Seems CRF best indicator for mortality

Br J Sports Med 2011;45:504-510 doi:10.1136/bjsm.2009.066209

• Original articles

Comparisons of leisure-time physical activity and cardiorespiratory fitness as predictors of all-cause mortality in men and women

1. D-C Lee1, 
2. X Sui1, 
3. F B Ortega2,3, 
4. Y-S Kim4, 
5. T S Church5, 
6. R A Winett6, 
7. U Ekelund7,
8. P T Katzmarzyk8, 
9. S N Blair1,9

+Author Affiliations

1. ¹Department of Exercise Science, Arnold School of Public Health, University of South Carolina, Columbia, South Carolina, USA
2. ²Unit for Preventive Nutrition, Department of Biosciences and Nutrition, Karolinska Institute, Hugginge, Sweden
3. ³Department of Physiology, School of Medicine, University of Granada, Granada, Spain
4. ⁴Department of Physical Education, College of Education, Seoul National University, Seoul, South Korea
5. ⁵Department of Preventive Medicine Research, Pennington Biomedical Research Center, Baton Rouge, Louisiana, USA
6. ⁶Center for Research in Health Behavior, Department of Psychology, Virginia Polytechnic Institute and State University, Blacksburg, Virginia, USA
7. ⁷Medical Research Council, Epidemiology Unit, Cambridge, UK
8. ⁸Population Science, Pennington Biomedical Research Center, Baton Rouge, Louisiana, USA
9. ⁹Department of Epidemiology and Biostatistics, Arnold School of Public Health, University of South Carolina, Columbia, South Carolina, USA

1. Correspondence toDr Duck-Chul Lee, Department of Exercise Science, Arnold School of Public Health, University of South Carolina, 921 Assembly Street, Columbia, SC 29208, USA; lee23@mailbox.sc.edu

• Accepted 3 December 2009
• Published Online First 23 April 2010

Abstract

Objective To examine the combined associations and relative contributions of leisure-time physical activity (PA) and cardiorespiratory fitness (CRF) with all-cause mortality.

Design Prospective cohort study.

Setting Aerobics centre longitudinal study.

Participants 31 818 men and 10 555 women who received a medical examination during 1978–2002.

Assessment of risk factors Leisure-time PA assessed by self-reported questionnaire; CRF assessed by maximal treadmill test.

Main outcome measures All-cause mortality until 31 December 2003.

Results There were 1492 (469 per 10 000) and 230 (218 per 10 000) deaths in men and women, respectively. PA and CRF were positively correlated in men (r=0.49) and women (r=0.47) controlling for age (p<0.001 for both). PA was inversely associated with mortality in multivariable Cox regression analysis among men, but the association was eliminated after further adjustment for CRF. No significant association of PA with mortality was observed in women. CRF was inversely associated with mortality in men and women, and the associations remained significant after further adjustment for PA. In the PA and CRF combined analysis, compared with the reference group “not meeting the recommended PA (<500 metabolic equivalent-minute/week) and unfit”, the relative risks (95% CIs) of mortality were 0.62 (0.54 to 0.72) and 0.61 (0.44 to 0.86) in men and women “not meeting the recommended PA and fit”, 0.96 (0.61 to 1.53) and 0.93 (0.33 to 2.58) in men and women “meeting the recommended PA and unfit” and 0.60 (0.51 to 0.70) and 0.56 (0.37 to 0.85) in men and women “meeting the recommended PA and fit”, respectively.

Conclusions CRF was more strongly associated with all-cause mortality than PA; therefore, improving CRF should be encouraged in unfit individuals to reduce risk of mortality and considered in the development of future PA guidelines.

Cardiorespiratory Fitness as a Quantitative Predictor of All-Cause Mortality and Cardiovascular Events in Healthy Men and Women

ABSTRACT

ABSTRACT | METHODS | RESULTS | COMMENT | ARTICLE INFORMATION | REFERENCES

Context Epidemiological studies have indicated an inverse association between cardiorespiratory fitness (CRF) and coronary heart disease (CHD) or all-cause mortality in healthy participants.

Objective To define quantitative relationships between CRF and CHD events, cardiovascular disease (CVD) events, or all-cause mortality in healthy men and women.

Data Sources and Study Selection A systematic literature search was conducted for observational cohort studies using MEDLINE (1966 to December 31, 2008) and EMBASE (1980 to December 31, 2008). The Medical Subject Headings search terms used included exercise tolerance, exercise test, exercise/physiology, physical fitness, oxygen consumption, cardiovascular diseases, myocardial ischemia, mortality, mortalities, death, fatality, fatal, incidence, or morbidity. Studies reporting associations of baseline CRF with CHD events, CVD events, or all-cause mortality in healthy participants were included.

Data Extraction Two authors independently extracted relevant data. CRF was estimated as maximal aerobic capacity (MAC) expressed in metabolic equivalent (MET) units. Participants were categorized as low CRF (<7.9 METs), intermediate CRF (7.9-10.8 METs), or high CRF (≥10.9 METs). CHD and CVD were combined into 1 outcome (CHD/CVD). Risk ratios (RRs) for a 1-MET higher level of MAC and for participants with lower vs higher CRF were calculated with a random-effects model.

Data Synthesis Data were obtained from 33 eligible studies (all-cause mortality, 102 980 participants and 6910 cases; CHD/CVD, 84 323 participants and 4485 cases). Pooled RRs of all-cause mortality and CHD/CVD events per 1-MET higher level of MAC (corresponding to 1-km/h higher running/jogging speed) were 0.87 (95% confidence interval [CI], 0.84-0.90) and 0.85 (95% CI, 0.82-0.88), respectively. Compared with participants with high CRF, those with low CRF had an RR for all-cause mortality of 1.70 (95% CI, 1.51-1.92; P < .001) and for CHD/CVD events of 1.56 (95% CI, 1.39-1.75; P < .001), adjusting for heterogeneity of study design. Compared with participants with intermediate CRF, those with low CRF had an RR for all-cause mortality of 1.40 (95% CI, 1.32-1.48; P < .001) and for CHD/CVD events of 1.47 (95% CI, 1.35-1.61; P < .001), adjusting for heterogeneity of study design.

Conclusions Better CRF was associated with lower risk of all-cause mortality and CHD/CVD. Participants with a MAC of 7.9 METs or more had substantially lower rates of all-cause mortality and CHD/CVD events compared with those with a MAC of less 7.9 METs.

Coronary heart disease (CHD) is a major cause of disability and premature death throughout the world.1 Epidemiological studies have demonstrated an inverse association between physical fitness and the incidence of CHD or all-cause mortality in healthy or asymptomatic participants. Physical fitness is typically expressed as cardiorespiratory fitness (CRF) and is assessed by exercise tolerance testing2; however, it is rare for clinicians to consider CRF when evaluating future risk of CHD.3

A major reason for lack of consideration of CRF as a marker of CHD risk may be that the quantitative association of CRF for cardiovascular risk is not well established. The degree of risk reduction associated with each incremental higher level of CRF, the criteria for low CRF, and the magnitude of risk associated with low CRF have been inconsistent among studies. Our goal of this meta-analysis was to systematically review the quantitative relationship between CRF and all-cause mortality and CHD or cardiovascular disease (CVD) events in healthy individuals.

May 20, 2009, Vol 301, No. 19 >

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Clinical Review | May 20, 2009CLINICIAN'S CORNER

Cardiorespiratory Fitness as a Quantitative Predictor of All-Cause Mortality and Cardiovascular Events in Healthy Men and WomenA Meta-analysis

Satoru Kodama, MD, PhD; Kazumi Saito, MD, PhD; Shiro Tanaka, PhD; Miho Maki, MS; Yoko Yachi, RD, MS; Mihoko Asumi, MS; Ayumi Sugawara, RD; Kumiko Totsuka, RD; Hitoshi Shimano, MD, PhD; Yasuo Ohashi, PhD; Nobuhiro Yamada, MD, PhD; Hirohito Sone, MD, PhD

A1C less than 4% increased mortality

A1C less than 4% increased mortality

Low hemoglobin A1c and risk of all-cause mortality among US adults without diabetes.
Carson AP, Fox CS, McGuire DK, Levitan EB, Laclaustra M, Mann DM, Muntner P.

Department of Epidemiology, University of Alabama at Birmingham, 35294-0022, USA. apcarson@uab.edu

Abstract
BACKGROUND: Among individuals without diabetes, elevated hemoglobin A1c (HbA1c) has been associated with increased morbidity and mortality, but the literature is sparse regarding the prognostic importance of low HbA1c.

METHODS AND RESULTS: National Health and Nutrition Examination Survey III (NHANES III) participants, 20 years and older, were followed up to 12 years (median follow-up, 8.8 years) for all-cause mortality. Cox proportional hazards regression was used to calculate hazard ratios (HR) and 95% confidence intervals (CI) for the association between HbA1c levels and all-cause mortality for 14 099 participants without diabetes. There were 1825 deaths during the follow-up period. Participants with a low HbA1c (<4.0%) had the highest levels of mean red blood cell volume, ferritin, and liver enzymes and the lowest levels of mean total cholesterol and diastolic blood pressure compared with their counterparts with HbA1c levels between 4.0% and 6.4%. An HbA1c <4.0% versus 5.0% to 5.4% was associated with an increased risk of all-cause mortality (HR, 3.73; 95% CI, 1.45 to 9.63) after adjustment for age, race-ethnicity, and sex. This association was attenuated but remained statistically significant after further multivariable adjustment for lifestyle, cardiovascular factors, metabolic factors, red blood cell indices, iron storage indices, and liver function indices (HR, 2.90; 95% CI, 1.25 to 6.76).

CONCLUSIONS: In this nationally representative cohort, low HbA1c was associated with increased all-cause mortality among US adults without diabetes. Additional research is needed to confirm these results and identify potential mechanisms that may be underlying this association.

A1C less than 5% had lowest rate of CVD and Mortality

A1c concentrations less than 5% had the lowest rates of cardiovascular disease and mortality.

Ann Intern Med. 2004 Sep 21;141(6):413-20.

Association of hemoglobin A1c with cardiovascular disease and mortality in adults: the European prospective investigation into cancer in Norfolk.
Khaw KT, Wareham N, Bingham S, Luben R, Welch A, Day N.

University of Cambridge, School of Clinical Medicine, Medical Research Council Epidemiology Unit, Addenbrooke's Hospital, Cambridge, United Kingdom. kk101@medschl.cam.ac.uk.

Comment in:

Ann Intern Med. 2004 Sep 21;141(6):I12.
Ann Intern Med. 2004 Sep 21;141(6):475-6.
ACP J Club. 2005 Mar-Apr;142(2):52.

Abstract
BACKGROUND: Increasing evidence suggests a continuous relationship between blood glucose concentrations and cardiovascular risk, even below diagnostic threshold levels for diabetes.

OBJECTIVE: To examine the relationship between hemoglobin A1c, cardiovascular disease, and total mortality.

DESIGN: Prospective population study.

SETTING: Norfolk, United Kingdom.

PARTICIPANTS: 4662 men and 5570 women who were 45 to 79 years of age and were residents of Norfolk.

MEASUREMENTS: Hemoglobin A1c and cardiovascular disease risk factors were assessed from 1995 to 1997, and cardiovascular disease events and mortality were assessed during the follow-up period to 2003.

RESULTS: In men and women, the relationship between hemoglobin A1c and cardiovascular disease (806 events) and between hemoglobin A1c and all-cause mortality (521 deaths) was continuous and significant throughout the whole distribution. The relationship was apparent in persons without known diabetes. Persons with hemoglobin A1c concentrations less than 5% had the lowest rates of cardiovascular disease and mortality. An increase in hemoglobin A1c of 1 percentage point was associated with a relative risk for death from any cause of 1.24 (95% CI, 1.14 to 1.34; P < 0.001) in men and with a relative risk of 1.28 (CI, 1.06 to 1.32; P < 0.001) in women. These relative risks were independent of age, body mass index, waist-to-hip ratio, systolic blood pressure, serum cholesterol concentration, cigarette smoking, and history of cardiovascular disease. When persons with known diabetes, hemoglobin A(1c) concentrations of 7% or greater, or a history of cardiovascular disease were excluded, the result was similar (adjusted relative risk, 1.26 [CI, 1.04 to 1.52]; P = 0.02). Fifteen percent (68 of 521) of the deaths in the sample occurred in persons with diabetes (4% of the sample), but 72% (375 of 521) occurred in persons with HbA1c concentrations between 5% and 6.9%.

LIMITATIONS: Whether HbA1c concentrations and cardiovascular disease are causally related cannot be concluded from an observational study; intervention studies are needed to determine whether decreasing HbA1c concentrations would reduce cardiovascular disease.

CONCLUSIONS: The risk for cardiovascular disease and total mortality associated with hemoglobin A1c concentrations increased continuously through the sample distribution. Most of the events in the sample occurred in persons with moderately elevated HbA1c concentrations. These findings support the need for randomized trials of interventions to reduce hemoglobin A1c concentrations in persons without diabetes.