https://immattersacp.org/archives/2014/04/hypertension.htm

For hypertension, how low to go?

Updated blood pressure guidelines may have created more questions than closure, internists have found, as they try to determine how aggressively to treat the condition and what goals to set for subpopulations of patients, such as those with diabetes. Experts react to the “paradigm shift” in lowering hypertension.


After years of waiting for updated blood pressure guidelines, doctors must now sort through a thicket of recent recommendations and some related controversy regarding when and how patients should be treated.

The long-awaited JNC 8 guidelines, compiled by panel members appointed to the Eighth Joint National Committee and published online Dec. 18, 2013, in the Journal of the American Medical Association, consolidated 9 recommendations regarding hypertension, which government statistics show impacts 29% of U.S. adults. That same month, the American Society of Hypertension (ASH) and the International Society of Hypertension (ISH) released their own set of management guidelines in the Journal of Clinical Hypertension. Also last year, 2 European societies teamed up to publish their own guidance.

From left Befikir Astil MD a PGY-2 resident and ACP ResidentslashFellow Member and James W Reed MD MACP a professor of medicine and chief of the medical service at Grady Memorial Hospital for the
(From left) Befikir Astil, MD, a PGY-2 resident and ACP Resident/Fellow Member, and James W. Reed, MD, MACP, a professor of medicine and chief of the medical service at Grady Memorial Hospital for the Morehouse School of Medicine in Atlanta, consult with Krystal Green about hypertension. Photo by Julius Grimes/KreativTouch Photography

To date, the bulk of the post-publication debate has involved how aggressively to treat mild hypertension. The guidelines published in JAMA adopt a more liberal approach, resetting the systolic treatment threshold in adults ages 60 and older from the 140 mm Hg recommended by JNC 7 to 150 mm Hg. The authors, who cite the lack of randomized evidence showing much cardiovascular payoff below 150 mm Hg, also note that no changes are needed for patients doing well on existing drugs.

That guidance represents “a paradigm shift” regarding mild hypertension treatment, said Harlan Krumholz, MD, a cardiologist who directs the Yale-New Haven Hospital Center for Outcomes Research and Evaluation in Connecticut. “It's a recognition that we don't really have the strength of trial evidence to impose the kind of thresholds that we've ordinarily accepted and disseminated,” he said. “That certainly doesn't mean that there's not benefit, but it also means we don't have definitive evidence of benefit either.”

Meanwhile, the recent ASH/ISH guidelines reaffirm the traditional threshold of 140/90 mm Hg. And some doctors worry about throttling back at all on blood pressure control. “I think that they [the JNC 8 panel authors] are sending a message that as long as the blood pressure is under 150, it's fine,” said James W. Reed, MD, MACP, a professor of medicine and chief of endocrinology and metabolism at Morehouse School of Medicine and chief of the medical service at Grady Memorial Hospital in Atlanta.

“I don't think that that's the message that you want to send,” he said. “I don't find that very helpful in trying to control one of the fastest-growing diseases we have in the world.”

The 150 mm Hg debate

Both the JNC 8 panel guidelines and the ASH/ISH guidelines agree on a diastolic goal, directing that the lower reading should be maintained below 90 mm Hg. But the ASH/ISH guidelines reiterate that the traditional systolic guardrail of 140 mm Hg should remain firm, with the possible exception of using 150 mm Hg in frail adults age 80 and older.

The JNC 8 guidelines also faced public criticism from a subset of panel members. A titled “minority view” published online Jan. 14 by Annals of Internal Medicine said that the new systolic threshold will leave many older high-risk individuals, such as black patients and those with heart disease, more vulnerable and would unravel advances made in reducing cardiovascular disease, particularly stroke.

During guideline deliberations, that group of panel members was never comfortable with the 150/90 threshold, but it was the most appropriate given the randomized evidence, said Raymond Townsend, MD, a JAMA author who directs the Penn Hypertension program at the University of Pennsylvania in Philadelphia.

“When push came to shove and we had to say something about blood pressure goals, we really couldn't defend the 140/90,” said Dr. Townsend, noting that all of the recommendations were looked at by 16 external reviewers and 5 federal agencies prior to their JAMA submission.

“No one challenged us to say that this is wrong,” he said, regarding the proposed 150 mm Hg. “They didn't like it. But they could not come up with a reason why it's wrong.”

The 150 mm Hg recommendation was influenced in part by the real-life implications of doctors pushing too hard for lower readings, Dr. Townsend said. “If you try to knock the pressure down from 146 to 138 with a fourth, fifth or sixth antihypertensive drug, you can't demonstrate to me benefit from that,” he said. “But you sure can demonstrate a lot of potential adverse effects from more medication.”

The treatment conundrum stems from a disconnect between the epidemiological evidence and what drug studies have shown to date, Dr. Krumholz said. While epidemiologic studies have found that people with naturally lower blood pressure are less vulnerable to cardiac disease, it's been more difficult to illustrate that using drugs to achieve those lower readings has similar cardiovascular benefit, he said.

As one example, Dr. Krumholz cited the large-scale ACCORD (Action to Control Cardiovascular Risk in Diabetes) trial, in which treating adults with type 2 diabetes to a systolic level of below 120 mm Hg provided no benefit over a less aggressive target of 140 mm Hg. “That's given people pause about saying, ‘Gee, I can equate lowering blood pressure with lowering risk,’” he said.

But the authors of the Annals critique worry about the cardiovascular damage that could result from a less stringent approach. They point out that the average systolic reading, based on data from the National Health and Nutrition Examination Survey, is 136 mm Hg for adults age 60 and older getting treatment, far below the recommended JAMA threshold.

The treatment conundrum in hypertension stems from a disconnect between the epidemiological evidence and what drug studies have shown to date said Harlan Krumholz MD Photo by iStock
The treatment conundrum in hypertension stems from a disconnect between the epidemiological evidence and what drug studies have shown to date, said Harlan Krumholz, MD. Photo by iStock

Among individuals older than 60 not taking drugs, the median systolic blood pressure is 152 mm Hg, which indicates that roughly half of older adults wouldn't require medication under the new criteria, said Jackson Wright Jr., MD, PhD, FACP, the lead Annals author. Among individuals greater than age 60 under treatment, the median systolic blood pressure is 134 mm Hg, suggesting that it would be appropriate to reduce treatment in these high-risk individuals. He plans to continue to focus on achieving a systolic goal of less than 140 mm Hg for nearly all of the patients he treats, with the possible exception of frail elderly patients age 80 and older.

“We have grave concerns about backing off on treatment and suggest that there is a real possibility of causing harm in patients who are treated to 150 versus 140,” said Dr. Wright, who also directs the clinical hypertension program at University Hospitals Case Medical Center in Cleveland.

Other guidance

The JNC 8 panel, convened in 2008 by the National Heart, Lung and Blood Institute (NHLBI), only reviewed randomized controlled studies in reaching its recommendations. (The prior panel's guidelines, JNC 7, were published in 2003.) In mid-2013, the federal agency announced that it would withdraw from developing guidelines. In JAMA, the panel members said that they had decided to pursue independent publication to get their findings out but stressed that the report is not sanctioned by the NHLBI.

The JNC 8 panel confined its evidence review to randomized trials with more than 100 participants; its recommendations were graded accordingly based upon the evidence. The ASH/ISH authors didn't perform a similar review, instead describing their guidelines as a “broad statement on the management of hypertension.”

The guidelines from the JNC 8 panel also incorporated some expert opinion. For example, the controversial new 150/90 mm Hg threshold for older adults was given the strongest evidentiary grade of A. But the corollary recommendation not to change drug management in patients doing well on their existing regimen was graded E, indicating that it was based on expert opinion.

They also based another recommendation, to reaffirm the 140/90 mm Hg threshold in adults under age 60, on expert opinion. There is insufficient randomized evidence in that age group to support a specific systolic goal, they wrote. Plus, diastolic studies have determined that reducing a patient's lower reading below 90 mm Hg is likely also to result in a systolic decline to below 140 mm Hg, they wrote.

Younger patients diagnosed with rising blood pressure must weigh several factors as they consider if and when to start medication, Dr. Krumholz said. While those adults face more years of heart and stroke risk, they also could be taking medication for potentially decades, with the related risks of side effects. “I do have concerns about lifelong therapy,” he said.

Other treatment guidance from the JNC 8 panel's guidelines includes the following:

  • For adults with diabetes or chronic kidney disease, the JAMA authors recommend a treatment threshold of 140/90 mm Hg. Those figures were based on expert opinion, in light of insufficient randomized evidence. The ASH/ISH guidelines adopt the same benchmark, stating that while some prior guidelines recommended 130/80 mm Hg, the “clinical benefits of this lower target have not been established.”
  • For initial hypertension treatment, several drug classes were recommended in non-black patients, including those with diabetes: a thiazide-type diuretic, calcium-channel blocker, angiotensin-converting enzyme (ACE) inhibitor or angiotensin-receptor blocker. (Evidence grade: B.) The guidelines discourage the use of beta-blockers as a first-line drug, citing 1 study finding that the class was associated with a higher risk of heart attack and stroke.
  • Specifically in black patients, the initial use of a thiazide-type diuretic or a calcium-channel blocker was recommended rather than an ACE inhibitor. (The evidence was graded a C for black patients with diabetes and a B for black patients overall.)

The authors said that the move away from an ACE inhibitor in black patients was based on the findings in a subgroup of black patients (diabetics and non-diabetics) in the large-scale ALLHAT (Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial), in which a thiazide-type diuretic provided more cardiovascular protection compared to an ACE inhibitor.

But Dr. Reed said such a race-based distinction is not justified, given the protective effects of ACE inhibitors against kidney complications. He takes sharp issue with many of the recommendations published in JAMA. “The primary reason we use ACE inhibitors is we know what effect they have on renal failure,” he said, pointing to the vulnerability of black diabetics to this disorder.

The higher systolic threshold also could lead to inadequate treatment for older black patients in general, said Dr. Reed, a concern that was reiterated in the Annals critique. Although the JNC 8 panel's recommendations exclude older adults with diabetes or chronic kidney disease from the higher systolic threshold, the Annals authors wrote, that still leaves many high-risk patients vulnerable to less blood pressure control, including black patients and those with other risk factors, such as heart disease.

The sometimes conflicting guidelines also may erode a unified blood pressure management approach, Dr. Reed said. Where the various recommendations diverge, “it depends upon which ones the practicing physician is going to buy into,” he said. “I think it's just going to cause more confusion.”

Clinical applications

Prior to the JNC 8 panel's guidelines, some primary care doctors were already pulling back a bit on medication in older patients, particularly if they were worried about their vulnerability to dizziness and falling, said Fred Ralston Jr., MD, MACP, a general internist practicing in Fayetteville, Tenn., and a former president of ACP.

But the guidelines provide some clinical flexibility to push more for lifestyle changes first, particularly more exercise in younger patients, Dr. Ralston said. If a patient has mild hypertension but cholesterol and other heart risk factors that aren't worrisome, “I'll be much more likely to focus on exercise. If other risk factors are present I'll be more inclined to consider medication or at least earlier follow-up.”

Doctors should use the latest guidelines and related debate as an opportunity to have a frank conversation with patients, Dr. Krumholz said. “It's wrong to impose a one-size-fits-all on any of this, especially when there is some uncertainty around the evidence,” he said.

Some patients with mild hypertension will jump at any step that could potentially lower their heart attack or stroke risk, while others may be wary of medication. Either choice is reasonable, Dr. Krumholz said. A key part of that conversation, he said, “is giving them permission to make a choice that may not be the same choice that the doctor would make.”

One rare source of agreement is the need for more randomized trials. In that regard, the Systolic Blood Pressure Intervention Trial (SPRINT) will provide some badly needed insight into whether less than 140 mm Hg or 120 mm Hg is a better target for nondiabetic adults age 50 or older, Dr. Townsend said. Dr. Townsend couldn't cite another randomized study in the works that would distinguish what he's dubbed another “gray zone”—the relative benefits of treating to 140 mm Hg versus 150 mm Hg.

And SPRINT, launched in 2010, is not projected to be completed until 2018.