The association between cardiorespiratory fitness and cardiovascular risk may be modulated by known cardiovascular risk factors

Am Heart J. 2015 Jun;169(6):916-923.e1. doi: 10.1016/j.ahj.2015.02.023. Epub 2015 Mar 13.


Background: We aimed to evaluate whether reduced cardiovascular fitness has a direct or indirect effect for the development of cardiovascular disease.

Methods: We investigated 15,595 men and women who were annually screened in a tertiary medical center. All subjects were free of ischemic heart disease and had completed maximal exercise stress test according to the Bruce protocol at their first visit. Fitness was categorized into age- and sex-specific quintiles (Q) according to Bruce protocol treadmill time with Q1 as lowest fitness. Subjects were categorized at baseline into 3 groups: low fitness (Q1), moderate fitness (Q2-Q4), and high fitness (Q5). The primary end point of the current analysis was the development of a first cardiovascular event during follow-up.

Results: Mean age of study patients was 48 ± 10 years, and 73% were men. A total of 679 events occurred during 92,092 person-years of follow-up. Kaplan-Meier survival analysis showed that the cumulative probability of cardiovascular events at 6 years was significantly higher among subjects with low fitness (P < .001). Low fitness was associated with known cardiovascular risk factors, including hypercholesterolemia (odds ratio [OR] 1.58, 95% CI 1.31-1.89), diabetes mellitus (OR 2.32, 95% CI 1.58-3.41), and obesity (OR 10.46, 95% CI 8.43-12.98). The effect of low fitness on cardiovascular events was no longer significant when including diabetes mellitus, hypercholesterolemia, and obesity as mediators (hazard ratio 0.99, 95% CI 0.82-1.19).

Conclusions: The association between cardiovascular fitness and adverse cardiovascular outcomes may be modulated through traditional cardiovascular risk factors. These findings need to be further validated in prospective clinical trials.

MeSH terms

  • Adult
  • Cardiovascular Diseases / epidemiology*
  • Cardiovascular Diseases / etiology
  • Cardiovascular Physiological Phenomena*
  • Comorbidity
  • Diabetes Complications
  • Female
  • Humans
  • Hypercholesterolemia / complications
  • Israel / epidemiology
  • Male
  • Middle Aged
  • Obesity / complications
  • Physical Fitness*
  • Prospective Studies
  • Respiratory Physiological Phenomena*
  • Risk Factors