Background In asymptomatic populations, physical activity is inversely associated with the risk of cardiovascular death, but it is not known if physical activity compensates for adverse effects of multiple cardiovascular risk factors.

The aim of this study was to assess if the positive association of a clustering of cardiovascular risk factors (CRFs) with cardiovascular disease (CVD) mortality could be weakened by exercise training.

Methods We followed 53 542 individuals who were free from known CVD, among which 3751 had CRF, from baseline between 1984 and 1986 until the date of death from any cause, or until the end of follow-up (31 December 2004). We used the Cox proportional hazards model to estimate HR of cardiovascular death.

Results The HR of death from CVD among people with CRF was 1.38 (95% CI 1.28 to 1.48) compared to those without CRF. The association was stronger among women than in men. In people with CRF, cardiovascular mortality was inversely related to physical activity: risk was 24% lower (HR 0.76, 95% CI 0.61 to 0.95) in the physically active compared to the inactive group. Compared to inactive people without CRF, people with CRF who reported no activity had 41% higher risk of cardiovascular death (HR 1.41, 95% CI 1.16 to 1.70).

Conclusion These data show that individuals with CRF are at greater risk of premature cardiovascular death compared to people without CRF, and that the risk of people with CRF who were physically active appears to be comparable to that of inactive individuals without CRF.