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Colchicine for COVID-19; Metabolic Syndrome Prevalence: It’s TT HealthWatch!

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Colchicine for COVID-19; Metabolic Syndrome Prevalence: It's TT HealthWatch!

TTHealthWatch 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.

This week’s topics include colchicine for heart complications of COVID, black versus white patients with COVID-19 hospitalization, prevalence of metabolic syndrome in the U.S., and ACE inhibitors and ARBs and COVID.

Program notes:

0:45 Hospitalization and mortality among black and white patients with COVID-19

1:47 About 40% were hospitalized

2:44 More likely to be in service occupation

3:47 Chronic inflammation?

4:00 Colchicine for heart damage in COVID-19

5:00 Patients experience higher mortality with heart impact

6:02 Decrease inflammation?

7:02 Could be a stepping stone to a larger study

7:12 ACE inhibitors and ARBs in COVID

8:13 Increase ACE receptor?

9:10 Don’t stop your medication

9:45 Prevalence of metabolic syndrome in U.S.

10:42 Prevalence just shy of 35%

11:44 Several risk factors for severe COVID infection

13:10 End

Transcript:

Elizabeth Tracey: Can colchicine be used to treat heart injury in people with COVID-19?

Rick Lange: Do certain blood pressure medicines increase your risk of developing, or severity of, COVID infection?

Elizabeth: Has the prevalence of metabolic syndrome increased in the U.S.?

Rick: And hospitalization and mortality among black patients and white patients that have COVID infection.

Elizabeth: That’s what we’re talking about this week on TT HealthWatch, your weekly look at the medical headlines from Texas Tech University Health Sciences Center in El Paso. I’m Elizabeth Tracey, a Baltimore-based medical journalist.

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

Elizabeth: Rick, in a double bow to current events, why don’t we turn directly to the New England Journal of Medicine? This is an article that’s taking a look at hospitalization and mortality among black patients and white patients with COVID-19.

Rick: This study follows on the observation that has highlighted age and sex-related differences in health outcomes in people that have COVID infection, and concern specifically that black patients may have worse outcomes and a higher risk of mortality associated with the infection. The investigators did this retrospective cohort study where they analyzed data from patients that were seen within an integrated delivery health system — that’s in Louisiana — and they did this study between March 1st and April 11th. They looked at almost 3,500 COVID-19 positive patients. About 70% were black and about 30% were white.

The black patients had a higher prevalence of obesity, diabetes, hypertension, and chronic disease, compared to the white patients, and we know, by the way, this increases the risk of developing severe COVID infection. About 40% of the patients were hospitalized.

Black race was one of the major risk factors in addition to increasing age, a higher burden of illness, whether individuals were on public insurance — that is Medicare or Medicaid — whether they resided in a low-income area, and obesity. Among the patients who died, 71% were black.

When they looked at the hospital mortality, interestingly enough, being black did not increase the risk of mortality. About 77% of the patients who were hospitalized with COVID-19 and 71% of those who died were, in fact, black, whereas being black only comprised 31% of the population.

Elizabeth: I think that this is a moving target. I don’t think we have all of the factors in line yet that account for the fact that brown and black people seem to be experiencing a disproportionate amount of this COVID-19 disease.

Rick: The authors hypothesize there are several things that may explain it and oftentimes minorities or people of color are more likely to be in the service occupations, where they may be more likely to be exposed.

The African Americans, or the blacks, had a much higher prevalence of chronic disease than the white population. It may be that they waited longer to receive access to care and we know that happens in individuals that are on Medicare or Medicaid or are self-insured.

Then finally, there may be a different immune response. There are some reports that suggest that individuals with African ancestry have a stronger inflammatory response than people from a European ancestry.

Elizabeth: I would just note that a study that was done here in Baltimore was looking at seroconversion among different populations and found that here, in this area, 40% of Hispanics had seroconverted. One factor that they identified in there was the closeness of living quarters and how it’s very difficult to avoid exposure to someone who’s ill.

Rick: Absolutely. That’s been shown in other populations and in other countries as well, particularly underdeveloped countries that are having a very rampant rate.

Elizabeth: I think, as we look at this retrospectively, I bet that one of the factors that’s going to emerge is chronic inflammation over a long period of time, if we had a way to really assess that. Let’s turn to JAMA Network Open. This is a really small study, but one that I thought was rather interesting. We know that one of the dire impacts of COVID-19 is the damage to the heart. It’s a small study that was done in Greece and they used colchicine to see if they could ameliorate the impact of the infection on the heart.

They were able to accrue in this study only 105 patients and they did that largely during the month of April. And that’s because the rate of infection declined so much in Greece that they weren’t able to accrue adequate patients in order to make it a bigger study. So I thought that was actually good news.

They were at 16 tertiary hospitals in Greece, which also says to me, “Wow, you couldn’t have had that many patients if you had to go to 16 different hospitals in order to accrue the proper number.” They randomized them about half and half to receive either colchicine or not, and then they looked at high-sensitivity cardiac troponin values and C-reactive protein values in these two groups of patients. One piece of background that’s kind of interesting to note is that patients who are COVID-19 positive with active myocardial injury, with elevated troponin levels, are at a very high risk with mortality rates reaching about 40%.

To make a long story short, they actually were able to show that colchicine was able to decrease D-dimer values, but not in the C-reactive protein values. There are a bunch of caveats. One of them being a small study, but also that the patients were also treated with a lot of other drugs in the midst of this, so teasing out the impact of colchicine is really a little bit of a challenge. In any case, I’m of the opinion of the editorialists that it would be good to expand this into a group that’s much bigger so we could see if this is borne out.

Rick: Colchicine is an oral medication that’s used for anti-inflammatory properties, particularly for things like pericarditis, inflammation of the sac surrounding the heart. The primary goal was to see whether colchicine can be used to decrease the inflammation associated with it. And what they showed was it didn’t really do that, that the C-reactive proteins weren’t that high in the baseline group, high-sensitivity troponins weren’t that high, and the colchicine really didn’t decrease them. Although, as you mentioned, it did decrease D-dimer, which is associated with blood clots that can form.

Now, it wasn’t a primary endpoint, so that’s always a problem. That is when you identify something that you didn’t look for, you wonder whether it’s a random effect. There did seem to be some clinical benefit, as you mentioned. This is what I call a hypothesis-generating study, not conclusive by any stretch of the imagination.

Elizabeth: No, but I think well worth ramping up because clinically there’s so much experience with colchicine. And even if it does reduce all that clotting events that take place, that’s a really good outcome too.

Rick: Well, if in fact it does, that would be a nice outcome. The major virtue of colchicine is it’s been around for centuries. Most people tolerate it. The major side effect is diarrhea and about half the patients had this. This can be a stepping stone to a larger study. The question is, is it beneficial in COVID patients? That still remains unanswered in my mind.

Elizabeth: Let’s turn to yours, your next one. That’s in the Journal of the American Medical Association, angiotensin-converting enzyme inhibitors or ARBs and what’s that do with regard to COVID-19 infection?

Rick: These are two antihypertensive — or blood pressure — medications, angiotensin-converting enzyme inhibitors, also called ACE inhibitors, or angiotensin receptor blockers, ARBs. They’re routinely used for people that have hypertension, or even for diabetics to help prevent kidney disease. Early on, it was noted that hypertension is associated with an increased risk of having severe COVID infections and people wondered, “Gosh, is it really the hypertension or it’s the medications that we use?”

Now, why would these medications be associated with that potentially? The virus binds to the ACE receptor. If you’re given an ACE receptor inhibitor, then potentially you get more receptors on the cells, and more receptors mean more virus can actually enter the cells.

ACE receptors are ubiquitous throughout the body, but are particularly in the lungs and in the nasopharynx. The thought was for people that were on ACE inhibitors that would increase the ACE receptor, it could perhaps increase the severity of the disease or increase susceptibility. There have been a number of studies looking at various populations. This is an unusual one in that it is a population study. It’s conducted in Denmark.

They used the Danish national administrative registry from the end of February to early May to ask two questions, “Do individuals on an ACE inhibitor or an ARB have an increased risk of having severe COVID infection?” Secondly, “Do they have an increased likelihood of developing the infection?”

In the retrospective cohort of almost 4,500 patients, individuals that were on an ACE or an ARB did not have a significantly increased risk of severe infection. Does it increase the likelihood that people would get the disease? When they examine that in what’s called a nested case control analysis, those individuals that took ARBs or ACE inhibitors did not have an increased risk of developing it. The bottom line is for individuals that are on an ACE inhibitor or an ARB, they get infected, don’t stop the medication.

Elizabeth: I guess one of the questions that I find a little bit intriguing is would it be possible to actually occupy those receptors, the ACE-2 receptors, utilizing these things and decrease the risk of infection?

Rick: Elizabeth, it’s interesting because that’s one the treatments that’s being proposed, and that is developing antibodies to those receptors. You would have to give it prophylactically, so you’d have to be able to identify which patients are likely to get it and see whether that could benefit. Those studies are ongoing right now. Hopefully, in the future, we can report on those.

Elizabeth: Let’s finally turn to a letter in the Journal of the American Medical Association, and this is the trends in the prevalence of metabolic syndrome in the United States. I picked this one because we know that diabetes is a risk factor for COVID-19 infection and more severe disease. Metabolic syndrome, of course, is its precursor.

Previous studies showed that the prevalence was about 33% in adults and that remained stable from 2007 to 2012. This is, of course, data from NHANES, the National Health and Nutrition Examination Survey, from 2011 to 2016.

There’s self-reported race/ethnicity that’s evaluated in this particular study. They take a look with regard to metabolic syndrome at three factors: high-density lipoprotein cholesterol, systolic blood pressure, and fasting plasma glucose levels. And they also, of course, take a look at different ages.

They had 17,048 participants. Their ultimate weighted metabolic syndrome prevalence was just shy of 35%. This did not differ significantly between men and women. It did increase significantly in those aged 20 to 39 years over this time period and was also more common in women, Asians, and Hispanics. It also increased with increasing age, achieving almost 50% among those aged at least 60 years in this particular survey.

I find this extremely concerning because, as I said, it’s like the precursor to frank diabetes. I’m also wondering about, if you have metabolic syndrome, does that put you at increased risk for severe COVID-19 disease? Obviously, outside the scope of this particular assessment.

Rick: Elizabeth, as you mentioned, metabolic syndrome is defined by obesity — that is an increased waist circumference — having elevated triglycerides, a low HDL, diabetes or prediabetes, and hypertension. We know that several of those are risk factors for COVID infection already. We know that obesity is. We know that hypertension is. We know that diabetes is as well.

That constellation of syndrome would certainly increase the risk not only of having COVID infection, but when combined with age, an increased risk of mortality as well. It’s concerning that it’s happening in larger prevalence in younger populations and also in minority populations that sometimes don’t receive as good care.

Elizabeth: I think it would be really great if somehow we could get our arms around this and reverse these trends. It’s unclear to me exactly how we’re going to do that.

Rick: Obviously, lifestyle modification plays a really important role and that would be the first step that’s prior to giving any medications. But when they’re needed, obviously, we want to make sure that they’re available to these populations. Again, it’s disconcerting that it’s happening in a younger population and in a minority setting as well.

Elizabeth: I would just note that again, based on research we’ve reported on before, that among young COVID patients who end up either hospitalized or in the ICU, obesity is the major determinant of that. That goes hand-in-hand with this.

Rick: Our encouragement is to use lifestyle modifications to prevent chronic diseases.

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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