavorable (0–2 metrics). Patients with favorable ICH profiles had a lower prevalence and severity of subclinical atherosclerosis than those with unfavorable or intermediate ICH profiles as estimated by CAC. This inverse association of CAC with ICH metrics was evident whether the presence of coronary calcium was defined as CAC score >0, CAC score >100, or CAC score >400. Patients with favorable ICH profiles had odds of coronary calcium (CAC>0) less than half of those for patients with unfavorable profiles (odds ratio 0.41; 95% confidence interval, 0.34–0.50) and patients with intermediate ICH profiles had odds of detectable CAC 32% lower (odds ratio 0.68; 95% confidence interval, 0.57–0.82). Conclusions—A statistically significant association was found between a favorable level of ICH metrics and less or absent subclinical atherosclerosis as measured by CAC underscoring the importance of primordial prevention.

Age- and sex-based nomograms from coronary artery calcium scores as determined by electron beam computed tomography

We present data for 18,785 patients undergoing electron beam computed tomography, dividing them by sex and age (using 5-year age increments) to determine coronary artery calcium scores representing the 50th and 75th percentiles for each group. Because risk stratification is an integral part of determining therapies for coronary artery disease, age- and sex-based scores may be more clinically useful than total coronary artery calcium scores alone.

An empirical evaluation of the Acsm Guidelines for Exercise Testing

The American College of Sports Medicine (ACSM) has published exercise guidelines identifying individuals who should have an exercise test prior to clearance for exercise participation and whether a physician should supervise the test. These age and health status criteria (apparently healthy, higher risk, and diseased) were developed using clinical judgement and opinion rather than empirical data. Thus, there is a need to validate the recommendations with actual data. We studied the results of 24,332 maximal treadmill tests in men (n = 18,076) and women (n = 5,626) as they associated with age and baseline health status. Commonly accepted criteria for abnormal exercise tests were used (i.e., 1 mm ST segment depression at 0.08 s, systolic blood pressure drop with exercise, complex ventricular ectopy, etc.). There were 895 and 183 abnormal exercise tests in men and women, respectively. Men and women who were apparently healthy had lower abnormality rates per 1,000 tests than those considered to be at higher risk for coronary heart disease and those who had preexisting disease. Further, when those who were at higher risk were considered, those men with only one risk factor had significantly lower abnormality rates than did men with more than one risk factor (95% confidence intervals (CI) per 1,000 tests: 1 risk factor = 36.1-46.4; greater than 1 risk factor = 47.5-62.5). Abnormality rates in women with 1 risk factor were also lower than those in their peers with greater than 1 risk factor, but not statistically so (95% CI per 1,000 tests: 1 risk factor = 24.9-43.0; greater than 1 risk factor = 25.3-54.4).(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiorespiratory fitness and coronary artery calcification in women.

INTRODUCTION Cardiorespiratory fitness (fitness) has been shown to be inversely associated with coronary heart disease morbidity and mortality. The cardioprotective mechanisms of fitness are not well defined. The goal of this study was to assess the relationship between coronary artery calcification as a measure of atherosclerotic burden and fitness in a large population of generally healthy women. METHODS 5341 women ages 40-90 years seen between 1997 and 2007 underwent maximal treadmill exercise testing and coronary artery calcium (CAC) scanning. Fitness was reported in METs estimated from maximal treadmill time, grade, and speed. CAC was characterized dichotomously as CAC=0 versus CAC>0, and CAC<100 versus CAC≥100. Multiple logistic regression models were used to calculate the adjusted odds ratio of any CAC (CAC>0) and CAC≥100. Fitness was added to these models continuously and categorically based on standard and sample-specific cut-points. RESULTS With a mean age of 52.0 years, the overall prevalence of detectable CAC was 19.9% and CAC≥100 was 6.8%. Univariable analysis showed a modest inverse relationship between fitness and CAC>0 (24% in low fit versus 19% in high fit, p-trend=0.006), with a similar trend observed for CAC≥100. In multivariable models, age adjustment diminished this association and the relationship was no longer statistically significant after adjustment for traditional risk factors. CONCLUSIONS The cardioprotective benefit of fitness does not appear to be mediated by an effect independent of traditional risk factors on the development of calcified coronary atherosclerosis as measured by electron beam tomography.