Vitamins and the Heart; CRP and COPD: It’s PodMed Double T!

Allergies & Asthma

PodMed Double T is a weekly podcast from Texas Tech. In it, Elizabeth Tracey, director of electronic media for Johns Hopkins Medicine, and Rick Lange, MD, president of the Texas Tech University Health Sciences Center in El Paso, look at the top medical stories of the week. A transcript of the podcast is below the summary.

This week’s topics include antibiotics for pneumonia, C-reactive protein (CRP) and chronic obstructive pulmonary disease (COPD) exacerbations, factors related to lower extremity amputation, and supplements.

Program notes:

0:44 Supplements and cardiovascular outcomes

1:45 Some reduced risk with some supplements

2:45 Relies on a healthy diet

3:16 Pneumonia treatment with antibiotics

4:16 Treated appropriately in hospital

5:15 Keep as short as possible

6:05 COPD, C-reactive protein and antibiotic use

7:05 No evidence of harm in not using antibiotics

8:05 Used clinical criteria in the past

9:03 Peripheral arterial disease and microvascular disease, and amputation

10:01 Amputation over 9 years

11:01 How to identify

12:08 End


Elizabeth Tracey: Are supplements of any good whatsoever?

Rick Lange, MD: Can disease in the small blood vessels contribute to amputations?

Elizabeth: Can we use C-reactive protein to decide if people with lung disease need an antibiotic?

Rick: And when treating pneumonia with antibiotics, is shorter duration better?

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 July 12th, 2019.

Rick: And I’m Rick Lange, President of the Texas Tech University Health Sciences Center in El Paso, where I’m also Dean of the Paul L. Foster School of Medicine.

Elizabeth: Rick, I’d like to start, if you don’t mind, with Annals of Internal Medicine. This is a really gigantic meta-meta-analysis. I call it that twice because it actually includes previous meta-analyses within this compilation of all the data — almost a million participants if you put the whole thing together — and they were taking a look at the randomized controlled trials and meta-analyses that looked at supplements. And these were a number of different supplements, and they were looking specifically at the outcome of cardiovascular disease and mortality.

They took a look at nutritional supplements including vitamin B, vitamin A, multivitamins, antioxidants, iron, and also dietary interventions such as the Mediterranean diet, folic acid, polyunsaturated fatty acids, and here’s what they found — that reducing salt intake had a modest impact on cardiovascular outcomes. Omega-3 fatty acid use and folate supplementation could reduce some risk for some cardiovascular outcomes in adults and combined calcium plus vitamin D might actually increase the risk for stroke. All the rest of those ones — the vitamin B, vitamin A, multivitamins, and all of that other stuff — had no impact whatsoever.

Rick: This is important because three out of four people in the United States take some sort of dietary supplements. By the way, this is a $300 billion a year business, and many individuals in my practice come in taking a variety of vitamins hoping to improve their cardiovascular outcomes. There really is not any significant benefit.

Now, you highlighted two potential benefits. One was the use of omega-3 fatty acids. Recently, there have been two very good randomized trials, one in general population and the other in patients that had diabetes that failed to confirm any benefit at all. With regard to the use of folate, there was one study in China that suggested it could lower the risk of stroke, but in the United States where many of our foods are folate-fortified, there really is no benefit at all.

Elizabeth: I guess what I would add to that is just the idea that this also relies on a pretty comprehensive and a pretty healthy diet.

Rick: Not only a healthy diet, but when we look at the U.S., many of our diets are fortified with vitamins already. I agree. You might say, “Well, this is unique to the U.S. population,” but that’s where a lot of the supplements are being taken. When I tell people in my clinic that there’s no evidence that the supplements improve their outcome, they look at me like I don’t know what I’m talking about, like, “Obviously, you haven’t seen the latest information.” And this is the latest information.

Elizabeth: OK. Since we’re in Annals of Internal Medicine, would you like to switch to yours?

Rick: Yeah, let’s talk about pneumonia treatment with regard to antibiotics. The time-honored treatment of pneumonia was based upon poor data. It was based upon the fact that a week has 7 days, and when we treat people with antibiotics, we give them somewhere between 1 and 2 weeks of antibiotic therapy. But there have been a lot of studies recently that showed that shorter durations of antibiotic therapy are just as effective. If it’s a community-acquired pneumonia — 5 days of antibiotics, and if it’s a hospital-associated pneumonia, it’s about 7 days of antibiotics.

What this study did was looked at 43 hospitals in what’s called the Michigan Hospital Medicine Safety Consortium to examine antibiotic use [in] this kind of run-of-the-mill pneumonia to ask, “How often do people receive what is thought to be the current duration of therapy, and is longer better?” After looking at almost 6,500 general-care medical patients with pneumonia, two-thirds of them received excessive antibiotic therapy.

And for many of these individuals, what happened was they got treated in the hospital for the appropriate amount of time, and they got discharged from the hospital on another 5 to 7 days of antibiotics. In fact, about 92% excess duration of antibiotic use was in the outpatient setting, when, by the way, they could have gotten just 1 or 2 days.

When they looked at the outcome, those that received longer antibiotics, they didn’t do any better. In fact, every day they were on antibiotics, there was a 5% risk that they had a complication related to that. Gastrointestinal complications or diarrhea or fungal infections, secondary. What this should alert health care providers and people that are receiving antibiotics for pneumonia is the shorter duration of therapy, 5 to 7 days, is adequate and lowers their complication rate.

Elizabeth: Right. And then you didn’t talk about — but we are well aware — the more antibiotics that are out there and the longer people are taking them, the more resistant organisms we’re going to come up with.

Rick: Absolutely. This is really important as we talk about antibiotic stewardship, and you’re going to talk about this in relationship to treating COPD. We want to target the antibiotic therapy to individuals that are going to benefit. We want to keep the therapy as short as possible, and we want to keep it as narrow as possible so we don’t develop either resistant organisms or complicated infections like C. diff.

Elizabeth: In the study that you were just talking about, one of the speculations that I saw in it was that physicians just are kind of lazy, like they just discharge people with their antibiotic and, “I’m just going to give you this much, and that’ll be that.”

Rick: Elizabeth, that’s a good point because what you would like to do is say, “You need to have 5 days of antibiotics. You got 4 days in the hospital. Let me give you a prescription for one more day.” That’s not typically what we do. We just give a 5- to 7-day prescription and send the patient home. In some ways, we are being lazy about it, but I’m not sure that many physicians realize that, in fact, it may harm the patient. This is an opportunity for us to get smarter about it. It’s better for the patients and it’s better for antibiotic stewardship.

Elizabeth: Since you foreshadowed already what we’re going to talk about next, let’s turn to the New England Journal of Medicine, and this study taking a look at point of care testing for C-reactive protein, or CRP, as a way to predict when patients who have chronic obstructive pulmonary disease come in whether they really need an antibiotic prescription or not. This study was undertaken in England and Wales, and they enrolled 86 general medicine practices. In the course of the study, they had 653 patients who had COPD come in and they, for half of them, administered this CRP test at point of care and then the other half of the group received the usual care.

The upshot of it was a lower percentage of patients in the CRP-guided group than in the usual group received an antibiotic prescription at their initial consultation, so about half of the folks in the CRP-guided group did versus almost 70% of the ones who didn’t have that. When they followed these people out, there was no evidence of harm in not prescribing antibiotics for the people with the COPD.

The editorialists talk about this thing called the Anthonisen criteria — which have been historically what people rely on to determine whether to prescribe an antibiotic or not, and this was based on a randomized trial that’s about 30 years old in patients with COPD and showed that, when they received antibiotic therapy, that resulted in a better outcome. It’s a 30-year-old study — that’s a pretty long time ago and I think it is appropriate to re-examine this issue.

They also point out, though, that this point-of-care C-reactive protein test in the U.K. was something that’s practical, but here in the United States, it may not be very practical because of considerations about reimbursement as well as just administering that test at point of care.

Rick: Taking a step back, when people have an exacerbation of their COPD, it may be bacterial in nature or it could be for some other reason. In the past, we tried to use clinical criteria. Does the person have increased dyspnea — trouble breathing? Do they have increased sputum volume and is their sputum more purulent? Does it look more infected? If the person had two of those three criteria, they gave them antibiotics. If they had one or none of those criteria, they didn’t.

The C-reactive protein is a much better indication of whether there’s inflammation. It’s non-specific, but it indicates inflammation. In these particular individuals, many of these individuals who would have gotten antibiotics on the basis of the clinical criteria, when the C-reactive protein was negative, they didn’t get it and their clinical outcomes were the same.

Elizabeth: And again, one of the other aspects of prescribing antibiotics in these folks when they have COPD is that there is evidence that their airways can be colonized by multidrug-resistant bacteria and may ultimately predict, then, a much worse clinical outcome.

Rick: It’s one of the reasons we want to minimize antibiotic therapy to the shortest duration and only to the patients that are going to benefit from it.

Elizabeth: Let’s turn to your final one. That’s in Circulation.

Rick: We’ve talked before about the presence of peripheral arterial disease, atherosclerotic disease, or blockage in the large blood vessels that feed the extremities, primarily the lower extremities. We know that’s associated with things like heart attack and stroke. The more peripheral arterial disease one has, the more likely they are to have insufficient blood flow and ultimately require an amputation if not appropriately treated.

And we measure that, by the way, by what’s called an ankle brachial index, measuring the blood pressure in the limbs, upper and lower limbs. But what’s interesting is that some individuals end up having amputation and don’t have peripheral arterial disease. Their large vessels look fine. What they have is disease in the small blood vessels.

What these authors tried to do was to look at what the contribution of microvascular disease was in a large patient population. And they picked the veterans because we have information on them from over a 10-year period, from 2003 to 2014. There were over 125,000 veterans that had not had previous amputation at baseline. And they looked at the rate of amputation over the course of 9 years. There was about 1.16 amputations per thousand person-years.

When they adjusted for all the usual cofactors — hypertension, diabetes, cigarette smoking, cholesterol — the presence of microvascular disease alone increased the risk of having an amputation by about four-fold. If they had peripheral arterial disease in the large blood vessels, it increased the risk of an amputation by about 14-fold. But if you had both, peripheral arterial disease and microvascular disease, it increased the risk by 23-fold. This indicates that the presence of microvascular disease increases the risk of amputation either alone or even amplifies the risk in people with peripheral arterial disease.

Elizabeth: And something that the authors cautioned, people really need to be paying attention to clinicians.

Rick: It is. Now what that means is in the U.S., or at least in this population, the veterans, as many as 1 in 6 below-the-knee amputations result from microvascular disease without peripheral vascular disease.

Elizabeth: It seems rather curious to me that this should be a previously unidentified factor.

Rick: Well, Elizabeth, we’ve known about it because oftentimes people with diabetes have microvascular disease, but nobody has really ever quantitated it or certainly looked at whether it amplifies the risk for peripheral arterial disease. This is the first and largest study we’ve been able to do that, but we’ve known about this for a long period of time.

The interesting thing is how do you know if someone has microvascular disease? Well, it not only affects the lower extremities, but it affects other things, so retinopathy. That is small blood vessel disease in their eyes or neuropathy, or nephropathy in their kidneys. That’s how they identified these individuals that had microvascular disease. They already had one or more of these other organs affected.

Elizabeth: So definitely red flags, then, for clinicians to look out for.

Rick: Absolutely. Clinicians should routinely be asking about these even in people that don’t have evidence of peripheral arterial disease.

Elizabeth: On that note, 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 up and make healthy choices.


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