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1.  Association between muscular strength and mortality in men: prospective cohort study 
Objective To examine prospectively the association between muscular strength and mortality from all causes, cardiovascular disease, and cancer in men.
Design Prospective cohort study.
Setting Aerobics centre longitudinal study.
Participants 8762 men aged 20-80.
Main outcome measures All cause mortality up to 31 December 2003; muscular strength, quantified by combining one repetition maximal measures for leg and bench presses and further categorised as age specific thirds of the combined strength variable; and cardiorespiratory fitness assessed by a maximal exercise test on a treadmill.
Results During an average follow-up of 18.9 years, 503 deaths occurred (145 cardiovascular disease, 199 cancer). Age adjusted death rates per 10 000 person years across incremental thirds of muscular strength were 38.9, 25.9, and 26.6 for all causes; 12.1, 7.6, and 6.6 for cardiovascular disease; and 6.1, 4.9, and 4.2 for cancer (all P<0.01 for linear trend). After adjusting for age, physical activity, smoking, alcohol intake, body mass index, baseline medical conditions, and family history of cardiovascular disease, hazard ratios across incremental thirds of muscular strength for all cause mortality were 1.0 (referent), 0.72 (95% confidence interval 0.58 to 0.90), and 0.77 (0.62 to 0.96); for death from cardiovascular disease were 1.0 (referent), 0.74 (0.50 to 1.10), and 0.71 (0.47 to 1.07); and for death from cancer were 1.0 (referent), 0.72 (0.51 to 1.00), and 0.68 (0.48 to 0.97). The pattern of the association between muscular strength and death from all causes and cancer persisted after further adjustment for cardiorespiratory fitness; however, the association between muscular strength and death from cardiovascular disease was attenuated after further adjustment for cardiorespiratory fitness.
Conclusion Muscular strength is inversely and independently associated with death from all causes and cancer in men, even after adjusting for cardiorespiratory fitness and other potential confounders.
PMCID: PMC2453303  PMID: 18595904
2.  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
3.  A Prospective Study of Muscular Strength and All-cause Mortality in Men with Hypertension 
To assess the impact of muscular strength on mortality in men with hypertension.
Muscular strength is inversely associated with mortality in healthy men, but this association has not been examined in men with hypertension.
We followed 1506 hypertensive men aged ≥ 40 years enrolled in the Aerobics Center Longitudinal Study from 1980 to 2003. Participants received an extensive medical examination at baseline. Muscular strength was quantified by combining one repetition maximum (1-RM) measures for leg and bench press, and cardiorespiratory fitness (CRF) assessed by maximum exercise test on a treadmill.
During an average follow-up of 18.3 years, 183 deaths occurred. Age adjusted death rates per 10 000 man-years across incremental thirds of muscular strength were 81.8, 65.5 and 52.0 (P<0.05 for linear trend). Multivariable Cox regression hazard ratios were 1.0 (reference), 0.81 (95% confidence interval, 0.57 to 1.14), and 0.59 (0.40 to 0.86) across incremental thirds of muscular strength. After further adjustment for CRF, those participants in the upper third of muscular strength still had a lower risk of death (0.66; 0.45 to 0.98). In the muscular strength and CRF combined analysis, men simultaneously in the upper third of muscular strength and high fitness group had the lowest mortality risk among all combination groups (0.49; 0.30 to 0.82), with men in the lower third of muscular strength and low fitness group as reference.
High levels of muscular strength appear to protect hypertensive men against all-cause mortality, and this is in addition to the benefit provided by CRF.
PMCID: PMC3098120  PMID: 21527158
Hypertension; muscular strength; cardiorespiratory fitness; mortality
4.  Muscle strength in adolescent men and risk of cardiovascular disease events and mortality in middle age: a prospective cohort study 
BMC Medicine  2014;12:62.
Ischemic heart disease and stroke are two severe types of cardiovascular disease (CVD), a major contributor to the global burden of disease. The preventive framework currently includes promotion of both adequate cardiorespiratory and muscular fitness. Although muscle fitness is established as an indicator of health, it is currently unknown whether muscle strength is associated with later CVD independently of cardiorespiratory fitness.
We studied 38,588 Swedish men who in 1969 to 1970 (typically aged 18 years) completed compulsory conscription. Using the mean standardized score of three isometric muscle strength tests performed at conscription (hand grip, elbow flexion and knee extension), we categorized the subjects into three groups with the 25th to 75th percentile defining the reference category. We followed the cohort until 2012 for diagnosed CVD events and mortality via national health care registers and the national cause of death register. To estimate hazard ratios (HR) for CVD events (coronary heart disease or stroke) and CVD mortality we used Cox proportional hazard models adjusted for body mass index, smoking, alcohol consumption, cardiorespiratory fitness and socioeconomic status.
Men with high muscle strength in adolescence had a decreased risk of later CVD events (HR 0.88, 95% confidence interval 0.77 to 0.99), whereas we observed no increased risk in men with low muscle strength (0.99, 0.86 to 1.13). However, low muscle strength was associated with increased risk of CVD mortality during middle age (1.31, 1.02 to 1.67).
Muscle strength in adolescent men is inversely associated with later CVD events and CVD mortality in middle age, independently of cardiorespiratory fitness and other important confounders. Thus, the role of muscle fitness in the prevention and pathogenesis of CVD warrants increased attention.
PMCID: PMC4006633  PMID: 24731728
Cardiovascular disease; Coronary heart disease; Stroke; Muscle strength; Prevention; Epidemiology
5.  Muscular Strength and Incident Hypertension in Normotensive and Prehypertensive Men 
The protective effects of cardiorespiratory fitness (CRF) on hypertension (HTN) are well known; however, the association between muscular strength and incidence of HTN has yet to be examined.
This study evaluated the strength-HTN association with and without accounting for CRF.
Participants were 4147 men (20–82 years) in the Aerobics Center Longitudinal Study for whom an age-specific composite muscular strength score was computed from measures of a 1-repetition maximal leg and a 1-repetition maximal bench press. CRF was quantified by maximal treadmill exercise test time in minutes. Cox proportional hazards regression analysis was used to estimate hazard ratios (HRs) and 95% confidence intervals of incident HTN events according to exposure categories.
During a mean follow-up of 19 years, there were 503 incident HTN cases. Multivariable-adjusted (excluding CRF) HRs of hypertension in normotensive men comparing middle and high strength thirds to the lowest third were not significant at 1.17 and 0.84, respectively. Multivariable-adjusted (excluding CRF) HRs of hypertension in baseline prehypertensive men comparing middle and high strength thirds to the lowest third were significant at 0.73 and 0.72 (p=.01 each), respectively. The association between muscular strength and incidence of HTN in baseline prehypertensive men was no longer significant after control for CRF (p=.26).
The study indicated that middle and high levels of muscular strength were associated with a reduced risk of HTN in prehypertensive men only. However, this relationship was no longer significant after controlling for CRF.
PMCID: PMC2809142  PMID: 19927030
physical fitness; blood pressure; cohort study; epidemiology
6.  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
7.  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
8.  Muscular strength in male adolescents and premature death: cohort study of one million participants 
Objectives To explore the extent to which muscular strength in adolescence is associated with all cause and cause specific premature mortality (<55 years).
Design Prospective cohort study.
Setting Sweden.
Participants 1 142 599 Swedish male adolescents aged 16-19 years were followed over a period of 24 years.
Main outcome measures Baseline examinations included knee extension, handgrip, and elbow flexion strength tests, as well as measures of diastolic and systolic blood pressure and body mass index. Cox regression was used to estimate hazard ratios for mortality according to muscular strength categories (tenths).
Results During a median follow-up period of 24 years, 26 145 participants died. Suicide was a more frequent cause of death in young adulthood (22.3%) than was cardiovascular diseases (7.8%) or cancer (14.9%). High muscular strength in adolescence, as assessed by knee extension and handgrip tests, was associated with a 20-35% lower risk of premature mortality due to any cause or cardiovascular disease, independently of body mass index or blood pressure; no association was observed with mortality due to cancer. Stronger adolescents had a 20-30% lower risk of death from suicide and were 15-65% less likely to have any psychiatric diagnosis (such as schizophrenia and mood disorders). Adolescents in the lowest tenth of muscular strength showed by far the highest risk of mortality for different causes. All cause mortality rates (per 100 000 person years) ranged between 122.3 and 86.9 for the weakest and strongest adolescents; corresponding figures were 9.5 and 5.6 for mortality due to cardiovascular diseases and 24.6 and 16.9 for mortality due to suicide.
Conclusions Low muscular strength in adolescents is an emerging risk factor for major causes of death in young adulthood, such as suicide and cardiovascular diseases. The effect size observed for all cause mortality was equivalent to that for well established risk factors such as elevated body mass index or blood pressure.
PMCID: PMC3502746  PMID: 23169869
9.  A non-exercise testing method for estimating cardiorespiratory fitness: associations with all-cause and cardiovascular mortality in a pooled analysis of eight population-based cohorts 
European Heart Journal  2012;34(10):750-758.
Cardiorespiratory fitness (CRF) is a key predictor of chronic disease, particularly cardiovascular disease (CVD), but its assessment usually requires exercise testing which is impractical and costly in most health-care settings. Non-exercise testing cardiorespiratory fitness (NET-F)-estimating methods are a less resource-demanding alternative, but their predictive capacity for CVD and total mortality has yet to be tested. The objective of this study is to examine the association of a validated NET-F algorithm with all-cause and CVD mortality.
Methods and results
The participants were 32 319 adults (14 650 men) aged 35–70 years who took part in eight Health Survey for England and Scottish Health Survey studies between 1994 and 2003. Non-exercise testing cardiorespiratory fitness (a metabolic equivalent of VO2max) was calculated using age, sex, body mass index (BMI), resting heart rate, and self-reported physical activity. We followed participants for mortality until 2008. Two thousand one hundred and sixty-five participants died (460 cardiovascular deaths) during a mean 9.0 [standard deviation (SD) = 3.6] year follow-up. After adjusting for potential confounders including diabetes, hypertension, smoking, social class, alcohol, and depression, a higher fitness score according to the NET-F was associated with a lower risk of mortality from all-causes (hazard ratio per SD increase in NET-F 0.85, 95% confidence interval: 0.78–0.93 in men; 0.88, 0.80–0.98 in women) and CVD (men: 0.75, 0.63–0.90; women: 0.73, 0.60–0.92). Non-exercise testing cardiorespiratory fitness had a better discriminative ability than any of its components (CVD mortality c-statistic: NET-F = 0.70–0.74; BMI = 0.45–0.59; physical activity = 0.60–0.64; resting heart rate = 0.57–0.61). The sensitivity of the NET-F algorithm to predict events occurring in the highest risk quintile was better for CVD (0.49 in both sexes) than all-cause mortality (0.44 and 0.40 for men and women, respectively). The specificity for all-cause and CVD mortality ranged between 0.80 and 0.82. The net reclassification improvement of CVD mortality risk (vs. a standardized aggregate score of the modifiable components of NET-F) was 27.2 and 21.0% for men and women, respectively.
The CRF-estimating method NET-F that does not involve exercise testing showed consistent associations with all-cause and cardiovascular mortality, and it had good discrimination and excellent risk reclassification improvement. As such, it merits further attention as a practical and potentially and useful risk prediction tool.
PMCID: PMC3590456  PMID: 22555215
Epidemiology; Non-exercise testing; Cardiorespiratory fitness; Cardiovascular disease; Physical activity; Health Survey for England
10.  Association of Early Repolarization Pattern on ECG with Risk of Cardiac and All-Cause Mortality: A Population-Based Prospective Cohort Study (MONICA/KORA) 
PLoS Medicine  2010;7(7):e1000314.
In a population-based cohort study of middle-aged people in Central Europe, Stefan Kääb and colleagues find an association between electrocardiographic early repolarization pattern and mortality risk.
Early repolarization pattern (ERP) on electrocardiogram was associated with idiopathic ventricular fibrillation and sudden cardiac arrest in a case-control study and with cardiovascular mortality in a Finnish community-based sample. We sought to determine ERP prevalence and its association with cardiac and all-cause mortality in a large, prospective, population-based case-cohort study (Monitoring of Cardiovascular Diseases and Conditions [MONICA]/KORA [Cooperative Health Research in the Region of Augsburg]) comprised of individuals of Central-European descent.
Methods and Findings
Electrocardiograms of 1,945 participants aged 35–74 y, representing a source population of 6,213 individuals, were analyzed applying a case-cohort design. Mean follow-up was 18.9 y. Cause of death was ascertained by the 9th revision of the International Classification of Disease (ICD-9) codes as documented in death certificates. ERP-attributable effects on mortality were determined by a weighted Cox proportional hazard model adjusted for covariables. Prevalence of ERP was 13.1% in our study. ERP was associated with cardiac and all-cause mortality, most pronounced in those of younger age and male sex; a clear ERP-age interaction was detected (p = 0.005). Age-stratified analyses showed hazard ratios (HRs) for cardiac mortality of 1.96 (95% confidence interval [CI] 1.05–3.68, p = 0.035) for both sexes and 2.65 (95% CI 1.21–5.83, p = 0.015) for men between 35–54 y. An inferior localization of ERP further increased ERP-attributable cardiac mortality to HRs of 3.15 (95% CI 1.58–6.28, p = 0.001) for both sexes and to 4.27 (95% CI 1.90–9.61, p<0.001) for men between 35–54 y. HRs for all-cause mortality were weaker but reached significance.
We found a high prevalence of ERP in our population-based cohort of middle-aged individuals. ERP was associated with about a 2- to 4-fold increased risk of cardiac mortality in individuals between 35 and 54 y. An inferior localization of ERP was associated with a particularly increased risk.
Please see later in the article for the Editors' Summary
Editors' Summary
Cardiovascular diseases—disorders that affect the heart and the circulation—are the leading cause of death in the developed world. About half of cardiovascular deaths occur when the heart suddenly stops pumping (sudden cardiac arrest). The muscular walls of the four heart chambers contract in a set pattern to pump blood around the body. The heart's internal electrical system controls the rate and rhythm of these contractions and, if this system goes wrong, an abnormal heart beat or “arrhythmia” develops. Some arrhythmias—in particular, ventricular fibrillation in which the walls of the two lower heart chambers quiver or “fibrillate” instead of pumping—can cause sudden cardiac arrest and immediate loss of consciousness. Death follows within minutes in 95% of cases but immediate cardiopulmonary resuscitation (CPR; chest compression to pump the heart and inflation of the lungs by mouth-to-mouth resuscitation) can keep a person alive until a defibrillator can be used to restore the normal heart beat. People who survive sudden cardiac arrest can be given anti-arrhythmia drugs or have a pacemaker implanted to stabilize their heart beat.
Why Was This Study Done?
The beating heart generates tiny electric waves that can be detected by electrodes on the skin. The pattern of these waves (an electrocardiogram or ECG) provides information about the heart's health. One wave pattern that is often seen on ECGs is the “early repolarization pattern” (ERP), which some studies suggest is associated with an increased risk of cardiac death. Here, the researchers investigate the prevalence of ERP (the proportion of a population with ERP) and its association with death from heart-related problems (cardiac mortality) and from any cause (all-cause mortality) in the MONICA/KORA prospective, population-based case-cohort study. The MONICA Project (MONitoring of Trends and Determinants in CArdiovascular Disease) has studied cardiovascular disease in 10 million people in 21 countries; KORA denotes the study done in the Augsburg region of Germany. In a prospective study, specific baseline characteristics of the study's participants are determined and the participants are followed to see who experiences a predefined outcome. A case-cohort study investigates a randomly selected subcohort (subgroup) of the original participants of a study and any participants who experience the predefined outcome instead of all the participants.
What Did the Researchers Do and Find?
The researchers selected 1945 MONIKA/KORA participants aged 35–74 years from a source population of about 6,000 people using a case-cohort study design. They analyzed the ECGs (recorded in 1984–1985 or 1989–1990) of this subcohort and ascertained the cause of death for those participants who died during the 18.9 year average follow-up. The overall prevalence of ERP in the study was 13.1%, report the researchers, and ERP was associated with cardiac mortality, particularly among younger and male participants. Specifically, among men and women aged 35–54 years, having ERP was associated with a nearly doubled risk of cardiac death. Among men aged 35–54 years, having ERP was associated with an increase in the risk of cardiac death by 2.65-fold. An ERP localized to the bottom of the heart (inferior localization) was associated with an increased risk of cardiac death among both sexes by more than 3-fold and among men by more than 4-fold in this age group. Finally, ERP was also significantly associated with an increased risk of all-cause mortality but less strongly than with cardiac mortality.
What Do These Findings Mean?
These findings suggest that the prevalence of ERP among the middle-aged people in the MONICA/KORA study is high (and somewhat higher than previously reported). They also show a clear association between ERP and the risk of cardiac death among 35–54-year-old people, particularly among men, but because of the study design, these findings do not show that ERP actually causes cardiac death; it could simply be a susceptibility marker. The researchers note that the increased risk of cardiac death associated with ERP is of a similar size to that associated with some other ECG abnormalities. However, although it might be worth paying special attention to young people with an inferior localization of ERP, finding ERP in a person without symptoms and without a family history of sudden cardiac death should not lead to further investigations or any preventative therapy, they suggest, because the absolute risk of cardiac arrest in such people is very low.
Additional Information
Please access these Web sites via the online version of this summary at
The US National Heart Lung and Blood Institute provides information on cardiovascular conditions, including sudden cardiac arrest and on arrhythmias
The American Heart Association also information on sudden cardiac death and on arrhythmias
The German Cardiac Society (Deutsche Gesellschaft fr Kardiologie) and the German Heart Foundation (Deutsche Herzstiftung) provide further information (in German) on cardiovascular conditions
The Heart Rhythm Foundation provides information on all aspects of heart arrhythmia
The Fondation Leducq Alliance Against Sudden Cardiac Death provides information on sudden cardiac arrest
MedlinePlus provides links to other resources about cardiac arrest and arrhythmias (in English and Spanish)
The MedlinePlus Encyclopedia has a page on electrocardiograms (in English and Spanish)
The Nobel Foundation provides an interactive electrocardiogram game
More information about the MONICA project and the KORA Study or is available
PMCID: PMC2910598  PMID: 20668657
11.  Height and risk of death among men and women: aetiological implications of associations with cardiorespiratory disease and cancer mortality 
OBJECTIVES—Height is inversely associated with cardiovascular disease mortality risk and has shown variable associations with cancer incidence and mortality. The interpretation of findings from previous studies has been constrained by data limitations. Associations between height and specific causes of death were investigated in a large general population cohort of men and women from the West of Scotland.
DESIGN—Prospective observational study.
SETTING—Renfrew and Paisley, in the West of Scotland.
SUBJECTS—7052 men and 8354 women aged 45-64 were recruited into a study in Renfrew and Paisley, in the West of Scotland, between 1972 and 1976. Detailed assessments of cardiovascular disease risk factors, morbidity and socioeconomic circumstances were made at baseline.
MAIN OUTCOME MEASURES—Deaths during 20 years of follow up classified into specific causes.
RESULTS—Over the follow up period 3347 men and 2638 women died. Height is inversely associated with all cause, coronary heart disease, stroke, and respiratory disease mortality among men and women. Adjustment for socioeconomic position and cardiovascular risk factors had little influence on these associations. Height is strongly associated with forced expiratory volume in one second (FEV1) and adjustment for FEV1 considerably attenuated the association between height and cardiorespiratory mortality. Smoking related cancer mortality is not associated with height. The risk of deaths from cancer unrelated to smoking tended to increase with height, particularly for haematopoietic, colorectal and prostate cancers. Stomach cancer mortality was inversely associated with height. Adjustment for socioeconomic position had little influence on these associations.
CONCLUSION—Height serves partly as an indicator of socioeconomic circumstances and nutritional status in childhood and this may underlie the inverse associations between height and adulthood cardiorespiratory mortality. Much of the association between height and cardiorespiratory mortality was accounted for by lung function, which is also partly determined by exposures acting in childhood. The inverse association between height and stomach cancer mortality probably reflects Helicobacter pylori infection in childhood resulting in—or being associated with—shorter height. The positive associations between height and several cancers unrelated to smoking could reflect the influence of calorie intake during childhood on the risk of these cancers.

Keywords: height; cancer; cardiorespiratory disease
PMCID: PMC1731616  PMID: 10715741
12.  The Obesity Paradox and Cardiorespiratory Fitness 
Journal of Obesity  2012;2012:951582.
Cardiorespiratory fitness as an explanation for the obesity paradox warrants further examination. We evaluated independent and joint associations of cardiorespiratory fitness and adiposity with all-cause mortality in 811 middle-aged (age, 53.3 ± 7.2 years) male never smokers without documented cardiopulmonary disease or diabetes from the Veterans Exercise Testing Study (VETS). Cardiorespiratory fitness was quantified in metabolic equivalents (METs) using final treadmill speed and grade achieved on a maximal exercise test. Subjects were grouped for analysis by METs: unfit (lowest third) and fit (upper two-thirds); and by body mass index (kg/m2): nonobese (18.5−29.9) and obese (≥30.0). Associations of baseline fitness and adiposity measures with all-cause mortality were determined by Cox proportional hazards analysis adjusted for age, ethnicity, hypertension, hypercholesterolemia, family history of coronary artery disease, and cardiovascular medication use. In multivariate analysis, mortality risk for obese/fit men did not differ significantly from the nonobese/fit reference group. However, compared to the reference group, nonobese and obese unfit men were 2.2 (P = 0.01) and 1.9 (P = 0.03) times more likely to die, respectively. Cardiorespiratory fitness altered the obesity paradox such that mortality risk was lower for both obese and nonobese men who were fit.
PMCID: PMC3317120  PMID: 22523668
13.  Maximal Exercise Electrocardiography Responses and Coronary Heart Disease Mortality Among Men With Diabetes Mellitus 
Circulation  2008;117(21):2734-2742.
An abnormal ECG during maximal exercise testing has been shown to be a powerful predictor of future coronary heart disease (CHD) mortality in asymptomatic men. However, little is known about the relationship between exercise ECG responses and CHD risk in men with diabetes mellitus.
Methods and Results
We examined the association between exercise ECG responses and mortality in 2854 men with documented diabetes mellitus (mean age 49.5 years) who completed a maximal treadmill exercise test during the period from 1974 to 2001 and who were without a previous cardiovascular disease (CVD) event at baseline. Mortality due to all causes, CHD, and CVD were the main outcome measures across categories of exercise ECG responses, with stratification by cardiorespiratory fitness, quantified as treadmill test duration. During an average follow-up of 16 years, 441 deaths (210 CVD and 133 CHD) were identified. Across normal, equivocal, and abnormal exercise ECG groups, age- and examination year-adjusted CHD mortality rates per 10 000 person-years were 23.0, 48.6, and 69.0, respectively (Ptrend<0.001). After further adjustment for fasting plasma glucose level, smoking, body mass index, hypercholesterolemia, hypertension, family history of CVD or diabetes mellitus, abnormal resting ECG responses, and cardiorespiratory fitness, hazard ratios (95% confidence intervals) were 1.00 (referent), 1.68 (1.01 to 2.77), and 2.21 (1.41 to 3.46; Ptrend<0.001). Similar patterns of associations were noted between exercise ECG testing and both CVD and all-cause mortality risk.
Among men with diabetes mellitus, equivocal and abnormal exercise ECG responses were associated with higher risk of all-cause, CVD, and CHD mortality.
PMCID: PMC2875671  PMID: 18490521
exercise; electrocardiography; coronary disease; diabetes mellitus
14.  Cardiorespiratory Fitness and Long-Term Survival in “Low-Risk” Adults 
We sought to establish whether cardiorespiratory fitness had important implications for long-term cardiovascular risk among individuals classified as low risk by the Framingham Risk Score (10-year coronary heart disease risk <10%). Prognostic factors of long-term cardiovascular risk are needed for low-risk subjects who make up the largest percentage of the US population.
Methods and Results
The study population was composed of men and women, 30 to 50 years of age, who had a baseline medical exam at the Cooper Clinic, Dallas, TX, between 1970 and 1983. Eligible individuals were defined as at low risk for coronary heart disease by Framingham Risk Score at the time of study entry and had no history of diabetes (n=11 190). Cardiorespiratory fitness was determined by maximum graded exercise treadmill tests. Over an average 27±2-year period, 15% of low-fit (quintile 1) compared to 6% of high-fit (quintile 5) individuals died (P<0.001). A 1–metabolic equivalent level increase in baseline fitness was associated with an 11% reduction in all-cause deaths and an 18% reduction in deaths due to cardiovascular disease (CVD) after adjustment for age, sex, body mass index, systolic blood pressure, total cholesterol, blood glucose levels, smoking, and early family history of coronary disease. There was an incremental decrease in CVD risk with increasing fitness quintile, such that the high fit had the lowest adjusted 30-year CVD mortality rate (hazard ratio 0.29, 95% CI: 0.16–0.51) compared to the low fit.
Cardiorespiratory fitness is associated with a significant reduction in long-term CVD among individuals identified as low risk by Framingham Risk Score. These data suggest that preventive lifestyle interventions geared to optimize cardiorespiratory fitness, even among a “low-risk” subset, should be considered to improve CVD-free survival. (J Am Heart Assoc. 2012;1:e001354 doi: 10.1161/JAHA.112.001354.)
PMCID: PMC3487345  PMID: 23130161
cardiorespiratory fitness; risk, low; Framingham Risk Score; cardiovascular disease
15.  Burden of Total and Cause-Specific Mortality Related to Tobacco Smoking among Adults Aged ≥45 Years in Asia: A Pooled Analysis of 21 Cohorts 
PLoS Medicine  2014;11(4):e1001631.
Wei Zheng and colleagues quantify the burden of tobacco-smoking-related deaths for adults in Asia.
Please see later in the article for the Editors' Summary
Tobacco smoking is a major risk factor for many diseases. We sought to quantify the burden of tobacco-smoking-related deaths in Asia, in parts of which men's smoking prevalence is among the world's highest.
Methods and Findings
We performed pooled analyses of data from 1,049,929 participants in 21 cohorts in Asia to quantify the risks of total and cause-specific mortality associated with tobacco smoking using adjusted hazard ratios and their 95% confidence intervals. We then estimated smoking-related deaths among adults aged ≥45 y in 2004 in Bangladesh, India, mainland China, Japan, Republic of Korea, Singapore, and Taiwan—accounting for ∼71% of Asia's total population. An approximately 1.44-fold (95% CI = 1.37–1.51) and 1.48-fold (1.38–1.58) elevated risk of death from any cause was found in male and female ever-smokers, respectively. In 2004, active tobacco smoking accounted for approximately 15.8% (95% CI = 14.3%–17.2%) and 3.3% (2.6%–4.0%) of deaths, respectively, in men and women aged ≥45 y in the seven countries/regions combined, with a total number of estimated deaths of ∼1,575,500 (95% CI = 1,398,000–1,744,700). Among men, approximately 11.4%, 30.5%, and 19.8% of deaths due to cardiovascular diseases, cancer, and respiratory diseases, respectively, were attributable to tobacco smoking. Corresponding proportions for East Asian women were 3.7%, 4.6%, and 1.7%, respectively. The strongest association with tobacco smoking was found for lung cancer: a 3- to 4-fold elevated risk, accounting for 60.5% and 16.7% of lung cancer deaths, respectively, in Asian men and East Asian women aged ≥45 y.
Tobacco smoking is associated with a substantially elevated risk of mortality, accounting for approximately 2 million deaths in adults aged ≥45 y throughout Asia in 2004. It is likely that smoking-related deaths in Asia will continue to rise over the next few decades if no effective smoking control programs are implemented.
Please see later in the article for the Editors' Summary
Editors' Summary
Every year, more than 5 million smokers die from tobacco-related diseases. Tobacco smoking is a major risk factor for cardiovascular disease (conditions that affect the heart and the circulation), respiratory disease (conditions that affect breathing), lung cancer, and several other types of cancer. All told, tobacco smoking kills up to half its users. The ongoing global “epidemic” of tobacco smoking and tobacco-related diseases initially affected people living in the US and other Western countries, where the prevalence of smoking (the proportion of the population that smokes) in men began to rise in the early 1900s, peaking in the 1960s. A similar epidemic occurred in women about 40 years later. Smoking-related deaths began to increase in the second half of the 20th century, and by the 1990s, tobacco smoking accounted for a third of all deaths and about half of cancer deaths among men in the US and other Western countries. More recently, increased awareness of the risks of smoking and the introduction of various tobacco control measures has led to a steady decline in tobacco use and in smoking-related diseases in many developed countries.
Why Was This Study Done?
Unfortunately, less well-developed tobacco control programs, inadequate public awareness of smoking risks, and tobacco company marketing have recently led to sharp increases in the prevalence of smoking in many low- and middle-income countries, particularly in Asia. More than 50% of men in many Asian countries are now smokers, about twice the prevalence in many Western countries, and more women in some Asian countries are smoking than previously. More than half of the world's billion smokers now live in Asia. However, little is known about the burden of tobacco-related mortality (deaths) in this region. In this study, the researchers quantify the risk of total and cause-specific mortality associated with tobacco use among adults aged 45 years or older by undertaking a pooled statistical analysis of data collected from 21 Asian cohorts (groups) about their smoking history and health.
What Did the Researchers Do and Find?
For their study, the researchers used data from more than 1 million participants enrolled in studies undertaken in Bangladesh, India, mainland China, Japan, the Republic of Korea, Singapore, and Taiwan (which together account for 71% of Asia's total population). Smoking prevalences among male and female participants were 65.1% and 7.1%, respectively. Compared with never-smokers, ever-smokers had a higher risk of death from any cause in pooled analyses of all the cohorts (adjusted hazard ratios [HRs] of 1.44 and 1.48 for men and women, respectively; an adjusted HR indicates how often an event occurs in one group compared to another group after adjustment for other characteristics that affect an individual's risk of the event). Compared with never smoking, ever smoking was associated with a higher risk of death due to cardiovascular disease, cancer (particularly lung cancer), and respiratory disease among Asian men and among East Asian women. Moreover, the researchers estimate that, in the countries included in this study, tobacco smoking accounted for 15.8% of all deaths among men and 3.3% of deaths among women in 2004—a total of about 1.5 million deaths, which scales up to 2 million deaths for the population of the whole of Asia. Notably, in 2004, tobacco smoking accounted for 60.5% of lung-cancer deaths among Asian men and 16.7% of lung-cancer deaths among East Asian women.
What Do These Findings Mean?
These findings provide strong evidence that tobacco smoking is associated with a substantially raised risk of death among adults aged 45 years or older throughout Asia. The association between smoking and mortality risk in Asia reported here is weaker than that previously reported for Western countries, possibly because widespread tobacco smoking started several decades later in most Asian countries than in Europe and North America and the deleterious effects of smoking take some years to become evident. The researchers note that certain limitations of their analysis are likely to affect the accuracy of its findings. For example, because no data were available to estimate the impact of secondhand smoke, the estimate of deaths attributable to smoking is likely to be an underestimate. However, the finding that nearly 45% of the global deaths from active tobacco smoking occur in Asia highlights the urgent need to implement comprehensive tobacco control programs in Asia to reduce the burden of tobacco-related disease.
Additional Information
Please access these websites via the online version of this summary at
The World Health Organization provides information about the dangers of tobacco (in several languages) and about the WHO Framework Convention on Tobacco Control, an international instrument for tobacco control that came into force in February 2005 and requires parties to implement a set of core tobacco control provisions including legislation to ban tobacco advertising and to increase tobacco taxes; its 2013 report on the global tobacco epidemic is available
The US Centers for Disease Control and Prevention provides detailed information about all aspects of smoking and tobacco use
The UK National Health Services Choices website provides information about the health risks associated with smoking
MedlinePlus has links to further information about the dangers of smoking (in English and Spanish)
SmokeFree, a website provided by the UK National Health Service, offers advice on quitting smoking and includes personal stories from people who have stopped smoking, from the US National Cancer Institute, offers online tools and resources to help people quit smoking
PMCID: PMC3995657  PMID: 24756146
16.  The Association Between Cardiorespiratory Fitness and Risk of All-Cause Mortality Among Women With Impaired Fasting Glucose or Undiagnosed Diabetes Mellitus 
Mayo Clinic Proceedings  2009;84(9):780-786.
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; Ptrend=.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 (Ptrend=.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; Ptrend=.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.
Cardiorespiratory fitness, not body mass index, is a significant predictor of all-cause mortality among women with impaired fasting glucose or undiagnosed diabetes mellitus; assessing cardiorespiratory fitness levels provides important prognostic information independent of traditional risk factors. An exercise capacity lower than 7 metabolic equivalents was associated with a 1.5-fold higher risk of death.
PMCID: PMC2735427  PMID: 19720775
17.  Self-rated health status and cardiorespiratory fitness as predictors of mortality in men 
British journal of sports medicine  2011;45(14):1095-1100.
Self-rated health (SRH) and cardiorespiratory fitness (fitness) are independent risk factors for all-cause mortality. The purpose of this report is to examine the single and joint effects of these exposures on mortality risk. The study included 18,488 men who completed a health survey, clinical examination, and a maximal exercise treadmill test during 1987–2003. Cox regression analysis was used to quantify the associations of SRH and fitness with all-cause mortality. There were 262 deaths during 17 years of follow-up. There was a significant inverse trend (Ptrend < 0.05) for mortality across SRH categories after adjustment for age, examination year, body mass index, physical activity, smoking, alcohol consumption, abnormal ECG, hypertension, and hypercholesterolemia, cardiovascular disease, diabetes, and cancer. Adjustment for fitness attenuated the association (P value =0.09). We also observed an inverse association between fitness and mortality after controlling for the same covariates and SRH (Ptrend = 0.006). The combined analysis of SRH and fitness showed that fit men with good or excellent SRH had a 58% lower risk of mortality than their counterparts. SRH and fitness were both associated with all-cause mortality in men. Fit men with good or excellent SRH live longer than unfit men with poor or fair SRH.
PMCID: PMC3192266  PMID: 21659563
health status; men; mortality; physical fitness
18.  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
19.  Adiposity and Age Explain Most of the Association between Physical Activity and Fitness in Physically Active Men 
PLoS ONE  2010;5(10):e13435.
To determine if there is an association between physical activity assessed by the short version of the International Physical Activity Questionnaire (IPAQ) and cardiorespiratory and muscular fitness.
Methodology/Principal Findings
One hundred and eighty-two young males (age range: 20–55 years) completed the short form of the IPAQ to assess physical activity. Body composition (dual-energy X-Ray absorptiometry), muscular fitness (static and dynamic muscle force and power, vertical jump height, running speed [30 m sprint], anaerobic capacity [300 m running test]) and cardiorespiratory fitness (estimated VO2max: 20 m shuttle run test) were also determined in all subjects.
Activity-related energy expenditure of moderate and vigorous intensity (EEPAmoderate and EEPAvigorous, respectively) was inversely associated with indices of adiposity (r = −0.21 to −0.37, P<0.05). Cardiorespiratory fitness (VO2max) was positively associated with LogEEPAmoderate (r = 0.26, P<0.05) and LogEEPAvigorous (r = 0.27). However, no association between VO2max with LogEEPAmoderate, LogEPPAvigorous and LogEEPAtotal was observed after adjusting for the percentage of body fat. Multiple stepwise regression analysis to predict VO2max from LogEEPAwalking, LogEEPAmoderate, LogEEPAvigorous, LogEEPAtotal, age and percentage of body fat (%fat) showed that the %fat alone explained 62% of the variance in VO2max and that the age added another 10%, while the other variables did not add predictive value to the model [VO2max  = 129.6−(25.1× Log %fat) − (34.0× Log age); SEE: 4.3−1. min−1; R2 = 0.72 (P<0.05)]. No positive association between muscular fitness-related variables and physical activity was observed, even after adjusting for body fat or body fat and age.
Adiposity and age are the strongest predictors of VO2max in healthy men. The energy expended in moderate and vigorous physical activities is inversely associated with adiposity. Muscular fitness does not appear to be associated with physical activity as assessed by the IPAQ.
PMCID: PMC2956676  PMID: 20976154
20.  Differences in Physical Fitness and Cardiovascular Function Depend on BMI in Korean Men 
We investigated the associations between cardiovascular function and both body mass index and physical fitness in Korean men. The subjects were 2,013 men, aged 20 to 83 years, who visited a health promotion center for a comprehensive medical and fitness test during 2006-2009. The WHO's Asia-Pacific Standard Report definition of BMI was used in this study. Fitness assessment of cardiorespiratory endurance, muscular strength, muscular endurance, flexibility, power, agility, and balance were evaluated by VO2max (ml/kg/min), grip strength (kg), sit-ups (reps/min), sit and reach (cm), vertical jump (cm), side steps (reps/30s), and standing on one leg with eyes closed (sec), respectively. For cardiovascular function, we evaluated systolic blood pressure (SBP), diastolic blood pressure (DBP), resting heart rate (RHR), double product (DP), and vital capacity. There were significant decreases in cardiorespiratory endurance (p < 0.001), power (p < 0.001), and balance (p < 0.001), and increases in muscular strength (p < 0.001). Further, cardiovascular function, including SBP (p < 0.001), DBP (p < 0.001), double product (p < 0.001), and vital capacity (p=0.006) appeared to be lower for the obesity group. We conclude that an obese person exhibits lower fitness level and weaker cardiovascular function than a normal person.
Key pointsThe obese group had a lower fitness level, including cardiorespiratory endurance, power, and balance.Obese group demonstrated an increase in muscular strength.Obese group had higher blood pressure and weaker cardiovascular function, including DP and vital capacity, than the normal group.
PMCID: PMC3761729  PMID: 24149691
Body mass index; obesity; physical fitness; cardiovascular function
21.  Cardiorespiratory Fitness and Adiposity as Mortality Predictors in Older Adults 
Associations among cardiorespiratory fitness (thus referred to as “fitness”), adiposity, and mortality in older adults have not been adequately examined.
To examine these associations, we report on a 12-year follow-up of adults ages 60 years and older, in whom fitness was assessed by a maximal exercise test and adiposity was assessed by body mass index (BMI), waist circumference (WC), and percent body fat.
Design, Setting, and Patients
2603 adults (age 64.4±4.8 yr; 19.8% women) completed a baseline health examination at the Cooper Clinic during 1979-2001. Low fitness was defined as the lowest fifth of the gender-specific distribution of maximal treadmill exercise test duration. The distributions of BMI, WC, and percent body fat were grouped for analysis according to clinical guidelines.
Main Outcome Measures
All-cause mortality.
There were 450 deaths during an average follow-up of 12 years and 31 236 person-years of exposure. Death rates per 1000 person-years, adjusted for age, gender, and examination year were: 13.9, 13.3, 18.3, and 31.8 across BMI groups of 18.5-24.9, 25.0-29.9, 30.0-34.9, and ≥35 kg/m2, respectively (trend P=.01); 13.3 and 18.2 for normal and high WC (≥102 cm in men; ≥88 cm in women), respectively (P=.004); 13.7 and 14.6 for normal and high percent body fat (≥25% in men; ≥30% in women), respectively (P=.51); and 32.6, 16.6, 12.8, 12.3 and 8.1 across incremental fifths of fitness, respectively (P<.001). The association between WC and mortality persisted after further adjustment for smoking, baseline health status, and BMI (P=.02), but not after additional adjustment for fitness (P=.86). Fitness predicted mortality risk after further adjustment for smoking, baseline health, and either WC, BMI or percent body fat (P<.001).
Fitness is a significant mortality predictor in older adults independent of overall or abdominal adiposity. Practitioners should consider the importance of preserving functional capacity, by recommending regular physical activity for older individuals, normal weight and overweight alike.
PMCID: PMC2692959  PMID: 18056904
22.  Cardiorespiratory Fitness as a Predictor of Nonfatal Cardiovascular Events in Asymptomatic Women and Men 
American journal of epidemiology  2007;165(12):1413-1423.
Prospective data relating cardiorespiratory fitness (CRF) with nonfatal cardiovascular disease (CVD) events are limited to studies in men or studies of combined fatal and nonfatal CVD endpoints. The authors examined the association between CRF and nonfatal CVD events in 20,728 men and 5,909 women without CVD at baseline. All participants performed a maximal treadmill exercise test and completed a follow-up health survey in the Aerobics Center Longitudinal Study (Dallas, Texas) between 1971 and 2004. There were 1,512 events in men and 159 events in women during an average follow-up of 10 years. Across incremental CRF groups, age- and examination year-adjusted event rates per 10,000 person-years were 107.9, 75.2, and 50.3 in men (p trend <0.001) and 41.9, 27.7, and 20.8 in women (p trend = 0.002). After further adjustment for smoking, alcohol intake, family history of CVD, and abnormal exercise ECG responses, hazard ratios (95% confidence interval) were 1.00 (referent), 0.82 (0.72, 0.94), and 0.61 (0.53, 0.71) in men, p trend <0.001, and were 1.00 (referent), 0.74 (0.49, 1.13), and 0.63 (0.40, 0.98) in women, p trend = 0.05. After adjustment for other CVD predictors, the association remained significant in men but not in women.
PMCID: PMC2685148  PMID: 17406007
exercise; cardiovascular diseases; stroke; women; primary prevention
23.  Erectile Dysfunction Severity as a Risk Marker for Cardiovascular Disease Hospitalisation and All-Cause Mortality: A Prospective Cohort Study 
PLoS Medicine  2013;10(1):e1001372.
In a prospective Australian population-based study linking questionnaire data from 2006–2009 with hospitalisation and death data to June 2010 for 95,038 men aged ≥45 years, Banks and colleagues found that more severe erectile dysfunction was associated with higher risk of cardiovascular disease.
Erectile dysfunction is an emerging risk marker for future cardiovascular disease (CVD) events; however, evidence on dose response and specific CVD outcomes is limited. This study investigates the relationship between severity of erectile dysfunction and specific CVD outcomes.
Methods and Findings
We conducted a prospective population-based Australian study (the 45 and Up Study) linking questionnaire data from 2006–2009 with hospitalisation and death data to 30 June and 31 Dec 2010 respectively for 95,038 men aged ≥45 y. Cox proportional hazards models were used to examine the relationship of reported severity of erectile dysfunction to all-cause mortality and first CVD-related hospitalisation since baseline in men with and without previous CVD, adjusting for age, smoking, alcohol consumption, marital status, income, education, physical activity, body mass index, diabetes, and hypertension and/or hypercholesterolaemia treatment. There were 7,855 incident admissions for CVD and 2,304 deaths during follow-up (mean time from recruitment, 2.2 y for CVD admission and 2.8 y for mortality). Risks of CVD and death increased steadily with severity of erectile dysfunction. Among men without previous CVD, those with severe versus no erectile dysfunction had significantly increased risks of ischaemic heart disease (adjusted relative risk [RR] = 1.60, 95% CI 1.31–1.95), heart failure (8.00, 2.64–24.2), peripheral vascular disease (1.92, 1.12–3.29), “other” CVD (1.26, 1.05–1.51), all CVD combined (1.35, 1.19–1.53), and all-cause mortality (1.93, 1.52–2.44). For men with previous CVD, corresponding RRs (95% CI) were 1.70 (1.46–1.98), 4.40 (2.64–7.33), 2.46 (1.63–3.70), 1.40 (1.21–1.63), 1.64 (1.48–1.81), and 2.37 (1.87–3.01), respectively. Among men without previous CVD, RRs of more specific CVDs increased significantly with severe versus no erectile dysfunction, including acute myocardial infarction (1.66, 1.22–2.26), atrioventricular and left bundle branch block (6.62, 1.86–23.56), and (peripheral) atherosclerosis (2.47, 1.18–5.15), with no significant difference in risk for conditions such as primary hypertension (0.61, 0.16–2.35) and intracerebral haemorrhage (0.78, 0.20–2.97).
These findings give support for CVD risk assessment in men with erectile dysfunction who have not already undergone assessment. The utility of erectile dysfunction as a clinical risk prediction tool requires specific testing.
Please see later in the article for the Editors' Summary
Editors' Summary
Erectile dysfunction is the medical term used when a man is unable to achieve or sustain an erection of his penis suitable for sexual intercourse. Although a sensitive topic that can cause much embarrassment and distress, erectile dysfunction is very common, with an estimated 40% of men over the age of 40 years experiencing frequent or occasional difficulties. The most common causes of erectile dysfunction are medications, chronic illnesses such as diabetes, and drinking too much alcohol. Stress and mental health problems can also cause or worsen erectile dysfunction. There is also increasing evidence that erectile dysfunction may actually be a symptom of cardiovascular disease—a leading cause of death worldwide—as erectile dysfunction could indicate a problem with blood vessels or poor blood flow commonly associated with cardiovascular disease.
Why Was This Study Done?
Although previous studies have suggested that erectile dysfunction can serve as a marker for cardiovascular disease in men not previously diagnosed with the condition, few studies to date have investigated whether erectile dysfunction could also indicate worsening disease in men already diagnosed with cardiovascular disease. In addition, previous studies have typically been small and have not graded the severity of erectile dysfunction or investigated the specific types of cardiovascular disease associated with erectile dysfunction. In this large study conducted in Australia, the researchers investigated the relationship of the severity of erectile dysfunction with a range of cardiovascular disease outcomes among men with and without a previous diagnosis of cardiovascular disease.
What Did the Researchers Do and Find?
The researchers used information from the established 45 and Up Study, a large cohort study that includes 123,775 men aged 45 and over, selected at random from the general population of New South Wales, a large region of Australia. A total of 95,038 men were included in this analysis. The male participants completed a postal questionnaire that included a question on erectile functioning, which allowed the researchers to define erectile dysfunction as none, mild, moderate, or severe. Using information captured in the New South Wales Admitted Patient Data Collection—a complete record of all public and private hospital admissions, including the reasons for admission and the clinical diagnosis—and the government death register, the researchers were able to determine health outcomes of all study participants. They then used a statistical model to estimate hospital admissions for cardiovascular disease events for different levels of erectile dysfunction.
The researchers found that the rates of severe erectile dysfunction among study participants were 2.2% for men aged 45–54 years, 6.8% for men aged 55–64 years, 20.2% for men aged 65–74 years, 50.0% for men aged 75–84 years, and 75.4% for men aged 85 years and over. During the study period, the researchers recorded 7,855 hospital admissions related to cardiovascular disease and 2,304 deaths. The researchers found that among men without previous cardiovascular disease, those with severe erectile dysfunction were more likely to develop ischemic heart disease (risk 1.60), heart failure (risk 8.00), peripheral vascular disease (risk 1.92), and other causes of cardiovascular disease (risk 1.26) than men without erectile dysfunction. The risks of heart attacks and heart conduction problems were also increased (1.66 and 6.62, respectively). Furthermore, the combined risk of all cardiovascular disease outcomes was 1.35, and the overall risk of death was also higher (risk 1.93) in these men. The researchers found that these increased risks were similar in men with erectile dysfunction who had previously been diagnosed with cardiovascular disease.
What Do These Findings Mean?
These findings suggest that compared to men without erectile dysfunction, there is an increasing risk of ischemic heart disease, peripheral vascular disease, and death from all causes in those with increasing degrees of severity of erectile dysfunction. The authors emphasize that erectile dysfunction is a risk marker for cardiovascular disease, not a risk factor that causes cardiovascular disease. These findings add to previous studies and highlight the need to consider erectile dysfunction in relation to the risk of different types of cardiovascular disease, including heart failure and heart conduction disorders. However, the study's reliance on the answer to a single self-assessed question on erectile functioning limits the findings. Nevertheless, these findings provide useful information for clinicians: men with erectile dysfunction are at higher risk of cardiovascular disease, and the worse the erectile dysfunction, the higher the risk of cardiovascular disease. Men with erectile dysfunction, even at mild or moderate levels, should be screened and treated for cardiovascular disease accordingly.
Additional Information
Please access these websites via the online version of this summary at
Wikipedia defines erectile dysfunction (note that Wikipedia is a free online encyclopedia that anyone can edit)
MedlinePlus also has some useful patient information on erectile dysfunction
The Mayo Clinic has patient-friendly information on the causes of, and treatments for, erectile dysfunction, and also includes information on the link with cardiovascular disease
The National Heart Foundation of Australia provides information for health professionals, patients, and the general public about how to prevent and manage cardiovascular disease, including assessment and management of cardiovascular disease risk
PMCID: PMC3558249  PMID: 23382654
24.  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
25.  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

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