Trends in excess mortality associated with atrial fibrillation over 45 years (Framingham Heart Study): community based cohort study

Abstract

Objective: To assess temporal trends in the association between newly diagnosed atrial fibrillation and death.

Design: Community based cohort study.

Setting: Framingham Heart Study cohort, in 1972-85, 1986-2000, and 2001-15 (periods 1-3, respectively), in Framingham, MA, USA.

Participants: Participants with no atrial fibrillation, aged 45-95 in each time period, and identified with newly diagnosed atrial fibrillation (or atrial flutter) during each time period.

Main outcome measures: The main outcome was all cause mortality. Hazard ratios for the association between time varying atrial fibrillation and all cause mortality were calculated with adjustment for time varying confounding factors. The difference in restricted mean survival times, adjusted for confounders, between participants with atrial fibrillation and matched referents at 10 years after a diagnosis of atrial fibrillation was estimated. Meta-regression was used to test for linear trends in hazard ratios and restricted mean survival times over the different time periods.

Results: 5671 participants were selected in time period 1, 6177 in period 2, and 6174 in period 3. Adjusted hazard ratios for all cause mortality between participants with and without atrial fibrillation were 1.9 (95% confidence interval 1.7 to 2.2) in time period 1, 1.4 (1.3 to 1.6) in period 2, and 1.7 (1.5 to 2.0) in period 3 (P_trend=0.70). Ten years after diagnosis of atrial fibrillation, the adjusted difference in restricted mean survival times between participants with atrial fibrillation and matched referents decreased by 31%, from -2.9 years (95% confidence interval -3.2 to -2.5) in period 1, to -2.1 years (-2.4 to -1.8) in period 2, to -2.0 years (-2.3 to -1.7) in period 3 (P_trend=0.03).

Conclusions: No evidence of a temporal trend in hazard ratios for the association between atrial fibrillation and all cause mortality was found. The mean number of life years lost to atrial fibrillation at 10 years had improved significantly, but a two year gap compared with individuals without atrial fibrillation still remained.

Fig 1

Temporal trends for the association between newly diagnosed atrial fibrillation and all cause mortality. Data are hazard ratios (95% confidence intervals) for the association between time varying atrial fibrillation and death (in participants with v those without atrial fibrillation). Multivariable models were adjusted for the clinical covariates listed in table 1. Linear trends across time periods were tested by meta-regression models of log hazard ratios

Fig 2

Adjusted survival curves for participants with atrial fibrillation and matched referents. Kaplan-Meier curves since time of diagnosis of atrial fibrillation for participants with atrial fibrillation and referents, matched on age at diagnosis of atrial fibrillation, sex, and Framingham Heart Study cohort, adjusted for clinical covariates at age of diagnosis of atrial fibrillation. The adjusted difference in the restricted mean survival time at 10 years between participants with atrial fibrillation and referents is the area between the survival curves: −2.85 years (95% confidence interval −3.21 to −2.50) in time period 1, −2.10 years (−2.35 to −1.84) in period 2, and −1.99 years (95% CI −2.26 to −1.72) in period 3 (P_trend=0.03)