Relative associations of fitness and fatness to fibrinogen, white blood cell count, uric acid and metabolic syndrome.

OBJECTIVE: To examine the relation between fitness and fibrinogen, white blood cell count, uric acid and metabolic syndrome across levels of adiposity in apparently healthy, nonsmoking men. DESIGN: Cross-sectional study of 4057 men from the Aerobics Center Longitudinal Study examining the age-adjusted resting levels and risk of having a clinically significant elevation of fibrinogen, white blood cell count, uric acid and metabolic syndrome score across nine fitness-body fatness combinations. Fitness categories (low fitness, moderately fit or high fitness) were based on a maximal treadmill test. Body mass index (BMI) <25.0 was classified as normal weight, BMI > or = 25.0 but <30.0 as overweight and BMI > or = 30.0 as obese. RESULTS: Fitness (inversely) and BMI (directly) were independently related to the age-adjusted values of all four variables (P for trend P<0.0001 for each). For all four variables, the greatest age-adjusted risk of having a clinically relevant value was found in the low fitness-obese category and the lowest age-adjusted risk was found in the high fitness-normal weight group. CONCLUSION: Fibrinogen, white blood cells, uric acid and metabolic syndrome score are independently related to both fitness (inversely) and fatness (directly). Within levels of fatness, risk for significant elevations in fibrinogen, white blood cells, uric acid and metabolic syndrome score is lower for the higher fitness groups.

Exercise in the reduction of cardiovascular events. Lessons from epidemiologic trials.

In conclusion, much has been learned about the effects of exercise in reducing events in those with CHD. Some data are confusing, however, and some gaping holes exist in our understanding. Hopefully, new data forthcoming in the next 5 to 10 years will clear up this picture significantly. Meanwhile, cardiovascular exercise, coupled with other risk factor reduction, has been firmly established as a lifesaving and life-improving tool in those who have developed manifestations of CHD.

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.

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.

Incidental detection of preclinical renal tumors with electron beam computed tomography: report of 26 consecutive operated patients.

PURPOSE: The purpose of this work was to describe the positive predictive value of electron beam CT (EBCT) for diagnosis of solid renal tumors. METHOD: Among 11,932 consecutive patients undergoing screening EBCT, 27 cases met EBCT criteria for solid renal tumors. Twenty-six of 27 patients underwent surgery. RESULTS: Surgical pathology identified 25 solid renal tumors and 1 adrenal hemorrhage with thrombus. Twenty tumors were classified as T1N0M0, one was T2N0M0, and one was T3aN0M0. All tumor patients are clinically well at 1-41 months (mean 17 months) postoperatively. None of the patients had clinical signs or symptoms characteristic of renal malignancy. CONCLUSION: EBCT is an effective tool for detection of solid renal tumors in a healthy outpatient population (positive predictive value 0.96). The detection rate is low [0.2% (26/11,932) at our facility] in patients undergoing EBCT for other indications. The cost-effectiveness and sensitivity of this technique for solid renal tumor detection among various populations remain to be determined.

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.

Alcohol intake and incidence of type 2 diabetes in men.

OBJECTIVE: To evaluate the relation between alcohol intake and incidence of type 2 diabetes. RESEARCH DESIGN AND METHODS: This prospective study included 8,663 men with fasting plasma glucose measurements from at least two medical examinations. Alcohol intake was classified into five groups: nondrinkers and four quartiles (Qs) of drinkers according to the amount of alcohol intake. Type 2 diabetes was diagnosed by 1997 American Diabetes Association criteria. RESULTS: There were 149 incident cases of type 2 diabetes during 52,588 person-years of follow-up. There was a U-shaped association between alcohol intake and diabetes, with the lowest incidence of diabetes at Q2 (61.9-122.7 g/week). As compared with Q2, men in Q3 and Q4 had a 2.2- (95% CI 1.2-3.9, P = 0.01) and 2.4-fold (1.4-4.4, P<0.01) risk of developing diabetes, while nondrinkers and men in Q1 had 1.8- (1.0-3.3, P<0.05) and 1.4-fold (0.7-2.6, P = 0.34) higher risk of diabetes, respectively. These associations persisted after adjustment for age, fasting plasma glucose, smoking, BMI, blood pressure, serum triglyceride concentration, cardiorespiratory fitness, HDL cholesterol, waist circumference, and parental diabetes. CONCLUSIONS: We observed an elevated risk of developing type 2 diabetes in nondrinkers and men with high alcohol intakes, when compared with men who reported moderate alcohol intake. Men with a high alcohol intake may be able to reduce their risk of developing type 2 diabetes if they drink less.

Low fasting plasma glucose level as a predictor of cardiovascular disease and all-cause mortality.

BACKGROUND: Although medical textbooks usually classify fasting plasma glucose <70 or 80 mg/dL (<3.89 or 4.44 mmol/L) as abnormal, the prognosis for patients with low fasting plasma glucose is unclear. METHODS AND RESULTS: We conducted prospective cohort studies among 40 069 men and women to investigate the association between fasting plasma glucose levels and cardiovascular disease and all-cause mortality. We documented a U-shaped relation between fasting plasma glucose and mortality. In addition to diabetes and impaired fasting glucose levels, low fasting plasma glucose levels were also associated with high mortality. After multivariate adjustment for age, sex, study population, ethnicity, current smoking status, high blood pressure, total cholesterol, body mass index, triglycerides, history of cardiovascular disease and cancer, and a family history of cardiovascular disease, patients with fasting plasma glucose <70 mg/dL (<3.89 mmol/L) had a 3.3-fold increased risk of cardiovascular disease mortality, and patients with fasting plasma glucose 70 to 79 mg/dL (3.89 to 4.43 mmol/L) had a 2.4-fold increased risk compared with the risk in patients with fasting plasma glucose 80 to 109 mg/dL (4.44 to 6.05 mmol/L) (tests for trend P<0.0001). Participants with low fasting plasma glucose levels also had increased risk of all-cause mortality (test for trend P<0.0001). CONCLUSIONS: Participants with low fasting plasma glucose levels had a high risk of cardiovascular disease and all-cause mortality.

Low cardiorespiratory fitness and physical inactivity as predictors of mortality in men with type 2 diabetes.

BACKGROUND: Although physical activity is recommended as a basic treatment for patients with diabetes, its long-term association with mortality in these patients is unknown. OBJECTIVE: To evaluate the association of low cardiorespiratory fitness and physical inactivity with mortality in men with type 2 diabetes. DESIGN: Prospective cohort study. SETTING: Preventive medicine clinic. PATIENTS: 1263 men (50+/-10 years of age) with type 2 diabetes who received a thorough medical examination between 1970 and 1993 and were followed for mortality up to 31 December 1994. MEASUREMENTS: Cardiorespiratory fitness measured by a maximal exercise test, self-reported physical inactivity at baseline, and subsequent death determined by using the National Death Index. RESULTS: During an average follow-up of 12 years, 180 patients died. After adjustment for age, baseline cardiovascular disease, fasting plasma glucose level, high cholesterol level, overweight, current smoking, high blood pressure, and parental history of cardiovascular disease, men in the low-fitness group had an adjusted risk for all-cause mortality of 2.1 (95% CI, 1.5 to 2.9) compared with fit men. Men who reported being physically inactive had an adjusted risk for mortality that was 1.7-fold (CI, 1.2-fold to 2.3-fold) higher than that in men who reported being physically active. CONCLUSIONS: Low cardiorespiratory fitness and physical inactivity are independent predictors of all-cause mortality in men with type 2 diabetes. Physicians should encourage patients with type 2 diabetes to participate in regular physical activity and improve cardiorespiratory fitness.

Relationship between low cardiorespiratory fitness and mortality in normal-weight, overweight, and obese men.

CONTEXT: Recent guidelines for treatment of overweight and obesity include recommendations for risk stratification by disease conditions and cardiovascular disease (CVD) risk factors, but the role of physical inactivity is not prominent in these recommendations. OBJECTIVE: To quantify the influence of low cardiorespiratory fitness, an objective marker of physical inactivity, on CVD and all-cause mortality in normal-weight, overweight, and obese men and compare low fitness with other mortality predictors. DESIGN: Prospective observational data from the Aerobics Center Longitudinal Study. SETTING: Preventive medicine clinic in Dallas, Tex. PARTICIPANTS: A total of 25714 adult men (average age, 43.8 years [SD, 10.1 years]) who received a medical examination during 1970 to 1993, with mortality follow-up to December 31, 1994. MAIN OUTCOME MEASURES: Cardiovascular disease and all-cause mortality based on mortality predictors (baseline CVD, type 2 diabetes mellitus, high serum cholesterol level, hypertension, current cigarette smoking, and low cardiorespiratory fitness) stratified by body mass index. RESULTS: During the study period, there were 1025 deaths (439 due to CVD) during 258781 man-years of follow-up. Overweight and obese men with baseline CVD or CVD risk factors were at higher risk for all-cause and CVD mortality compared with normal-weight men without these predictors. Using normal-weight men without CVD as the referent, the strongest predictor of CVD death in obese men was baseline CVD (age- and examination year-adjusted relative risk [RR], 14.0; 95% confidence interval [CI], 9.4-20.8); RRs for obese men with diabetes mellitus, high cholesterol, hypertension, smoking, and low fitness were similar and ranged from 4.4 (95% CI, 2.7-7.1) for smoking to 5.0 (95% CI, 3.6-7.0) for low fitness. Relative risks for all-cause mortality in obese men ranged from 2.3 (95% CI, 1.7-2.9) for men with hypertension to 4.7 (95% CI, 3.6-6.1) for those with CVD at baseline. Relative risk for all-cause mortality in obese men with low fitness was 3.1 (95% CI, 2.5-3.8) and in obese men with diabetes mellitus 3.1 (95% CI, 2.3-4.2) and as slightly higher than the RRs for obese men who smoked or had high cholesterol levels. Low fitness was an independent predictor of mortality in all body mass index groups after adjustment for other mortality predictors. Approximately 50% (n = 1674) of obese men had low fitness, which led to a population-attributable risk of 39% for CVD mortality and 44% for all-cause mortality. Baseline CVD had population attributable risks of 51% and 27% for CVD and all-cause mortality, respectively. CONCLUSIONS: In this analysis, low cardiorespiratory fitness was a strong and independent predictor of CVD and all-cause mortality and of comparable importance with that of diabetes mellitus and other CVD risk factors.

The association between cardiorespiratory fitness and impaired fasting glucose and type 2 diabetes mellitus in men.

BACKGROUND: Several studies show an inverse association between self-reported physical activity and type 2 diabetes. It is not known whether physical activity or cardiorespiratory fitness is associated with the onset of objectively determined impaired fasting glucose and type 2 diabetes. OBJECTIVE: To determine whether cardiorespiratory fitness, an objective marker of physical activity, is associated with risk for impaired fasting glucose and type 2 diabetes. DESIGN: Population-based prospective study. SETTING: Preventive medicine clinic. PATIENTS: 8633 nondiabetic men (of whom 7511 did not have impaired fasting glucose) who were examined at least twice. MEASUREMENTS: Cardiorespiratory fitness (determined by a maximal exercise test on a treadmill), fasting plasma glucose level, and other clinical and personal characteristics and incidence of impaired fasting glucose and type 2 diabetes. RESULTS: During an average follow-up of 6 years, 149 patients developed type 2 diabetes and 593 patients developed impaired fasting glucose. After age, cigarette smoking, alcohol consumption, and parental diabetes were considered, men in the low-fitness group (the least fit 20% of the cohort) at baseline had a 1.9-fold risk (95% CI, 1.5- to 2.4-fold) for impaired fasting glucose and a 3.7-fold risk (CI, 2.4- to 5.8-fold) for diabetes compared with those in the high-fitness group (the most fit 40% of the cohort). The risk for impaired fasting glucose was elevated in older men and those with a higher body mass index. Age, body mass index, blood pressure, triglyceride level, and a history of parental diabetes were also directly related to risk for type 2 diabetes. CONCLUSIONS: Low cardiorespiratory fitness was associated with increased risk for impaired fasting glucose and type 2 diabetes. A sedentary lifestyle may contribute to the progression from normal fasting glucose to impaired fasting glucose and diabetes. Risk for type 2 diabetes was elevated in older persons and those with higher body mass index, blood pressure, and triglyceride levels and a parental history of diabetes.

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.

Controlling blood lipids part 1: a practical role for diet and exercise.

Dietary measures that can improve blood lipids include limiting consumption of saturated fats, trans fatty acids, simple sugars, and stearic acid and consuming adequate amounts of vitamins C and E and beta-carotene. Eating certain fish once a week may significantly lower the risk of sudden cardiac death. Aerobic exercise three times per week for 20 to 30 minutes at 60% to 80% of the age-predicted maximum heart rate may also improve lipid levels. Research indicates that modest fitness reduces overall mortality, and higher levels benefit those who have abnormally high cholesterol. Moderate alcohol consumption may influence a person's lipid profile favorably but is not recommended for nondrinkers.

Controlling blood lipids part 2: when and how to use medication.

Drug treatment for abnormal blood lipids includes bile acid sequestrants, fibric acid derivatives, statins, and niacin. Statins generally offer the best combination of safety and effectiveness. Hormone replacement therapy reduces the risk of coronary artery disease in postmenopausal women. The National Cholesterol Education Program offers clear guidelines as to what levels of low-density lipoprotein cholesterol (LDL-C) should trigger consideration of drug treatment, and the authors suggest what levels of high-density lipoprotein cholesterol should prompt treatment. Measurements of small dense LDL-C and lipoprotein(a) may also be helpful in decisions about drug treatment for selected patients.

Influences of cardiorespiratory fitness and other precursors on cardiovascular disease and all-cause mortality in men and women.

OBJECTIVE: To quantify the relation of cardiorespiratory fitness to cardiovascular disease (CVD) mortality and to all-cause mortality within strata of other personal characteristics that predispose to early mortality. DESIGN--Observational cohort study. We calculated CVD and all-cause death rates for low (least fit 20%), moderate (next 40%), and high (most fit 40%) fitness categories by strata of smoking habit, cholesterol level, blood pressure, and health status. SETTING: Preventive medicine clinic. STUDY PARTICIPANTS: Participants were 25341 men and 7080 women who completed preventive medical examinations, including a maximal exercise test. MAIN OUTCOME MEASURES: Cardiovascular disease and all-cause mortality. RESULTS: There were 601 deaths during 211996 man-years of follow-up, and 89 deaths during 52982 woman-years of follow-up. Independent predictors of mortality among men, with adjusted relative risks (RRs) and 95% confidence intervals (CIs), were low fitness (RR, 1.52;95% CI, 1.28-1.82), smoking (RR, 1.65; 95% CI, 1.39-1.97), abnormal electrocardiogram (RR, 1.64;95% CI, 1.34-2.01), chronic illness (RR, 1.63;95% CI, 1.37-1.95), increased cholesterol level (RR, 1.34; 95% CI, 1.13-1.59), and elevated systolic blood pressure (RR, 1.34; 95% CI, 1.13-1.59). The only statistically significant independent predictors of mortality in women were low fitness (RR, 2.10; 95% Cl, 1.36-3.21) and smoking (RR, 1.99; 95% Cl, 1.25-3.17). Inverse gradients were seen for mortality across fitness categories within strata of other mortality predictors for both sexes. Fit persons with any combination of smoking, elevated blood pressure, or elevated cholesterol level had lower adjusted death rates than low-fit persons with none of these characteristics. CONCLUSIONS: Low fitness is an important precursor of mortality. The protective effect of fitness held for smokers and nonsmokers, those with and without elevated cholesterol levels or elevated blood pressure, and unhealthy and healthy persons. Moderate fitness seems to protect against the influence of these other predictors on mortality. Physicians should encourage sedentary patients to become physically active and thereby reduce the risk of premature mortality.

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.

Changes in physical fitness and all-cause mortality. A prospective study of healthy and unhealthy men.

OBJECTIVE: To evaluate the relationship between changes in physical fitness and risk of mortality in men. DESIGN: Prospective study, with two clinical examinations (mean interval between examinations, 4.9 years) to assess change or lack of change in physical fitness as associated with risk of mortality during follow-up after the subsequent examination (mean follow-up from subsequent examination, 5.1 years). SETTING: Preventive medicine clinic. STUDY PARTICIPANTS: Participants were 9777 men given two preventive medical examinations, each of which included assessment of physical fitness by maximal exercise tests and evaluation of health status. MAIN OUTCOME MEASURES: All cause (n = 223) and cardiovascular disease (n = 87) mortality. RESULTS: The highest age-adjusted all-cause death rate was observed in men who were unfit at both examinations (122.0/10,000 man-years); the lowest death rate was in men who were physically fit at both examinations (39.6/10,000 man-years). Men who improved from unfit to fit between the first and subsequent examinations had an age-adjusted death rate of 67.7/10,000 man-years. This is a reduction in mortality risk of 44% (95% confidence interval, 25% to 59%) relative to men who remained unfit at both examinations. Improvement in fitness was associated with lower death rates after adjusting for age, health status, and other risk factors of premature mortality. For each minute increase in maximal treadmill time between examinations, there was a corresponding 7.9% (P = .001) decrease in risk of mortality. Similar results were seen when the group was stratified by health status, and for cardiovascular disease mortality. CONCLUSIONS: Men who maintained or improved adequate physical fitness were less likely to die from all causes and from cardiovascular disease during follow-up than persistently unfit men. Physicians should encourage unfit men to improve their fitness by starting a physical activity program.

The safety of exercise testing.

Although exercise testing is a safe activity for the vast majority of individuals being tested, complications during or soon after testing do occur, and safety is an extremely important consideration. In reviewing published rates of complications, it appears that complication rates around 5 per 10,000 tests and death rates around 0.5 per 10,000 tests might be expected. The rate of complications and deaths in our clinic is much lower than these published rates, but our population is, in general, a healthier population than those reported on in other studies. It is instructive to review the details of exercise tests in which complications have occurred, although sometimes it is impossible to predict that an untoward occurrence is imminent. Exercise testing soon after myocardial infarction or angioplasty can generally be conducted safely by knowledgeable professionals, although submaximal testing is recommended under these circumstances. Following accepted contraindications to testing and accepted indications for terminating an exercise test is still very important to ensure the safety of testing. If one desires to step outside these recognized guidelines, the anticipated benefits of testing must clearly outweigh the inherent risks. Any testing facility must have appropriate safety equipment, including a defibrillator, and personnel must be regularly drilled in responding to emergencies. In reviewing our experience at the Cooper Clinic, practical suggestions have been offered that should make exercise testing, which is already a very safe activity, even safer.