Milton Z. Nichaman

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

Epidemiologic studies of coronary heart disease and stroke in Japanese men living in Japan, Hawaii and California: Demographic, physical, dietary and biochemical characteristics

CORONARY heart disease and stroke continue to be the subjects of intensive epidemiologic study in many parts of the world. Particular research interest has been focused on the apparent differences in the prevalence and incidence of coronary heart disease among various racial and geographically separate population groups [l-4]. As a result of these intensive efforts to explain the epidemiology of these diseases and to determine methods of control, pioneering studies have established risk factors for coronary heart disease [.5-lo] and are now establishing such risk factors for cerebrovascular disease as well [l 1, 121. At present, multifactorial causation has been accepted, the strongest evidence being the demonstrated relationship between elevated blood lipid levels, elevated blood pressure levels, and heavy cigarette smoking with coronary atherosclerosis and its clinical manifestations [5-10, 13-161. Studies in many countries have shown that in most populations exhibiting a high serum cholesterol in men, there is also a high prevalence of coronary heart disease [17-191. Usually these people eat a diet high in fat, especially in the form of meat and dairy fat. In most populations with low cholesterol levels and a low prevalence of coronary heart disease, the intake of fat is low and the fat which is ingested is derived primarily from fish and vegetable oils [ 17-201.

Visceral Fat Is an Independent Predictor of All‐cause Mortality in Men

Objective: To examine the independent associations of abdominal fat (visceral and subcutaneous) and liver fat with all‐cause mortality.

Cardiorespiratory fitness is associated with lower abdominal fat independent of body mass index.

PURPOSE To determine whether, for a given body mass index (BMI), men with high cardiorespiratory fitness (CRF) have lower waist circumference (WC) and less total abdominal, abdominal subcutaneous, and visceral adipose tissue (AT) compared with men with low CRF. METHODS Subjects were categorized into HIGH CRF (N = 169) and LOW CRF (N = 124) groups based on age and CRF measured using a maximal treadmill test. Total abdominal, abdominal subcutaneous and visceral AT were measured by computerized tomography. RESULTS For a given BMI, men in the HIGH CRF group had significantly lower WC (P < 0.001), total abdominal (P < 0.001), visceral AT (P < 0.001), and abdominal subcutaneous AT (P < 0.001) compared with men in the LOW CRF group. CONCLUSION These findings suggest that the ability of CRF to attenuate the health risks associated with BMI may be partially mediated through a reduction in abdominal AT. Accordingly, our observations reinforce the importance of regular physical activity in the prevention and reduction of obesity-related health risk independent of a corresponding reduction in body weight.

Change in Level of Physical Activity and Risk of All-Cause Mortality or Reinfarction The Corpus Christi Heart Project

BackgroundThe role of physical activity (PA) in reducing the risk of all-cause mortality or reinfarction after a first myocardial infarction (MI) remains unresolved, particularly for minority populations. The association between change in level of PA and risk of death or reinfarction was studied in 406 Mexican American and non-Hispanic white women and men who survived a first MI. Methods and ResultsMI patients were interviewed at baseline and annually thereafter about PA, medical history, and risk factors of coronary heart disease. Change in level of PA after the index MI was categorized as (1) sedentary, no change (referent group), (2) decreased activity, (3) increased activity, and (4) active, no change. Over a 7-year period, the relative risk (95% CI) of death was as follows: 0.21 (0.10 to 0.44) for the active, no change group; 0.11 (0.03 to 0.46) for the increased activity group; and 0.49 (0.26 to 0.90) for the decreased activity group. The relative risk of reinfarction was as follows: 0.40 (0.24 to 0.66) for the active, no change group; 0.22 (0.09 to 0.50) for the increased activity group; and 0.93 (0.59 to 1.42) for the decreased activity group. ConclusionsThese findings are consistent with a beneficial role of PA for Mexican American and non-Hispanic white women and men who survive a first MI and have practical implications for the management of MI survivors.

The Relation of Diabetes to the Severity of Acute Myocardial Infarction and Post-Myocardial Infarction Survival in Mexican-Americans and Non-Hispanic Whites: The Corpus Christi Heart Project

The effect of diabetes on survival after myocardial infarction (MI) was examined in a prospective population-based study of individuals hospitalized with MI in a bi-ethnic community of Mexican-Americans and non-Hispanic whites. Among Mexican-Americans, 54% (331 of 610) had diabetes compared with 33% (192 of 589) of non-Hispanic whites (P < 0.001). Among those with diabetes, the prevalence of a history of a cardiac event before the index admission was significantly higher (odds ratio = 1.4, 95% confidence interval [CI] 1.1–1.8) than among nondiabetic subjects. During the index hospitalization, diabetic subjects received cardiac catheterization less frequently than did nondiabetic subjects (45.1 vs. 51.5%, P = 0.03). Diabetic subjects had lower estimated ejection fractions, and the number of coronary arteries with significant obstruction (> 75%) was higher (P < 0.001). The peak creatine phosphokinase and creatine phosphokinase myocardial isoenzyme (CK-MB) levels were similar in diabetic and nondiabetic subjects. Despite a similar infarct size, diabetic subjects had a higher incidence of congestive heart failure (relative ratio = 2.2, 95% CI 1.7–2.8), more adverse indexes of short-term and long-term prognosis, and a longer average hospital stay (12.1 vs. 8.9 days, P < 0.01). After adjustment for age, sex, and ethnicity, the cumulative risk for total mortality, over 44 months of follow-up, was 37.4% among diabetic compared with 23.3% among nondiabetic subjects (P < 0.001). Diabetic subjects had a higher 28-day case-fatality rate post-MI as well as higher long-term mortality. In conclusion, diabetic subjects have similar size infarcts compared with nondiabetic subjects, but they have a more complicated hospital course and higher total mortality post-MI. Diabetes had a similar adverse effect on post-MI mortality in both Mexican-Americans and non-Hispanic whites.

Higher blood pressure in middle-aged American adults with less education-role of multiple dietary factors: the INTERMAP study.

Extensive evidence exists that an inverse relation between education and blood pressure prevails in many adult populations, but little research has been carried out on reasons for this finding. A prior goal of the INTERMAP Study was to investigate this phenomenon further, and to assess the role of dietary factors in accounting for it. Of the 4680 men and women aged 40–59 years, from 17 diverse population samples in Japan, Peoples Republic of China, UK, and USA, a strong significant inverse education–BP relation was manifest particularly for the 2195 USA participants, independent of ethnicity. With participants stratified by years of education, and assessment of 100+ dietary variables from four 24-h dietary recalls and two 24-h urine collections/person, graded relationships were found between education and intake of many macro- and micronutrients, electrolytes, fibre, and body mass index (BMI). In multiple linear regression analyses with systolic BP (SBP) and diastolic BP (DBP) of individuals the dependent variables (controlled for ethnicity, other possible nondietary confounders), BMI markedly reduced size of education–BP relations, more so for women than for men. Several nutrients considered singly further decreased size of this association by ⩾10%: urinary 24-h Na and K excretion, Keys dietary lipid score, vegetable protein, fibre, vitamins C and B6, thiamin, riboflavin, folate, calcium, magnesium, and iron. Combinations of these dietary variables and BMI attenuated the education–SBP inverse coefficient by 54–58%, and the education–DBP inverse coefficient by 59–67%, with over half these effects attributable to specific nutrients (independent of BMI). As a result, the inverse education–BP coefficients ceased to be statistically significant. Multiple specific dietary factors together with body mass largely account for the more adverse BP levels of less educated than more educated Americans. Special efforts to improve eating patterns of less educated strata can contribute importantly to overcoming this and related health disparities in the population.

Community-wide coronary heart disease mortality in Mexican Americans equals or exceeds that in non-Hispanic whites: the Corpus Christi heart project ☆

PURPOSE Previous comparisons of coronary heart disease mortality between Mexican Americans and non-Hispanic whites have given paradoxic results: despite their adverse cardiovascular risk profiles, especially a greater prevalence of diabetes, Mexican Americans are reported to have lower rates of mortality from coronary heart disease. SUBJECTS AND METHODS We performed a community-based surveillance among all residents of Nueces County, Texas, aged 25 to 74 years, from 1990 to 1994. All death certificates were obtained and coded, and deaths potentially related to coronary heart disease were selected and validated by standardized methods blinded to ethnicity. Validated in-hospital and out-of-hospital coronary heart disease mortality was compared between 785 Mexican Americans and 862 non-Hispanic white women and men. RESULTS Validated coronary heart disease mortality in Mexican Americans exceeded that for non-Hispanic whites in the same community. Among women, definite coronary heart disease mortality was 40% greater among Mexican Americans (rate ratio [RR] 1.43, 95% confidence interval [CI]: 1.12 to 1.82), as was all coronary heart disease mortality (RR, 1.32, 95% CI: 1.08 to 1.63). Among men, Mexican Americans had greater rates of all (RR, 1.11; 95% CI: 0.96 to 1.28) and definite coronary heart disease mortality (RR, 1.16; 95% CI: 0.91 to 1.47), but the associations were not statistically significant. CONCLUSIONS When community-wide mortality rates from coronary heart disease are properly validated, Mexican Americans have rates equal to or higher than those of non-Hispanic whites. Community-based surveillance with validation of coronary heart disease as the cause of death is necessary to avoid the errors that occur with the use of death certificates alone.

Greater Incidence of Hospitalized Myocardial Infarction Among Mexican Americans Than Non-Hispanic Whites The Corpus Christi Heart Project, 1988-1992

BACKGROUND Since Mexican Americans have adverse patterns of risk factors for myocardial infarction relative to non-Hispanic whites, the incidence of myocardial infarction should be greater among Mexican Americans than among non-Hispanic whites. This expectation conflicts with reports generated from death certificate registries. METHODS AND RESULTS Data regarding myocardial infarction attacks and incident events were collected for a 4-year period in the Corpus Christi Heart Project, a population-based surveillance project for hospitalized coronary heart disease events. For both women and men, Mexican Americans experienced greater hospitalization rates for both attacks and incident events than non-Hispanic whites. Age-adjusted attack rate ratios comparing Mexican Americans with non-Hispanic whites were 1.59 (95% CI, 1.05 to 2.41) and 1.31 (95% CI, 1.18 to 1.45) among women and men, respectively. Corresponding incidence ratios were 1.52 (95% CI, 1.28 to 1.80) and 1.25 (95% CI, 1.10 to 1.42). CONCLUSIONS This is the first report documenting greater incidence of hospitalized myocardial infarction among Mexican Americans than among non-Hispanic whites, a biologically plausible finding given the risk factor patterns observed in the Mexican-American population. Public health planners and clinicians should be aware of the importance of myocardial infarction as a health problem in the Mexican-American population. Culturally appropriate prevention strategies should be developed for and tested in Mexican-American populations.

Development of Cardiovascular Risk Factors From Ages 8 to 18 in Project HeartBeat! Study Design and Patterns of Change in Plasma Total Cholesterol Concentration

BACKGROUND Project HeartBeat! is a longitudinal study of the development of cardiovascular risk factors as growth processes. Patterns of serial change, or trajectories, from ages 8 to 18 years for plasma total cholesterol concentration (TC) and percent body fat illustrate the design and synthetic cohort approach of the study. METHODS AND RESULTS Six hundred seventy-eight children (49.1% female, 20.1% black) entered the study at ages 8, 11, and 14 years and were followed up with examinations every 4 months for < or = 4 years. Multilevel analysis demonstrated trajectories for population mean values of TC and percent body fat in sex-specific synthetic cohorts from ages 8 to 18 years. Polyphasic patterns of change in TC were confirmed, with notable sex differences in age patterns and with minimum mean values of TC of 3.85 mmol/L for females and 3.59 for males. As illustrated by data for males, the approximate 75th percentile values of mean TC ranged from 4.78 mmol/L at its early peak to 4.06 at its late-teen nadir. Percent body fat exhibited a trajectory closely parallel with that for TC only for males and appeared to be unrelated for females. CONCLUSIONS The polyphasic trajectory for TC from ages 8 to 18 years differs between females and males, indicates marked age variation in 75th percentile values and, in males only, closely parallels the trajectory for percent body fat. These and other results indicate the value of both follow-up every 4 months across age intervals to detect rapid risk factor change and the synthetic cohort approach for gaining new insights into the dynamics and possible determinants of this change from ages 8 to 18 years.