During a median follow-up of 12.4 years, 644 out of 34221 women had at least one confirmed episode of incident AF. Baseline characteristics of the study population are shown in . Mean age was 55 ± 7 years, 16.8% of participants had a systolic BP ≥140 mmHg and 4.8% had a diastolic BP ≥90 mmHg.
There was a highly significant increase in risk of incident AF across increasing categories of systolic and diastolic BP. While multivariable adjustment somewhat attenuated these trends, both BP components remained strongly associated with incident AF (). Even women with systolic BP between 130–139 mmHg or diastolic BP between 85–89 mmHg, i.e. below the current threshold for diagnosing and treating hypertension,26, 27
had a significantly increased risk of incident AF (hazard ratio (95% confidence interval) 1.28 (1.00– 1.63), p=0.05, and 1.53 (1.05–2.23), p=0.03, respectively). When both BP components were entered in a joint multivariable model, we found a persistent risk gradient across systolic but not diastolic BP categories. Accordingly, adding diastolic BP to the multivariable systolic BP model did not improve model fit (likelihood ratio chi square 2.23, p=0.82).
Blood pressure and risk of incident atrial fibrillation
When we assessed baseline systolic and diastolic BP as continuous variables, we found an adjusted hazard ratio (95% confidence interval) of 1.16 (1.09–1.23), p<0.0001 per 10-mmHg increase of systolic BP and 1.17 (1.05–1.29), p=0.003 per 10-mmHg increase of diastolic BP. In a combined model systolic but not diastolic BP remained a significant predictor of incident AF (hazard ratio (95% confidence interval) per 10 mmHg increase 1.17 (1.08–1.27), p<0.0001 for systolic BP; and 0.98 (0.86–1.12), p=0.74 for diastolic BP).
When we examined the continuous relationship between directly reported BP measurements ascertained at 48 months and subsequent risk of AF, systolic but not diastolic BP was associated with AF (hazard ratio (95% confidence interval) per 10-mmHg increase 1.12 (1.05–1.19), p=0.001 for systolic, and 1.00 (0.90–1.12), p=0.94, for diastolic BP). In a combined model, systolic BP remained significantly related to incident AF (hazard ratio (95% confidence interval) 1.16 (1.08–1.25, p=0.0001), and an inverse association between diastolic BP and incident AF began to emerge (hazard ratio (95% confidence interval) 0.88 (0.78– 1.00), p=0.05).
Importantly, women with high normal systolic BP (130–139 mmHg) at 48 months continued to be at increased risk of subsequent AF (hazard ratio (95% confidence interval) 1.50 (1.12–2.02), p=0.006). At 48 months, there was an increased risk even among women with systolic BP between 120 and 129 mmHg (hazard ratio (95% confidence interval) 1.35 (1.01–1.82), p=0.04). When we subdivided diastolic BP at 48 months into one additional category (<65, 65 to 74, 75 to 80, 80–84, 85 to 89, 90 to 94 and >94 mmHg), we obtained the following adjusted hazard ratios (95% confidence intervals): 1.0, 0.97 (0.69–1.35), 0.65 (0.43–1.00), 0.92 (0.66–1.28), 0.91 (0.59–1.40), 1.01 (0.65–1.57), 1.38 (0.62–3.07). When diastolic BP categories were entered into the systolic BP model, a U-shaped relationship between diastolic BP and AF emerged (hazard ratio (95% confidence interval) 1.0, 0.84 (0.60–1.18), 0.52 (0.33–0.80), 0.67 (0.46–0.96), 0.62 (0.39–0.99), 0.67 (0.41–1.08), 0.86 (0.37–2.00)), associated with a borderline significant improvement in model fit (likelihood ratio 12.58, 6df, p=0.05). The addition of a quadratic diastolic BP term to this model provided a significant result (p=0.031), again suggesting a non-linear relationship.
In models where BP was updated over time, systolic BP remained a strong predictor of AF and women with systolic BP between 130 and 139 mmHg continued to have significantly elevated risks of AF as compared to women with a systolic BP <120 mmHg (hazard ratio (95% confidence interval) 1.37 (1.07–1.76), p=0.01) (, ). These analyses also suggest that lowering systolic BP <120 mmHg in women with systolic BP between 120–129 mmHg, 130–139 mmHg, 140–159 mmHg and ≥160 mmHg may be associated with reductions of incident AF of 12%, 27%, 42% and 55%, respectively.
Cumulative incidence of AF according to time-updated systolic and diastolic BP categories
Diastolic BP was also associated with incident AF in the updated model (p for linear trend 0.026). In an updated combined model, systolic BP remained strongly and positively associated with incident AF, also among women with BP values between 130 and 139 mmHg (hazard ratio (95% confidence interval) 1.43 (1.09–1.87), p=0.009), but the relationship between diastolic BP and AF became non-significant.
Findings were similar when we took into account the effect of antihypertensive treatment during follow-up. In these models, multivariable adjusted hazard ratios (95% confidence intervals) were 1.0, 1.10 (0.86–1.41), 1.28 (0.99–1.64), 1.54 (1.18–2.00) and 1.93 (1.26–2.97) for increasing systolic BP categories, and 1.0, 1.10 (0.81–1.51), 1.08 (0.79–1.46), 1.18 (0.81–1.71), 1.32 (0.88–1.96) and 1.32 (0.64–1.70) for increasing diastolic BP categories. Treatment by systolic or diastolic BP interaction terms were not statistically significant (p=0.80 and p=0.31, respectively).
In total, 47 women had a cardiovascular event prior to the development of new-onset AF. Censoring these women at the date of the cardiovascular event did attenuate but not offset the association between incident AF and baseline BP (), and linear trends across BP categories remained significant for systolic BP (p for linear trend=0.0001) and diastolic BP (p for linear trend=0.02). Results also did not significantly change if we excluded the 13.5% of women who took antihypertensive treatment at baseline (data not shown). Analysis for effect modification revealed that the risk of AF according to both systolic and diastolic BP was similar for women <65 years and those ≥65 years (p for interaction 0.32 and 0.39 for systolic and diastolic BP, respectively), and similar for those who took antihypertensive treatment at baseline and those who did not (p for interaction 0.24 and 0.75 for systolic and diastolic BP, respectively).