Heart rate adjustment of PR interval in middle-aged and older adults

Prolonged PR interval has been associated with adverse cardiac events. Consequently, the scientific community and regulatory agencies have become concerned about PR interval prolongation induced by cardioactive agents. We evaluated PR dependence on heart rate (HR) in 5757 men and women aged 40 years and older from the US third National Health and Nutrition Survey with the objective to determine if rate adjustment for the PR interval is warranted as is the case with QT interval. Electrocardiograms were computer-processed in a central electrocardiogram laboratory. There was a statistically significant negative correlation between PR and HR (r = -0.15; P < .001); notably weaker than that between QT and HR (r = -0.76; P < .001). Evaluation of subgroups stratified by sex, race, and age revealed a significant interaction between PR and HR with age (P = .006). A subsequent search for optimal rate-adjusted PR (PRa) formula that eliminates PR dependence on HR within each age group produced the formula: PRa = PR + 0.26 (HR - 70) for age group younger than 60 years and PRa = PR + 0.42 (HR - 70) for age group 60 years or older. The application of this formula in the study population effectively made the PR interval rate-invariant (residual slope of regression, -0.0054; 95% confidence interval, -0.064 to 0.053; P = .86). Based on the distribution of PRa, the 98th percentile limit of 220 milliseconds would be a reasonable overall threshold for defining first-degree AV block, with the 95th percentile limit of 205 as a threshold for borderline PR prolongation. In conclusion, the association between PR and HR is age- and rate-dependent and a separate rate-adjustment formula is needed for adults in younger and older age groups. The prognostic significance of the rate-adjusted PR needs to be investigated.