Visit-to-Visit Variability of Blood Pressure and Coronary Heart Disease, Stroke, Heart Failure, and Mortality: A Cohort Study

Abstract

Background: Variability of blood pressure (BP) across outpatient visits is frequently dismissed as random fluctuation around a patient's underlying BP.

Objective: To examine the association of visit-to-visit variability (VVV) of systolic BP (SBP) and diastolic BP with cardiovascular disease (CVD) and mortality outcomes.

Design: Prospective cohort study.

Setting: Post hoc analysis of ALLHAT (Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial).

Participants: 25 814 ALLHAT participants.

Measurements: The VVV of SBP was defined as the SD across SBP measurements obtained at 7 visits conducted from 6 to 28 months after ALLHAT enrollment. Participants without CVD events during the first 28 months of follow-up were followed from the 28-month visit through the end of active ALLHAT follow-up. Outcomes included fatal coronary heart disease (CHD) or nonfatal myocardial infarction, all-cause mortality, stroke, and heart failure.

Results: During follow-up, 1194 fatal CHD or nonfatal MI events, 1948 deaths, 606 strokes, and 921 heart failure events occurred. After multivariable adjustment, including for mean SBP, the hazard ratio comparing participants in the highest versus lowest quintile of SD of SBP (≥14.4 mm Hg vs. <6.5 mm Hg) was 1.30 (95% CI, 1.06 to 1.59) for fatal CHD or nonfatal MI, 1.58 (CI, 1.32 to 1.90) for all-cause mortality, 1.46 (CI, 1.06 to 2.01) for stroke, and 1.25 (CI, 0.97 to 1.61) for heart failure. Higher VVV of diastolic BP was also associated with CVD events and mortality.

Limitation: Long-term outcomes were not available.

Conclusion: Higher VVV of SBP is associated with an increased risk for CVD and mortality. Future studies should examine whether reducing VVV of BP lowers this risk.

Primary funding source: National Institutes of Health.

Figure 1

Design of the study evaluating the association of visit-to-visit variability of blood pressure and cardiovascular outcomes and all-cause mortality in the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). *Participants were followed for a mean of 2.7 to 2.9 years depending on the outcome (maximum: 5.7 years) following assessment of visit-to-visit variability of blood pressure.

Figure 2

Cumulative incidence of fatal coronary heart disease and non-fatal myocardial infarction, all-cause mortality, stroke, and heart failure by quintile of intra-individual standard deviation of systolic blood pressure.

Figure 3

Hazard ratios for fatal coronary heart disease and non-fatal myocardial infarction, all-cause mortality, stroke, and heart failure associated with the highest versus lowest quintile of intra-individual standard deviation across ALLHAT follow-up visits conducted 6 to 28 months following baseline in selected sub-groups. Includes adjustment for age, gender, race/ethnicity, region of residence, randomization assignment, smoking status, body mass index, estimated glomerular filtration rate, diabetes, total cholesterol, history of myocardial infarction or stroke, history of coronary revascularization, atrial fibrillation on electrocardiogram, history of other atherosclerotic cardiovascular disease, major ST depression or T wave inversion, left ventricular hypertrophy, low high density lipoprotein cholesterol, aspirin use, use of blood pressure medications prior to study randomization, statin use, pulse pressure, medication adherence, antihypertensive medication classes being taken, changes in antihypertensive medication classes being taken, and mean systolic blood pressure. Blood pressure control was defined as systolic/diastolic blood pressure < 140/90 mm Hg. All p-values for interaction > 0.10 for each sub-group and outcome except comparing LVH on all-cause mortality (p=0.016) and Lisinopril and Chlorthalidone on stroke (p=0.083).

Figure 4

Hazard ratios for fatal coronary heart disease and non-fatal myocardial infarction, all-cause mortality, stroke, and heart failure associated with intra-individual standard deviation across ALLHAT follow-up visits conducted 6 to 28 months following baseline using restricted quadratic splines. The solid black line in each figure represents the hazard ratio and the grey shaded area represents the 95% confidence interval. The histogram represents the distribution of standard deviation of systolic blood pressure in the ALLHAT population. Includes adjustment for the following age, gender, race/ethnicity, region of residence, randomization assignment, smoking status, body mass index, estimated glomerular filtration rate, diabetes, total cholesterol, history of myocardial infarction or stroke, history of coronary revascularization, atrial fibrillation on electrocardiogram, history of other atherosclerotic cardiovascular disease, major ST depression or T wave inversion, left ventricular hypertrophy, low high density lipoprotein cholesterol, aspirin use, use of blood pressure medications prior to study randomization, statin use, pulse pressure, medication adherence, antihypertensive medication classes being taken, changes in antihypertensive medication classes being taken, and mean systolic blood pressure.