Blood pressure variability predicts cardiovascular events independently of traditional cardiovascular risk factors and target organ damage: a LIFE substudy

Background: Assessment of antihypertensive treatment is normally based on the mean value of a number of blood pressure (BP) measurements. However, it is uncertain whether high in-treatment visit-to-visit BP variability may be harmful in hypertensive patients with left ventricular hypertrophy (LVH). Methods: In 8505 patients randomized to losartan vs. atenolol-based treatment in the LIFE study, we tested whether BP variability assessed as SD and range for BP6–24months measured at 6, 12, 18 and 24 months of treatment was associated with target organ damage (TOD) defined by LVH on ECG and urine albumin/creatinine ratio at 24 months, and predicted the composite endpoint (CEP) of cardiovascular death, nonfatal myocardial infarction (MI) or stroke occurring after 24 months (CEP = 630 events). Results: In multiple regression models adjusted for mean BP6–24months and treatment allocation, neither high BP6–24months SD nor wide range were related to TOD at 24 months, except for a weak association between Sokolow–Lyon voltage and DBP6–24months SD and range (both &bgr; = 0.04, P < 0.01). Independently of mean BP6–24months, treatment allocation, TOD and baseline characteristics in Cox regression models, CEP after 24 months was associated with DBP6–24months SD [hazard ratio per 1 mmHg increase1.04, 95% confidence interval (95% CI) 1.01–1.06, P = 0.005], range (hazard ratio 1.02, 95% CI 1.01–1.03, P = 0.004), SBP6–24months SD (hazard ratio 1.01, 95% CI 0.99–1.02, P = 0.07) and range (hazard ratio 1.006, 95% CI 1.001–1.01, P = 0.04). Adjusted for the same factors, stroke was associated with DBP6–24months SD (hazard ratio 1.06, 95% CI 1.02–1.10, P = 0.001), range (hazard ratio 1.03, 95% CI 1.01–1.04, P = 0.001), SBP6–24months SD (hazard ratio 1.02, 95% CI 1.002–1.04, P = 0.04) and range (hazard ratio 1.008, 95% CI 1.001–1.02, P = 0.05), but MI was not. Conclusion: In LIFE patients, higher in-treatment BP6–24months variability was independently of mean BP6–24months associated with later CEP and stroke, but not with MI or TOD after 24 months.

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