Association of blood pressure variability with CV risk is irrespective of CV baseline risk

Blood pressure variability and risk of cardiovascular events and death in patients with hypertension and different baseline risks

Literature - Mehlum MH, Liestøl K, Kjeldsen SE, et al. - Eur Heart J 2018; published online ahead of print


Clinical and observational studies show that increased blood pressure (BP) variability contributes to the risk CV events and death, independently of the mean BP, particularly in high-risk patients [1,2]. In this analysis of the Valsartan Antihypertensive Long-term Use Evaluation (VALUE) trial, the CV risk associated with increased BP variability was evaluated in patients at different risk levels of baseline CV risk and whether the association was modified by any other factor.

In the VALUE trial, 15,245 patients with hypertension and at least one additional CV risk factor, were randomized to receive amlodipine 5 or 10 mg or valsartan 80 or 160 mg, on top of other BP lowering treatments, in order to reach the BP target of < 140/90 mmHg [3]. The target population for the present analysis consisted of patients without a CV event during the first 6 months of the study, who participated at a minimum of 3 visits from Visit 6 onwards (N=13,803).

The per-protocol population was defined as patients who had ≥3 per-protocol visits, i.e. visits with no pause in the allocated treatment during the 30 days before the visit. The classification of the CV risk was based on the Joint ESC Guidelines for classifying risk [4]. The primary effect variable was the time to the first composite CV endpoint of a cardiac event or stroke.

Main results

  • During a mean follow-up of 4.0 years (SD: 0.8 years), 11.3% of patients had a CV event, 8.6% had a cardiac event, 3.2% a stroke and 0.6% had both a cardiac event and stroke.
  • Compared to patients with the lowest variability, those in the highest quintile of SD had an increased risk of a CV event (HR: 2.1; 95%CI: 1.7–2.4; P<0.0001). The risks of cardiac events and stroke were both increased (HR: 2.3, 95% CI:1.9–2.8; P<0.0001 and HR: 1.5, 95% CI 1.1–2.1; P=0.008, respectively) as were the risks of myocardial infarction (HR: 3.2, 95% CI 2.3–4.3; P<0.0001), congestive heart failure (HR: 3.1, 95% CI 2.2–4.3; P<0.0001), and ischemic stroke (HR: 1.9, 95% CI: 1.3–2.7; P<0.0001), but not hemorrhagic stroke (HR; 0.6, 95% CI: 0.3–1.5; P=0.3).
  • In sensitivity analyses, results were the same, except that the association for stroke was not statistically significant in the per-protocol population.
  • The association between visit-to-visit BP variability and CV events was similar in patients at moderate and very high risk (P for interaction=0.4).
  • There was a significantly increased risk of death (HR: 1.10; 95%CI: 1.04–1.17; P=0.002), equivalent to a 10% increase in risk for 5 mmHg increase in SD of visit-to-visit SBP.
  • Subgroup analyses showed that the association was stronger for younger patients (P for interaction=0.02), and for patients with established CV disease (P for interaction=0.04), as well as for patients with lower BP (P<0.0001).


Patients with hypertension and higher BP variability are at increased risk of CV events as compared with those with low BP variability, irrespective of CV baseline risk. The association is stronger in younger patients, and those with a lower BP.


1. Rothwell PM, Howard SC, Dolan E, et al. Prognostic significance of visit-to-visit variability, maximum systolic blood pressure, and episodic hypertension. Lancet 2010;375:895–905.

2. Muntner P, Whittle J, Lynch AI, et al. Visit-to-visit variability of blood pressure and coronary heart disease, stroke, heart failure, and mortality: a cohort study. Ann Intern Med 2015;163:329–338.

3. Julius S, Kjeldsen SE, Weber M, et al. Outcomes in hypertensive patients at high cardiovascular risk treated with regimens based on valsartan or amlodipine: the VALUE randomised trial. Lancet 2004;363:2022–2031.

4. Piepoli MF, Hoes AW, Agewall S, et al. 2016 European guidelines on cardiovascular disease prevention in clinical practice: the sixth joint task force of the European Society of Cardiology and Other Societies on Cardiovascular Disease Prevention in Clinical Practice. Developed with the special contribution of the European Association for Cardiovascular Prevention & Rehabilitation (EACPR). Eur Heart J 2016;37:2315–2381.

Find this article online at Eur Heart J 2018

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