Background: Cardiovascular disease, including severe coronary disease (SCD), is the leading non-cancer cause of death among people living with and beyond cancer. Previous studies have largely focused on the cardiotoxic effects of cancer chemotherapy and radiotherapy. However, emerging evidence suggests that pre-diagnostic lifestyle factors—such as obesity, physical inactivity, and tobacco smoking—may exacerbate cardiovascular risks after cancer.

Objective: The main objective of this study was to estimate associations between pre-cancer lifestyle factors and the risk of fatal and non-fatal SCD in individuals with and without cancer in the E3N French cohort. 

Methods: We used data from the E3N French prospective cohort, which follows nearly 100,000 women since 1990. Pre-cancer lifestyle factors include overweight/obesity (measured with BMI), physical activity, and smoking. We studied these factors via a healthy lifestyle index (HLI), with scores ranging from 0 to 4 for each of the 3 components, resulting in a 0 to 12 score. We defined SCD events as non-fatal myocardial infarction (MI), fatal MI, sudden cardiac death, coronary revascularisation (by angioplasty, stenting or coronary artery bypass grafting) for SCD with or without MI. We defined cancer survivors as individuals who survived at least one year after a first primary cancer diagnosis. We used Cox models to study the associations between baseline HLI and SCD events in participants with or without cancer during follow-up, with cancer status as a time-dependant covariate. We also adjusted models on age as time-scale, education level, height, menopausal status and use of hormone replacement therapy, prevalent hypertension, prevalent type-2-diabetes, adherence to Mediterranean diet, alcohol consumption and total energy intake. Finally, we studied interactions between HLI and cancer status on additive and multiplicative scales using the relative excess risk due to interaction (RERI) and the likelihood ratio test, respectively.

Results: We studied 62,793 women. During follow-up (1993-2014), we observed 10,069 cancers cases, and 1,330 SCD cases of which 160 after cancer. In the fully adjusted model, we highlighted a statistically significant inverse association between a one standard deviation (SD) increase of HLI and SCD risk (HR_oneSD 0.87, 95%CI 0.82-0.91). We observed the same trend among participants without cancer during follow-up (HR_oneSD 0.87, 95%CI 0.82-0.92) as well as in those with cancer during follow-up (HR_oneSD 0.84, 95%CI 0.72-0.98). Moreover, the multiplicative interaction between HLI and cancer status was not significant (p_interaction 0.82), as for the RERI (0.07, 95%CI -0.33-0.47). These results were stable in our sensitivity analyses.  

Conclusions: This study aimed to clarify how lifestyle and cancer interact to influence SCD risk. We observed no effect modification by cancer in the association between pre-cancer lifestyle habits and SCD. Healthy lifestyle habits therefore seems to be beneficial in the prevention of SCD risk, including in individuals who will develop cancer in the meantime.