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 independent 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 42-61 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. High sensitivity CRP was categorized as normal and high (≤ 3 and >3 mg/L, respectively) and CRF as low and high. A total of 148 SCD events occurred during a median follow-up of 28.9 years. Comparing high vs normal hsCRP, the multivariable-adjusted HR (95% CI) for SCD was 1.65 (1.11-2.45), which remained similar on further adjustment for CRF 1.62 (1.09-2.40). Comparing high vs low CRF, the multivariable-adjusted HR for SCD was 0.61 (0.42-0.89), which remained persistent after adjustment for hsCRP 0.64 (0.44-0.93). Compared with men who had normal hsCRP-low CRF, normal hsCRP-high CRF was associated with a decreased SCD risk 0.65 (0.43-0.99), high hsCRP-low CRF was associated with an increased SCD risk 1.72 (1.10-2.69), with no evidence of an association between high hsCRP-high CRF and SCD risk 0.86 (0.39-1.88). Positive additive and multiplicative interactions were found between hsCRP and CRF. In a middle-aged Finnish male population, both hsCRP and CRF are each independently associated with SCD risk. However, high CRF levels appear to offset the increased SCD risk related to high hsCRP levels.