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1.  Cross-sectional association between maximal estimated cardiorespiratory fitness, cardiometabolic risk factors and metabolic syndrome for men and women in the Aerobics Center Longitudinal Study 
To examine the relationship between estimated maximal cardiorespiratory fitness (CRF) and metabolic syndrome (MetS).
Aerobics Center Longitudinal Study (N=38,659) participants examined between 1979–2006.
We performed a cross-sectional analysis of participants to examine CRF levels defined as low (lower 20%), moderate (middle 40%) and high (upper 40%) of age/gender specific distributions versus NCEP derived MetSyn expressed as a summed z-score continuous variable. We used a general linear model for continuous variables, chi-square for distribution of categorical variables, and multiple linear regression for single and cumulative MetS scores adjusted for BMI, smoking status, alcohol intake and family history of cardiovascular disease.
We observed significant inverse trends for MetS vs. CRF in both genders (p-for-trend, < 0.001). CRF associations vs. individual components were: Waist circumference (men, β= −0.14, r2 = 0.78; women, β= −0.04, r2 = 0.71), triglycerides (men, β= −0.29, r2 = 0.18; women, β= −0.17, r2 = 0.18), HDL-cholesterol (men, β= 0.25, r2 = 0.17; women, β= 0.08, r2 = 0.19), fasting glucose (men, β= −0.09, r2 = 0.09; women, β= 0.09, r2 = 0.01), systolic blood pressure (men, β= −0.09, r2 = 0.09; women, β= −0.01, r2 = 0.21), and diastolic blood pressure (men, β= −0.07, r2 = 0.12; women, β= −0.05, r2 = 0.14). All associations except for systolic blood pressure (both genders) and glucose (women) are significant (p<0.001).
CRF demonstrated a strong inverse relationship with MetS in both genders with the strongest single associative component being waist circumference.
PMCID: PMC3622904  PMID: 23391253
Metabolic syndrome; exercise; fitness; syndrome X
2.  Body adiposity index and all-cause and cardiovascular disease mortality in men 
Obesity (Silver Spring, Md.)  2013;21(9):1870-1876.
To evaluate the association of body adiposity index (BAI) with all-cause and cardiovascular disease (CVD) mortality risk.
Design and Methods
The current analysis comprised 19 756 adult men who enrolled in the Aerobics Centre Longitudinal Study and completed a baseline examination during 1988-2002. All-cause and CVD mortality was registered till December 31, 2003.
During an average follow-up of 8.3 years (163 844 man-years), 353 deaths occurred (101 CVD deaths). Age- and examination year-adjusted hazard ratios (HRs) and 95% confidence intervals (95% CIs) for all-cause mortality risk were higher for men with high values of BMI (HR = 1.63, 95% CI = 1.19–2.23), waist circumference (1.55, 1.22-1.96) and percentage of body fat (%BF) (1.36, 1.04-1.31), but not for men with high values of BAI (1.28, 0.98-1.66). The HRs for CVD mortality risks were higher for men with high values in all adiposity measures (HRs ranged from 1.73 to 2.06). Most of these associations, however, became nonsignificant after adjusting for multiple confounders including cardiorespiratory fitness.
BAI is not a better predictor of all-cause and CVD mortality risk than BMI, waist circumference or %BF.
PMCID: PMC3695010  PMID: 23512375
Adiposity; body mass index; mortality; adults
3.  The intriguing metabolically healthy but obese phenotype: cardiovascular prognosis and role of fitness 
European Heart Journal  2012;34(5):389-397.
Current knowledge on the prognosis of metabolically healthy but obese phenotype is limited due to the exclusive use of the body mass index to define obesity and the lack of information on cardiorespiratory fitness. We aimed to test the following hypotheses: (i) metabolically healthy but obese individuals have a higher fitness level than their metabolically abnormal and obese peers; (ii) after accounting for fitness, metabolically healthy but obese phenotype is a benign condition, in terms of cardiovascular disease and mortality.
Methods and results
Fitness was assessed by a maximal exercise test on a treadmill and body fat per cent (BF%) by hydrostatic weighing or skinfolds (obesity = BF% ≥25 or ≥30%, men or women, respectively) in 43 265 adults (24.3% women). Metabolically healthy was considered if meeting 0 or 1 of the criteria for metabolic syndrome. Metabolically healthy but obese participants (46% of the obese subsample) had a better fitness than metabolically abnormal obese participants (P < 0.001). When adjusting for fitness and other confounders, metabolically healthy but obese individuals had lower risk (30–50%, estimated by hazard ratios) of all-cause mortality, non-fatal and fatal cardiovascular disease, and cancer mortality than their metabolically unhealthy obese peers; while no significant differences were observed between metabolically healthy but obese and metabolically healthy normal-fat participants.
(i) Higher fitness should be considered a characteristic of metabolically healthy but obese phenotype. (ii) Once fitness is accounted for, the metabolically healthy but obese phenotype is a benign condition, with a better prognosis for mortality and morbidity than metabolically abnormal obese individuals.
PMCID: PMC3561613  PMID: 22947612
Cardiovascular diseases; Heart diseases; Metabolic syndrome; Mortality; Obesity; Physical fitness
4.  Cardiorespiratory Fitness as a Predictor of Dementia Mortality in Men and Women 
There is evidence that physical activity may reduce the risk of developing Alzheimer’s disease and dementia. However, few reports have examined the physical activity-dementia association with objective measures of physical activity. Cardiorespiratory fitness (hereafter called fitness) is an objective reproducible measure of recent physical activity habits.
We sought to determine whether fitness is associated with lower risk for dementia mortality in women and men.
We followed 14,811 women and 45,078 men, ages 20-88 at baseline, for an average of 17 years. All participants completed a preventive health examination at the Cooper Clinic in Dallas, Texas during 1970-2001. Fitness was measured with a maximal treadmill exercise test, with results expressed in maximal metabolic equivalents (METs). The National Death Index identified deaths through 2003. Cox proportional hazards models were used to examine the association between baseline fitness and dementia mortality, adjusting for age, sex, examination year, body mass index, smoking, alcohol use, abnormal ECGs, and health status.
There were 164 deaths with dementia listed as the cause during 1,012,125 person-years of exposure. Each 1-MET increase in fitness was associated with a 14% lower adjusted risk of dementia mortality (95% confidence interval, CI 6%-22%). With fitness expressed in tertiles, adjusted hazard ratios (HRs) for those in the middle and high fitness groups suggest their risk of dementia mortality was less than half that of those in the lowest fitness group (respectively: HR 0.44, CI 0.26-0.74; HR 0.49, CI 0.26-0.90).
Greater fitness was associated with lower risk of mortality from dementia in a large cohort of men and women.
PMCID: PMC3908779  PMID: 21796048
physical fitness; cognitive function; Alzheimer’s disease; vascular dementia; metabolic equivalents (METs)
5.  Percentage of deaths attributable to poor cardiovascular health lifestyle factors: Findings from the Aerobics Center Longitudinal Study 
We assessed the effects of the four newly defined American Heart Association (AHA) lifestyle factors on mortality by examining the associated population attributable fractions (PAFs) of these factors.
Slightly modified AHA cardiovascular health factors (smoking, BMI, cardiorespiratory fitness, and diet) were measured among 11,240 (24% women) participants from the Aerobics Center Longitudinal Study between 1987 and 1999. The cohort was followed to December 31, 2003 or death. PAFs were calculated as the proportionate reduction in death attributable to identified risk factors.
During an average 12 years of follow-up, 268 deaths occurred. Low fitness had the highest PAFs at the 5th, 10th, and 15th year of follow-up, respectively: 6.6%, 6.4%, and 5.5%. Current smokers had the second highest PAFs at the 5th, 10th, and 15th year of follow-up, respectively: 5.4%, 5.2%, and 5.0%. Additional adjusting for other confounders in the model did not change the above associations. The PAFs for overweight or obesity and unhealthy diet were not significant in the current analyses.
Assuming a causal relationship between smoking, low fitness and mortality, avoidance of both would have prevented 13% of the deaths in the current population. Preventive interventions to increase physical activity and stop smoking would most likely promote longevity.
PMCID: PMC3777646  PMID: 24058738
6.  Longitudinal Cardiorespiratory Fitness Algorithms for Clinical Settings 
Non-exercise algorithms are cost-effective methods to estimate cardiorespiratory fitness (CRF) in healthcare settings. The limitation of current non-exercise models is that they were developed with cross-sectional data.
To extend the non-exercise research by developing algorithms for men and women using longitudinal data on indicators available in healthcare settings.
The sample included 1325 women (aged 20–78 years) and 10,040 men (aged 20–86 years) who completed from two to 21 maximal treadmill tests between 1977 and 2005. The data were analyzed in 2011 and 2012. The dependent variable was CRF measured by treadmill test. The independent variables were age, body composition (percentage fat or BMI); waist circumference, self-reported physical activity; resting heart rate; and smoking behavior.
Linear mixed-models regression showed that all variables were independently related to CRF. There was a positive association between CRF and physical activity. Higher levels of body composition were linked to lower CRF. High resting heart rate and smoking resulted in lower estimates of CRF. The error estimates of the percentage fat algorithms were: women, 1.41 METs (95% CI=1.35, 1.47); and men, METs 1.54 (95% CI=1.51, 1.55). The BMI models were somewhat less accurate: women, METs 1.51 (95% CI=1.45, 1.58); and men, 1.66 METs (95% CI=1.63, 1.68).
These results showed that the CRF of women and men can be estimated from easily obtained health indicators. The longitudinal non-exercise algorithms provide models to accurately estimate CRF changes associated with aging and provide cost-effective algorithms to track CRF over time with health indicators available in healthcare settings.
PMCID: PMC3479664  PMID: 23079174
7.  Effects of Muscular Strength on Cardiovascular Risk Factors and Prognosis 
Physical fitness is one of the strongest predictors of individual future health status. Together with cardiorespiratory fitness (CRF), muscular strength (MusS) has been increasingly recognized in the pathogenesis and prevention of chronic disease. We review the most recent literature on the effect of MusS in the development of cardiovascular disease (CVD), with special interest in elucidating its specific benefits beyond those from CRF and body composition. MusS has shown an independent protective effect on all-cause and cancer mortality in healthy middle-aged men, as well as in men with hypertension (HTN) and patients with heart failure. It has also been inversely associated with age-related weight and adiposity gains, risk of HTN, and prevalence and incidence of the metabolic syndrome. In children and adolescents, higher levels of muscular fitness have been inversely associated with insulin resistance, clustered cardiometabolic risk and inflammatory proteins. Generally, the influence of muscular fitness was weakened but remained protective after considering CRF. Also interestingly, higher levels of muscular fitness seems to some extent counteract the adverse cardiovascular profile of overweight and obese individuals. As many of the investigations have been conducted with non-Hispanic white men, it is important to examine how race/ethnicity and gender may affect these relationships. To conclude, most important effects of resistance training (RT) are also summarized, to better understand how higher levels of muscular fitness may result in a better cardiovascular prognosis and survival.
PMCID: PMC3496010  PMID: 22885613
muscular strength; cardiorespiratory fitness; cardiovascular disease; resistance training
8.  Decline in Cardiorespiratory Fitness and Odds of Incident Depression 
Studies of physical activity and incidence of physician-diagnosed depression have been limited to a single estimate of self-reported physical activity exposure, despite follow-up periods lasting many years.
To examine longitudinal change in cardiorespiratory fitness, an objective marker of habitual physical activity, and incident depression complaints made to a physician.
Cardiorespiratory fitness assessed at four clinic visits between 1971 and 2006, each separated by an average of 2–3 years, was used to objectively measure cumulative physical activity exposure in cohorts of 7936 men and 1261 women, aged 20–85 years, from the Aerobics Center Longitudinal Study who did not complain of depression at their first clinic visit in 1971–2003. Data were analyzed in August 2010.
Across subsequent visits, there were 446 incident cases in men and 153 cases in women. After adjustment for age, time between visits, BMI at each visit, and fitness at Visit 1, each 1-minute decline in treadmill endurance (i.e., a decline in cardiorespiratory fitness of approximately 1 half-MET) between ages 51 and 55 years in men and ages 53 and 56 years in women, increased the odds of incident depression complaints by approximately 2% and 9.5%, respectively. The increased odds remained significant but were attenuated to 1.3% and 5.4% after further adjustment at each visit for smoking, alcohol use, chronic medical conditions, anxiety, and sleep problems.
Maintenance of cardiorespiratory fitness during late middle-age, when decline in fitness typically accelerates, helps protect against the onset of depression complaints made to a physician.
PMCID: PMC3478961  PMID: 22992353
9.  A prospective study of cardiorespiratory fitness and breast cancer mortality 
Physical activity may protect against breast cancer. Few prospective studies have evaluated breast cancer mortality in relation to cardiorespiratory fitness, an objective marker of physiologic response to physical activity habits.
We examined the association between cardiorespiratory fitness and risk of death from breast cancer in the Aerobics Center Longitudinal Study. Women (N=14,811), aged 20 to 83 years with no prior breast cancer history, received a preventive medical examination at the Cooper Clinic in Dallas, TX, between 1970 and 2001. Mortality surveillance was completed through December 31, 2003. Cardiorespiratory fitness was quantified as maximal treadmill exercise test duration and was categorized for analysis as low (lowest 20% of exercise duration), moderate (middle 40%), and high (upper 40%). At baseline, all participants were able to complete the exercise test to at least 85% of their age-predicted maximal heart rate.
A total of 68 breast cancer deaths occurred during follow-up (mean=16 years). Age-adjusted breast cancer mortality rates per 10,000 woman-years were 4.4, 3.2, and 1.8 for low, moderate, and high cardiorespiratory fitness groups, respectively (trend P = 0.008). After further controlling for body mass index, smoking, drinking, chronic conditions, abnormal exercise electrocardiogram responses, family history of breast cancer, oral contraceptive use, and estrogen use, hazard ratios (95% CI) for breast cancer mortality across incremental cardiorespiratory fitness categories were 1.00 (referent), 0.67 (0.35–1.26), 0.45 (0.22–0.95); trend P = 0.04.
These results indicate that cardiorespiratory fitness is associated with a reduced risk of dying from breast cancer in women.
PMCID: PMC3774121  PMID: 19276861
Epidemiology; Prevention; Death from breast cancer; Physical activity
10.  Muscular strength and adiposity as predictors of adulthood cancer mortality in men 
We examined the associations between muscular strength, markers of overall and central adiposity and cancer mortality in men.
Prospective cohort study including 8,677 men aged 20-82 years followed from 1980 to 2003. Participants were enrolled in The Aerobics Centre Longitudinal Study, the Cooper Clinic in Dallas, Texas, U.S. Muscular strength was quantified by combining 1-repetition maximal measures for leg and bench presses. Adiposity was assessed by body mass index (BMI), percent body fat, and waist circumference.
Cancer death rates per 10,000 person-years adjusted for age and examination year were: 17.5, 11.0, and 10.3 across incremental thirds of muscular strength (P=0.001); 10.9, 13.4, and 20.1 across BMI groups of 18.5-24.9, 25.0-29.9, and ≥30kg/m2, respectively (P=0.008); 11.6 and 17.5 for normal (<25%) and high percent body fat (≥25%), respectively (P=0.006); and 12.2 and 16.7 for normal (≤102 cm) and high waist circumference (>102 cm), respectively (P=0.06). After adjusting for additional potential confounders, hazard ratios (95% confidence intervals) were 1.00 (referent), 0.65 (0.47-0.90), and 0.61 (0.44-0.85) across incremental thirds of muscular strength, respectively (P=0.003 for linear trend). Further adjustment for BMI, percent body fat, waist circumference, or cardiorespiratory fitness had little effect on the association. The associations of BMI, percent body fat, or waist circumference with cancer mortality did not persist after further adjusting for muscular strength (all P≥0.1).
Higher levels of muscular strength are associated with lower cancer mortality risk in men, independent of clinically established measures of overall and central adiposity, and other potential confounders.
PMCID: PMC3762582  PMID: 19366909
Muscular strength; obesity; cancer; cardiorespiratory fitness; resistance exercise
11.  Effects of Cardiorespiratory Fitness on Aging-glucose Trajectory in a Cohort of Healthy Men 
Annals of epidemiology  2012;22(9):617-622.
We modeled the age-related trajectory of glucose and determined if cardiorespiratory fitness altered the trajectory in a cohort of men from the Aerobics Center Longitudinal Study.
10,092 men free of diagnosed diabetes, CVD, and cancer, aged 20 to 90 years, completed from 2 to 21 health examinations between 1977 and 2005. Cardiorespiratory fitness was measured by a maximal treadmill exercise test and normalized for age. The covariates included waist circumference, hypertension, elevated cholesterol, smoking behavior and physical activity.
Linear mixed models regression analysis showed that fasting glucose increased at a linear rate with aging. Glucose increased at a yearly rate of 0.17 mg/dL (95% confidence interval: 0.16, 0.19). Fitness had little influence on the aging glucose trajectory below age 35, but significantly influenced the trend after age 35 (P for interaction <0.001). The aging-related glucose increases in low fit men (0.25 mg/dL per year) was higher than average fit (0.15 mg/dL per year) and high fit (0.13 mg/dL per year) men.
The aging-related glucose increases in low fit men was nearly double that of high fit men. Our results may suggest that it is possible to delay the age-related glucose impairment through increasing one’s fitness.
PMCID: PMC3723333  PMID: 22763087
Fasting glucose; aging; physical fitness
12.  Adults with Greater Weight Satisfaction Report More Positive Health Behaviors and Have Better Health Status Regardless of BMI 
Journal of Obesity  2013;2013:291371.
Background. Prior studies suggest that weight satisfaction may preclude changes in behavior that lead to healthier weight among individuals who are overweight or obese. Objective. To gain a better understanding of complex relationships between weight satisfaction, weight-related health behaviors, and health outcomes. Design. Cross-sectional analysis of data from the Aerobics Center Longitudinal Study (ACLS). Participants. Large mixed-gender cohort of primarily white, middle-to-upper socioeconomic status (SES) adults with baseline examination between 1987 and 2002 (n = 19,003). Main Outcome Variables. Weight satisfaction, weight-related health behaviors, chronic health conditions, and clinical health indicators. Statistical Analyses Performed. Chi-square test, t-tests, and linear and multivariate logistic regression. Results. Compared to men, women were more likely to be dieting (32% women; 18% men) and had higher weight dissatisfaction. Men and women with greater weight dissatisfaction reported more dieting, yo-yo dieting, and snacking and consuming fewer meals, being less active, and having to eat either more or less than desired to maintain weight regardless of weight status. Those who were overweight or obese and dissatisfied with their weight had the poorest health. Conclusion. Greater satisfaction with one's weight was associated with positive health behaviors and health outcomes in both men and women and across weight status groups.
PMCID: PMC3686087  PMID: 23862054
13.  Impairment of activities of daily living and incident heart failure in community-dwelling older adults 
European Journal of Heart Failure  2012;14(6):581-587.
Instrumental activities of daily living (IADLs) are tasks that are necessary for independent community living. These tasks often require intact physical and cognitive function, the impairment of which may adversely affect health in older adults. In the current study, we examined the association between IADL impairment and incident heart failure (HF) in community-dwelling older adults.
Methods and results
Of the 5795 community-dwelling adults, aged ≥65 years, in the Cardiovascular Health Study, 5511 had data on baseline IADL and were free of prevalent HF. Of these, 1333 (24%) had baseline IADL impairment, defined as self-reported difficulty with one or more of the following tasks: using the telephone, preparing food, performing light and heavy housework, managing finances, and shopping. Propensity scores for IADL impairment, estimated for each of the 5511 participants, were used to assemble a cohort of 1038 pairs of participants with and without IADL impairment who were balanced on 42 baseline characteristics. Centrally adjudicated incident HF occurred in 26% and 21% of matched participants with and without IADL impairment, respectively, during >12 years of follow-up [matched hazard ratio (HR) 1.33; 95% confidence interval (CI) 1.11–1.59; P = 0.002]. Unadjusted and multivariable-adjusted HRs for incident HF before matching were 1.77 (95% CI 1.56–2.01; P < 0.001) and 1.33 (95% CI 1.15–1.54; P < 0.001), respectively. IADL impairment was also associated with all-cause mortality (matched HR 1.19; 95% CI 1.06–1.34; P = 0.004).
Among community-dwelling older adults free of baseline HF, IADL impairment is a strong and independent predictor of incident HF and mortality.
PMCID: PMC3359859  PMID: 22492539
Instrumental activities of daily living; Incident heart failure; Propensity score
14.  A home-based exercise intervention to increase physical activity among people living with HIV: study design of a randomized clinical trial 
BMC Public Health  2013;13:502.
While combination antiretroviral therapy has extended the life expectancy of those infected with human immunodeficiency virus (HIV), there is a high prevalence of comorbidities that increase the risk of cardiovascular morbidity and mortality among people living with HIV/AIDS (PLWHA). The side effects associated with antiretroviral therapy (ART) lead to multiple metabolic disorders, making the management of these metabolic issues and risk of cardiovascular disease (CVD) in those treated with ART a critical issue. Clinical research trials, primarily clinical exercise, rarely include this population due to unique challenges in research methods with underserved minority populations living with a life threatening illness like HIV/AIDS. This paper describes the rationale and design of a randomized clinical trial evaluating the feasibility of a home-based exercise program designed to increase physical activity (PA) and reduce the risk of CVD in PLWHA.
PLWHA being treated with ART will be randomly assigned to one of two groups: a home-based PA intervention or standard care. All participants will receive an educational weight loss workbook and pedometer for self-monitoring of PA. Only those in the intervention group will receive additional elastic Thera-bands® for strength training and behavioral telephone based coaching.
This study will evaluate the feasibility of a home-based program designed to increase PA among PLWHA. Further, it will evaluate the effectiveness of such a program to decrease modifiable risk factors for CVD as a secondary outcome. This study was funded by the NIH/NINR R21 Grant 1R21NRO11281.
Trial registration
Clinical Trial Identifier NCT01377064
PMCID: PMC3668143  PMID: 23706094
Randomized trial; Cardiovascular disease; HIV; Physical activity; Self care; Study design
15.  Ideal Cardiovascular Health and Mortality: Aerobics Center Longitudinal Study 
Mayo Clinic Proceedings  2012;87(10):944-952.
To analyze the relationship of ideal cardiovascular health to disease-specific death.
Patients and Methods
We used data from the Aerobics Center Longitudinal Study from October 9, 1987, to March 3, 1999, to estimate the prevalence of ideal cardiovascular health in 11,993 individuals (24.3% women) and to examine its relationship with deaths from all causes, cardiovascular disease (CVD), and cancer.
During a mean follow-up of 11.6 years, 305 deaths occurred: 70 (23.0%) from CVD and 127 (41.6%) from cancer. In the entire cohort, only 29 individuals (0.2%) had 7 ideal metrics. After adjusting for age, sex, examination year, alcohol intake, and parental history of CVD, risk of death due to CVD was 55% lower in those participants who met 3 or 4 ideal metrics (hazard ratio, 0.45; 95% confidence interval, 0.27-0.77) and 63% lower in those with 5 to 7 ideal metrics (hazard ratio, 0.37; 95% confidence interval, 0.15-0.95), compared with those who met 0 to 2 ideal metrics. Although not significant, there was also a trend toward lower risk of death due to all causes across incremental numbers of ideal metrics. No association was observed for deaths due to cancer.
The prevalence of ideal cardiovascular health was extremely low in a middle-aged cohort of men and women recruited between 1987 and 1999. The American Heart Association construct reflects well the subsequent risk of CVD, as reflected by graded CVD mortality in relation to the number of ideal metrics.
PMCID: PMC3538395  PMID: 23036670
ACLS, Aerobics Center Longitudinal Study; AHA, American Heart Association; BMI, body mass index; CVD, cardiovascular disease; ICD, International Classification of Diseases; MET, metabolic equivalent; NHANES, National Health and Nutrition Examination Survey
16.  Changes in Fitness and Fatness on the Development of Cardiovascular Disease Risk Factors: Hypertension, Metabolic Syndrome, and Hypercholesterolemia 
Our aim was to examine the independent and combined associations of changes in fitness and fatness with the subsequent incidence of the cardiovascular disease (CVD) risk factors of hypertension, metabolic syndrome, and hypercholesterolemia.
The relative and combined contributions of fitness and fatness to health are controversial, and few studies are available on the associations of changes in fitness and fatness with the development of CVD risk factors.
We followed 3,148 healthy adults who received at least three medical examinations. Fitness was determined by a maximal treadmill test. Fatness was expressed by percent body fat and body mass index. Changes in fitness and fatness between the first and second examinations were categorized into loss, stable, or gain groups.
During the 6-year follow-up after the second examination, 752, 426, and 597 adults developed hypertension, metabolic syndrome, and hypercholesterolemia, respectively. Maintaining or improving fitness was associated with lower risk of developing each outcome, whereas increasing fatness was associated with higher risk of developing each outcome, after adjusting for possible confounders and fatness or fitness for each other (all p for trend <0.05). In the joint analyses, the increased risks associated with fat gain appeared to be attenuated, although not completely eliminated, when fitness was maintained or improved. In addition, the increased risks associated with fitness loss were also somewhat attenuated when fatness was reduced.
Both maintaining or improving fitness and preventing fat gain are important to reduce the risk of developing CVD risk factors in healthy adults.
PMCID: PMC3293498  PMID: 22322083
cardiorespiratory fitness; body fatness; hypertension; metabolic syndrome; hypercholesterolemia
17.  Long-Term Effects of Changes in Cardiorespiratory Fitness and Body Mass Index on All-Cause and Cardiovascular Disease Mortality in Men: The Aerobics Center Longitudinal Study 
Circulation  2011;124(23):2483-2490.
The combined associations of changes in cardiorespiratory fitness and body mass index (BMI) with mortality remain controversial and uncertain.
Methods and Results
We examined the independent and combined associations of changes in fitness and BMI with all-cause and cardiovascular disease (CVD) mortality in 14 345 men (mean age 44 years) with at least two medical examinations. Fitness, in metabolic equivalents (METs), was estimated from a maximal treadmill test. BMI was calculated using measured weight and height. Changes in fitness and BMI between the baseline and last examinations over 6.3 years were classified into loss, stable, or gain groups. During 11.4 years of follow-up after the last examination, 914 all-cause and 300 CVD deaths occurred. The hazard ratios (95% confidence intervals) of all-cause and CVD mortality were 0.70 (0.59 to 0.83) and 0.73 (0.54 to 0.98) for stable fitness, and 0.61 (0.51 to 0.73) and 0.58 (0.42 to 0.80) for fitness gain, respectively, compared with fitness loss in multivariable analyses including BMI change. Every 1-MET improvement was associated with 15% and 19% lower risk of all-cause and CVD mortality, respectively. BMI change was not associated with all-cause or CVD mortality after adjusting for possible confounders and fitness change. In the combined analyses, men who lost fitness had higher all-cause and CVD mortality risks regardless of BMI change.
Maintaining or improving fitness is associated with a lower risk of all-cause and CVD mortality in men. Preventing age-associated fitness loss is important for longevity regardless of BMI change.
PMCID: PMC3238382  PMID: 22144631
exercise capacity; obesity; mortality; cardiovascular disease; epidemiology
18.  Usefulness of Serum Bilirubin and Cardiorespiratory Fitness as Predictors of Mortality in Men 
The American journal of cardiology  2011;108(10):1438-1442.
Elevated serum bilirubin has been suggested to reduce the risk of mortality. Cardiorespiratory fitness (CRF) has also been reported to have inverse association with all-cause and cardiovascular disease (CVD) mortality. The association between serum bilirubin, all-cause and CVD mortality and the effect of CRF on the observed association was investigated. A total of 1279 men, ages 30-82 years old, who underwent baseline medical examinations during 1974 to 1997 at the Cooper Clinic in Dallas, Texas. During an average of 17 years follow-up, 698 men died, with 253 deaths due to CVD (36%). Men in the highest bilirubin quartiles had significantly lower risk of all-cause mortality compared to men in the lowest quartiles (p for trend=0.0043), after adjusting for age and examination year. This inverse association remained significant after further adjustment for known confounders (p for trend=0.0018). Additional adjustment for treadmill time attenuated the association (p trend=0.0090). Similar patterns of association were observed between serum bilirubin quartiles and CVD mortality. CRF was inversely associated with all-cause mortality (p for trend < .0001) after adjusting for age and examination year. This inverse association also was observed after further adjusting for known confounders (p for trend=0.0004). After additional adjustment for serum bilirubin, the association between the CRF and all-cause mortality remained significant (p for trend = 0.0012). All-cause mortality and CVD mortality were significantly lower among men in the moderate to high fit quartiles in both the low and high bilirubin groups. In Conclusion both serum bilirubin level and CRF level were strongly and independently associated with all-cause and CVD mortality.
PMCID: PMC3206143  PMID: 21864819
serum bilirubin; cardiorespiratory fitness; cardiovascular disease; men; mortality
19.  The Obesity Paradox, Cardiorespiratory Fitness, and Coronary Heart Disease 
Mayo Clinic Proceedings  2012;87(5):443-451.
To investigate associations of cardiorespiratory fitness (CRF) and different measures of adiposity with cardiovascular disease (CVD) and all-cause mortality in men with known or suspected coronary heart disease (CHD).
Patients and Methods
We analyzed data from 9563 men (mean age, 47.4 years) with documented or suspected CHD in the Aerobics Center Longitudinal Study (August 13, 1977, to December 30, 2002) using baseline body mass index (BMI) and CRF (quantified as the duration of a symptom-limited maximal treadmill exercise test). Waist circumference (WC) and percent body fat (BF) were measured using standard procedures.
There were 733 deaths (348 of CVD) during a mean follow-up of 13.4 years. After adjustment for age, examination year, and multiple baseline risk factors, men with low fitness had a higher risk of all-cause mortality in the BMI categories of normal weight (hazard ratio [HR], 1.60; 95% confidence interval [CI], 1.24-2.05), obese class I (HR, 1.38; 95% CI, 1.04-1.82), and obese class II/III (HR, 2.43; 95% CI, 1.55-3.80) but not overweight (HR, 1.09; 95% CI, 0.88-1.36) compared with the normal-weight and high-fitness reference group. We observed a similar pattern for WC and percent BF tertiles and for CVD mortality. Among men with high fitness, there were no significant differences in CVD and all-cause mortality risk across BMI, WC, and percent BF categories.
In men with documented or suspected CHD, CRF greatly modifies the relation of adiposity to mortality. Using adiposity to assess mortality risk in patients with CHD may be misleading unless fitness is considered.
PMCID: PMC3538467  PMID: 22503065
ACLS, Aerobics Center Longitudinal Study; BF, body fat; BMI, body mass index; CHD, coronary heart disease; CI, confidence interval; CRF, cardiorespiratory fitness; CVD, cardiovascular disease; DM, diabetes mellitus; HR, hazard ratio; HTN, hypertension; WC, waist circumference
20.  Left Ventricular Diastolic Function and Exercise Capacity in Community-Dwelling Adults ≥ 65 Years of Age without Heart Failure 
The American Journal of Cardiology  2011;108(5):735-740.
Left ventricular diastolic dysfunction (LVDD) has been reported to have strong correlation with exercise capacity. However, this relationship has not been studied extensively in community-dwelling older adults. Data on pulse and tissue Doppler echocardiographic estimates of resting early (E) and atrial (A) transmitral peak inflow and early (Em) mitral annular velocities, and six-minute walk test were obtained from 89 community-dwelling older adults (mean age, 74; range, 65 -93 years; 54% women), without a history of heart failure. Overall, 47% had cardiovascular morbidity and 60% had normal diastolic function (E/A 0.75 -1.5 and E/Em <10). Among the 36 individuals with LVDD, 83%, 14% and 3% had grade I (E/A<0.75, regardless of E/Em), II (E/A 0.75–1.5 and E/Em ≥10) and III (E/A>1.5 and E/Em ≥10) LVDD respectively. Those with LVDD were older (77 versus 73 years; p=0.001) and tended to have a higher prevalence of cardiovascular morbidity (58% versus 40%; p=0.083). LVDD negatively correlated with six-minute walk distance (1013 versus 1128 feet; R=−0.25; p=0.017). This association remained significant despite adjustment for cardiovascular morbidity (R=−0.35; p=0.048), but lost significance when adjusted for age (R=−0.32; p=0.105), both age and cardiovascular morbidity (R=−0.38; p=0.161), and additional adjustment for sex, race, body mass index, and systolic blood pressure (R=−0.44; p=0.365). In conclusion, most community-dwelling older adults without heart failure had normal left ventricular diastolic function or grade-I LVDD. Although LVDD was associated with decreased performance on a six-minute walk test, that association was no longer evident after adjustment for age, body mass index and cardiovascular morbidity.
PMCID: PMC3324348  PMID: 21704282
Left Ventricular Diastolic Function; Exercise Capacity; Older Adults; Cardiovascular Morbidity
21.  Body Mass Index as a Predictor of Hypertension Incidence Among Initially Healthy Normotensive Women 
American journal of hypertension  2008;21(6):613-619.
Few prospective studies have evaluated the risk for incident hypertension (HTN) across the normal range of body mass index (BMI). Even fewer studies included body composition and fat distribution measurements in their analyses. In the Aerobics Center Longitudinal Study, we examined HTN risk in women across a wide spectrum of baseline BMI (kg/m2) values and also studied waist circumference (WC, cm), percent body fat, fat mass (FM, kg), and fat-free mass (FFM, kg) on incident HTN in subgroup analyses.
A total of 5,296 healthy normotensive women between 20 and 77 years of age completed a baseline examination during 1971–2004, and were followed for HTN incidence. Incident HTN was identified using mail-back surveys.
A total of 592 women reported HTN during a mean 16.7 years of follow-up. Higher BMI, even within the “normal” range, was associated with greater risk of HTN. Compared with women in the lowest fifth of BMI (18.5–20.0 kg/m2), the hazard ratios (HRs) (95% confidence interval (CI)) of developing HTN for women with a BMI of 20.1–21.2, 21.3–22.5, 22.6–24.7, and >24.7 were 1.19 (0.89–1.60), 1.33 (0.99–1.78), 1.36 (1.03–1.81), and 2.01 (1.52–2.66), respectively (Ptrend < 0.001). In a subgroup (n = 3,189) with complete data on all the five adiposity measures, significant positive associations with HTN were seen across incremental fifths of BMI, percent body fat, and FM (Ptrend < 0.05 each), but not WC and FFM.
Clinicians should emphasize the importance of weight management for the primary prevention of HTN in women.
PMCID: PMC3410431  PMID: 18437123
22.  Estimated Functional Capacity Predicts Mortality in Older Adults 
To examine associations between functional capacity estimated from cardiorespiratory fitness (CRF) and mortality risks in adults aged 60 and older.
Prospective study, averaging 13.6 years follow-up.
Preventive medical clinic.
Four thousand sixty adults who completed preventive medical examinations between 1971 and 2001; 24.7% women, mean age ± standard deviation 64.6 ± 4.9, body mass index (BMI) 25.9 ± 3.8 kg/m2.
CRF was quantified as metabolic equivalents (METs) achieved during maximal treadmill exercise. The lowest 20% of the age- and sex-specific MET distribution was defined as having low CRF, the middle 40% moderate CRF, and the upper 40% high CRF. Cox regression was used to estimate death rates (per 1,000 person-years), hazard ratios (HRs), and their 95% confidence intervals (CIs).
Nine hundred eighty-nine deaths occurred during follow-up. Death rates adjusted for age, sex, and examination year were 30.9, 18.3, and 13.4 for all causes (P<.001); 15.9, 8.6, and 5.4 for cardiovascular disease (CVD) (P<.001); and 6.1, 4.9, and 4.2 for cancer (P=.04) for subjects with low, moderate, and high CRF, respectively. After adjusting for smoking, abnormal electrocardiograms at rest or while exercising, percentage of age-predicted maximal heart rate achieved during exercise testing, baseline medical conditions, BMI, hypercholesterolemia, and family CVD and cancer history, subjects with high CRF had notably lower mortality risk than those with low CRF from all causes (HR = 0.59, 95% CI = 0.47–0.74) and from CVD (HR = 0.57, 95% CI = 0.41–0.80).
CRF is an important independent predictor of death in older adults. The results add to the existing evidence that promoting physical activity in older adults provides substantial health benefits, even in the oldest old.
PMCID: PMC3410432  PMID: 17979958
functional capacity; exercise testing; mortality; cardiovascular diease; metabolic equivalents (METs)
23.  A Prospective Study of Cardiorespiratory Fitness and Risk of Type 2 Diabetes in Women 
Diabetes care  2007;31(3):550-555.
The purpose of this study was to determine the independent and joint associations of cardiorespiratory fitness (CRF) and BMI with the incidence of type 2 diabetes in women.
An observational cohort of 6,249 women aged 20–79 years was free of baseline cardiovascular disease, cancer, and diabetes. CRF was measured using a maximal treadmill exercise test. BMI was computed from measured height and weight. The incidence of type 2 diabetes was identified primarily by 1997 American Diabetes Association criteria.
During a 17-year follow-up, 143 cases of type 2 diabetes occurred. Compared with the least fit third, the multivariate (including BMI)-adjusted hazard ratio (HR) (95% CI) was 0.86 (0.59–1.25) for the middle third and 0.61 (0.38–0.96) for the upper third of CRF. For BMI, the multivariate (including CRF)-adjusted HR (95% CI) was 2.34 (1.55–3.54) for overweight individuals and 3.70 (2.12–6.44) for obese individuals, compared with normal-weight patients. In the combined analyses, overweight/obese unfit (the lowest one-third of CRF) women had significantly higher risks compared with normal-weight fit (the upper two-thirds of CRF) women.
Low CRF and higher BMI were independently associated with incident type 2 diabetes. The protective effect of CRF was observed in individuals who were overweight or obese, but CRF did not eliminate the increased risk in these groups. These findings underscore the critical importance of promoting regular physical activity and maintaining normal weight for diabetes prevention.
PMCID: PMC3410433  PMID: 18070999
24.  In reply 
Mayo Clinic Proceedings  2012;87(2):209-210.
PMCID: PMC3497993
25.  Dose–response effects of exercise training on the subjective sleep quality of postmenopausal women: exploratory analyses of a randomised controlled trial 
BMJ Open  2012;2(4):e001044.
To investigate whether a dose–response relationship existed between exercise and subjective sleep quality in postmenopausal women. This objective represents a post hoc assessment that was not previously considered.
Parallel-group randomised controlled trial.
Clinical exercise physiology laboratory in Dallas, Texas.
437 sedentary overweight/obese postmenopausal women.
Participants were randomised to one of four treatments, each of 6 months of duration: a non-exercise control treatment (n=92) or one of three dosages of moderate-intensity exercise (50% of VO2peak), designed to meet 50% (n=151), 100% (n=99) or 150% (n=95) of the National Institutes of Health Consensus Development Panel physical activity recommendations. Exercise dosages were structured to elicit energy expenditures of 4, 8 or 12 kilocalories per kilogram of body weight per week (KKW), respectively. Analyses were intent to treat.
Primary outcome measures
Continuous scores and odds of having significant sleep disturbance, as assessed by the Sleep Problems Index from the 6-item Medical Outcomes Study Sleep Scale. Outcome assessors were blinded to participant randomisation assignment.
Change in the Medical Outcomes Study Sleep Problems Index score at 6 months significantly differed by treatment group (control: −2.09 (95% CI −4.58 to 0.40), 4 KKW: −3.93 (−5.87 to −1.99), 8 KKW: −4.06 (−6.45 to −1.67), 12 KKW: −6.22 (−8.68 to −3.77); p=0.04), with a significant dose–response trend observed (p=0.02). Exercise training participants had lower odds of having significant sleep disturbance at postintervention compared with control (4 KKW: OR 0.37 (95% CI 0.19 to 0.73), 8 KKW: 0.36 (0.17 to 0.77), 12 KKW: 0.34 (0.16 to 0.72)). The magnitude of weight loss did not differ between treatment conditions. Improvements in sleep quality were not related to changes in body weight, resting parasympathetic control or cardiorespiratory fitness.
Exercise training induced significant improvement in subjective sleep quality in postmenopausal women, with even a low dose of exercise resulting in greatly reduced odds of having significant sleep disturbance.
Trial registration number identifier: NCT00011193.
Article summary
Article focus
Sleep disturbance is prevalent in postmenopausal women, with 35%–60% reporting significant sleep problems.
Effective, safe and easily available treatment options for disturbed sleep in postmenopausal women are lacking.
There has been equivocal evidence as to whether exercise improves sleep in postmenopausal women, though possible dose–response effects have been noted.
Key messages
Exercise resulted in significant improvement in subjective sleep quality in postmenopausal women, with reduced odds of having sleep disturbance at postintervention with even 50% of the recommended dose of exercise for adults.
The effects of exercise on sleep quality were independent of changes in body weight, resting parasympathetic control or cardiorespiratory fitness.
Strengths and limitations of this study
The study constitutes the largest randomised controlled trial on exercise and sleep quality, using a structured dose of exercise and a validated measure of sleep quality.
Only self-reported sleep was assessed; objective measurement of sleep, with either actigraphy or polysomnography, was not conducted.
Despite the high prevalence of sleep disturbance in the sample, participants were not selected on the basis of sleep complaints.
PMCID: PMC3400065  PMID: 22798253

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