Relationship Between Low Cardiorespiratory Fitness and Mortality in Normal-Weight, Overweight, and Obese Men

Context  Recent guidelines for treatment of overweight and obesity include recommendations for risk stratification by disease conditions and cardiovascular disease (CVD) risk factors, but the role of physical inactivity is not prominent in these recommendations. Objective  To quantify the influence of low cardiorespiratory fitness, an objective marker of physical inactivity, on CVD and all-cause mortality in normal-weight, overweight, and obese men and compare low fitness with other mortality predictors. Design  Prospective observational data from the Aerobics Center Longitudinal Study. Setting  Preventive medicine clinic in Dallas, Tex. Participants  A total of 25,714 adult men (average age, 43.8 years [SD, 10.1 years]) who received a medical examination during 1970 to 1993, with mortality follow-up to December 31, 1994. Main Outcome Measures  Cardiovascular disease and all-cause mortality based on mortality predictors (baseline CVD, type 2 diabetes mellitus, high serum cholesterol level, hypertension, current cigarette smoking, and low cardiorespiratory fitness) stratified by body mass index. Results  During the study period, there were 1025 deaths (439 due to CVD) during 258,781 man-years of follow-up. Overweight and obese men with baseline CVD or CVD risk factors were at higher risk for all-cause and CVD mortality compared with normal-weight men without these predictors. Using normal-weight men without CVD as the referent, the strongest predictor of CVD death in obese men was baseline CVD (age- and examination year-adjusted relative risk [RR], 14.0; 95% confidence interval [CI], 9.4-20.8); RRs for obese men with diabetes mellitus, high cholesterol, hypertension, smoking, and low fitness were similar and ranged from 4.4 (95% CI, 2.7-7.1) for smoking to 5.0 (95% CI, 3.6-7.0) for low fitness. Relative risks for all-cause mortality in obese men ranged from 2.3 (95% CI, 1.7-2.9) for men with hypertension to 4.7 (95% CI, 3.6-6.1) for those with CVD at baseline. Relative risk for all-cause mortality in obese men with low fitness was 3.1 (95% CI, 2.5-3.8) and in obese men with diabetes mellitus 3.1 (95% CI, 2.3-4.2) and as slightly higher than the RRs for obese men who smoked or had high cholesterol levels. Low fitness was an independent predictor of mortality in all body mass index groups after adjustment for other mortality predictors. Approximately 50% (n = 1674)of obese men had low fitness, which led to a population-attributable risk of 39% for CVD mortality and 44% for all-cause mortality. Baseline CVD had population attributable risks of 51% and 27% for CVD and all-cause mortality, respectively. Conclusions  In this analysis, low cardiorespiratory fitness was a strong and independent predictor of CVD and all-cause mortality and of comparable importance with that of diabetes mellitus and other CVD risk factors.      

Androgen suppression and radiation vs radiation alone for prostate cancer: a randomized trial

Context  Comorbidities may increase the negative effects of specific anticancer treatments such as androgen suppression therapy (AST). Objectives  To compare 6 months of AST and radiation therapy (RT) to RT alone and to assess the interaction between level of comorbidity and all-cause mortality. Design, Setting, and Patients  At academic and community-based medical centers in Massachusetts, between December 1, 1995, and April 15, 2001, 206 men with localized but unfavorable-risk prostate cancer were randomized to receive RT alone or RT and AST combined. All-cause mortality estimates stratified by randomized treatment group and further stratified in a postrandomization analysis by the Adult Comorbidity Evaluation 27 comorbidity score were compared using a log-rank test. Main Outcome Measure  Time to all-cause mortality. Results  As of January 15, 2007, with a median follow-up of 7.6 (range, 0.5-11.0) years, 74 deaths have occurred. A significant increase in the risk of all-cause mortality (44 vs 30 deaths; hazard ratio [HR], 1.8; 95% confidence interval [CI], 1.1-2.9; P = .01) was observed in men randomized to RT compared with RT and AST. However, the increased risk in all-cause mortality appeared to apply only to men randomized to RT with no or minimal comorbidity (31 vs 11 deaths; HR, 4.2; 95% CI, 2.1-8.5; P < .001). Among men with moderate or severe comorbidity, those randomized to RT alone vs RT and AST did not have an increased risk of all-cause mortality (13 vs 19 deaths; HR, 0.54; 95% CI, 0.27-1.10; P = .08). Conclusions  The addition of 6 months of AST to RT resulted in increased overall survival in men with localized but unfavorable-risk prostate cancer. This result may pertain only to men without moderate or severe comorbidity, but this requires further assessment in a clinical trial specifically designed to assess this interaction. Trial Registration  clinicaltrials.gov Identifier: NCT00116220      

Mediterranean diet, lifestyle factors, and 10-year mortality in elderly European men and women: the HALE project

Context  Dietary patterns and lifestyle factors are associated with mortality from all causes, coronary heart disease, cardiovascular diseases, and cancer, but few studies have investigated these factors in combination. Objective  To investigate the single and combined effect of Mediterranean diet, being physically active, moderate alcohol use, and nonsmoking on all-cause and cause-specific mortality in European elderly individuals. Design, Setting, and Participants  The Healthy Ageing: a Longitudinal study in Europe (HALE) population, comprising individuals enrolled in the Survey in Europe on Nutrition and the Elderly: a Concerned Action (SENECA) and the Finland, Italy, the Netherlands, Elderly (FINE) studies, includes 1507 apparently healthy men and 832 women, aged 70 to 90 years in 11 European countries. This cohort study was conducted between 1988 and 2000. Main Outcome Measures  Ten-year mortality from all causes, coronary heart disease, cardiovascular diseases, and cancer. Results  During follow-up, 935 participants died: 371 from cardiovascular diseases, 233 from cancer, and 145 from other causes; for 186, the cause of death was unknown. Adhering to a Mediterranean diet (hazard ratio [HR], 0.77; 95% confidence interval [CI], 0.68-0.88), moderate alcohol use (HR, 0.78; 95% CI, 0.67-0.91), physical activity (HR, 0.63; 95% CI, 0.55-0.72), and nonsmoking (HR, 0.65; 95% CI, 0.57-0.75) were associated with a lower risk of all-cause mortality (HRs controlled for age, sex, years of education, body mass index, study, and other factors). Similar results were observed for mortality from coronary heart disease, cardiovascular diseases, and cancer. The combination of 4 low risk factors lowered the all-cause mortality rate to 0.35 (95% CI, 0.28-0.44). In total, lack of adherence to this low-risk pattern was associated with a population attributable risk of 60% of all deaths, 64% of deaths from coronary heart disease, 61% from cardiovascular diseases, and 60% from cancer. Conclusion  Among individuals aged 70 to 90 years, adherence to a Mediterranean diet and healthful lifestyle is associated with a more than 50% lower rate of all-causes and cause-specific mortality.      

Green tea consumption and mortality due to cardiovascular disease, cancer, and all causes in Japan: the Ohsaki study

Context  Green tea polyphenols have been extensively studied as cardiovascular disease and cancer chemopreventive agents in vitro and in animal studies. However, the effects of green tea consumption in humans remain unclear. Objective  To investigate the associations between green tea consumption and all-cause and cause-specific mortality. Design, Setting, and Participants  The Ohsaki National Health Insurance Cohort Study, a population-based, prospective cohort study initiated in 1994 among 40 530 Japanese adults aged 40 to 79 years without history of stroke, coronary heart disease, or cancer at baseline. Participants were followed up for up to 11 years (1995-2005) for all-cause mortality and for up to 7 years (1995-2001) for cause-specific mortality. Main Outcome Measures  Mortality due to cardiovascular disease, cancer, and all causes. Results  Over 11 years of follow-up (follow-up rate, 86.1%), 4209 participants died, and over 7 years of follow-up (follow-up rate, 89.6%), 892 participants died of cardiovascular disease and 1134 participants died of cancer. Green tea consumption was inversely associated with mortality due to all causes and due to cardiovascular disease. The inverse association with all-cause mortality was stronger in women (P = .03 for interaction with sex). In men, the multivariate hazard ratios of mortality due to all causes associated with different green tea consumption frequencies were 1.00 (reference) for less than 1 cup/d, 0.93 (95% confidence interval [CI], 0.83-1.05) for 1 to 2 cups/d, 0.95 (95% CI, 0.85-1.06) for 3 to 4 cups/d, and 0.88 (95% CI, 0.79-0.98) for 5 or more cups/d, respectively (P = .03 for trend). The corresponding data for women were 1.00, 0.98 (95% CI, 0.84-1.15), 0.82 (95% CI, 0.70-0.95), and 0.77 (95% CI, 0.67-0.89), respectively (P<.001 for trend). The inverse association with cardiovascular disease mortality was stronger than that with all-cause mortality. This inverse association was also stronger in women (P = .08 for interaction with sex). In women, the multivariate hazard ratios of cardiovascular disease mortality across increasing green tea consumption categories were 1.00, 0.84 (95% CI, 0.63-1.12), 0.69 (95% CI, 0.52-0.93), and 0.69 (95% CI, 0.53-0.90), respectively (P = .004 for trend). Among the types of cardiovascular disease mortality, the strongest inverse association was observed for stroke mortality. In contrast, the hazard ratios of cancer mortality were not significantly different from 1.00 in all green tea categories compared with the lowest-consumption category. Conclusion  Green tea consumption is associated with reduced mortality due to all causes and due to cardiovascular disease but not with reduced mortality due to cancer.      

Favorable cardiovascular risk profile in young women and long-term risk of cardiovascular and all-cause mortality

Context  For women, impact of cardiovascular risk factors measured in young adulthood, particularly favorable (low-risk) profile, on mortality has been difficult to assess due to low short-term death rates. Objective  To assess the relationship of baseline coronary risk factor status to mortality from coronary heart disease (CHD), cardiovascular diseases (CVDs), and all causes in young women. Design  Prospective cohort study. Setting and Participants  A total of 7302 women aged 18 to 39 years without prior CHD or major electrocardiographic abnormalities screened between 1967 and 1973 for the Chicago Heart Association Detection Project in Industry. Risk groups were defined using national guidelines for values of systolic and diastolic blood pressure, serum cholesterol level, body mass index, presence of diabetes, and smoking status. Participants were divided into 4 groups: low risk, 0 risk factors high but 1 or more unfavorable, 1 only risk factor high, and 2 or more risk factors high. Main Outcome Measures  All-cause mortality, CHD mortality, and CVD mortality; hazard ratio of outcome measures comparing low-risk group with other groups. Results  Only 20% met low-risk criteria; 59% had high levels of 1 or more risk factors. During an average follow-up of 31 years, there were 47 CHD deaths, 94 CVD deaths, and 469 deaths from all causes. The age-adjusted CVD death rate per 10 000 person-years was lowest for low-risk women and increased with the number of risk factors, ie, 1.5, 1.7, 5.0, and 9.1 for low-risk; 0, 1, and 2 or more risk factors high, respectively. Multivariate-adjusted CVD mortality hazard ratio for low-risk women was 0.19 (95% confidence interval, 0.08-0.45) compared with women with 2 or more risk factors high. Similar patterns were observed for CHD and all-cause mortality and for both blacks and whites. Conclusion  For women with favorable levels for all 5 major risk factors at younger ages, CHD and CVD are rare; long-term and all-cause mortality are much lower compared with others.      

Risk of lung cancer among white and black relatives of individuals with early-onset lung cancer

Context  Evidence exists that lung cancer aggregates in families and recent findings of a chromosomal region linked to lung cancer susceptibility support a genetic component to risk. Family studies of early-onset lung cancer patients offer a unique opportunity to evaluate lifetime risk of lung cancer in relatives. Objective  To measure lung cancer aggregation and estimate lifetime risk among relatives of early-onset cases and population-based controls. Design and Setting  Familial aggregation and cumulative risk estimates from interview data of incident cases and concurrently ascertained controls between 1990 and 2003 in metropolitan Detroit, Mich. Participants  The study included 7576 biological mothers, fathers, and siblings of 692 early-onset cases and 773 frequency-matched controls. One third of the population was black. Main Outcome Measures  Cumulative lifetime risk of lung cancer, stratified by race and smoking behavior in relatives of early-onset cases and controls. Results  Smokers with a family history of early-onset lung cancer in a first-degree relative had a higher risk of developing lung cancer with increasing age than smokers without a family history. An increase in risk occurs after age 60 years in these individuals, with 17.1% (SE 2.4%) of white case relatives and 25.1% (SE 5.8%) of black case relatives diagnosed with lung cancer by age 70 years. Relatives of black cases were at statistically significant increased risk of lung cancer compared with relatives of white cases (odds ratio, 2.07, 95% confidence interval, 1.29-3.32) after adjusting for age, sex, pack-years, pneumonia, and chronic obstructive lung disease. Conclusions  First-degree relatives of black individuals with early-onset lung cancer have greater risk of lung cancer than their white counterparts, and these risks are further amplified by cigarette smoking. These data provide estimates of lung cancer risk that can be used to offer counseling to family members of patients with early-onset lung cancer.      

Cause-specific excess deaths associated with underweight, overweight, and obesity

Context  The association of body mass index (BMI) with cause-specific mortality has not been reported for the US population. Objective  To estimate cause-specific excess deaths associated with underweight (BMI <18.5), overweight (BMI 25-<30), and obesity (BMI 30). Design, Setting, and Participants  Cause-specific relative risks of mortality from the National Health and Nutrition Examination Survey (NHANES) I, 1971-1975; II, 1976-1980; and III, 1988-1994, with mortality follow-up through 2000 (571 042 person-years of follow-up) were combined with data on BMI and other covariates from NHANES 1999-2002 with underlying cause of death information for 2.3 million adults 25 years and older from 2004 vital statistics data for the United States. Main Outcome Measures  Cause-specific excess deaths in 2004 by BMI levels for categories of cardiovascular disease (CVD), cancer, and all other causes (noncancer, non-CVD causes). Results  Based on total follow-up, underweight was associated with significantly increased mortality from noncancer, non-CVD causes (23 455 excess deaths; 95% confidence interval [CI], 11 848 to 35 061) but not associated with cancer or CVD mortality. Overweight was associated with significantly decreased mortality from noncancer, non-CVD causes (–69 299 excess deaths; 95% CI, –100 702 to –37 897) but not associated with cancer or CVD mortality. Obesity was associated with significantly increased CVD mortality (112 159 excess deaths; 95% CI, 87 842 to 136 476) but not associated with cancer mortality or with noncancer, non-CVD mortality. In further analyses, overweight and obesity combined were associated with increased mortality from diabetes and kidney disease (61 248 excess deaths; 95% CI, 49 685 to 72 811) and decreased mortality from other noncancer, non-CVD causes (–105 572 excess deaths; 95% CI, –161 816 to –49 328). Obesity was associated with increased mortality from cancers considered obesity-related (13 839 excess deaths; 95% CI, 1920 to 25 758) but not associated with mortality from other cancers. Comparisons across surveys suggested a decrease in the association of obesity with CVD mortality over time. Conclusions  The BMI-mortality association varies by cause of death. These results help to clarify the associations of BMI with all-cause mortality.      

Ingested arsenic, cigarette smoking, and lung cancer risk: a follow-up study in arseniasis-endemic areas in Taiwan

Context  Arsenic has been documented as a lung carcinogen in humans in only a few follow-up studies, which were limited by a small number of cases or the lack of information on cigarette smoking. Objectives  To elucidate the dose-response relationship between ingested arsenic and lung cancer and to assess the effect of cigarette smoking on the arsenic–lung cancer association. Design, Setting, and Participants  A total of 2503 residents in southwestern and 8088 in northeastern arseniasis-endemic areas in Taiwan were followed up for an average period of 8 years. Information on arsenic exposure, cigarette smoking, and other risk factors was collected at enrollment through standardized questionnaire interview. Main Outcome Measures  The incidence of lung cancer was ascertained through linkage with national cancer registry profiles in Taiwan (January 1985-December 2000). The joint effect of arsenic and cigarette smoking was estimated by both etiologic fraction and synergy index. Results  There were 139 newly diagnosed lung cancer cases during a follow-up period of 83 783 person-years. After adjustment for cigarette smoking and other risk factors, there was a monotonic trend of lung cancer risk by arsenic level in drinking water of less than 10 to 700 µg/L or more (P<.001). The relative risk was 3.29 (95% confidence interval, 1.60-6.78) for the highest arsenic level compared with the lowest. The etiologic fraction of lung cancer attributable to the joint exposure of ingested arsenic and cigarette smoking ranged from 32% to 55%. The synergy indices ranged from 1.62 to 2.52, indicating a synergistic effect of ingested arsenic and cigarette smoking on lung cancer. Conclusions  There was a significant dose-response trend of ingested arsenic on lung cancer risk, which was more prominent among cigarette smokers. The risk assessment of lung cancer induced by ingested arsenic should take cigarette smoking into consideration.      

Computed tomography screening and lung cancer outcomes

Context  Current and former smokers are currently being screened for lung cancer with computed tomography (CT), although there are limited data on the effect screening has on lung cancer outcomes. Randomized controlled trials assessing CT screening are currently under way. Objective  To assess whether screening may increase the frequency of lung cancer diagnosis and lung cancer resection or may reduce the risk of a diagnosis of advanced lung cancer or death from lung cancer. Design, Setting, and Participants  Longitudinal analysis of 3246 asymptomatic current or former smokers screened for lung cancer beginning in 1998 either at 1 of 2 academic medical centers in the United States or an academic medical center in Italy with follow-up for a median of 3.9 years. Intervention  Annual CT scans with comprehensive evaluation and treatment of detected nodules. Main Outcome Measures  Comparison of predicted with observed number of new lung cancer cases, lung cancer resections, advanced lung cancer cases, and deaths from lung cancer. Results  There were 144 individuals diagnosed with lung cancer compared with 44.5 expected cases (relative risk [RR], 3.2; 95% confidence interval [CI], 2.7-3.8; P<.001). There were 109 individuals who had a lung resection compared with 10.9 expected cases (RR, 10.0; 95% CI, 8.2-11.9; P<.001). There was no evidence of a decline in the number of diagnoses of advanced lung cancers (42 individuals compared with 33.4 expected cases) or deaths from lung cancer (38 deaths due to lung cancer observed and 38.8 expected; RR, 1.0; 95% CI, 0.7-1.3; P = .90). Conclusions  Screening for lung cancer with low-dose CT may increase the rate of lung cancer diagnosis and treatment, but may not meaningfully reduce the risk of advanced lung cancer or death from lung cancer. Until more conclusive data are available, asymptomatic individuals should not be screened outside of clinical research studies that have a reasonable likelihood of further clarifying the potential benefits and risks.      

Serum uric acid and cardiovascular mortality the NHANES I epidemiologic follow-up study, 1971-1992. National Health and Nutrition Examination Survey

Context  Although many epidemiological studies have suggested that increased serum uric acid levels are a risk factor for cardiovascular mortality, this relationship remains uncertain. Objective  To determine the association of serum uric acid levels with cardiovascular mortality. Design and Setting  Cross-sectional population-based study of epidemiological follow-up data from the First National Health and Nutrition Examination Survey (NHANES I) from 1971-1975 (baseline) and data from NHANES I Epidemiologic Follow-up Study (NHEFS). Participants  A total of 5926 subjects who were aged 25 to 74 years and had serum uric acid level measurements at baseline. Main Outcome Measures  Ischemic heart disease mortality, total cardiovascular mortality, and all-cause mortality, compared by quartiles of serum uric acid level. Results  In an average of 16.4 years of follow-up, 1593 deaths occurred, of which 731 (45.9%) were ascribed to cardiovascular disease. Increased serum uric acid levels had a positive relationship to cardiovascular mortality in men and women and in black and white persons. Deaths due to ischemic heart disease in both men and women increased when serum uric acid levels were in the highest quartile compared with the lowest quartile (men, >416 vs <321 µmol/L; risk ratio, 1.77 [95% confidence interval {CI}, 1.08-3.98]; women, >333 vs <238 µmol/L; risk ratio, 3.00 [95% CI, 1.45-6.28]). Cox regression analysis showed that for each 59.48-µmol/L increase in uric acid level, cardiovascular mortality and ischemic heart disease mortality increased. Hazard ratios for men were 1.09 (95% CI, 1.02-1.18) and 1.17 (95% CI, 1.06-1.28), and for women were 1.26 (95% CI, 1.16-1.36) and 1.30 (95% CI, 1.17-1.45), respectively, after adjustment for age, race, body mass index, smoking status, alcohol consumption, cholesterol level, history of hypertension and diabetes, and diuretic use. Further analysis, stratifying by cardiovascular risk status, diuretic use, and menopausal status, confirmed a significant association of uric acid and cardiovascular mortality in all subgroups except among men using diuretics (n=79) and men with 1 or more cardiovascular risk factors (n=1140). Conclusion  Our data suggest that increased serum uric acid levels are independently and significantly associated with risk of cardiovascular mortality.