Results
Among 6188 participants from NHANES III (mean age 58.1 years, SE±13.1; 55.0% female), 4463 (72.1%) were white. PR prolongation was present in 7.6% (N = 472) of the participants, of whom 61.2% had QRS axis ≤37°. Table 1 shows characteristics of participants stratified by PR prolongation and QRS axis. Participants with both PR prolongation and QRS axis ≤37° were more likely to be elderly, male, low-income, have prolonged P-wave duration, and take anti-hypertensive medications as well as atrioventricular node medications than the other groups, especially the group without PR prolongation.
During the recorded a median follow-up time of 298 months (IQR: 16–69 months), a total of 3541 deaths occurred. The mortality rate was highest among participants with PR prolongation and QRS axis ≤37° (5.23 per 100 person-years) and was the least among those without PR prolongation and QRS axis >37° (2.29 per 100 person-years). Mortality was lower in those with PR prolongation but QRS axis >37° than in those without PR prolongation but QRS axis ≤37° (2.82/100 person-years vs. 3.11/100 person-years). Figure 2 shown Kaplan–Meier survival curves in the four groups, with statistically significant differences between all groups.
Firstly, we entered both PR prolongation and QRS axis ≤37° in the same model as two separate variables. In the unadjusted model, both were associated with an increased risk of all-cause mortality (PR prolongation: [HR: 1.59, 95% CI: 1.43-1.78]; QRS axis ≤37°: [HR: 1.45, 95% CI: 1.35-1.55]). However, in the adjusted full model (adjusted for age, sex, race, income, smoke status, BMI, diabetes mellitus, family history of CVD, antihypertensive medications use, AV nodal drug use, cancer, HDL cholesterol, heart rate, diastolic blood pressure, systolic blood pressure, QRS duration, P-wave duration, corrected QT interval, Negative P-wave V1), we found that the strength of the association between the two and death was weakened (PR prolongation: [HR: 1.03, 95% CI: 0.92-1.15], QRS axis ≤37°: [HR: 1.01, 95% CI: 0.94-1.15]).
Then we combined PR interval and QRS axis (normal PR interval and QRS axis >37°, normal PR interval and QRS axis ≤37° [reference group], prolonged PR interval and QRS axis >37°, prolonged PR interval and QRS axis ≤37°) and included them in the Cox proportional hazards model for analysis (Table 2). When compared with normal PR interval and QRS axis ≤37°, prolonged PR interval and QRS axis ≤37° was associated with a 1.8-fold increased risk of mortality in the unadjusted model. After adjustment for all risk factors and potential confounders, the risk of mortality remained the highest in the concomitant prolonged PR interval and QRS axis ≤37° (HR: 1.20, 95% CI: 1.04-1.39). The lowest-risk group for death was the group with prolonged PR interval and QRS axis >37° (HR: 0.80, 95% CI: 0.65-0.98). The results of the fully adjusted model are presented in Figure 3.
Finally, we substituted the 4-level variable by the 3-level variable (Normal PR interval [reference group], Prolonged PR interval and QRS axis >37°, Prolonged PR interval and QRS axis ≤37°) in the full Cox proportional hazards model and additionally undertook sensitivity and subgroup analysis (Table 3). When compared with normal PR interval, prolonged PR interval and QRS axis ≤37° was associated with increased risk of mortality (HR: 1.18, 95% CI: 1.03-1.36). In sensitivity analysis, results were similar to those of our primary analysis. And similar direction of the results was observed when we examined the association between different combinations of PR interval and QRS axis with mortality in subgroups of NHANES-III participants stratified by age, sex, race, diabetes mellitus and antihypertensive medications use with no significant interactions between the components of each subgroup.