We examined individual and joint associations among high-sensitivity C-reactive protein (CRP), cardiorespiratory fitness (fitness), and mortality in healthy men and women. Between January 1, 2000 and December 31, 2016, 30,077 adults (31.3% women) received a comprehensive physical examination. Fitness was determined from maximal treadmill exercise test duration. Participants were categorized as unfit (Quintile 1) and fit (Quintiles 2-5), and by normal (<2 mg/L) and elevated (≥2 mg/L) CRP categories. Adjusted hazard ratios (HRs) with 95% confidence interval (CI) for all-cause mortality were computed with Cox regression. During an average of 10.1 years of follow-up, 576 deaths occurred. Following adjustment for age, smoking status, sex, exam year, body mass index, systolic blood pressure, total cholesterol, triglyceride:high-density lipoprotein ratio, and fasting glucose, HR (95% CI) for all-cause mortality were 1.0 (referent) and 1.52 (1.14-2.02) for fit and unfit categories, respectively. Corresponding values for normal and elevated CRP categories were 1.0 and 1.50 (1.20-1.89), respectively. When grouped by fitness and CRP category, there was significantly greater mortality risk in the unfit than the fit category within the elevated CRP category (HR = 1.77 (1.14-2.75)), but not in the normal CRP category (HR = 1.38 (0.96-1.98)). Each 1 metabolic equivalent increment in fitness and 1 mg/L increment in CRP were associated with 10.0% (95% CI: 5.1-14.8%) decreased and 7.3% (95% CI: 2.0%-12.9%) increased mortality hazard, respectively. Compared to the unfit, fit individuals have an attenuated mortality risk within each CRP category. Thus, higher fitness appears to provide some protection against all-cause mortality, particularly among those with elevated levels of inflammation.
Keywords: Fitness; all-cause mortality; inflammation.