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Is BP Variability a Stronger Determinant of CV Outcomes than Mean Pressure?

Is BP Variability a Stronger Determinant of CV Outcomes than Mean Pressure?

The ASCOT-BPLA trial has shown new analyses that variability in blood pressure is a much stronger determinant of both stroke and coronary disease outcome throughout the trial than average blood pressure.

The second paper was published in the March 2010 issue of the Lancet. The post hoc analyses of randomized trials of cardiovascular disease showed that, independent of mean blood pressure, visit-to-visit variability of systolic blood pressure was a stronger predictor of stroke. This subject hadn't been investigated in any large-scale studies. The first large analysis to illustrate this was done by the Lancet Neurology. Their study is quite powerful because it is based on 1.1 million measurements of BP.


Mean BP doesn't have any effects on coronary outcome and it has a very small effect of average BP on stroke. The variation in BP as measured between visits, known as visit-to-visit variability, over a period of five years was by far the strongest predictor of cardiovascular outcomes, despite the fact that within-visit BP variability and variability assessed by 24-hour ambulatory BP monitoring (ABPM) did predict cardiovascular outcomes. 


An entirely new observation was also found in the Lancet Neurology paper, which is the differential effect of drugs on the variability. The study found that calcium-channel blockers (CCBs) cause a reduction in the BP variability, while beta blockers actually increase the BP variability. The differences in stroke and CHD outcomes between atenolol-based and amlodipine-based treatment in ASCOT was completely explained by adjusting for BP variability.


Also published in the Lancet, a separate systemic review and meta-analysis meanwhile found that the greatest reduction in visit-to-visit BP variability is brought about by calcium antagonists and diuretics. Independent from mean systolic blood pressure, they were also associated with the best stroke prevention. The least effective in stroke prevention were the beta blockers, which dose-dependently increased the variability of blood pressure. In this review, ACE inhibitors and angiotensin-receptor blockers (ARBs) had also increased interindividual variation in systolic BP. The CCBs had the strongest effect, which seems to be almost a unique property of this class of drugs.


The analysis also discovered some other interesting findings. Within the trial population, higher BP variability seemed to be associated with diabetes, history of smoking, a prior history or vascular disease, and older age. These are all indicators of stiff blood vessels. The variability could be associated with stiffness, because it is common knowledge that when large vessels become stiff, they indicate future vascular disease. To determine whether the two variables measure the same underlying vascular pathological changes or not, the relation between long-term visit-to-visit variability in blood pressure and arterial stiffness should be studied.


There's a widespread belief in a review accompanying papers in the Lancet that underlying usual blood pressure can alone account for all blood-pressure-related risk of vascular events and for the benefits of antihypertensive drugs. This notion has come to underpin all the major clinical guidelines on diagnosis and treatment of hypertension. Other potentially informative measures have been neglected including variability in clinic blood pressure or maximum blood pressure reached, and the affects of antihypertensive drugs on these measures are still not known.


If somebody in the ASCOT-BPLA analysis had a lower intrapressure and higher variability, he/she was worse off than if he/she had a higher pressure with low variability. This hadn't been considered before. This means that random variations in BP shouldn't be ignored because they are telling something about the risk of the patient. So, if that patient isn't on CCBs, his/her doctor should think about switching to CCBs. This applies mainly to patients with hypertension who are over the age of 55; these patients make up 80% of those with hypertension. CCBs and diuretics are more effective in these patients, and they should be used first, as is mentioned in the British guidelines. However, there seems to be a probability that CCBs are better than diuretics.


These researchers have brought forth compelling findings that could eventually set the foundation for a major change in the practice of blood-pressure treatment for the prevention of cardiovascular diseases including stroke. So, before using drugs associated with low variability in blood pressure, clinicians should consider the case carefully.


Additionally, if the theory of central aortic blood pressure doesn't pan out, the findings may prove to be especially important, or if both can be applied in clinical practice in a complementary manner, particularly if the types of BP-lowering drugs that lower central aortic pressure and blood-pressure variability are from the same class or classes.


Many professionals believe that clinic blood pressure accounts for most of the risk and for the benefits of antihypertensive drugs. The new evidences make a strong argument for also measuring blood-pressure variability because it supplements blood pressure very well as a risk factor, however, they don't question the importance of mean blood pressure.


If there's no other compelling indication, most hypertension guidelines today recommend avoiding the use of beta blockers. This recommendation is stressed by the new analyses, and they might prompt reconsideration by those who keep beta blocker as the first-line treatment option. Nevertheless, to better characterize the effects of different classes of antihypertensive drugs on long-term blood-pressure variability, more studies are needed.

Prepared By: Dr. Mehyar Al-Khashroum
Edited By: Miss Araz Kahvedjian

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