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.