Elizabeth Tracey: How does high blood pressure when you’re young impact on cardiovascular outcomes?
Rick Lange, MD: Can a single blood test provide prognosis in people with coronary artery disease?
Elizabeth: Rather startling news about cases of gonorrhea.
Rick: We recommend low sodium for people with heart failure. Is there good evidence for that?
Elizabeth: That’s what we’re talking about this week on PodMed TT, your weekly look at the medical headlines from Texas Tech University Health Sciences Center in El Paso. I’m Elizabeth Tracey, a medical journalist at Johns Hopkins, and this will be posted on November 9th, 2018.
Rick: And I’m Rick Lange, President of the Texas Tech University Health Sciences Center in El Paso and Dean of the Paul L. Foster School of Medicine.
Elizabeth: Rick, in recognition of the fact that the American Heart Association conference is going on, why don’t we turn first to the Journal of the American Medical Association. We’re going to treat two studies together, taking a look at what I served up as, “Wow, what happens if you have high blood pressure early in your lifetime with regard to cardiovascular outcomes?” One of these is a truly gigantic study that was conducted in Korea — a study population of almost 2.5 million participants with a mean age of 31 years, and they also were able to measure blood pressure in these people two times during the study period from 2002 through 2005.
They took a look at what happens among these people, those that we’re going to classify as having hypertension, either stage 1 or stage 2, compared with normal blood pressure and cardiovascular outcomes. Sure enough, these young adults were at increased risk. In the second study, this is a domestic study, part of the CARDIA study, the Coronary Artery Risk Development in Young Adults started in March 1985.
There are quite a few African Americans in this study and some white participants aged 18 to 30 at the beginning of the study, and once again, taking a look at blood pressure measurements from first examination and then following these folks. The final cohort? 4,800+ adults, and among those with elevated blood pressure stage 1 hypertension and stage 2 hypertension before the age of 40 years, much higher risk for cardiovascular outcomes.
What I thought was really interesting about this study was the fact that it transcended two different ethnic groups. They think we’ve been tempted in the past to really say, “Well, we know that African Americans or blacks have a higher rate of hypertension, and so we’re not surprised by this outcome with regard to cardiovascular disease,” but this Korean population confirms that.
Rick: It’s interesting because this is measuring blood pressure in people under the age of 40, and the relative risk of having cardiovascular disease went up 67% for people that just had mildly increased blood pressure to over 249% increase for those that had stage 2 hypertension. As you mentioned, the Korean study is 2.5 million individuals. The other study in African Americans is a little bit less, but the data are very consistent.
Elizabeth: I think what I want to know — and is not addressed in these studies — is if we intervene, does that impact on the cardiovascular disease outcomes in this population?
Rick: Elizabeth, we talked last week that treating mild hypertension in older individuals can be associated with more harm than benefit. Now at least in this group, you can say, “Certainly non-pharmacologic measures don’t have any harm.” That is, decreasing obesity, increasing exercise, eating a healthy diet like a DASH diet — none of those is associated with any harm at all. We know that’s the first-line therapy. I would say I think the evidence, although inferential, is that in young individuals that we know that their cardiovascular risk is high, doing these non-pharmacologic measures would certainly improve their overall outcome. Now whether the use of medications will or not, that’s still unproven at this point.
Elizabeth: Right, and so I definitely would advocate for what you’re suggesting and also for a prospective study that would take a look at those very same factors to see what is their impact on cardiovascular disease outcomes?
Rick: The important thing is everybody under the age of 40 ought to know what their blood pressure is, and if it looks like it’s elevated, if it’s over 120/80, then at least start with non-pharmacologic measures to get it back in the normal range.
Elizabeth: I like that. Now let’s turn to one of yours, something that we’ve been advocating for years, in JAMA Internal Medicine, for folks with congestive heart failure. We need to reduce the salt in their diet. But gosh, is there really any evidence for that?
Rick: This is important because, at least in the U.S. alone, over 26 million individuals have heart failure. We know that there are a number of things that improve their outcome, and I’m talking about certain medications like beta blocker or ACE inhibitors or angiotensin receptor blockers. One of the first-line recommendations across the world is to put them on a low-salt diet, but if you look critically at whether there’s good evidence for that, this study would suggest there’s not.
These individuals systematically reviewed randomized clinical trials of reduced dietary salt intake in adults that were either inpatients or outpatients that had heart failure. They started with over 2,600 different refereed references. Only nine of them addressed this issue. That was in less than 500 individuals. What they found is for inpatients and outpatients there was no data that suggested that reduced salt intake improved their mortality or lowered their cardiovascular risk for serious outcomes — none at all. In the outpatient setting, there were some that suggested that reduced salt intake improved your symptoms and your exercise tolerance, whereas other studies didn’t. In general, all the studies were of low quality.
Elizabeth: Having worked with folks with congestive heart failure and heard from them just how very challenging it is to convert to a low-sodium diet, this could ultimately be good news for people’s self-management.
Rick: Part of that problem is because over two-thirds of the salt that we ingest isn’t added salt. It’s what’s in our usual food intake. I’m not saying that salt intake isn’t important, but I think we’d all have to agree that we don’t have good evidence at this particular point, so we need additional studies and some are ongoing. I look forward to reporting on those when the results are in.
Elizabeth: Just to nail this down just a little bit further, though. It seems that the a priori hypothesis is that since more salty things also kind of increase fluid intake, and it’s really the fluid that we’re worried about with regard to somebody’s congestive heart failure.
Rick: You’re right, Elizabeth. Increased salt is associated with increased fluid, but one has to wonder is it really just salt or is it the overall diet? For example, we know that diets that are high in salt are low in potassium. They’re high in phosphate. They’re low in dietary fibers, and all those things adversely affect health. Maybe instead of just focusing on salt, we need to be focused on the overall diet. We talked, again, about the DASH diet. It’s a high-potassium, low-salt diet with high fiber intake and a lot of fresh fruits and vegetables. That’s beneficial, so maybe we ought be focusing on the overall diet and not just a single nutrient.
Elizabeth: OK. Let’s turn from here to the New England Journal of Medicine, a report, of course, disturbing rise in the incidence of gonorrhea in the United States. Between 2013 and 2017, an increase of 67%, and also, antimicrobial susceptibility has decreased. So we’re getting this spread of resistant organisms, and now this is a report of a new agent for that. It’s unclear to me exactly how to say this. I’m going to call it zoliflodacin or ETX0914 for the treatment of urogenital gonorrhea, a single dose, so that’s pretty good.
In this phase 2 trial, they took a look at a total of 179 participants. There were 84 adverse events reported. This agent was actually pretty efficacious in treating the urogenital and rectal gonorrhea infections in this group, but not in the pharyngeal infections, and that’s something that I’ve been hearing an awful lot about lately. So I guess we still have concerns about that. We still need something to be able to help treat the infection in people who get it in their mouth.
Rick: This becomes important because the incidence of gonorrhea has gone up substantially. In fact, there were over 550,000 cases reported last year. And drug resistance and multidrug resistance has also been an issue. It’s not recommended that it be treated with a single antibiotic, but actually dual antibiotics. So we need new treatment, and this new agent and this is called spiropyrimidinetrione. It’s undergoing fast-track designation by the FDA. As you mentioned, a single oral dose was effective in eradicating urogenital gonorrhea in about 96% to 97% of patients, so that’s good news. Less so with pharyngeal gonorrhea.
Elizabeth: It is good news that we have something, at least, that looks like it’s emerging as a good treatment for this.
Rick: You’re right. We haven’t had breakthrough medication for gonorrhea in decades, and that’s why this is on fast-track designation. Now this is a relatively small study, a total of 180 patients divided between two different doses of the new antibiotic and one of the old antibiotic for comparison. So this needs to be studied again in a larger trial. It’s going to be hard to assess what the side effects… most of these were GI side effects in that small number of patients, so we need a larger study to, again, look more at efficacy in different patient populations and side effects as well.
Elizabeth: Let us turn, then, to your last one. That’s in Annals of Internal Medicine, a look at troponin and its predicted value.
Rick: Elizabeth, most of our listeners know that troponin is a protein that’s unique to cardiac muscle, and when there’s injury to cardiac muscle, it’s released into the bloodstream. It’s how we use, for example, to detect whether someone has had a heart attack. We have the ability to take uniquely small concentrations of it, what’s called high-sensitivity cardiac troponin. What these individuals did was they took a group of patients that had known coronary artery disease. There were about 600 of them and they measured plasma, high sensitivity of cardiac troponin in them. Then they put them on a treadmill to see which of those had inducible ischemia, that is they have insufficient blood flow to certain areas of the heart.
If you had a very low level, there was a 90% chance that you didn’t have inducible ischemia. If you did, there was a 97% chance it was relatively small. Then over the course of 3 years, these individuals had no cardiovascular death. Then they applied this to another 118 patients in the validation group, and they showed the same thing. These patients overall did well. This suggests that in people with known coronary artery disease, a very low level of this cardiac troponin can exclude inducible ischemia in about 90% of individuals. You might ask, “How many people did this apply to?” Even in the people with coronary artery disease, only about 1 in 5 or 1 in 4 had this low level. It at least identifies a low-risk population in patients with known coronary artery disease.
Elizabeth: How does it fit, then, as far as you’re concerned?
Rick: Elizabeth, I’m not sure we know how it fits right now. I guess if you have known coronary artery disease and this level is pretty low, you might tell the individual, “Well, your overall prognosis is pretty good.” But interestingly enough, you’re not going to change therapy. You’re not going to reduce the antiplatelet agents. You’re not going to reduce the statins or other medications they’ve been on. Other than providing prognostic information, I’m not sure that it really changes therapy.
Elizabeth: OK, on that note, then, that’s a look at this week’s medical headlines from Texas Tech. I’m Elizabeth Tracey.
Rick: And I’m Rick Lange. Y’all listen and make healthy choices