ME 02-1 IS LOWER REALLY BETTER? ISSUE OF THE J CURVE HYPOTHESIS IN HYPERTENSION

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Abstract

The J curve hypothesis propose that the relation between blood pressure and risk for cardiovascular events is non-linear. Instead of a decreased risk with lower blood pressure, the risk increases at lower blood pressures. This issue has been discussed for many years, and is still a hot topic. The debates have most often had its origin in the question about how far blood pressure should be lowered with antihypertensive drugs.

One one hand, we know that many patients with hypertension is not treated to targets according to guidelines and that this contributes to the high risk for cardiovascular diseases in patients with hypertension. On the other hand, overtreatment could be one reason for the subobtimal effect of antihypertensive drugs on cardiovascular diseases.

The issue about a J curve in the effect of antihypertensive drugs is complicated.

The relation between blood pressure and cardiovascular risk is different for different cardiovascular outcomes. For example, the risk for intracerebral hemorrhage seem to increase steeper at higher blood pressure than for most other outcomes. On the other hand, the risk for abdominal aortic aneurysm increases only modestly with higher blood pressure. In addition, end stage renal disease and cognitive decline could have other relations between blood pressure and risk. Age, cardiovascular disease and diabetes have also been found to modify the relation between risk and outcome.

Earlier this year, we published a meta-analysis of randomized controlled trials with antihypertensive drugs in patients with diabetes mellitus (ref). Included trials had to compare treatment with an antihypertensive drug against placebo, two antihypertensive agents against one or one blood pressure target against another target. The studies were stratified according to blood pressure at randomization (baseline blood pressure), mimicking the situation you as a clinician meet when you decide to recommend a patients additional antihypertensive therapy or not. We contacted authors to receive data from diabetic subgroups in large studies. Thus, we were able to include more studies than in previous systematic reviews in this field. All together, we included data from 49 randomized controlled trials, including 73 738 patients.

The systematic review showed that the effect of antihypertensive drugs on cardiovascular outcomes is different at different blood pressure levels. For most outcomes, adding antihypertensive drugs were beneficial in patients with diabetes mellitus and high blood pressure. However, this benefit decreased with decreasing blood pressure. The risk for cardiovascular death increased when therapy was added in patents with diabetes and systolic blood pressure below 140 mmHg. The benefits of adding antihypertensive treatment at different blood pressure levels are summarized in the figure below.

Thus, in patients with diabetes, the relations between treatment effect of antihypertensive drugs are different at different blood pressure levels. Treatment effects differ for different cardiovascular outcomes. These data question previous guidelines that recommend a systolic blood pressure target below 130 mmHg in patients with diabetes mellitus.

In a very recent systematic review, we have reexamined the relation between randomization blood pressure and cardiovascular stratified for different baseline blood pressures. The meta-analyses include patients with and without diabetes, with and without previous cardiovascular disease etc. Altogether, 58 trials with 290 000 patients were included. The study shows that the effect of blood pressure lowering on cardiovascular outcomes is dependent on baseline systolic blood pressure but also differ between different subsets of patients. This study is under review and the results will be presented during the lecture.

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