Cardiorespiratory Fitness, Coronary Artery Calcium, and Cardiovascular Disease Events in a Cohort of Generally Healthy Middle-Age Men: Results From the Cooper Center Longitudinal Study
Open accessAbstract
Background: A robust literature demonstrates that coronary artery calcification (CAC) and cardiorespiratory fitness (CRF) are independent predictors of cardiovascular disease (CVD) events. Much less is known about the joint associations of CRF and CAC with CVD risk. In the setting of high CAC, high versus low CRF has been associated with decreased CVD events. The goal of this study was to assess the effect of continuous levels of CRF on CVD risk in the setting of increasing CAC burden. Methods: We studied 8425 men without clinical CVD who underwent preventive medicine examinations that included an objective measurement of CRF and CAC between 1998 and 2007. There were 383 CVD events during an average follow-up of 8.4 years. Parametric proportional hazards regression models based on a Gompertz mortality rule were used to estimate total CVD incidence rates at 70 years of age as well as hazard ratios for the included covariates. Results: CVD events increased with increasing CAC and decreased with increasing CRF. Adjusting for CAC level (scores of 0, 1–99, 100–399, and ≥400), for each additional MET of fitness, there was an 11% lower risk for CVD events (hazard ratio, 0.89; 95% confidence interval, 0.84-0.94). When CAC and CRF were considered together, there was a strong association between continuous CRF and CVD incidence rates in all CAC groups. Conclusions: In a large cohort of generally healthy men, there is an attenuation of CVD risk at all CAC levels with higher CRF.
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Some studies have shown that endurance exercise reduces the risk for ischaemic events regardless of CAC score, and this reduction is greatest at the higher CAC scores.
“Some studies have shown that endurance exercise reduces the risk for ischaemic events regardless of CAC score, and this reduction is greatest at the higher CAC scores.24,26”
From Lifelong endurance exercise and its relation with coronary atherosclerosis (2023) · cites this paper as [26]
The Abstract reports lower CVD event risk with higher cardiorespiratory fitness at all CAC levels, and the Discussion reports a stronger inverse association as CAC burden increased. But this observational study of generally healthy men did not test whether endurance exercise itself reduces ischaemic events; the Clinical Implications section explicitly says it did not examine the effect of changes in fitness on CVD risk. (LLM, conf=0.88)
Experimental — accuracy not yet measuredCardiovascular fitness reduces the risk of ischaemic events regardless of CAC score.
“Although cardiovascular fitness reduces the risk of ischaemic events regardless of CAC score,24”
From Resting and exercise-induced occult hypertension and coronary atherosclerosis in male masters endurance athletes (2026) · cites this paper as [24]
The Conclusions report that, at every CAC level, greater cardiorespiratory fitness was associated with lower total cardiovascular disease (CVD) incidence in generally healthy men. The paper does not establish that fitness causes the reduction, and its outcome was total CVD events rather than specifically ischaemic events (CVD Event Ascertainment; Conclusions). (LLM, conf=0.88)
Experimental — accuracy not yet measuredA high CAC is linked with an increased prevalence of adverse coronary events irrespective of fitness.
“there is emerging evidence that a high CAC is linked with an increased prevalence of adverse coronary events irrespective of fitness.”
From Resting and exercise-induced occult hypertension and coronary atherosclerosis in male masters endurance athletes (2026) · cites this paper as [24]
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“23 Although cardiovascular fitness reduces the risk of ischaemic events regardless of CAC score, 24 there is emerging evidence that a high CAC is linked with an increased prevalence of adverse coronary events irrespective of fitness.”
- Authors
- Radford, N. B., DeFina, L. F., Leonard, D., Barlow, C. E., Willis, B. L., Gibbons, L. W., Gilchrist, S. C., Khera, A., & Levine, B. D.
- Affiliations
- Cooper Clinic (US)
- Cooper Institute (US)
- The University of Texas MD Anderson Cancer Center (US)
- The University of Texas Southwestern Medical Center (US)
- Texas Health Dallas (US)
- ORCID
- Venue
- Circulation
- Published
- 2018-05
- Volume
- 137
- Issue
- 18
- Pages
- 1888-1895
- ISSN
- 0009-7322 (ISSN-L)
- 1524-4539
- OpenAlex
- W2895848152
- Cited by
- 120
- References
- 3
- Citations by year
- 2026: 15 · 2025: 17 · 2024: 13 · 2023: 12 · 2022: 12 · 2021: 17 · 2020: 20 · 2019: 8 · 2018: 6
- FWCI
- 8.86
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Circulation (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Aeronautics and Space Administration
- National Space Biomedical Research Institute
- Topics
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Cardiac Imaging and Diagnostics
- Health Sciences › Medicine › Complementary and alternative medicine › Cardiovascular and exercise physiology
- Health Sciences › Medicine › Physiology › Physical Activity and Health
- Keywords
- cardiorespiratory fitness, coronary artery calcium, cardiovascular risk, coronary artery calcification, middle-aged men, cardiovascular events
- MeSH terms
- Cardiorespiratory Fitness, Adult, Age Factors, Aged, Cardiovascular Diseases, Coronary Artery Disease, Health Status, Humans, Longitudinal Studies, Male, Middle Aged, Prognosis, Risk Factors, Sex Factors, Texas, Time Factors, Incidence, Risk Assessment, Vascular Calcification
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