Wednesday, July 07, 2010

Treatment-targets in hypertension

We have to congratulate Rhonda Cooper-DeHoff and her co-authors on their recent article in the Journal of the American Medical Association on: "Tight blood pressure control and cardiovascular outcomes among hypertensive patients with diabetes and coronary artery disease" reporting a sub-group analysis from the INVEST study.

This adds another sub-group analysis to the long discussion about the "J"-curve found in blood pressure vs. cardiovascular out-comes in hypertension studies. See, for example, this review by Alberto Zanchetti and co-workers from 2009. Similar results were found in the ONTARGET and VALUE and TNT trials. In all these trials the risk of a cardiovascular end-point starts to increase when pressure goes below 120 mmHg. Which also holds true for the INVEST trial. One important new point is that in the INVEST trial the all-cause-mortality - the first among equals of end-points - also increases with lowered systolic blood pressure. Although it is only significantly increased at pressures lower than 110 mmHg the trend is increasing already from 130 mmHg.

An important point is that all these trials concern the treatment of high risk patients. An untreated systolic blood pressure between 120 and 130 mmHg is rather considered pre-hypertension and is associated with increased risk, and will probably be indicated for treatment once the proper trials have been done. However, if you are a patient with hypertension, diabetes and coronary artery disease there is more and more evidence indicating that your pressure should be lowered with moderation.

What the field still lacks is a randomised controlled study where patients are randomised to either systolic blood pressure below 130 mmHg or between 130 and 140 mmHg. Before that there is no certain way of distinguishing the ability to get below 130mmHg from the intent to lower blood pressure below 130mmHg. That is, if there are, for example, a population of more pressure-labile patients that are at higher risk or if there is some other uncontrolled reason for this larger risk.

While some guidelines are lagging a little, the core result was known at least a year ago, and is reflected in the 2009 guidelines from the European Society of Hypertension where the target for diabetic patients have been adjusted upwards to higher than 130 and lower than 140 mmHg.

The next question is: "Why is this so?"

What happens with in high risk patients with serious co-morbidities that makes them vulnerable to aggressive lowering of blood pressure? I think it has to do partly with changes in the microvasculature that adapts the circulatory system to higher pressures, i.e. remodeling and hypertrophy; and partly with end-organ damage in the form of fibrosis and reduced capillary density making an increased capillary pressure important for a sufficient fluid and nutrient exchange over the capillary walls.

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