Cardiorespiratory Fitness, Inflammation, and Risk of Sudden Cardiac Death in Middle-Aged Men.

Inflammation and cardiorespiratory fitness (CRF) are each independently related to the risk of sudden cardiac death (SCD). The interplay between CRF, inflammation and SCD is not well understood. We aimed to study the separate and joint associations of inflammation (high-sensitivity C-reactive protein [hsCRP]) and CRF with SCD risk in a cohort of Caucasian men. In 1,749 men aged 42 to 61 years without a history of coronary heart disease at baseline, serum hsCRP was measured using an immunometric assay, and CRF was assessed using a respiratory gas exchange analyzer during exercise testing. hsCRP was categorized as normal and high (≤3 and >3 mg/L, respectively) and CRF as low and high (median cutoff). A total of 148 SCD events occurred during a median follow-up of 28.9 years. Comparing high versus normal hsCRP, the multivariable-adjusted hazard ratio (95% confidence interval) for SCD was 1.65 (1.11 to 2.45), which remained similar on further adjustment for CRF 1.62 (1.09 to 2.40). Comparing high versus low CRF, the multivariable-adjusted hazard ratio for SCD was 0.61 (0.42 to 0.89), which remained persistent after adjustment for hsCRP 0.64 (0.44 to 0.93). Compared with normal hsCRP-low CRF, normal hsCRP-high CRF was associated with a decreased SCD risk of 0.65 (0.43 to 0.99), high hsCRP-low CRF was associated with an increased SCD risk of 1.72 (1.10 to 2.69), with no evidence of a relationship between high hsCRP-high CRF and SCD risk 0.86 (0.39 to 1.88). Positive additive and multiplicative interactions were found between hsCRP and CRF. In a middle-aged Finnish male population, both hsCRP and CRF are independently associated with SCD risk. However, high CRF levels appear to offset the increased SCD risk related to high hsCRP levels.