Cardiorespiratory Fitness, CAC, and CVD Events in Healthy Men

Study Questions:

In there a relationship between continuous levels of cardiorespiratory (CR) fitness and cardiovascular disease (CVD) risk in the setting of increasing coronary artery calcium (CAC) burden?


The study, conducted at the Cooper Clinic between 1998-2007, included 8,425 men without clinical CVD who underwent preventive medicine examinations that included measurement of CR fitness and CAC. The great majority were white, well educated, and employer or self-referred and had access to preventive health care. There were 383 CVD events during an average follow-up of 8.4 years. Those with coronary revascularization within 90 days of the initial exam were excluded. Parametric proportional hazards regression models were used to estimate total CVD incidence rates at age 70 as well as hazard ratios (HRs) for the included covariates (+ statins).


Men with the highest fitness levels were younger, leaner, less likely to smoke, and had lower blood pressure, blood glucose, and triglycerides, and were less likely to be on statin therapy. Total CVD incidence rates ranged from 1.3 per 1,000 person-years in those with no CAC to 18.9 per 1,000 person-years in those with CAC ≥400. For hard CVD events, incidence rates ranged from 0.9 per 1,000 person-years with no CAC to 5.9 per 1,000 person-years for those with CAC ≥400. P for trend was < 0.001 for both total and hard CVD events. In the lowest fit (5 MET) participants in the 25-year follow-up group, there was a near five-fold increase in annual total CVD incidence rates in participants with CAC ≥400 compared to those with a CAC score of 0 and a two-fold increase in those with 15 MET capacity. CVD events increased with increasing CAC and decreased with increasing CR fitness. 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 (HR, 0.89; 95% confidence interval, 0.84, 0.94). When CAC and CR fitness were considered together, there was a strong association between continuous CR fitness and CVD incidence rates in all CAC groups.


In a large cohort of generally healthy men, there is an attenuation of CVD risk at all CAC levels with higher CR fitness.


Coronary artery calcification and CR fitness are each predictors of CVD events independent of CV risk factors and in both high- and low-risk persons independent of age. In a previous study from the same group, LaMonte (2006) reported that CR fitness ≥10 MET was associated with a 75% reduction in coronary events. In healthy men, an increase in CR fitness of >1 MET would require regular moderate or intense exercise.

Clinical Topics: Diabetes and Cardiometabolic Disease, Dyslipidemia, Prevention, Sports and Exercise Cardiology, Atherosclerotic Disease (CAD/PAD), Lipid Metabolism, Nonstatins, Novel Agents, Statins, Sports and Exercise and ECG and Stress Testing

Keywords: Blood Glucose, Blood Pressure, Coronary Artery Disease, Exercise Test, Glucose, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Male, Middle Aged, Physical Fitness, Primary Prevention, Plaque, Atherosclerotic, Risk Factors, Smoke, Triglycerides

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