Metabolic heterogeneity in the risk of cancer among patients with cardiovascular diseases and diabetes

The co-occurrence of cardiovascular diseases (CVDs) and cancer may worsen patient outcomes and burden the healthcare system. We aimed to evaluate metabolic patterns of cancer risk and to characterize the heterogeneity of such an association across cancer and CVD subtypes. We analyzed a database of 108,735 adults without a cancer diagnosis at baseline who underwent echocardiography between 2000 and 2024. We obtained cancer, cancer-related hospitalization, and mortality data from Israel's National Registries. CVD was defined as heart failure, ischemic heart disease, atrial fibrillation, left heart disease, or stroke. We estimated the risk-factor-adjusted association between CVD and cancer incidence, cancer-related hospitalizations, and mortality. During a median follow-up of 5 years, 3,972 (4% of all patients) developed cancer. At baseline, 52,648 patients (48%) had CVD, which was associated with a higher risk of cancer after multivariable adjustment (HR = 1.35, 95%CI: 1.24–1.48). CVD accounted for 11.1% of the adjusted, cohort-specific population-attributable fraction for cancer and was associated with nine distinct types of cancer. Overall, diabetes was associated with a 14% increase in the risk of cancer in patients with CVD. Among patients with established CVD, each 1% increase in HbA1c was associated with a 0.77% increase in the absolute 5-year risk of cancer diagnosis. CVD was also associated with an adjusted 118% higher incidence of second primary cancer, a 69% increase in cancer-related hospitalizations, and a higher all-cause mortality following cancer diagnosis. CVDs are associated with a higher incidence of nine distinct subtypes of cancer, with differences across cardiometabolic impairment. Positive associations of HbA1c and blood pressure with cancer risk highlight the importance of diabetes and hypertension in patients with established CVD. CVD was associated with a higher risk of cancer, second primary cancer, a high population-attributable fraction for cancer, more cancer-related hospitalizations, and increased mortality. Recognizing this association may enhance cancer prevention, promote early diagnosis, and develop personalized treatment for patients with CVD.