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Risk of Cancer After Diagnosis of Cardiovascular Disease
Quick Takes
- A diagnosis of CVD is associated with an increased risk of incident cancer compared to those without CVD after controlling for multiple shared risk factors.
- Atherosclerotic CVD is associated with an increased risk of incident cancer compared to nonatherosclerotic CVD.
Study Questions:
Is there an association between cardiovascular disease (CVD) and the development of cancer?
Methods:
This was a retrospective cohort study of patients ≥18 years of age enrolled in the IBM MarketScan Research Databases since 2009 with no cancer diagnosis in the first 24 months of enrollment. During a 24-month run-in period, patients were stratified by presence or absence of CVD and then by subtype of CVD (atherosclerotic or nonatherosclerotic). CVD was defined as International Classification of Disease (ICD), 9th (ICD-9) or 10th (ICD-10) edition codes corresponding to coronary artery disease, peripheral arterial disease, cerebrovascular disease, heart failure, valvular disease, congenital heart disease, and atrial fibrillation. Patients were excluded if they did not have 36 months of follow-up data, had only one CVD diagnosis code, or had cancer detected in the 3 months following a change in CVD status. The primary outcome was incident cancer. Time-dependent analysis with Cox proportional hazards modeling was performed adjusting for multiple CV risk factors including age, sex, diabetes, hypertension, chronic kidney disease, hyperlipidemia, statin use, health care contacts, region, and insurance type. A sensitivity analysis with performed excluding heart failure from the definition of CVD (n = 877,928). A secondary analysis used health risk assessment (HRA) data for 1,257,493 patients, which provided information on body mass index and smoking status.
Results:
A total of 27,108,227 patients with and without CVD were included with a mean age of 43.3 years, 55.7% were female, and the median follow-up was 33 months. Patients with atherosclerotic CVD (n = 3,446,027) were older, more likely to be men, and had more comorbidities compared to patients with nonatherosclerotic CVD (n = 2,235,574). Patients in the HRA cohort were younger with lower rates of comorbidities compared to the primary cohort.
Patients with CVD were at a higher risk of developing incident cancer compared to those without CVD (hazard ratio [HR], 1.12; 95% confidence interval [CI], 1.11-1.13). Both atherosclerotic (HR, 1.2; 95% CI, 1.19-1.21) and nonatherosclerotic (HR, 1.08; 95% CI, 1.07-1.08) CVD were associated with higher cumulative incidence of cancer compared to those without CVD. Atherosclerotic CVD was also associated with a higher risk of incident cancer compared to the nonatherosclerotic CVD group (HR, 1.11; 95% CI, 1.11-1.12). Results were consistent with the primary analysis after censoring patients with heart failure and when utilizing HRA data. Atherosclerotic CVD was associated with higher risk for cancers of the lung, bladder, colon, head and neck, liver, prostate, pancreas, kidney, lymphoma, leukemia, and other hematologic malignancies and lower risk of breast, ovarian, and uterine cancers compared to nonatherosclerotic CVD.
Conclusions:
Increased incidence of cancer is associated with the presence of CVD and risk is higher for individuals with atherosclerotic CVD compared to nonatherosclerotic CVD.
Perspective:
This represents the largest study to date exploring the relationship between CVD, particularly atherosclerotic CVD and cancer risk. A shared pathophysiological link between CVD and cancer may be present given the risk of incident cancer remained after controlling for multiple shared risk factors and after excluding patients with heart failure. Whether this link is due to inflammation, metabolic changes, immune cell activation, or other causes remains to be determined. While this study evaluated a multitude of common risk factors, remaining confounders exist, such as physical inactivity, environmental exposures, alcohol, and sociodemographic factors. The association between atherosclerotic CVD and specific cancer subtypes warrants further investigation, as this could aid in the development of proactive cancer screening protocols. Interestingly, there was an inverse relationship between atherosclerotic CVD and development of breast, ovarian, and uterine cancers.
Clinical Topics: Arrhythmias and Clinical EP, Cardio-Oncology, Congenital Heart Disease and Pediatric Cardiology, Heart Failure and Cardiomyopathies, Prevention, Valvular Heart Disease, Atherosclerotic Disease (CAD/PAD), Atrial Fibrillation/Supraventricular Arrhythmias, Congenital Heart Disease, CHD and Pediatrics and Arrhythmias, CHD and Pediatrics and Prevention, CHD and Pediatrics and Quality Improvement, Acute Heart Failure, Smoking
Keywords: Atherosclerosis, Atrial Fibrillation, Body Mass Index, Cardiotoxicity, Cardiovascular Diseases, Cerebrovascular Disorders, Coronary Artery Disease, Heart Defects, Congenital, Heart Failure, Heart Valve Diseases, Neoplasms, Patient Care Team, Peripheral Arterial Disease, Risk Assessment, Risk Factors, Secondary Prevention, Smoking
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