Pollution and Antibiotic Resistance; Troponin and Mortality

— Also in TTHealthWatch: statins for cardioprotection in cancer patients on chemotherapy


TTHealthWatch is a weekly podcast from Texas Tech. In it, Elizabeth Tracey, director of electronic media for Johns Hopkins Medicine in Baltimore, 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 air pollution and antibiotic resistance; a statin for helping heart function when chemotherapy is needed; sugar-sweetened beverages and liver health; and troponin and mortality.

Program notes:

0:40 Troponin and mortality

1:40 44% in those with elevated levels

2:41 Routine measurement?

3:10 Air pollution and antibiotic resistance

4:10 First global estimate

5:10 Discharged into environments

6:10 Contributed to 0.5 million deaths

6:30 Statins and chemotherapy

7:30 Followed for 12 months

8:32 Sugar-sweetened drinks and liver problems

9:29 Almost 21 years of follow up

10:32 Increased risk of metabolic disease

11:54 End


Elizabeth: What does air pollution have to do with antibiotic resistance?

Rick: How can lowering cholesterol make chemotherapy safer?

Elizabeth: What are some of the additional risks of sugar-sweetened beverages?

Rick: What happens when you order a blood test without an indication?

Elizabeth: That's what we're talking about this week on TTHealthWatch, 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 Texas Tech University Health Sciences Center in El Paso, where I'm also dean of the Paul L. Foster School of Medicine.

Elizabeth: Okay. With that clever quip, I'm going to say to you, "You go ahead, sir." Let's talk about one of yours first.

Rick: It's titled "The association between troponin levels and median mortality in 20,000 hospital patients." Now, troponin level is a blood test that's used to detect injury to the heart muscle. We typically use it when we suspect someone has a heart attack. With heart attack, there is injury to heart muscle. You can detect that in the blood.

These investigators did something unusual. They took 20,000 consecutive patients and they said, "We're going to order this test regardless of whether the person has a known heart issue or symptoms. We want to see if there is any relation or association between that and mortality."

In 20,000 patients, about 91% of them had the blood test done without an indication; 9% actually had some sort of heart issue. What they discovered was, if that blood level of cardiac troponin was elevated, it was substantially associated with mortality even in individuals that didn't have an indication for the test. The mortality over the course of about 2½ years was 44% in those whose blood test was elevated, versus only about 12% in those in whom it wasn't. So, now you have this test -- you didn't really have an indication for it -- now you realize this is associated with increased mortality. What do you do with that information?

Elizabeth: Well, it's really very interesting, isn't it? I'd ask you to speculate first on what you think the biological underpinnings of this are.

Rick: Okay. Because there wasn't a lot of clinical data on all these patients, we always have to do a multivariable analysis. In other words, maybe it's not the blood test, but it's some other associated condition that could affect it. For example, people who have chronic kidney disease or they could have undetected cardiovascular disease. But the vast majority of these individuals actually died of malignancy, not a cardiovascular disease. About half of them died of a malignancy and only 12% of those who had the test without an indication actually died of cardiovascular disease. What we don't know is if detecting this gives us any therapy that actually improves their outcome. I think a study like this leads to more questions than it does answers.

Elizabeth: And I would alternatively suggest that is it possible that if we started routinely measuring troponin levels, it might raise the index of suspicion that there could be something else going on that we need to look further for?

Rick: Well, only if there aren't other risk factors already identified. Let's say someone came in not with a heart attack, but heart failure, or a malignancy or severe lung disease, or kidney disease. We already know those people are at a higher risk, so the addition of a blood test wouldn't necessarily add anything.

Elizabeth: Okay. Let's mention that's in Heart, a BMJ journal.

Now, let's turn to The Lancet -- we'll stay across the pond -- to a very interesting association, I thought. They are reporting on the association between particulate matter, specifically PM 2.5 air pollution -- that's 2.5 microns -- and clinical antibiotic resistance.

When I first read this headline, it piqued my interest because I thought, "Now those are two seemingly disparate things." They began, of course, with reminding us all that particulate matter has variable sizes and we're also seeing that it's increasing all over the globe.

They took a number of databases where they looked at data from 2000 to 2018. Looking at this PM 2.5 distribution and antibiotic resistance, they used all kinds of univariate and multivariable analyses to come up with this association. They call this the first global estimate of antibiotic resistance and burden of premature death that's attributable to antibiotic resistance that results from this PM 2.5 pollution.

Basically, they said, "Yes, indeed, antibiotic resistance does increase as PM 2.5 increases." This is especially a problem in certain parts of the world. There are other, of course, important factors, all kinds of agricultural things and pollution from industry. This is yet one more important factor that has a lot more impact in the Middle East and in other places than currently it does in the Northern Hemisphere, for example.

Rick: This is a concept called One Health. The health of our entire ecosystem isn't really divided between what happens in the animal or the plant or the human kingdom, but really the health of each of these ecosystems affects the health of the other. We've talked about the fact that overuse of antibiotics in humans and animals exacerbates the antibiotic resistance elements. These antibiotic-resistant organisms are then discharged into environments like the wastewater, agricultural manure application, evaporation, and they can actually be transferred from the environment to humans through drinking water, food, air, and inhalation.

This particulate matter that you described has no boundaries. I'm very surprised because this is the first study that actually ties pollution, particulate air matter, to antibiotic resistance. The particulate matter can carry organisms that are antibiotic-resistant. It can also carry genes that can be transferred among microorganisms to increase antibiotic resistance as well. So this was a fascinating study.

Elizabeth: Interestingly, they, of course, claim it as the first global analysis. Because it was such a novel idea for me, I did a literature search on it also and found that this idea has been percolating out there for a while -- I would say for a minimum 5 years in the literature that I was able to identify.

Rick: Let's put some numbers so our listeners can understand it. Their estimate is that antibiotic resistance derived from this particulate matter contributed to about half a million premature deaths. If we were to lower targets to what the WHO recommends, we could reduce antibiotic resistance by about 17%.

Elizabeth: No doubt we're going to hear more about this. Now, let's turn to again something that I thought was a real curiosity, the use of a statin for things that might happen as a result of cancer treatment. That's in JAMA.

Rick: Most of our listeners will be aware that statins are cholesterol-lowering medications and that's what they're primarily used for, but they also have other properties as well. They are antioxidants and anti-inflammatory medications. There was some suggestion they can make chemotherapy safer.

Specifically, there is a group of chemotherapeutic drugs called anthracyclines. They are used in things like breast cancer, gynecologic cancer, and lymphoma. They are widely used and at higher doses they are associated with a decrease in heart function. That's increased in people that are older, that have other underlying heart conditions, and a higher dose of chemotherapy has been given. In animal models and some observational studies, it was suggested that statins could actually lower the risk of that.

These investigators who decided to study that took 300 individuals that were getting anthracyclines, half of whom got placebo and half of them got just a routine dose of the statin, 40 mg of atorvastatin at night. They followed these individuals over the course of 12 months.

The individuals who have received placebo, 22% of them had a decline in their heart function whereas those that received a statin it was about 9%. We know that if you detect that now, about 2 to 10 years later it increases the risk of heart failure as well. This medication is routinely available. It cost pennies and doesn't have any significant side effects. This is a really good news story.

Elizabeth: Also, just such a curiosity. I would love to know what the backstory is on this. Who noticed among their patients that, "Oops. Mr. Jones, I have him on a statin already and, look, he has this heart function that seems to be sustained versus declining"?

Rick: There is some biologic plausibility. It was particularly helpful in older individuals, in those who received the higher dose of chemotherapy, and also in those who had underlying cardiac conditions. Well, I think we can say if someone is already on a statin, they should continue it. If they're at high risk for having heart dysfunction from chemotherapy, then those individuals ought to be considered as well.

Elizabeth: Finally, let's turn to -- also in JAMA -- sugar-sweetened and artificially sweetened beverages and the risk of liver cancer and chronic liver disease mortality.

The authors start with a rather startling statistic to me. They assert that approximately 65% of adults in the U.S. consume sugar-sweetened beverages every day. They took data from the Women's Health Initiative among women who were recruited from 1993 to 1998 at 40 clinical centers in the U.S., and then were followed up to March 1 of 2020.

They assessed their sugar-sweetened beverage intake on their food frequency questionnaire. They looked at the primary outcomes of liver cancer incidence and mortality due to chronic liver disease. That could be death from non-alcoholic fatty liver disease (NASH), fibrosis, cirrhosis, alcoholic liver disease, and chronic hepatitis.

Over this period of time to almost 21 years of follow-up, 207 women developed liver cancer and 148 died from chronic liver disease. For those who consume one or more servings of sugar-sweetened beverages per day, their risk of liver cancer was 18.0 versus 10 per 100,000 person-years. Their risk of chronic liver disease mortality was 17.7 versus 7.1 per 100,000 person-years. These things definitely seem to increase one's risk of liver cancer and death from chronic liver disease

Rick: It just about doubles the risk of having mortality from liver cancer. Other studies have reported an association of sugar-sweetened beverages with the risk of breast cancer, colorectal cancer, and prostate cancers as well.

Interestingly enough, they also did a corollary study looking at artificially sweetened beverages and they realized that those aren't associated with an increased risk of liver disease or death from liver cancer. There is some biological possibility because we know that with an increased risk of metabolic disease, diabetes, and obesity -- all of those increase the risk of cancer.

There are metabolites in sugar-sweetened beverages, things like taurine and phenylalanine, that have been associated with liver cancer in the past. But many of these have other chemicals, things like caramel color, citric acid, organic diols, and other things. The long and the short is if you want to reduce your risk of prostate cancer, breast cancer, liver cancer, or colorectal cancer, stopping or decreasing the amount of sugar-sweetened beverages you drink is a way to get there.

Elizabeth: Indeed, and finally let me just note that among those who consumed sugar-sweetened beverages in this population, they were generally younger, less physically active, higher proportions were non-Hispanic Black, never drank alcohol, interestingly, lower education level, higher BMI -- kind of a composite picture of the consumption of these things.

Rick: Unfortunately, I can't think of a single positive health outcome associated with sugar-sweetened beverages.

Elizabeth: On that note, that is absolutely the perfect place to sum this up. That's a look at this week's medical headlines from Texas Tech. I'm Elizabeth Tracey.

Rick: AndI'm Rick Lange. Y'all listen up and make healthy choices.