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Resting heart rate (RHR) has long been recognized as an independent predictor of cardiovascular risk. However, whether temporal changes in RHR influence the risk of death from ischemic heart disease (IHD) in the general population is not known.To assess the association of long-term longitudinal changes in RHR with the risk of dying from IHD.A prospective cohort study of 13 499 men and 15 826 women without known cardiovascular disease in Norway. Resting heart rate was measured on 2 occasions around 10 years apart in the Nord-Trøndelag County Health Study. The second RHR measurement was obtained between August 1995 and June 1997, with subsequent mortality follow-up until December 31, 2008. A total of 60 participants were lost to follow-up, all due to emigration from Norway. Using Cox regression analyses, adjusted hazard ratios (AHRs) were estimated of death from IHD related to changes in RHR over time. In a corresponding analysis, death from all causes also was assessed.During a mean (SD) of 12 (2) years of follow-up, 3038 people died, and 388 deaths were caused by IHD. An increase in RHR was associated with increased risk of death from IHD. Compared with participants with a RHR of less than 70 beats/min at both measurements (8.2 deaths/10 000 person-years), the AHR was 1.9 (95% CI, 1.0-3.6) for participants with a RHR of less than 70 beats/min at the first measurement but greater than 85 beats/min at the second measurement (17.2 deaths/10 000 person-years). For participants with RHRs between 70 and 85 beats/min at the first measurement and greater than 85 beats/min at the second measurement (17.4 deaths/10 000 person-years), the AHR was 1.8 (95% CI, 1.2-2.8). The association of change in RHR with IHD mortality was not linear (P = .003 for quadratic trend), suggesting that a decrease in RHR showed no general mortality benefit. Excluding the first 3 years of follow-up did not substantially alter the findings. The associations for total mortality were similar but generally weaker than those observed for IHD mortality.Among men and women without known cardiovascular disease, an increase in RHR over a 10-year period was associated with increased risk of death from IHD and also for all-cause mortality.