Coexisting atrial fibrillation and cancer: time trends and associations with mortality in a nationwide Dutch study

Abstract

Background and aims: Coexisting atrial fibrillation (AF) and cancer challenge the management of both. The aim of the study is to comprehensively provide the epidemiology of coexisting AF and cancer.

Methods: Using Dutch nationwide statistics, individuals with incident AF (n = 320 139) or cancer (n = 472 745) were identified during the period 2015-19. Dutch inhabitants without a history of AF (n = 320 135) or cancer (n = 472 741) were matched as control cohorts by demographic characteristics. Prevalence of cancer/AF at baseline, 1-year risk of cancer/AF diagnosis, and their time trends were determined. The association of cancer/AF diagnosis with all-cause mortality among those with AF/cancer was estimated by using time-dependent Cox regression.

Results: The rate of prevalence of cancer in the AF cohort was 12.6% (increasing from 11.9% to 13.2%) compared with 5.6% in the controls; 1-year cancer risk was 2.5% (stable over years) compared with 1.8% in the controls [adjusted hazard ratio (aHR) 1.52, 95% confidence interval (CI) 1.46-1.58], which was similar by cancer type. The rate of prevalence of AF in the cancer cohort was 7.5% (increasing from 6.9% to 8.2%) compared with 4.3% in the controls; 1-year AF risk was 2.8% (stable over years) compared with 1.2% in the controls (aHR 2.78, 95% CI 2.69-2.87), but cancers of the oesophagus, lung, stomach, myeloma, and lymphoma were associated with higher hazards of AF than other cancer types. Both cancer diagnosed after incident AF (aHR 7.77, 95% CI 7.45-8.11) and AF diagnosed after incident cancer (aHR 2.55, 95% CI 2.47-2.63) were associated with all-cause mortality, but the strength of the association varied by cancer type.

Conclusions: Atrial fibrillation and cancer were associated bidirectionally and were increasingly coexisting, but AF risk varied by cancer type. Coexisting AF and cancer were negatively associated with survival.

Keywords: Atrial fibrillation; Incidence; Mortality; Neoplasms; Prevalence.

Structured Graphical Abstract

Prevalence, incidence, time trend, and association with all-cause mortality of coexisting atrial fibrillation and cancer in the Netherlands. AF, atrial fibrillation; aHR, adjusted hazard ratio; CI, confidence interval.

Figure 1

Study design and inclusion of the study populations. *Details about the identification of Dutch inhabitants between 2015 and 2019 who were considered eligible for the study are provided in Supplementary data online, Figure S1. ^†A diagnosis of atrial fibrillation (or cancer) was considered incident when there was no previous diagnosis record of atrial fibrillation (or cancer) within the prior 5 years (see Supplementary data online, Figure S2). A total of 42 446 unique individuals from the source population were included in both the incident atrial fibrillation cohort and the incident cancer cohort. ^‡There were 305 999 unique individuals among the matched control cohort without atrial fibrillation history (for the incident atrial fibrillation cohort) and 454 940 unique individuals among the matched control cohort without cancer history (for the incident cancer cohort). A total of 25 221 unique individuals from the source population were included in both the control cohort for the incident atrial fibrillation cohort and the control cohort for the incident cancer cohort. #The follow-up started from the index date of each individual until 1 year after, or when the outcome event (i.e. cancer or atrial fibrillation) was first diagnosed, or until the date of death, whichever came first. For the matched control cohort, they would also be censored when they were diagnosed with atrial fibrillation (or cancer)

Figure 2

The prevalence of cancer among the incident atrial fibrillation cohort and the prevalence of atrial fibrillation among the incident cancer cohort vs. that in the control cohorts. For readability, the names of cancer types in the figure were shortened. Detailed descriptions can be found in Supplementary data online, Table S2. CNS, central nervous system

Figure 3

Cumulative incidence curves for cancer diagnosed after incident atrial fibrillation or atrial fibrillation diagnosed after incident cancer vs. that in the control cohorts. Individuals who had a history of cancer (or atrial fibrillation) at baseline were excluded from this analysis. The cumulative incidence curves were plotted using the cumulative incidence competing risk method, in which all-cause death was considered as a competing event. The control cohorts would also be censored when atrial fibrillation (or cancer) was diagnosed during the 1-year follow-up, which was also considered as a competing event

Figure 4

The one-year cumulative incidence of cancer diagnosed after incident atrial fibrillation vs. that in the control cohort. For readability, the names of cancer types in the figure were shortened. Detailed descriptions can be found in Supplementary data online, Table S2. Individuals who had a history of cancer at baseline were excluded from this analysis. The cumulative incidence was estimated by the cumulative incidence competing risk method, in which all-cause death was considered as a competing event. The control cohort would also be censored when atrial fibrillation was diagnosed during the 1-year follow-up, which was also considered as a competing event. The hazard ratios refer to the hazard of cancer diagnosis (overall or of a specific type) in the incident atrial fibrillation cohort compared with that in the control cohort, which were estimated by cause-specific Cox regression, after adjusting for age, sex, immigration background, standardized household income, and various comorbidities (or medical history). CNS, central nervous system; CI, confidence interval; HR, hazard ratio

Figure 5

The one-year cumulative incidence of atrial fibrillation diagnosed after incident cancer vs. that in the control cohort. For readability, the names of cancer types in the figure were shortened. Detailed descriptions can be found in Supplementary data online, Table S2. Individuals who had a history of atrial fibrillation at baseline were excluded from this analysis. The cumulative incidence was estimated by the cumulative incidence competing risk method, in which all-cause death was considered as a competing event. The control cohort would also be censored when cancer was diagnosed during the 1-year follow-up, which was also considered as a competing event. The hazard ratios refer to the hazard of atrial fibrillation diagnosis in the incident cancer cohort (overall or of a specific type) compared with that in the control cohort, which were estimated by cause-specific Cox regression, after adjusting for age, sex, immigration background, standardized household income, and various comorbidities (or medical history). For female- or male-specific cancer (as indicated), only the female or male individuals in the control cohort were included as the reference group. CNS, central nervous system; CI, confidence interval; HR, hazard ratio

Figure 6

Time trends in coexisting atrial fibrillation and cancer. The hazard ratios refer to the hazard of cancer/atrial fibrillation diagnosis in the incident atrial fibrillation/cancer cohort diagnosed in different calendar years compared with that of the same cohort diagnosed in 2015, which were estimated by cause-specific Cox regression, after adjusting for age, sex, immigration background, standardized household income, and various comorbidities (or medical history). CI, confidence interval; HR, hazard ratio

Figure 7

The association of cancer/atrial fibrillation diagnosed after incident atrial fibrillation/cancer with all-cause mortality. For readability, the names of cancer types in the figure were shortened. Detailed descriptions can be found in Supplementary data online, Table S2. Individuals who had a history of cancer (or atrial fibrillation) at baseline were excluded from this analysis. The individuals were followed for 1 year after the incident atrial fibrillation (or cancer) diagnosis or until all-cause mortality, whichever came first, while cancer (or atrial fibrillation) diagnosed during the follow-up was treated as a time-dependent exposure to estimate its association with all-cause mortality by multivariable Cox regression, with adjustment for time-fixed covariates (identified at baseline), including age, sex, immigration background, standardized household income, and various comorbidities (or medical history). For the analyses of developing non–sex-specific cancer among the incident atrial fibrillation cohort, the individuals were also censored when sex-specific cancer was diagnosed and vice versa (as indicated). CNS, central nervous system; HR, hazard ratio; CI, confidence interval