Risk Related to Variation in Blood Pressure

Study Questions:

Is visit-to-visit variability in blood pressure (BP) associated with cardiovascular (CV) risk in patients with stable coronary heart disease (CHD)?

Methods:

Data were from the STABILITY trial, a randomized trial of darapladib versus placebo in patients with established CHD. Participants were enrolled between December 2008 and April 2010 from 663 centers in 39 countries. Participants were included if they had CHD, which included previous myocardial infarction (MI), percutaneous coronary intervention, or coronary artery bypass grafting, or multivessel CHD. In addition, at least one of the following additional predictors of CV risk was required: age of ≥60 years, diabetes requiring pharmacotherapy, a high-density lipoprotein <40 mg/dl, current smoking, moderate renal dysfunction, or polyvascular arterial disease. The original study found no difference in CV outcomes between the two treatment arms, which were therefore lumped together in the present analysis. BP variability was assessed by the standard deviation (SD) of systolic BP, the SD of diastolic BP, maximum BP, and minimum BP, from five measurements (baseline and months 1, 3, 6, and 12) during the first year after randomization. The primary outcome of interest was a composite of time to CV death, MI, or stroke.

Results:

Of the 15,828 participants included in the original study, 13,794 participants were included in the present analysis. Mean age was 65 years, 81.6% were male and 78.3% were white, and 77.7% had a history of hypertension. Mean (SD) average BP during the first year of study was 131.0 (13.7) mm Hg over 78.3 (8.3) mm Hg. Mean (SD) of the visit-to-visit SD was 9.8 (4.8) mm Hg for systolic and 6.3 (3.0) mm Hg for diastolic BP. Over a median follow-up of 2.6 years, 1,010 patients met the primary endpoint, a composite of time to CV death, MI, or stroke. After adjusting for average BP during the first year of study, baseline vascular disease, treatment, renal function, and CV risk factors, the primary endpoint was associated with a SD of systolic BP (hazard ratio for highest vs. lowest tertile, 1.30; 95% confidence interval [CI], 1.10-1.53; p = 0.007), and with SD of diastolic BP (hazard ratio for highest vs. lowest tertile, 1.38; 95% CI, 1.18-1.62; p < 0.001). Peaks and troughs in BP were also independently associated with adverse events.

Conclusions:

The authors concluded that among patients with stable CHD, higher visit-to-visit variation of both systolic and diastolic BP are strong predictors of increased risk of CV events, independently of mean BP.

Perspective:

This secondary analysis suggests that variation in BP is associated with increased CV disease risk among those with CHD. Understanding the possible mechanisms and whether variation over days to weeks is associated with risk would be important, given the numbers of patients who report large variations in BP readings.

Keywords: Blood Pressure, Cardiovascular Diseases, Coronary Artery Bypass, Coronary Artery Disease, Diabetes Mellitus, Hypertension, Lipoproteins, HDL, Metabolic Syndrome, Myocardial Infarction, Percutaneous Coronary Intervention, Primary Prevention, Renal Insufficiency, Risk Factors, Smoking, Stroke, Vascular Diseases


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