Blood Pressure Variability and Risk of CV Events

Study Questions:

Is blood pressure (BP) variability associated with an increased risk of cardiovascular events (CVEs) and death in hypertensive patients at different risk levels?

Methods:

The VALUE (Valsartan Antihypertensive Long-Term Use Evaluation) trial was a randomized controlled trial of valsartan versus amlodipine in patients with hypertension and different risks of CVEs, followed for a mean of 4.2 years. Patients could receive hydrochlorothiazide (or loop diuretics in case of impaired renal function) or other BP-lowering drugs if needed to reach BP <140/90 mm Hg. The authors calculated standard deviation (SD) of mean systolic BP (mSBP) from visits from 6 months onward in patients with ≥3 visits and no events during the first 6 months. The risk of CVEs was compared in the highest and lowest quintile of visit-to-visit BP variability, using Cox regression. For analysis of death, variability was analyzed as a continuous variable.

Results:

Mean age was 67.1 years, 42.5% were female, about 46% had coronary heart disease, and 20% had a previous stroke. Visits averaged 8.7 (1.7). Baseline average SBP was 154.6 mm Hg. Of 13,803 patients included, 1,557 (11.3%) had a CVE and 1,089 (7.9%) died. Patients in the highest quintile of SD had a mSBP variability of >13.7 mm Hg compared to <5.8 mm Hg in the lowest quintile, which was associated with an increased risk of CVEs (hazard ratio [HR], 2.1; p < 0.0001), and a 5 mm Hg increase in standard deviation of SBP was associated with a 10% increase in the risk of death (HR, 1.10; 95% confidence interval [CI], 1.04–1.17; p = 0.002). There was an increased risk of total cardiac events, ischemic strokes, myocardial infarction, and chronic heart failure. Within-visit SBP variability was associated with an increased risk of a CVE (HR, 1.15; 95% CI, 1.03-1.29; p = 0.01). Associations were stronger among younger patients and patients with lower SBP, and similar between patients with different baseline risks, except for higher risk of death among patients with established CV disease.

Conclusions:

Higher visit-to-visit SBP variability is associated with an increased risk of CVEs in patients with hypertension, irrespective of baseline risk of CVEs. Associations were stronger in younger patients and in those with lower mSBP.

Perspective:

Among the many implications of the findings include that standardized methods of home BP monitoring should be a regular practice for several days after a change in medication, and at least once a week thereafter. The results should be reported to the office, with adjustments made to reduce variability of morning and possibly evening BP taken regardless of the baseline clinical risk and BP achieved. Also, the practice of discarding the first BP measurement needs to be reassessed.

Keywords: Amlodipine, Antihypertensive Agents, Blood Pressure, Blood Pressure Monitoring, Ambulatory, Coronary Disease, Heart Failure, Hydrochlorothiazide, Hypertension, Metabolic Syndrome, Myocardial Infarction, Primary Prevention, Risk, Stroke, Systole


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