Are you ready for some more uncertainty about blood pressure treatment?

Decisions about blood pressure have gotten more difficult over the past couple of years as experts in the U.S. have failed to reach consensus on recommendations about when drug therapy should be started. Now there's new evidence that could make the decisions even more challenging.

Let's review first where there is agreement. Around the world, high blood pressure causes a lot of harm. Your risk of health problems — such as heart disease, stroke and kidney disease — increases with higher blood pressure. Your lifestyle can influence your blood pressure. A healthful diet, at least moderate physical activity and weight control can bring down your blood pressure. Those are good habits for everyone, in fact.

Medicines can help reduce the risk for people with higher blood pressure, say 150 millimeters of mercury and above for systolic pressure, the top number. Too many people have untreated and uncontrolled marked elevations of blood pressure and many devastating health problems could be prevented if we could help people get proper treatment.

What about medicines for people whose blood pressure is high but less than 150? Most doctors agree that people younger than 60 would do well to keep their blood pressure less than 140. The consensus is that the benefit of drugs for those who didn't respond to lifestyle changes exceeds the risks of treatment.

Some believe that for older patients, who may be more sensitive to medications, the recommendations should be more permissive and not push for treatment that brings blood pressure below 140. Then there's the SPRINT trial, whose results were released last November and suggested that people without diabetes, even older people, would benefit by seeking to get their blood pressure down to around 120.

Another study, called HOPE-3 for short, added important evidence about the treatment of blood pressure that will further unsettle the field. The findings were published April 2 by in The New England Journal of Medicine.

The researchers in the study randomized 12,705 people with at least one cardiovascular risk factor (like high cholesterol) to get blood pressure medication or placebo. At the time of randomization, the average systolic blood pressure was 138. Some people's pressures were higher and some were lower, or course. In fact, a third of the people had a beginning blood pressure less than 132.

So what did HOPE-3 find? The blood pressure medications worked. Study participants in the group that got blood pressure medicine had their systolic blood pressure lowered about 6 points more than those in the placebo group. However, after almost six years of follow-up, the investigators determined that lower blood pressure didn't translate into lower risk. The risks of death from cardiovascular causes, heart attacks, strokes and other problems weren't different between the groups.

The investigators explored the data further and found some evidence that the group in the highest third of blood pressure at the start (an average top number of 154) seemed to have a lower risk, while the group in the lowest third at the start (average of 122) seemed to do worse. These analyses were planned at the outset of the study, so we tend to give them a bit more weight.

So what happened?

HOPE-3 used common antihypertensive medications, an angiotensin receptor blocker called candesartan and a diuretic called hydrochlorothiazide. Could the results be explained by something about these medications?

Participants in the study had an average age of 65 years, about half were women, a quarter were smokers and almost all were overweight. Was there something special about them?

Or could it be that pushing blood pressure to ever-lower levels, even in a group at modest risk of heart disease and stroke, is just not producing benefit?

We don't know for sure.

The field is waiting eagerly for the next version of national guidelines about blood pressure. A group of experts in the field will look at all the evidence and give its opinion about whom to treat and when.

But how useful will general guidelines be for individual patients, given the conflicting evidence? How confidently will the experts be able to recommend strategies for people in the middle range of blood pressure?

The ultimate decision about treatment for each person should be informed by the fact that a definitive benefit hasn't been consistently shown for lowering blood pressure below 140 in people without known disease (we call this primary prevention). The results of the HOPE-3 indicate that the lower your blood pressure is, the less likely you are to benefit from starting drug therapy.

As always, if your blood pressure is in the range where there is controversy and you want to lower your blood pressure, your best first move is to adopt a healthful lifestyle and see what happens — and, of course, talk with your physician. Meanwhile, experts will be poring over the recent studies to try to reconcile the disparate results.

In medicine, we like it when the latest data bring clarity to personal decisions about treatments. But the reality is that studies often go in different directions and leave us even more uncertain about what to do next. That uncertainty, though, is still important information as you consider your options.

The disappointing conclusion about blood pressure is that we need more studies and more evidence. We also need better evidence — information that is more precise about what is likely to happen to us personally if we take medications for blood pressure.

We need to move faster to get the knowledge that is attuned to our personal characteristics and that can guide our decisions about the blood pressure number that's best and also the drug that would work best for each of us, if we need one. This is the hope of President Obama's Precision Medicine Initiative. Given the mixed evidence we have, this new era of knowledge cannot come fast enough.

Harlan Krumholz is a cardiologist and the Harold H. Hines Jr. Professor of Medicine at Yale School of Medicine. He directs the Yale-New Haven Hospital Center for Outcomes Research and Evaluation and is a co-director of the Robert Wood Johnson Foundation Clinical Scholars Program.

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