The obesity paradox, cardiorespiratory fitness, and coronary heart disease

ObjectiveTo 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 MethodsWe 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.ResultsThere 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.ConclusionIn 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.     

Maximal Exercise Electrocardiographic Responses and Coronary Heart Disease Mortality Among Men With Metabolic Syndrome

OBJECTIVE: To examine the association between abnormal exercise electrocardiographic (E-ECG) test results and mortality (all-cause and that resulting from coronary heart disease [CHD] or cardiovascular disease [CVD]) in a large population of asymptomatic men with metabolic syndrome (MetS).PATIENTS AND METHODS: A total of 9191 men (mean age, 46.9 years) met the criteria of having MetS. All completed a maximal E-ECG treadmill test (May 14, 1979, through April 9, 2001) and were without a previous CVD event or diabetes at baseline. Main outcomes were all-cause mortality, mortality due to CHD, and mortality due to CVD. Cox regression analysis was used to quantify the mortality risk according to E-ECG responses.RESULTS: During a follow-up of 14 years, 633 deaths (242 CVD and 150 CHD) were identified. Mortality rates and hazard ratios (HRs) across E-ECG responses were the following: for all-cause mortality: HR, 1.36; 95% confidence interval (CI), 1.09-1.70 for equivocal responses and HR, 1.41; 95% CI, 1.12-1.77 for abnormal responses (P_trend<.001); for mortality due to CVD: HR, 1.29; 95% CI, 0.88-1.88 for equivocal responses and HR, 2.04; 95% CI, 1.46-2.84 for abnormal responses (P_trend<.001); and for mortality due to CHD: HR, 1.62; 95% CI, 1.02-2.56 for equivocal responses and HR, 2.45; 95% CI, 1.62-3.69 for abnormal responses (P_trend<.001). A positive gradient for CHD, CVD, and all-cause mortality rates across E-ECG categories within 3, 4, or 5 MetS components was observed (P<.001 for all).CONCLUSION: Among men with MetS, an abnormal E-ECG response was associated with higher risk of all-cause, CVD, and CHD mortality. These findings underscore the importance of E-ECG tests to identify men with MetS who are at risk of dying.ACLS = Aerobics Center Longitudinal Study; CHD = coronary heart disease; CI = confidence interval; CRF = cardiorespiratory fitness; CVD = cardiovascular disease; DM = diabetes mellitus; ECG = electrocardiography; E-ECG = exercise ECG; HR = hazard ratio; MET = metabolic equivalent; MetS = metabolic syndrome; NDI = National Death Index; SRI = stress-recovery indexMetabolic syndrome (MetS) is a clustering of cardiovascular disease (CVD) risk factors,¹ including abdominal obesity, atherogenic dyslipidemia, elevated blood pressure, and insulin resistance,² that currently affects nearly 25% of Americans and is a growing concern because of increasing rates of obesity and hypertension.³ Because many of the components of MetS are associated with an increased risk of CVD and death, a noninvasive diagnosis of subclinical CVD in patients with MetS is important and may optimize secondary preventive interventions in this high-risk population.We showed earlier that abnormal exercise electrocardiographic (E-ECG) results during maximal exercise testing was associated with an elevated risk of incident coronary heart disease (CHD), CVD, and all-cause mortality in 2854 men with diabetes mellitus (DM).⁴ Thus, although DM is considered a CHD risk equivalent, important additional information for risk stratification can be obtained from exercise testing. We also showed that exercise testing can be used to identify women with impaired fasting glucose, a predecessor to DM and MetS, who are at high risk of all-cause mortality.⁵ Callaham et al⁶ studied 1747 US veterans with DM and showed that exercise-induced ST-segment depression was associated with more CVD events during a mean follow-up of 2 years than was observed in participants without ST-segment depression. In a study of 45 patients with exercise-induced silent ischemia, Weiner et al⁷ reported that patients with DM had worse outcomes in terms of CVD events than persons without DM.Currently, no known studies have evaluated the association between abnormal E-ECG responses and all-cause, CHD, and CVD mortality risk in men with MetS. Although sparse, some studies have examined the association between E-ECG responses and CHD risk in men with components of MetS. Ekelund et al⁸ reported that positive findings on E-ECG was an independent predictor of CVD events in men with hypercholesterolemia. Laukkanen et al⁹ reported that exercise-induced ischemia was associated with a higher risk of adverse outcomes in persons at high risk of CHD. Bigi et al¹⁰ suggested that the stress-recovery index (SRI) predicts all-cause mortality in persons with hypertension.Therefore, our study primarily aimed to evaluate the association between abnormal E-ECG test results and mortality (all-cause and that due to CHD or CVD) in a large population of asymptomatic men with MetS. We showed earlier that a maximal E-ECG test performed in asymptomatic men free of CVD can predict future risk of CHD death,¹¹ and that an abnormal test result was a more powerful predictor of risk in those with DM than those without the diagnosis.⁴ The current study will expand this earlier report and focus on men with MetS.     

The importance of waist circumference in the definition of metabolic syndrome: prospective analyses of mortality in men

OBJECTIVE: The purpose of this study was to compare the predictive ability of the National Cholesterol Education Panel (NCEP), revised NCEP (NCEP-R), and International Diabetes Federation (IDF) metabolic syndrome criteria for mortality risk, and to examine the effects of waist circumference on mortality within the context of these criteria. RESEARCH DESIGN AND METHODS: The sample included 20,789 white, non-Hispanic men 20-83 years of age from the Aerobics Center Longitudinal Study. The main outcome measures were all-cause and cardiovascular disease (CVD) mortality over 11.4 years of follow-up. RESULTS: The proportions of men with the metabolic syndrome were 19.7, 27, and 30% at baseline, respectively, according to NCEP, NCEP-R, and IDF criteria. A total of 632 deaths (213 CVD) occurred. The relative risks (RRs) and 95% CIs of all-cause mortality were 1.36 (1.14-1.62), 1.31 (1.11-1.54), and 1.26 (1.07-1.49) for the NCEP, NCEP-R, and IDF definitions, respectively. The corresponding RRs for CVD mortality were 1.79 (1.35-2.37), 1.67 (1.27-2.19), and 1.67 (1.27-2.20). Additionally, there was a significant trend for a higher risk of CVD mortality across waist circumference categories (<94, 94-102, and >102 cm) among men with at least two additional metabolic syndrome risk factors (P = 0.01). CONCLUSIONS: The prediction of mortality with IDF and NCEP metabolic syndrome criteria was comparable in men. Waist circumference is a valuable component of metabolic syndrome; however, the IDF requirement of an elevated waist circumference warrants caution given that a large proportion of men with normal waist circumference have multiple risk factors and an increased risk of mortality.     

The Association Between Cardiorespiratory Fitness and Risk of All-Cause Mortality Among Women With Impaired Fasting Glucose or Undiagnosed Diabetes Mellitus

OBJECTIVE: To evaluate the independent and joint associations among cardiorespiratory fitness (CRF), body mass index, and risk of mortality from any cause among women with impaired fasting glucose (IFG) or undiagnosed diabetes mellitus (DM).PATIENTS AND METHODS: Female patients (N=3044; mean age, 47.4 years) with IFG or undiagnosed DM completed a maximal exercise treadmill test (between January 26, 1971, and March 21, 2001). The women had no history of a cardiovascular disease event or diagnosed DM at baseline. Cardiorespiratory fitness was defined categorically as low (bottom 20%), moderate (middle 40%), or high (upper 40%) according to previously published Aerobics Center Longitudinal Study guidelines. Body mass index was calculated as the weight in kilograms divided by the height in meters squared (kg/m²).RESULTS: During a 16-year follow-up period, 171 deaths occurred. There was an inverse association between CRF and all-cause mortality risk. Women with moderate or high CRF were at lower risk of mortality (moderate CRF, 35% lower; high CRF, 36% lower; P_trend=.03) than those with low CRF. An exercise capacity lower than 7 metabolic equivalents was associated with a 1.5-fold higher risk of death than an exercise capacity of 9 metabolic equivalents or higher (P_trend=.05). The multivariate adjusted hazard ratios (HRs), including adjustments for CRF, were higher for heavier patients than for patients of normal weight (overweight patients: HR, 0.86; 95% confidence interval, 0.57-1.30; obese patients: HR, 1.19; 95% confidence interval, 0.70-2.03; P_trend=.84). Combined analyses showed that women who were overweight or obese and unfit (low CRF) were at more than twice the risk of death than women who were of normal weight and fit (moderate or high CRF).CONCLUSION: Cardiorespiratory fitness, not body mass index, is a significant predictor of all-cause mortality among women with IFG or undiagnosed DM. Assessing CRF levels provides important prognostic information independent of traditional risk factors.ACLS = Aerobics Center Longitudinal Study; BMI = body mass index; CI = confidence interval; CRF = cardiorespiratory fitness; CVD = cardiovascular disease; DM = diabetes mellitus; HR = hazard ratio; IFG = impaired fasting glucose; MET = metabolic equivalentImpaired fasting glucose (IFG) has been associated with an elevated risk of premature mortality.^1,2 Recently, greater attention has been directed toward IFG in efforts to reduce the development of diabetes mellitus (DM) and cardiovascular disease (CVD). In 2003, the American Diabetes Association recommended that the definition of IFG be expanded to include fasting glucose concentrations between 100 mg/dL and 125 mg/dL (to convert to mmol/L, multiply by 0.0555), as opposed to the previous concentrations of 110 mg/dL to 125 mg/dL.³ In 2002, 54 million people in the United States aged 20 years or older had IFG, representing 26% of the total US population; this number would be higher if the more stringent definition were used.⁴ In 2005, 20.8 million people (7% of the total US population) in the same age group had DM.⁴ Half of these cases of DM were expected to be undiagnosed and asymptomatic.⁵ The risk of premature CVD and death is 2 to 4 times higher for persons with DM than for those of equivalent age without DM.^6,7 Therefore, the detection and treatment of CVD risk factors may be particularly important for preventing CVD among persons with asymptomatic IFG and DM.A low cardiorespiratory fitness (CRF) level is a predictor of all-cause mortality among men with type 2 DM.⁸ Recent studies^9,10 have also reported a strong and independent association between CRF and mortality among men with DM in all body mass index (BMI) and body fatness groups.¹¹ However, most previous studies have focused on the association between CRF and mortality among either men only or men and women who are sedentary but apparently healthy.^8,9,12For editorial comment, see page 771There is a strong independent association between obesity and all-cause mortality among both men and women.^13-17 Most studies have found that this association is J-shaped or U-shaped. Like CRF studies, most obesity studies have focused on the association between obesity and mortality in women, men, or both men and women in the general population, regardless of any disease state.^13-16 Few studies have focused on persons with IFG and undiagnosed DM, especially women. To our knowledge, no previous study has concurrently evaluated the association between CRF, overweight or obesity status as reflected by BMI, and death among women with IFG. Therefore, the primary aim of this study was to evaluate the association between CRF and risk of all-cause mortality among women with IFG or undiagnosed DM.     

Metabolic syndrome and all-cause mortality in older men and women

Eur J Clin Invest 2012; 42 (9): 1000-1009 ABSTRACT: Background Prevalence of metabolic syndrome (MetS) increases with age, but its association with all-cause mortality in older persons remains uncertain. This study investigated the association of all-cause mortality with MetS and its individual components in older men and women. Methods A total of 917 men and 1043 women aged 65?years and older from two Italian population-based cohorts were included in the study. MetS was defined according to four different definitions: National Cholesterol Education Program (NCEP), NCEP revised according to the American Heart Association and National Heart Lung Blood Institute (NCEP-R), International Diabetes Organization (IDF) and Joint Interim Statement (JIS). All of these definitions include abdominal obesity, hyperglycaemia, hypertriglyceridaemia, low high-density lipoprotein cholesterol and hypertension. Hazard Ratios (HR) and their corresponding 95% confidence interval (95%CI) estimated from multivariable-adjusted Cox regression models were used to investigate the associations of all-cause mortality with baseline MetS status and individual MetS components. Results After 6·5?±?1·8?years of follow-up, there were 179 deaths among women and 193 among men. Mortality risk was increased in women with MetS by any definition, regardless of individual components, but limited to age 70-79?years (NCEP, HR?=?2·02, 95%CI, 1·16-3·53; NCEP-R, HR?=?2·51, 95%CI, 1·45-4·34; IDF, HR?=?2·16, 95%CI, 1·26-3·72; JIS, HR?=?2·16, 95%CI, 1·26-3·72). Mortality risk of men was associated with hypertriglyceridaemia below age 70?years (HR?=?2·50, 95%CI, 1·19-5·25), but unrelated to MetS status. Conclusions Metabolic Syndrome is associated with all-cause mortality in older women but not in men. The association, however, is limited to a narrow age range.     

Prevalence, metabolic features, and prognosis of metabolically healthy obese Italian individuals: the Cremona Study

OBJECTIVE

Some obese individuals have normal insulin sensitivity. It is controversial whether this phenotype is associated with increased all-cause mortality risk.

RESEARCH DESIGN AND METHODS

Fifteen-year all-cause mortality data were obtained through the Regional Health Registry for 2,011 of 2,074 Caucasian middle-aged individuals of the Cremona Study, a population study on the prevalence of diabetes in Italy. Individuals were divided in four categories according to BMI (nonobese: <30 kg/m²; obese: ≥30 kg/m²) and estimated insulin resistance (insulin sensitive: homeostasis model assessment of insulin resistance <2.5; insulin resistant ≥2.5).

RESULTS

Obese insulin-sensitive subjects represented 11% (95% CI 8.1–14.5) of the obese population. This phenotype had similar BMI but lower waist circumference, blood pressure, fasting glucose, triglycerides, and fibrinogen and higher HDL cholesterol than obese insulin-resistant subjects. In the 15-year follow-up, 495 deaths (cardiovascular disease [CVD]: n = 221; cancer: n = 180) occurred. All-cause mortality adjusted for age and sex was higher in the obese insulin-resistant subjects (hazard ratio 1.40 [95% CI 1.08–1.81], P = 0.01) but not in the obese insulin-sensitive subjects (0.99 [0.46–2.11], P = 0.97) when compared with nonobese insulin-sensitive subjects. Also, mortality for CVD and cancer was higher in the obese insulin-resistant subjects but not in the obese insulin-sensitive subjects when compared with nonobese insulin-sensitive subjects.

CONCLUSIONS

In contrast to obese insulin-resistant subjects, metabolically healthy obese individuals are less common than previously thought and do not show increased all-cause, cancer, and CVD mortality risks in a 15-year follow-up study.Metabolically healthy obese (MHO) individuals are considered as a subset of obese subjects without metabolic abnormalities (such as insulin resistance, proatherogenic lipoprotein profile, proinflammatory state, or hypertension) and a model for better understanding the pathogenesis of insulin resistance (1–3). The prevalence of the MHO phenotype in the general population, the reasons for not developing metabolic alterations, and the less aggressive therapeutic approach with respect to obese individuals with metabolic abnormalities are currently debated (4,5). In the Framingham Offspring Study, Meigs et al. (6) found that MHO individuals do not have increased risk of incident diabetes and cardiovascular disease (CVD). Conversely, in the Third National Health and Nutrition Examination Survey (NHANES III), Kuk et al. (7) reported increased all-cause mortality associated with the MHO phenotype. Finally, in a Scandinavian study (8), middle-aged overweight/obese subjects without metabolic syndrome also had an increased risk of CVD when compared with normal-weight individuals without metabolic syndrome. The present study shows the prevalence of the MHO phenotype, its metabolic features, and 15-year all-cause, CVD, and cancer mortality rates in the Caucasian population of the Cremona Study (9,10).     

Trying to lose weight, losing weight, and 9-year mortality in overweight U.S. adults with diabetes

OBJECTIVE: The aim of this study was to examine the relationships between intention to lose weight, actual weight loss, and all-cause mortality among overweight individuals with diabetes. RESEARCH DESIGN AND METHODS: We performed a prospective analysis among 1,401 overweight diabetic adults aged > or =35 years sampled in the National Health Interview Survey. The previous year intention to lose weight and weight change were assessed by self-report. Nine-year mortality rates were examined according to intent to lose weight and weight loss, which were adjusted for age, sex, education, ethnicity, smoking, initial body weight, and diabetes complications. RESULTS: Individuals trying to lose weight had a 23% lower mortality rate (hazard rate ratio [HRR] 0.77, 95% CI 0.61-0.99) than those who reported not trying to lose weight. This association was as strong for those who failed to lose weight (0.72, 0.55-0.96) as for those who succeeded in losing weight (0.83, 0.63-1.08). Trying to lose weight was beneficial for overweight (BMI 25-30 kg/m2) individuals (0.62, 0.46-0.83) but not for obese (BMI>30) individuals (1.17, 0.72-1.92). Overall weight loss, without regard to intent, was associated with an increase of 22% (1.22, 0.99-1.50) in the mortality rate. This increase was largely explained by unintentional weight loss, which was associated with a 58% (1.58, 1.08-2.31) higher mortality rate. CONCLUSIONS: Overweight diabetic adults trying to lose weight have a reduced risk of all-cause mortality, independent of whether they lose weight. Actual weight loss is associated with increased mortality only if the weight loss is unintentional.     

The metabolic syndrome increases cardiovascular mortality in Taiwanese elderly

Background   The prevalence of the metabolic syndrome (MetS) is high among the elderly. However, evidence that mortality increases with MetS is rare. In this study, we investigated the relationship between MetS, cardiovascular disease (CVD) and all cause mortality in the elderly.
Materials and methods   A total 10 547 participants, aged 65 years and older, of baseline cohort were recruited from four nationwide Health Screening Centres in Taiwan from 1998 to 1999. The metabolic syndrome was defined according to the America Heart Association/National Heart Lung Blood Institute definition. Cox proportional hazards regression analyses were used to estimate the relative risks (RRs) of CVD and all cause mortality for those with MetS for up to 8 years of follow-up.
Results   The baseline prevalence of MetS was 50·1% (45·6% in men and 54·4% in women, respectively). A total of 1312 participants died; of these, 300 participants died from CVD. Adjusted for age, gender, smoking, total cholesterol and estimated glomerular filtration rate, the RRs for CVD and all cause mortality among participants with MetS were 1·48 (95% confidence interval = 1·16–1·90) and 1·16 (1.03–1.30), respectively, for participants compared to those without MetS. The mean RRs for CVD, however, ranged from 1·21 to 5·31 among different combinations of MetS components.
Conclusion   The elderly with MetS, compared to those without MetS, had a higher CVD and all cause mortality in Taiwan. Furthermore, different combinations of MetS components posed different risks to the mortality, which deserves further research in the future.     

Obesity and metabolic syndrome as related to cardiovascular disease

The metabolic syndrome (MetS) constitutes a multifaceted disorder, including obesity, dyslipidemia, hyperglycemia and hypertension, associated with an increased propensity towards cardiovascular disease (CVD). Besides this, accumulating data suggest the involvement of nontraditional, novel, cardiovascular risk factors in MetS. Among them, insulin resistance seems to possess a predominant role in MetS-related CVD in obese patients. Furthermore, adipose tissue fatty acid metabolism, increased incidence of oxidative stress and endothelial dysfunction, and excessive production of adipocyte derivatives, known as adipokines, have all been proposed to contribute to the pathogenesis of CVD in obese patients with MetS. Lifestyle interventions, such as weight loss and increased physical activity, have long been the cornerstone for the treatment of obesity-related disorders. With the exception of obesity, pharmaceutical interventions targeting each disorder of MetS have yielded considerable improvement in cardiovascular morbidity and mortality. The long-term management of obesity and its complications seems promising but requires further investigation.     

Impact of obesity on outcomes in patients with acute respiratory syndrome

ObjectivesWe assessed the relationship between obesity and all-cause mortality in patients with acute respiratory distress syndrome (ARDS).MethodsIn this retrospective cohort study, patient data were extracted from the eICU Collaborative Research Database and the Medical Information Mart for Intensive Care Database III. Body mass index (BMI) was grouped according to World Health Organization classifications: underweight, normal weight, overweight, obese. Cox regression models estimated hazard ratios (HRs) and 95% confidence intervals (CIs) of all-cause mortality related to obesity.ResultsParticipants included 185 women and 233 men, mean age 70.7 ± 44.1 years and mean BMI 28.7 ± 8.1 kg/m². Compared with normal weight patients, obese patients tended to be younger (60.1 ± 13.7 years) and included more women (51.3% vs. 49.0%). In the unadjusted model, HRs (95% CIs) of 30-day mortality for underweight, overweight, and obesity were 1.57 (0.76, 3.27), 0.64 (0.39, 1.08), and 4.83 (2.25, 10.35), respectively, compared with those for normal weight. After adjustment, HRs (95% CIs) of 30-day mortality for underweight, overweight, and obesity were 1.82 (0.85, 3.90), 0.59 (0.29, 1.20), and 3.85 (1.73, 8.57), respectively, compared with the reference group; 90-day and 1-year all-cause mortalities showed similar trends.ConclusionsObesity was associated with increased all-cause mortality in patients with ARDS.     

High Burden of Subclinical and Cardiovascular Disease Risk in Adults With Metabolically Healthy Obesity: The Atherosclerosis Risk in Communities (ARIC) Study

OBJECTIVEIt is controversial whether adults who are obese but “metabolically healthy” have cardiovascular disease (CVD) risk comparable with that of normal-weight adults. High-sensitivity cardiac troponin T (hs-cTnT), a biomarker of myocardial damage, is useful in characterizing subclinical CVD. We categorized obesity phenotypes and studied their associations with subclinical and clinical CVD and CVD subtypes, including heart failure (HF).RESEARCH DESIGN AND METHODSWe conducted cross-sectional and prospective analyses of 9,477 adults in the Atherosclerosis Risk in Communities (ARIC) study. We used the Adult Treatment Panel III criteria and BMI to define obesity phenotypes as follows: metabolically healthy normal weight, metabolically healthy overweight, metabolically healthy obese, metabolically unhealthy normal weight, metabolically unhealthy overweight, and metabolically unhealthy obese.RESULTSAt baseline (1990–1992), mean age was 56 years, 56% were female, 23% were Black, and 25% had detectable hs-cTnT (≥6 ng/L). Over a median of 17 years of follow-up, there were 2,603 clinical CVD events. Those with the metabolically healthy obese (hazard ratio [HR] 1.38, 95% CI 1.15–1.67), metabolically unhealthy normal weight (HR 1.51, 95% CI 1.30–1.76), metabolically unhealthy overweight (HR 1.60, 95% CI 1.41–1.82), and metabolically unhealthy obese (HR 2.14, 95% CI 1.88–2.44) phenotypes had higher CVD risks in comparison with metabolically healthy normal weight. Detectable hs-cTnT (≥6 ng/L) was associated with higher CVD risk, even among metabolically healthy normal-weight adults. Metabolically healthy obese adults had higher HF risk (HR 1.65, 95% CI 1.30–2.09) in comparison with metabolically healthy normal weight.CONCLUSIONSThe metabolically healthy obese phenotype was associated with excess burden of clinical CVD, primarily driven by an excess risk of HF. hs-cTnT was useful in stratifying CVD risk across all obesity phenotypes, even among obese individuals who appear otherwise metabolically healthy.     

Metabolic syndrome: risk factor distribution and 18-year mortality in the multiple risk factor intervention trial

OBJECTIVE: To examine the long-term association of metabolic syndrome with mortality among those at high risk for cardiovascular disease (CVD). RESEARCH DESIGN AND METHODS: A total of 10,950 Multiple Risk Factor Intervention Trial (MRFIT) survivors were followed for mortality an additional median 18.4 years (1980-1999). Proportional hazards models examined multivariate-adjusted risks associated with Adult Treatment Panel III-defined metabolic syndrome conditions, with BMI substituted for waist circumference. RESULTS: At MRFIT annual visit 6, 4,588 (41.9%) men, mean age (+/-SD) 53.0 +/- 5.9 years, had metabolic syndrome and 6,362 did not. Comparing men with metabolic syndrome to men without, adjusted hazard ratios (HRs) were 1.21 (95% CI 1.13-1.29), 1.49 (1.35-1.64), and 1.51 (1.34-1.70) for 18-year total, CVD, and coronary heart disease mortality, respectively. Among men with metabolic syndrome, elevated glucose (1.54 [1.34-1.78]) and low HDL cholesterol (1.45 [1.17-1.54]) were most predictive of CVD mortality, followed by elevated BMI (1.34 [1.17-1.54]), elevated blood pressure (1.25 [0.98-1.58]), and elevated triglycerides (1.06 [0.86-1.30]). In contrast, for men without metabolic syndrome, the HR for low HDL cholesterol was 1.02 (0.86-1.22). Among metabolic syndrome men with no nonfatal CVD event, smokers with elevated LDL cholesterol showed higher CVD mortality (1.79 [1.22-2.63]) compared with nonsmokers without elevated LDL cholesterol; this additional risk was even greater for metabolic syndrome men with a nonfatal CVD event (2.11 [1.32-3.38]). CONCLUSIONS: Metabolic syndrome is associated with an increased risk of mortality. Among those with metabolic syndrome, risk is further increased by having more metabolic syndrome conditions, by cigarette smoking, and by elevated LDL cholesterol. Primary prevention of each metabolic syndrome condition should be emphasized, and presence of each condition should be treated in accordance with current guidelines.     

Use of Functional Aerobic Capacity Based on Stress Testing to Predict Outcomes in Normal,Overweight, and Obese Patients

ObjectiveTo determine the poorly studied relationship between functional aerobic capacity (FAC) as measured by treadmill stress testing and mortality in normal, overweight, and obese patients.Patients and MethodsPatients were identified retrospectively from the stress testing database at Mayo Clinic in Rochester, Minnesota. We selected 5328 male nonsmokers (mean ± SD age, 51.8±11.5 years) without baseline cardiovascular disease who were referred for treadmill exercise testing between January 1, 1986, and December 31, 1991, and classified them by body mass index (BMI) into normal-weight (18.5-24.9 kg/m²), overweight (25.0-29.9 kg/m²), and obese (≥30 kg/m²) categories. Functional aerobic capacity was assessed by maximal exercise test results based on age- and sex-specific metabolic equivalents, and patients were stratified into fitness quintiles. Cox proportional hazards analysis was used to determine the relationship of all-cause mortality to fitness in each BMI category.ResultsThere were 322 deaths during 14 years of follow-up. After adjustment for age and exercise confounders, FAC predicted mortality in the 3 BMI groups. Hazard ratios for FAC less than 80% of predicted vs a reference group with normal BMI and fitness (FAC ≥100%) were 1.754 (95% CI, 0.874-3.522), 1.962 (1.356-2.837), and 1.518 (1.056-2.182) for the normal, overweight, and obese groups, respectively. The CIs of the hazard ratios overlapped with no statistically significant differences (P>.05).ConclusionA significant increase in mortality occurs with FAC below 80% of predicted for overweight and obese subjects and below 70% for normal weight subjects. Our results suggest that clinicians need not adjust the standard for low fitness in obese patients.     

Similar 9-year mortality risks and reproducibility for the World Health Organization and American Diabetes Association glucose tolerance categories: the Hoorn Study

OBJECTIVE: To compare the risks of all-cause and cardiovascular disease (CVD) mortality in the American Diabetes Association (ADA) and World Health Organization (WHO) glucose tolerance categories after 9 years of follow-up in the Hoorn Study and to study the test-retest reproducibility of those categories. RESEARCH DESIGN AND METHODS: In this population-based cohort study of 2,468 elderly men and women, subjects were classified according to both the WHO and the ADA criteria. Causes of death were extracted from the medical records. Age- and sex-adjusted relative risks were estimated by Cox's proportional hazards model. Reproducibility of the diagnostic criteria was assessed in a sample of 1,109 subjects with duplicate oral glucose tolerance tests. RESULTS: Subjects with known diabetes had a four to five times higher risk of all-cause and CVD mortality compared with normal subjects (P<0.05). The relative risks of all-cause mortality were 1.67 (95% CI 1.09-2.57) and 1.56 (1.00-2.43) for newly diagnosed diabetic subjects according to the WHO and ADA criteria, respectively. The WHO and ADA criteria had similar levels of reproducibility The overall K was 0.59 (0.54-0.64) for WHO criteria and 0.61 (0.56-0.66) for ADA criteria. For the category of newly diagnosed diabetes according to WHO or ADA, the percentages of agreement for the second test compared with the first test were 77% (85/110) and 74% (74/100), respectively. CONCLUSIONS: Both sets of diagnostic criteria identify criteria-specific diabetic subjects with an increased mortality risk compared with normal subjects, and the reproducibility of both criteria is similar.     

Exercise capacity and body composition as predictors of mortality among men with diabetes

OBJECTIVE: To quantify the relation of fitness to mortality among men with diabetes, adjusted for BMI and within levels of BMI. RESEARCH DESIGN AND METHODS: In this observational cohort study, we calculated all-cause death rates in men with diabetes across quartiles of fitness and BMI categories. Study participants were 2,196 men with diabetes (average age 49.3 years, SD 9.5) who underwent a medical examination, including a maximal exercise test, during 1970 to 1995, with mortality follow-up to 31 December 1996. RESULTS: We identified 275 deaths during 32,161 person-years of observation. Risk of all-cause mortality was inversely related to fitness. For example, in the fully adjusted model, the risk of mortality was 4.5 (2.6-7.6), 2.8 (1.6-4.7), and 1.6 (0.93-2.76) for the first, second, and third fitness quartiles, respectively, with the fourth quartile (highest fitness level) as the referent (P for trend <0.0001). There was no significant trend across BMI categories for mortality after adjustment for fitness. Similar results were found when the fitness-mortality relation was examined within levels of body composition. In normal-weight men with diabetes, the relative risks of mortality were 6.6 (2.8-15.0), 3.2 (1.4-7.0), and 2.2 (1.1-4.6) for the first, second, and third quartiles of fitness, respectively, as compared with the fourth quartile (P for trend <0.0001). We found similar results in the overweight and obese weight categories. CONCLUSIONS: There was a steep inverse gradient between fitness and mortality in this cohort of men with documented diabetes, and this association was independent of BMI.     

Association of Changes in Physical Activity and Adiposity With Mortality and Incidence of Cardiovascular Disease: Longitudinal Findings From the UK Biobank

ObjectiveTo examine the association of changes in physical activity and adiposity with all-cause mortality and incident cardiovascular disease (CVD).MethodsPhysical activity, body mass index (BMI), body fat percentage, waist circumference, and waist to hip ratio changes were categorized on the basis of public health and clinical guidelines. Among 29,610 participants (mean ± SD follow-up, 5.1±2.1 years), 545 deaths and 2970 CVD events occurred. Participants were observed from baseline (March 13, 2006, to October 10, 2010) and follow-up (August 1, 2012 to November 9, 2018) assessment through March 31, 2021.ResultsCompared with stable-insufficient physical activity, increasing physical activity to meet guidelines at follow-up was associated with lower all-cause mortality (hazard ratio, 0.64 [0.49 to 0.85]) and CVD (0.83 [0.72 to 0.96]) risk. This risk was similar to that of those who achieved physical activity guidelines at both time points (all-cause mortality, 0.74 [0.60 to 0.92]; CVD, 0.88 [0.79 to 0.99]). For obese and overweight participants, decreasing BMI category was associated with a lower CVD risk (0.70 [0.47 to 1.04]) similar to the risk of those who had a healthy weight at both time points (0.85 [0.76 to 0.96]). In the joint analyses, the only combination that lowered all-cause mortality and CVD risk was physical activity increase and adiposity decrease over time (eg, CVD risk: BMI, 0.64 [0.42 to 0.96]; body fat percentage, 0.76 [0.55 to 0.97]; waist circumference, 0.66 [0.48 to 0.89]; waist to hip ratio, 0.78 [0.62 to 0.97]) compared with the reference group (stable physical activity and adiposity).ConclusionIncreases in physical activity to meet guidelines lowered all-cause mortality and CVD risk equal to that of those who continually met guidelines. The risk was effectively eliminated in those who had concurrent adiposity decrease.     

Cardiorespiratory fitness attenuates metabolic risk independent of abdominal subcutaneous and visceral fat in men

OBJECTIVE: Moderate to high levels of cardiorespiratory fitness (CRF) are associated with a lower risk of the metabolic syndrome and all-cause mortality. Unknown is whether CRF attenuates health risk for a given level of abdominal visceral fat, subcutaneous fat, and/or waist circumference. RESEARCH DESIGN AND METHODS: The sample studied comprised 297 apparently healthy men with available computed tomography or magnetic resonance imaging scans of the abdomen, metabolic data, and maximal treadmill exercise test results. Men were categorized into low-CRF (20%, n = 56), moderate-CRF (40%, n = 94), and high-CRF (40%, n = 147) groups based on age and exercise test results. All analyses were adjusted for age. RESULTS: For a given level of waist circumference, visceral fat, or subcutaneous fat, the high-CRF group had lower triglyceride levels (P < 0.05) and higher HDL cholesterol levels than the low- or moderate-CRF groups. There was a significant group interaction (P < 0.01) for blood pressure, indicating that the increase in blood pressure per unit increase in visceral fat or waist circumference was greater in men in the low-CRF group compared with the high-CRF group. The relative risks of having the metabolic syndrome were 1.8 (95% CI 1.0-3.1) and 1.6 (0.9-2.7) times higher in the low- and moderate-CRF groups, respectively, compared with the high-CRF group after adjusting for age, visceral fat, and subcutaneous fat (P for trend = 0.06). CONCLUSIONS: High levels of CRF are associated with a substantial reduction in health risk for a given level of visceral and subcutaneous fat.     

Overweight Without Central Obesity,Cardiovascular Risk,and All-Cause Mortality

Objective

To assess the association of overweight without central obesity with risks of mortality.

体质量指数与慢性心力衰竭死亡率相关性的Meta分析

目的系统评价体质量指数(BMI)与慢性心力衰竭(CHF)患者死亡率的相关性。方法计算机检索PubMed、EMbase、The Cochrane Library、CNKI、WanFang Data和VIP数据库,搜集BMI与CHF患者死亡率相关的队列研究,检索时限均从建库至2019年6月。由2名研究者独立筛选文献、提取资料并评价纳入研究的偏倚风险后,采用Stata 12.0软件进行Meta分析。结果共纳入20个队列研究,包括91 572例CHF患者。Meta分析结果显示:与正常体质量相比,低体质量CHF患者的全因死亡率更高[HR=1.48,95%CI(1.36,1.62),P<0.001],超重[HR=0.86,95%CI(0.78,0.94),P=0.002]和肥胖[HR=0.78,95%CI(0.68,0.90),P=0.001]CHF患者的全因死亡率更低。结论当前证据表明,低体质量CHF患者的全因死亡率较高,超重和肥胖CHF患者的全因死亡率较低。受纳入研究数量和质量限制,上述结论尚待更多高质量研究予以验证。     

The Influence of Change in Cardiorespiratory Fitness With Short-Term Exercise Training on Mortality Risk From The Ball State Adult Fitness Longitudinal Lifestyle Study

ObjectiveTo assess the influence of changes in cardiorespiratory fitness (CRF) after exercise training on mortality risk in a cohort of self-referred, apparently healthy adults.Patients and MethodsA total of 683 participants (404 men, 279 women; mean age: 42.7±11.0 y) underwent two maximal cardiopulmonary exercise tests (CPX) between March 20, 1970, and December 11, 2012, to assess CRF at baseline (CPX1) and post-exercise training (CPX2). Participants were followed for an average of 29.8±10.7 years after their CPX2. Cox proportional hazards models were performed to determine the relationship of CRF change with mortality, with change in CRF as a continuous variable, as well as a categorical variable. A Wald chi-square test was used to compare the coefficients estimating the relationship of peak oxygen consumption (VO_2peak) at CPX1 with VO_2peak measured at CPX2 with time until death for all-cause mortality.ResultsDuring the follow-up period there were 180 deaths. When assessed independently, there were 20% (95% CI, 10–49%) and 38% (95% CI, 7–66%) lower mortality risks per 1 metabolic equivalent improvement in CRF (P<.01) in men and women, respectively, after multivariable adjustment. Those that remained unfit had ～2-fold higher risk for all-cause mortality compared with those that remained fit and CRF at CPX2 was a stronger predictor of all-cause mortality than at CPX1 (P=.02).ConclusionImproving CRF through exercise training lowers mortality risk. Clinicians should encourage individuals to participate in exercise training to improve CRF to lower risk of mortality.