Large Meta-Analysis Links Higher Levels of Cardiorespiratory Fitness to Lower Risk of Death and Cardiovascular Disease

Fran Lowry

May 20, 2009

May 20, 2009 (Ibaraki, Japan) — A higher level of cardiorespiratory fitness is associated with a lower risk of all-cause mortality, coronary heart disease (CHD) and cardiovascular disease (CVD) events, according to a meta-analysis of 33 trials comprising more than 187 000 healthy men and women published in the May 20, 2009 issue of the Journal of the American Medical Association [1].

Dr Satoru Kodama (University of Tsukuba Institute of Clinical Medicine, Ibaraki, Japan) and colleagues found that participants with the lowest level of cardiorespiratory fitness had a 70% higher risk for all-cause mortality and a 56% higher risk for CHD/CVD events compared with participants with the highest level of cardiorespiratory fitness. Participants with intermediate levels of cardiorespiratory fitness had a 40% higher risk for all-cause mortality and a 47% higher risk for CHD/CVD events than participants with the highest cardiorespiratory fitness.

Because the study showed cardiorespiratory fitness to be such a strong predictor of mortality and CVD/CHD risk, Kodama and colleagues suggest that it be made a part of routine CVD/CHD risk assessment. "It is possible that prediction of CHD risk could be improved by including cardiorespiratory fitness with already established risk factors for CHD," they write.

Physical fitness experts concur. "Organizations such as the National Institutes of Health and the American Heart Association should convene consensus panels to make recommendations for including cardiorespiratory fitness in risk-prediction equations," Dr Steven N Blair (University of South Carolina, Columbia) told heartwire in email correspondence.

Survival of the Fittest

Cardiorespiratory fitness is assessed by exercise tolerance testing, but it is rare for clinicians to consider cardiorespiratory fitness when evaluating future risk of CHD, write Kodama et al. "A major reason for lack of consideration of cardiorespiratory fitness as a marker of CHD risk may be that the quantitative association of cardiorespiratory fitness for cardiovascular risk is not well established," they write. "The degree of risk reduction associated with each incremental higher level of cardiorespiratory fitness, the criteria for low cardiorespiratory fitness, and the magnitude of risk associated with low cardiorespiratory fitness have been inconsistent among studies."

They systematically reviewed observational cohort studies using MEDLINE (1966 to December 31, 2008) and EMBASE (1980 to December 31, 2008) and selected studies reporting associations of baseline cardiorespiratory fitness with CHD events, CVD events, or all-cause mortality in men and women. Data were obtained on all-cause mortality for 102 980 participants and 6910 cases and on CHD/CVD for 84 323 participants and 4485 cases.

Cardiorespiratory fitness was estimated as maximal aerobic capacity (MAC) expressed in metabolic equivalent (MET) units, with one MET corresponding to 3.5 mL/min/kg of oxygen consumption. Participants were categorized as low cardiorespiratory fitness (<7.9 METs), intermediate cardiorespiratory fitness (7.9–10.8 METs), or high cardiorespiratory fitness (>10.9 METs), and risk ratios (RRs) for a 1-MET-higher level of MAC (corresponding to a 1-km/h-higher running/jogging speed) and for participants with lower vs higher cardiorespiratory fitness were calculated with a random-effects model.

Pooled Risk Ratios Per 1-MET-Higher Level of MAC

Outcome RR 95% CI
All-cause mortality 0.87 0.84–0.90
CHD/CVD events 0.85 0.82–0.88


Risk Ratios for Low Cardiorespiratory Fitness Compared With High, Intermediate Cardiorespiratory Fitness

  RR 95% CI p
Compared with high cardiorespiratory fitness      
All-cause mortality 1.70 1.51–1.92 <0.001
CHD/CVD events 1.56 1.39–1.75 <0.001
Compared with intermediate cardiorespiratory fitness      
All-cause mortality 1.40 1.32–1.48 <0.001
CHD/CVD events 1.47 1.35–1.61 <0.001

"These analyses suggest that a minimal cardiorespiratory fitness of 7.9 METs may be important for significant prevention of all-cause mortality and CHD/CVD," the study authors write. The results also indicate that the minimum cardiorespiratory-fitness level that is associated with significantly lower event rates is 9 METs for men at age 40, 8 METs for men at age 50, and 7 METs for men at age 60. For women, it is 7 METs at age 40, 6 METs at age 50, and 5 METs at age 60.

"If the cardiorespiratory-fitness level is expressed in terms of walking speed, men around 50 years of age must be capable of continuous walking at a speed of 4 mph and women must continuously walk at 3 mph for prevention of CHD," Kodama et al write.

Include Cardiorespiratory Fitness as a Risk Factor for CVD

The authors conclude "We suggest that cardiorespiratory fitness, which can be readily assessed by an exercise stress test, could be useful for prediction of CHD/CVD and all-cause mortality risk in a primary-care medical practice."

Blair agreed. He told heartwire , "The literature review was thorough, and the meta-analysis was well done. I agree with the authors that the evidence shows that cardiorespiratory fitness has a very strong inverse association with all-cause mortality and CHD/CVD. This strong and independent association is important, and I also agree with the authors that general risk-prediction equations certainly should include cardiorespiratory fitness. I think it is a major mistake to continue to exclude cardiorespiratory fitness in risk stratification of patients."

Weighing in with his comments on the study, Dr Philip Ades (University of Vermont [UVM] Medical College, Burlington) said that many studies have shown that exercise capacity predicts overall mortality and rate of future cardiac events. "So the general concept is not new," he told heartwire in an interview. "What is noteworthy about this study, however, are the very large numbers, which give it considerable statistical power, and the rigor of the meta-analysis, which was very well done. This study affirms, with a lot of statistical clout, the close relationship between fitness and important medical outcomes such as death and coronary disease."

Ades, who heads the cardiovascular rehab unit at UVM, agrees that clinicians should use cardiorespiratory fitness as a predictor of risk but says that doing a stress test on everyone above the age of 40 or 50 is not feasible.

Stress testing can open a can of worms, he said in an interview. "This is a very complicated question. There can be false positives and false negatives, and the false positives can lead to more expensive tests. It is not cost-effective."

A much better alternative would be to use fitness testing selectively and spend increasingly limited healthcare dollars on a campaign to get people to adopt a healthy lifestyle, Ades said. "Over 65% of Americans are overweight, more than 50% don't exercise, and 20% smoke. So do we want to spend our money on stress tests, or do we want to spend our money on public policy that would encourage people to walk, eat well, stay thin, and not smoke? To me it's a no-brainer. That action should trump prediction."


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