Direct Measures of Low Cardio Fitness Better Predict Mortality

October 31, 2018

Low cardiorespiratory fitness (CRF) levels as assessed by peak oxygen uptake (VO₂) predict mortality more accurately than low CRF as typically estimated in clinical practice, supporting wider use of directly measured peak VO₂ as a prognosticator in apparently healthy adults, a new report concludes.

In a prospective study of more than 4000 adults from the community followed for an average of 24 years, a single peak VO₂ measurement was inversely and independently related to death from any cause and cardiovascular (CV) and cancer mortalities.

An analysis by sex showed the same all-cause mortality association for both women and men in the lowest vs highest fitness tertiles, but fitness predicted CV better in men and cancer mortality better in women.

The findings, said to support recent calls to consider CRF as a clinical vital sign and to use estimated CRF more widely in clinical practice, was published October 29 in the Journal of the American College of Cardiology with lead author Mary T. Imboden, PhD, Ball State University, Muncie, Indiana.

Acknowledging that poor CRF has long been considered a predictor of mortality, the report says that most relevant studies have "used a variety of indirect methods and thresholds to define fitness levels. This has led to variability in the reported degree of risk reduction associated with improving estimated CRF and the magnitude of risk associated with low-fitness."

The current analysis considers CRF both as estimated and as indicated by peak VO₂ and shows "that both are good measures, but we do provide some evidence here that if you have the directly measured value, it's an even more accurate indicator," Leonard A. Kaminsky, PhD, Ball State University, told theheart.org | Medscape Cardiology.

Measuring peak VO₂ in an exercise laboratory can yield other useful information as well, he and the report note, "such as ventilatory threshold, exercise ventilatory power, and circulatory power," and can allow "improved accuracy in the intensity component of an exercise prescription."

That performing an exercise test to measure peak VO₂ can potentially allow robust measurements of several other prognostic indicators, Kaminsky said, is another argument in support of its broader clinical use.

Kaminsky was a member of the writing group behind a 2016 American Heart Association (AHA) scientific statement on CRF in clinical practice, "A Case for Fitness as a Clinical Vital Sign." Among its conclusions: small gains in CRF "are associated with considerably (10% to 30%) lower adverse cardiovascular event rates," and "efforts to improve CRF should become a standard part of clinical encounters."

At a minimum, the report says, "all adults should have CRF estimated each year using a nonexercise algorithm during their annual healthcare examination." But also, "ideally all adults should have CRF estimated using a maximal test, if feasible using cardiopulmonary exercise, on a regular basis similar to other preventative services."

The latter point is consistent with the current study in arguing that peak VO₂ is "the gold standard that you would strive for, to have the best measurement," Kaminsky said in an interview.

"The old thinking was that this measure was really difficult to do, and costly, and that you need expensive equipment and trained personnel," he said. "A lot of those things have diminished over the past 20 years. There are many more trained professionals out there, the technology's improved, the efficiency to do these tests is there."

And when there is a clinical indication for a maximal exercise test, "certainly we would advocate that adding peak VO₂ would not be that difficult," Kaminsky said.

"This study confirms what has been known for a very long time, that CRF is a good marker for mortality," agreed Benjamin D. Levine, MD, University of Texas Southwestern Medical Center, Dallas, also an author of the AHA statement on CRF but not involved with the current study.

However, he told theheart.org | Medscape Cardiology, "Measuring peak VO₂ is no easier now than it has been for decades, and still requires specialized equipment. Most good exercise labs can measure it. But it is still more complicated and involved than just measuring treadmill performance, which has been well validated and is likely good enough for a prediction tool that has only a rough relationship with mortality anyway."

The current analysis involved 1811 women and 2326 men (mean age, 43 years), self-referred to the Ball State Adult Fitness Program Longitudinal Lifestyle Study (BALL ST) cohort, who were initially free of CV disease and cancer. All underwent a comprehensive health assessment, including a maximal cardiopulmonary exercise test, between 1968 and 2016 and were followed for mortality for a mean of 24.2 years, the report notes.

In adjusted analysis, all-cause mortality went down 3.3% for every 1 mL/kg per min increment in baseline peak VO₂, or 11.6% for each metabolic equivalent (MET). Corresponding CV mortality fell by 4.6% for every 1 mL/kg per min (16.1% per MET) increase and cancer mortality by 4.0% for every 1 mL/kg per min (14.0% per MET) increase.

Hazard Ratio* (HR, 95% CI) for Mortality Outcomes, Lowest CRF Tertile vs the Highest CRF Tertile
End Point All Subjects Men Women
All-cause mortality 1.73 (1.20–3.50) 1.67 (1.18–2.38) 1.63 (1.02–2.47)
CV mortality 2.27 (1.20–3.49) 2.94 (1.44–5.37) 1.22 (0.46–2.96)
Cancer mortality 2.07 (1.18–3.36) 1.38 (0.82–1.97) 3.94 (1.41–8.96)
*Adjusted for age, CRF testing year, traditional CV risk factors, and (over all subjects) sex.

"This is one of the few population studies with the assessment of directly measured respiratory gases" at cardiopulmonary exercise testing, write Jari A. Laukkanen, MD, PhD, University of Jyväskylä, and Urho M. Kujala, MD, PhD , Central Finland Health Care District, Jyväskylä, Finland, in an accompanying editorial.

"The assessment of CRF has achieved significant clinical merit and is considered to be a vital part of patient risk assessment. This growing body of evidence should be an impetus for all healthcare providers to incorporate CRF improvement as a high priority in the overall clinical treatment approach to patients with chronic diseases."

However, they note, "Conclusive research evidence from intervention studies linking an increased physical exercise level with improved CRF to decreased mortality is still lacking."

Kaminsky discloses serving as an advisor to ENDO Medical. The remaining authors report that they have no relevant disclosures. Laukkanen and Kujala report they have no relevant disclosures. Levine has recently reported he has no relevant disclosures.

J Am Card Cardiol. October 29, 2018. Article, Editorial

Follow Steve Stiles on Twitter: @SteveStiles2. For more from theheart.org | Medscape Cardiology, follow us on Twitter and Facebook.

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