Increased risk of non-hematological cancer in young patients with aortic stenosis: a retrospective cohort study

Abstract

Background: We have previously reported an increased risk for non-hematological malignancies in young patients with moderate or severe aortic stenosis (AS). These findings were the result of a post-hoc analysis from a large echocardiography database and needed verification. Our aim was to determine, using a different study population, whether young patients with AS are at increased risk for cancer.

Methods: A large echocardiographic database was used to identify patients (age ≥ 20 years) with moderate or severe AS (study group) and patients without aortic stenosis (comparative group). The new occurrence of non-hematological malignancies was determined after the index date (first echo with moderate or severe AS or first recorded echo in the control group).

Results: The final study group included 7013 patients with AS and 98,884 without AS. During a median follow-up of 6.9 years (3.0-11.1) there were 10,705 new cases of non-hematological cancer. The crude incidence rate of cancer was higher in AS compared to non-AS patients (22.3 vs. 13.7 per 1000 patient-year, crude HR 1.58 (95%CI 1.46-1.71). After adjustment for relevant covariates, there was no difference between groups (HR 0.93, 95% CI 0.86-1.01). Only patients in the lowest age quartile (20-49.7 years), had an increased adjusted risk of cancer (HR 1.91, 95%CI 1.08-3.39). The HR for the risk of cancer associated with AS was inversely proportional to age (P < 0.001 for the interaction between AS and age).

Conclusions: Young patients with moderate or severe AS may have an increased risk for cancer. Cancer surveillance should be considered for young patients with AS.

Keywords: Age; Aortic stenosis; Cancer; Risk.

Fig. 1

Study population selection flowchart. AS = aortic stenosis, AVR = aortic valve replacement, CABG = coronary artery bypass grafting, IQR = interquartile range, IR = incidence rate, MVR = mitral valve replacement

Fig. 2

Incidence of cancer and mortality in patients with and without AS. Cumulative incidence function (CIF) for the distribution of time to non-hematological malignancies (a) and Kaplan-Meier curves for mortality (b). Death was considered a competing event for cancer (a). Solid line represents patients without AS and dotted line patients with AS

Fig. 3

The interaction between age and AS and the risk of cancer. Adjusted HR* for non-hematological malignancies in AS as a function of age. Dotted lines represent the 95% confidence interval (CI). *Adjusted for age (continuous variable), sex, ethnicity, socioeconomic status, smoking, alcohol abuse, obesity, diabetes mellitus, previous history of cancer and aspirin and statin use. HR = hazard ratio

Fig. 4

Incidence of cancer by age. Cumulative incidence function (CIF) for the distribution of time to non-hematological malignancies stratified by age quartiles. Death was considered a competing event for cancer. Increased incidence of cancer is evident only in the lowest age quartile. Solid line represents patients with no AS and dotted lines represent patients with AS