COMMENTARY

Controversies in Hypertension: The Impact of Age in Hypertension Care

Henry R. Black, MD

Disclosures

January 12, 2016

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Editor's Note: Henry R. Black, MD, discusses the role of age in the management of hypertension with Joseph L. Izzo Jr, MD, Professor of Medicine; Department of Medicine, State University of New York at Buffalo

Henry R. Black, MD: Hi. I'm Dr Henry Black. I'm an adjunct professor of medicine at the Langone New York University School of Medicine, and I'm here today with my friend and colleague, Dr Joe Izzo.

Joseph L. Izzo Jr, MD: I'm Joe Izzo. I'm professor of medicine at the University of Buffalo and chief of medicine at the Erie County Medical Center in Buffalo.

Controversies in Hypertension

Dr Black: We've worked together on many things over the year —JNC 7[1]—and now you're starting a series called "Controversies in Hypertension."[2] What's that all about?

Dr Izzo: It's a feature of the Journal of the American Society of Hypertension that seeks to fill in the gaps, meaning there are many areas where we don't have black-and-white information, and we rely on expert opinion to figure out what to do. In fact, most questions in medicine would fall into that category.

How Old Is Old?

Dr Black: What in particular are you focusing on first?

Dr Izzo: Our first article has to do with the impact of age in blood pressure care. The format is that there is an introduction followed by two opinions that need not be diametrically opposed but which diverge in important ways. The idea is to really get people thinking.

Dr Black: I used to say that anybody 15 years older than I am was old. I don't say that anymore, of course, since I am now in that group. How do you define older age? What do you select? Is there a difference in how you treat people who are older compared with younger? Where's the cut point?

Dr Izzo: Well, if we step back for a minute—let's just look at current guidelines, and we can compare among European and North American guidelines. The general approach has been that age really does matter, and that one can dichotomize populations at some arbitrary middle age, 55 or 60 years. Thereafter, we treat in a right-handed way for people over this threshold, and in a left-handed way for people under. This is preposterous.

Dr Black: It makes no sense. We don't become old when we go from 55 to 56, or from 60 to 61. So what do we do?

Dr Izzo: This is, of course, a real issue, because at the extremes of age there may be differences. For my money, it's really the concept of frailty in older people. And also comorbidities, which are, of course, more prevalent. Those are what dictate the treatment, not something that we impute for hypertension that isn't real in the first place.

Dr Black: If you used the Framingham Heart Score, most points come as you get older and make you a high-risk individual.

Dr Izzo: Yes, but how does high risk affect what you do for blood pressure? You still should lower it to the most reasonable number for a particular patient. That's where the controversy comes in. What's a reasonable number?

Dr Black: SPRINT[3] puts a new look on this. SPRINT was supposed to look at people who were not covered in ACCORD,[4,5] which was all about diabetics. You couldn't be in the SPRINT trial if you had diabetes. So what did SPRINT teach us?

Dr Izzo: The comparison between SPRINT and ACCORD is inevitable. And, of course, the message that most people took home from ACCORD is, it doesn't matter.

Dr Black: They took home the wrong message—that you don't have to be aggressive.

Dr Izzo: That's right.

Dr Black: And 150 mm Hg was a number that the so-called JNC 8[6] decided to use. There was no reason to pick 150 mm Hg.

Dr Izzo: None whatever. That's purely opinion in a document that the authors called "evidence-based." What folly.

What's Evidence in Evidence-Based Medicine?

Dr Black: I'm not a big fan of evidence-based medicine because we usually don't have reliable evidence to decide what to do in the usual patient. Are you a fan of evidence-based medicine?

Dr Izzo: Well, if you define evidence as the totality of information that one could bring to bear on a particular point, then I'm in favor of evidence-based medicine. But that's not what's being done today. We can only look at clinical trials, or so say the putative experts in the field. And if you take a look at that JNC 8 writing group product, they only cited a handful of clinical trials instead of looking at the entire literature.

Dr Black: Well, of all the trials looked at, there were only eight that they considered good. None were considered excellent. As a veteran of SHEP[7] and ALLHAT,[8] it's pretty hard to say that the individual you're treating in front of you would've qualified for those trials. And certainly we don't know what happens after that.

Dr Izzo: And then we get into the concept of: Is the absence of evidence, evidence of absence of effect of a drug? Absolutely not. But the take-home message for the less sophisticated reader might be that it doesn't matter, like ACCORD. And then if we don't have any evidence, guideline writers may just throw in their opinion, which is what happened in JNC 8. It also happened in the NICE guidelines in Britain. It also happened to a degree in the European Society of Hypertension,[9] and then in another writing group representing the American Society and the International Society of Hypertension.[10] Where did we get these numbers, 55 or 60? They're ridiculous.

Dr Black: So, what would you do?

Dr Izzo: For me, as always, there has to be this richness of base of information. Do we know a scientific mechanism well enough that it's really not controversial? Two: Do we have epidemiologic evidence? Three: Do we have other types of clinical studies? In this case, it's pharmaceutical development studies to get to points related to whether drug A works in older people or drug B in younger people. And the answer is, we did have that information. Instead of looking at any of that, the ridiculous rules set forth by the NHLBI for evidence-based guidelines really handcuffed the writers of that document and forced them into a position where they had to make statements that are just plain silly.

Dr Black: I bristle at the term "personalized medicine," using genetics to do that. We've been doing that as long as we've had epidemiology. We pick certain groups that seem to be at high risk as opposed to others. You don't need genes or DNA to tell you that. We have enough epidemiologic evidence to tell us.

Dr Izzo: Not in our business. I think there are genetic businesses. Certain cancers are definitively genetic. Cholesterol management has got a genetic piece to it. Not hypertension [management].

Measuring Blood Pressure

Dr Black: If you were to evaluate a patient now, an older patient—you could pick the age you want to consider "older"—what would you do in your initial evaluation of that individual?

Dr Izzo: That's different from a younger person?

Dr Black: Or maybe you don't even need to consider age; if you measure the blood pressure, you just treat them without doing any evaluation.

Dr Izzo: And measure the blood pressure accurately. And recognize that there's increased blood pressure variability in the older people, meaning that we better have nonoffice readings and competent office readings of blood pressure, too. Then the clinician has to triangulate between those two numbers.

Dr Black: So should we do what the British have done and do ambulatory blood pressure monitoring on everybody that we think is hypertensive?

Dr Izzo: The Canadians are trying to do [that], too. In the ideal world? Maybe so. And I'm in favor of these self-actuated blood pressure readings in a medical office where there is no provider involved, because that alerting reaction and the conditioned response—the white coat effect—really clouds everything we do. I think probably 25% of the people entered into the drug development studies only had white coat hypertension in the first place, and that doesn't respond to therapy. So we have a clouded opinion of what the drugs do.

Dr Black: But then you have masked hypertension, something we realize is much more common than we used to think.

Dr Izzo: Maybe, maybe not.

Dr Black: What do you think?

Dr Izzo: In the studies I did, we looked at 10,000 ambulatory tracings. In the lower blood pressure ranges, below 140 mm Hg, you'll see a tendency for the home blood pressures to exceed those measured in the physicians' office. In the people over 140 mm Hg, it goes the other way. And now the higher the ambient blood pressure, the greater the white coat effect. So for me, masked hypertension doesn't mean very much.

Dr Black: So you can't necessarily feel reassured if your blood pressure is okay at home because it might be high somewhere else?

Dr Izzo: Well, it could, but then how is the white coat effect generalized? I don't think there are very good studies of this. The risk attendant to the white coat effect is fairly marginal compared with the risk, let's say, of 24-hour ambulatory pressure. That's a more precise determination. You've got multiple numbers with the advantage of having a mean, a more stable number. And I think what drives the long-term decision-making is having enough numbers, and also recognizing these variations and divergences. But what does it need? It needs expert interpretation.

Dr Black: It isn't the number, it's the interpretation. There are some studies that show that if you measure it at home, measure it with an accurate machine, you need 24 to 28 numbers over a 2-week period. That gives you a good sense of the mean. Now, when we send people home to measure their blood pressure, it's usually once. It's certainly not going to be for 2 weeks. And then you bring the numbers in, and then they've got to be interpreted. Just having the number doesn't cut it with me.

Dr Izzo: Sure. And then you've got to take the time to do the mean. You have to then look at the mean in the context of the total variation of the pressure. We've not set up systems to do that.

The Salt Problem

Dr Black: One thing that's happened in this city, in New York City, is that we're finally printing sodium levels in food. This is the key nutrient when it comes to blood pressure. It's not the fat. It's not something else. It's the amount of sodium in the food.

Dr Izzo: You really believe that?

Dr Black: I think it depends. We see very few people who really eat tremendous amounts of salt, but it's nice to know, because you can make a choice as an individual. I think there are old studies by Henkin[11] that showed that if you cut the salt down, within a month, foods that you used to like taste much too salty. And you can—

Dr Izzo: Well, that's true. But this whole concept of salt sensitivity has gotten lost in the shuffle. It's real. There are salt-sensitive people. We don't know whether we can reset our "saltastat," but I won't dispute your comment that we can do better with lowering salt. When you take resistant hypertensives, though, the people who get the most advice (and often the worst advice)—lowering salt intake in those people doesn't necessarily have much impact at all on blood pressure.

Treatment

Dr Black: What about treatment? Do you start with one drug? Do you start with two drugs? What's your goal of treatment?

Dr Izzo: Well, you know me. I start with two drugs. I don't fool around. I don't titrate drugs, except for, in a way, diuretics. And beta-blockers in people who have questions about cardiac performance. But when it comes to drugs like RAS blockers, meaning ACE inhibitors, ARBs—I won't call spironolactone a RAS blocker—but drugs like that, there's no reason not to start it at full dose.

Dr Black: All they do is have a longer duration of action. They're not necessarily more effective; they just work for a longer time.

Dr Izzo: I think that's right.

Dr Black: The older ones, anyway.

Dr Izzo: Flatter dose response—amlodipine's another drug that I use extensively and generally starting at a mid-range of about 5 mg.

A 75-Year-Old Patient

Dr Black: So, what's your advice to a patient or to a referring physician about an elderly individual? I'll give you an example. I'll make them 75, so they're elderly by most anybody's criteria. They come in to you; they have no complaints. You have routine tests which show that electrolytes are normal, renal function has an eGFR. We'll talk about the value of that, of, say, 55 mL/min/1.73 m2.

Dr Izzo: You want to raise my blood pressure, don't you?

Dr Black: What else do you do? How do you evaluate them? Where do you start?

Dr Izzo: You've also opened the door by using 75 years, of course. Given these SPRINT results that I suspect we'll get back to, honestly, I don't treat them very differently than I would somebody under 75 or under 50. There are minimal trends toward reduced effectiveness of RAS blockers in older people. The way it's been presented—and the British were the first to make this mistake—is that an older person, 56 years and beyond, doesn't respond to a RAS blocker. That's not true. In fact, there are several drug development studies,[12] mine included, that prove the point. Now, diuretics and CCBs are not ineffective in younger people, either.

Dr Black: Right.

High or Low Renin

Dr Izzo: I'll buy the race thing a little bit. It is true that the magnitude of the response to a CCB or a diuretic is greater than to a RAS blocker, but we're only talking about a few millimeters on average. And there are many people of both races who respond equally well to either side of the equation—the one side being the diuretic or the CCB for the "low-renin hypertensive," and the other side being the RAS blocker for the "high renin" type hypertensive.

Dr Black: So you would never bother to characterize somebody as low or high renin. I never did.

Dr Izzo: No. The functional response to the drug does it for me. So if the blood pressure drops like a stone on a RAS blocker, that is a high-renin person. But you're absolutely right: There's no reason to measure plasma renin activity.

Heart Failure as an Endpoint -- The Difference Between SPRINT and ACCORD

Dr Black: What about further cardiac tests? Heart failure is something that was measured in SPRINT that had never been considered an endpoint before. Why is it now?

Dr Izzo: Well, not in the blood pressure trials as much. And if you compare SPRINT to ACCORD, my supposition is that the real difference between the two studies is the fact that the composite endpoint in SPRINT included heart failure, and in ACCORD it did not. Going back, even to your famous SHEP study, what was the biggest impact?

Dr Black: On stroke.

Dr Izzo: Well, it was heart failure, too.

Dr Black: Heart failure was there, but stroke was our primary endpoint.

Dr Izzo: That's right. But if you look at the magnitude of the fall, fewer endpoints, mind you, but a greater potential benefit if you were at risk for heart failure. I think that's exactly what happened between ACCORD and SPRINT, one even mentioned by the authors.

Planning the Studies: Inclusion or Noninclusion of Heart Failure?

Dr Black: One of the things you point out, which is clear to me, is that the planning of a study, certainly of that magnitude and time and expense, has to be so careful. And it's usually not vetted by the right people before you actually start working on it.

Dr Izzo: I couldn't agree more. And this whole business of inclusion or non-inclusion of heart failure has plagued a number of cardiovascular studies and has really caused consternation and lack of clarity in what to do.

To get back to your question about older people: "At 75, are they at greater risk for heart failure?" Yes, they are, particularly for preserved ejection fraction heart failure with sudden decompensations. Now, those people don't die; they just get rehospitalized.

What can we do to prevent that? I don't think we know enough about that, but I think we can guess that that's a group that can and should be targeted, and treated effectively à la SPRINT.

What did the SPRINT people get? They got a lot of diuretics. They got RAS blockers that they might not otherwise have gotten, and then any other agent that the investigators wanted to use.

When you boil it down, that more effective therapy that is lowering the blood pressure also included other potential protective effects, at least in the minds of some people, like ACE inhibitors and coronary artery disease. I don't think it's clear yet whether that's a blood pressure effect.

Dr Black: They compared a goal, not a regimen, and half of the people didn't get under 120 mm Hg, but that group still had benefit.

Expert Opinion and Patient Preference

Dr Black: This virtual patient I described—how often do you see them? What goal are you shooting for? These are things for which we have no idea what to do.

Dr Izzo: That's right. And so we're back to expert opinion. Now, I will grudgingly admit that you're an expert in this business.

Dr Black: And so are you.

Dr Izzo: Thank you.

But in any case, I think there's also something that's completely missing from all of these equations. And that is the doctor-patient relationship, the trust that the patient has in the doctor, the patient preferences that come in. And what you do and what I do is, we work with the people. If you look at the decisions that are made, a large percentage of what we do is not just a number—blood pressure—it's an assessment of the context in which drugs are used, taking into account anomalies that are peculiar to particular patients as well as their preferences.

Electronic Medical Records and Spending Time With Patients

Dr Black: One of the things that's aggravating me, and I'm sure you, is electronic medical records, where you don't talk to the patient any longer; you're talking to the computer. So whatever relationship you might have...

Dr Izzo: When I see the ophthalmologist, it's like this [mimics typing at a computer] and I'm over there [points away].

Dr Black: There are certainly benefits to having access to electronic records for background, but not when you're individually talking to the patient. But if you don't do any notes until everybody's left, you're going to be up until 11:00 at night every night, filling in things, and you don't necessarily remember the difference from patients after a while.

Dr Izzo: No, that's absolutely correct. That's been true pretty much from the beginning, but I think it's worse now, and it drives the patient away from the physician. The other thing is really just time. Eyeball-to-eyeball time. I'm in a unique situation where I can spend as much time as I want with a patient.

Dr Black: How did that happen?

Dr Izzo: Well, I'm subsidized as a professor, and I do my clinical work with people who have been basically passed off by other doctors. Two, three, four doctors. So it takes time to get into these situations.

The Nonadherence Issue

Dr Black: One of the things that we found in several situations is that the nonadherence issue for individuals that we saw was much lower than it is in a primary care situation, because individuals who've gone to the trouble of seeing a specialist are much more likely to listen to them, at least in my opinion.

Dr Izzo: I don't have any adherence problems. And it's easy to figure out who is nonadherent. All you've got to do is look them in the eye and say something like, "Can you really take all of these medications?" I don't think many people lie about it.

Dr Black: When Sackett and Haynes[13] studied this, the one thing we could rely on is that if you asked the patient, "Are you taking your pills?" and they say no, that's probably right. If they say yes, it's not right at all.

Dr Izzo: I'm not so cynical about that one. I think it's easy to draw people out if you know a few simple tricks. Do they trust you, for one. Do they think you're going to put a value judgment on them? If you don't project that on a patient, they're going to open up to you.

Dr Black: We have to be nonjudgmental always.

Upcoming Topics for Controversies in Hypertension

Dr Black: So, what's your next topic for Controversies in Hypertension?

Dr Izzo: We've got a bunch that I think are interesting. And, again, we're looking for real problems that doctors face. We're also looking for scientific issues. One of them, for example, is going to be on renal denervation. We don't have the final word on that.

Another is, what's the appropriate diuretic for somebody with modest renal impairment? And there's still an argument for thiazides that most people don't know about.

We're in the process of recruiting others for a variety of questions like this, and we hope to just get people talking and thinking about the issues. It's not something we'll solve in our lifetimes, or ever, with standard clinical trial information, which covers—what—1% of the decisions a doctor has to make in a day?

Dr Black: Joe, thank you very much for very insightful things. I look forward to these. And I'll probably actually read them. Thank you.

Dr Izzo: Thank you very much.

Disclosures: Dr Izzo has disclosed the following relevant financial relationships: None.

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