Background Variability of blood pressure (BP) across outpatient visits is frequently dismissed as random fluctuation around a patient’s underlying BP. Objective: Examine the association between visit-to-visit variability (VVV) of systolic and diastolic BP (SBP and DBP) on cardiovascular disease and mortality outcomes. Design Prospective cohort study Setting Post-hoc analysis of the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). Participants 25,814 ALLHAT participants. Measurements VVV of SBP was defined as the standard deviation (SD) across BP measurements obtained at 7 visits conducted from 6 to 28 months following ALLHAT enrollment. Participants free of cardiovascular disease events during the first 28 months of follow-up were followed from the month 28 study visit through the end of active ALLHAT follow-up. Outcomes included fatal coronary heart disease or non-fatal myocardial infarction, all-cause mortality, stroke and heart failure. Results There were 1194 cases of fatal CHD or non-fatal MI, 1948 deaths, 606 cases of stroke and 921 cases of heart failure during follow-up. After multivariable adjustment including mean SBP, the hazard ratio comparing participants in the highest versus lowest quintile of SD of SBP (≥14.4 mmHg versus <6.5 mmHg) was 1.30 (1.06–1.59) for fatal coronary heart disease or non-fatal myocardial infarction, 1.58 (1.32–1.90) for all-cause mortality, 1.46 (1.06–2.01) for stroke, and 1.25 (0.97–1.61) for heart failure. Higher VVV of DBP was also associated with cardiovascular disease events and mortality. Limitations Long-term outcomes were not available. Conclusions Higher VVV of SBP is associated with increased cardiovascular disease and mortality risk. Future studies should examine whether reducing VVV of BP lowers this risk. Primary funding source National Institutes of Health

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PPROXIMATELY 71 MILLION INdividuals in the United States have 1 or more types of cardiovascular disease (CVD), at least 65 million of whom have hypertension. 1 Although control of hypertension has been improving in recent years, among those treated, only about two-thirds have their hypertension controlled. 2 Seeking ways to reduce CVD morbidity and mortality by tailoring treatment to a patient's particular genotype is a laudable goal. To date, studies of gene polymorphisms in hypertension candidate genes, such as angiotensin-converting enzyme (ACE) and the angiotensin II receptor, have been shown to predict response to treatments such as ACE inhibition and angiotensin II blockade. 3 However, the use of information on genetic variability to predict response to antihypertensive therapy and, thus, guide therapeutic choices, has yet to be realized in the clinical setting.The NPPA (atrial natriuretic precursor A) gene is an attractive candidate for pharmacogenetic research. Found on chromosome 1p36, NPPA encodes the precursor from which atrial natriuretic polypeptide (ANP) is derived.Atrial natriuretic polypeptide controls extracellular fluid volume and electrolyte homeostasis, acting as a diuretic. 4 Animal studies show that genetically re-Author Affiliations are listed at the end of this article.