Associations of genetic and non-genetic cardiovascular health metrics with coronary artery disease incidence in cancer survivors

Cardiovascular disease (CVD) is a leading threat to long-term health in cancer survivors. This study aimed to evaluate whether integrating genetic risk with the composite cardiovascular health metric, the Life’s Essential 8 (LE8) score, can improve primary prevention and guide personalized survivorship care in this population. We conducted a retrospective cohort study including 21,751 cancer survivors and 87,004 matched non-cancer controls from the UK Biobank. For each participant, a LE8 score, encompassing eight CVD-related factors (diet, physical activity, nicotine exposure, sleep, body mass index, blood pressure, blood glucose, and non-high-density lipoprotein cholesterol), and a polygenic risk score (PRS) for coronary artery disease (CAD) were calculated. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for incident risk of CAD across LE8 (or individual LE8 components) and PRS levels and to examine their potential interactions. A higher LE8 score and a lower PRS were independently associated with reduced CAD risk in cancer survivors. Participants with a high LE8 score and low PRS had the lowest CAD risk (HR 0.22; 95% CI, 0.09 0.53) when compared with those with a low LE8 score and high PRS. Similar patterns were observed in matched controls who had a lower CAD incidence rate. Associations between optimal blood lipid levels (as defined in the LE8 score) seemed to be more pronounced in individuals with high PRS, although it did not reach statistical significance among cancer survivors (p for interaction with PRS = 0.14 and 0.011, respectively, in cancer survivors and matched controls). Subgroup analyses showed consistent associations between LE8 score and CAD risk in breast, prostate, colorectal, and malignant skin cancer survivors, but not in those with lymphoma or hematologic malignancies. Furthermore, the association between LE8 score and CAD risk was stronger 5–10 years after cancer diagnosis and among younger cancer survivors aged under 55 years. Both a higher LE8 score and lower PRS for CAD were independently associated with substantially reduced risk of incident CAD.