Sex differences in cancer incidence amongst people with cardiovascular disease: a large British population study

Abstract Background Studies have shown that patients with cardiovascular disease (CVD) have an incremental risk of death due to noncardiac causes. This is especially attributable to cancer developments during long term follow up. The two diseases share pathophysiological mechanisms that extend beyond traditional risk factors. With well-established sex disparities in CVD, it becomes imperative to investigate whether similar sex-based differences exist in both the incidence of cancer and cancer-related mortality, in participants with CVD vs those without CVD. Purpose We aim to analyse the sex differences in incident cancer and cancer-related mortality between people with and without CVD. Methods Participants were drawn from a large British population based prospective cohort study and followed up for a median of 26.2 years. Participants were stratified by sex and whether they developed CVD over the study follow-up. The cumulative incidence of cancer, excluding non-melanoma skin cancers were calculated. Sex-specific lifetime risks were determined accounting for competing risks of death. Cause-specific hazard ratios were determined using Royston-Parmar models. Models were adjusted for ethnicity and time-updated covaries, including material deprivation, CV risk factors, lifestyle factors, comorbidities, and medication. Participants’ CVD status was time-updated over the study follow-up as this was diagnosed. Results Out of a total of 22, 534 participants, free of cancer at baseline, 53.7% were women. Mean (standard deviation) age was 58.6 (9.3) for women and 59.5 (9.3) for men, at baseline. Men were older and had more comorbidities. Hypertension and obesity were risk factors more prevalent amongst men, while women were more likely to be smokers at baseline. Participants with CVD had more comorbidities, were more likely to smoke, have higher HbA1cs and be obese than those without CVD. The adjusted lifetime risks of incident cancer in participants with CVD at age 75 were higher in men (13.9%) compared to women (10.1%). This translates into a cause-specific hazard ratio (cHR) (99% confidence interval) for incident cancer (men vs. women) of 1.41 (1.27 - 1.55). Similar findings were demonstrated in participants with no CVD (10.2% for men and 8.2% for women), corresponding to a cHR of 1.27 (1.15 - 1.40). Furthermore, men had a higher risk of cancer-related mortality compared to women in participants with CVD 1.54 (1.33 - 1.78), as well as among participants without CVD 1.34 (1.17 - 1.53). Conclusion Our study showed an association between CVD and the lifetime cancer risk in both sexes after extensive adjustment. Furthermore, we show that men have a higher risk of cancer incidence and cancer-related mortality than women, regardless of comorbid CVD. However, these associations, were stronger in participants with CVD. It is vital to identify driving forces of such disparities to achieve health equity.