Rainfall and Mortality; Identifying Risk for Preeclampsia

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 transplanting kidneys from HIV-positive donors, identifying who’s at risk for preeclampsia, rainfall and mortality, and a new agent for metabolic dysfunction-associated steatohepatitis (MASH).

Program notes:

0:49 Rainfall events and daily mortality analysis

1:49 How quickly might such an event recur?

2:50 Some of the mechanisms

3:44 HIV-positive kidney donors

4:49 Been doing in South Africa since 2008

5:10 Identifying risk for preeclampsia

6:12 High systemic vascular resistance

7:14 Did not predict late term

8:10 Non-invasive test

8:21 Treatment of MASH

9:20 Death of liver cells and inflammation

10:30 Increased rate of COVID infection

11:37 End

Transcript:

Elizabeth: Does daily rainfall have anything to do with mortality?

Rick: Transplanting kidneys from donors that have HIV.

Elizabeth: Can we take a look at cardiac function and predict preeclampsia?

Rick: And treating liver disease associated with metabolic dysfunction.

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: Let’s just mention we’re very thankful to be back online.

Rick: It’s good to have that resolved.

Elizabeth: Let’s turn first, if you’re okay with it, to The BMJ, this “rainfall events and daily mortality analysis” across 645 global locations. This caught my eye, of course, because we have been having these hurricanes here in the United States and those have resulted in really unusual events. For some of those folks in Florida, both hurricanes hit them in a really short period of time, so this study was one that I looked at a little more carefully.

They were trying to examine the associations between characteristics of daily rainfall — including intensity, duration, and frequency — and all-cause, cardiovascular, and respiratory mortality. Daily mortality data with 109 million data points for that broken out into cardiovascular and respiratory deaths from 1980 to 2020. They also looked at this temporal relationship, which is how fast could we expect this particular event to come visit you again. Would that be 1 year, 2 years, or 5 years? How is that related to mortality?

Sure enough, what they found is that a day of extreme rainfall that was not expected to come back to that region for 5 years was significantly associated with increased all-cause, cardiovascular, and respiratory mortality. If it’s only a 2-year return period, you had slightly increased respiratory mortality. For a 1-year return period, there was no significant association. What this says to me is if you’re in a place where it doesn’t happen very often, it does have the potential to be a negative health impact.

Rick: There were some other things that modified this association: climate type, what the baseline variability in rainfall was, whether there was vegetation coverage, and whether it was urban versus rural. Usually, you associate rainfall with pathogens that cause infections, but for this we’re talking about cardiovascular disease, respiratory disease, and all-cause mortality. Does this have any policy implications at all?

Elizabeth: Absolutely. They talk about some of the mechanisms by which this intense rainfall could be problematic — major disruptions to healthcare access. It can also damage the infrastructure that exists with power outages and hindering essential medical services. Also compromising food and water quality, both by limiting access to those things as well as by allowing pathogenic microorganisms to spread. It produces an impact on mental health, increasing stress and anxiety, particularly exacerbating preexisting conditions. What are the policy implications to see if we can prepare for these things? I think we’ve had some life lessons in that recently here in this country.

Rick: We know these events are going to occur and we know it increases the risk of mortality. How do we inform the population to mitigate some of the causative factors that we’ve talked about?

Elizabeth: Which of your two would you like to go to?

Rick: Let’s talk about kidney transplantation from donors with HIV.

Elizabeth: That’s in the New England Journal of Medicine.

Rick: In this observational study done at 26 U.S. centers, they looked at individuals that had HIV and they were going to get a kidney transplant. Half of them got a kidney from a donor that did not have HIV and the other half got a kidney from a donor that did have HIV. These were all deceased owners by the way. How did the individuals do? What was their mortality?

The outcomes were similar whether the donor had HIV or not. Overall survival at 1 year was about 95%, 3 years about 86%, and the incidence of rejection at 3 years was about the same. There was no increased incidence of serious adverse events like infections or surgical complications, or vascular complications, or cancer with regard to who the donor was.

Elizabeth: What are the numbers with regard to alleviation of the number of people who were on the transplant list when these kidneys are utilized?

Rick: This study did not provide that information, but the background — and this is provided by the editorialist — is he has been doing this in South Africa since 2008. These results aren’t just unique to what we’re doing in the U.S. They can also apply to other countries where there are limited donors.

Elizabeth: More coming, no doubt, about this. But let’s hope that we get our arms around HIV and it just becomes a non-issue.

Let’s turn to the Journal of the American Heart Association, another important issue, and that’s preeclampsia. Preeclampsia, of course, is the development of high blood pressure in pregnancy and, gosh, can result in mortality for both mom and baby as well as lots of other complications.

These authors were taking a look at cardiovascular dysfunction associated with preeclampsia in women without fetal growth restriction. This is a case-cohort study in 906 pregnant women in Denmark with repeated third-trimester cardiac function assessments. They were comparing rates of hypertensive disorders of pregnancy in women with low, normal, and high cardiac output, and normal and high systemic vascular resistance, using this fetal growth restriction status and gestational age as their stratifiers.

In their analysis, including 249 women with preeclampsia, 42 of whom did have this fetal growth restriction and 119 women they found with gestational hypertension, high systemic vascular resistance was strongly associated with the development of hypertensive disorders of pregnancy. They also conclude that repeated measurements of third-trimester cardiovascular function might help identify those women who are at risk to develop preeclampsia in the absence of fetal growth restriction, which tips us off already.

Rick: When a woman who is pregnant has fetal growth restriction, her risk of preeclampsia is high. Okay. There are women whose fetuses appear to be normal. They appear to be otherwise normal and yet they still get preeclampsia. What does that tie to?

This particular study said, “Well, we hypothesize that what happens is their cardiac output goes down and as a result they develop preeclampsia.” In their study, it appeared that in fact, they could document a low cardiac output in these women that had preeclampsia. It predicted preeclampsia in women that had it in less than 37 weeks of gestation, but it didn’t predict it in those that had preeclampsia [at] more than 37 weeks. Okay, well, that’s kind of interesting, but should we be measuring cardiac output noninvasively in women? I don’t think this study yet provides that type of information. It generates a hypothesis.

Elizabeth: And pretty easy to measure, I would note. Then, I would also note that they identified other characteristics of women who ultimately went on to develop preeclampsia. Their median first-trimester blood pressure was higher, they were shorter, they were younger, and they had an elevated BMI.

Rick: Those, just like the cardiac output, all are associations; it doesn’t mean it’s causative. I hope this leads us on to a path that helps us identify what causes it, so we can prevent it.

Elizabeth: Right. And I think, as I said, I think if you identify all of those factors that are pretty easy to look at, including this noninvasive way of assessing cardiac output, maybe that’s going to help identify these folks earlier.

Rick: Although these are just associations, it’s nice that in this particular study it was a noninvasive test, it could be repeated, and it carries no risk associated with it. The future will tell how useful it will be in terms of identifying these women at risk.

Elizabeth: Let’s turn finally to The Lancet.

Rick: Treatment of metabolic dysfunction-associated liver disease. In particular, we’re talking about steatohepatitis. This is where there is fat accumulation in the liver and not just fat accumulation, but it causes inflammation and ultimately causes scarring or what we call fibrosis.

We talked before about the importance of trying to prevent it. It’s associated with metabolic dysfunction, obesity, hypertension, insulin resistance, diabetes, a sedentary lifestyle, and increased cholesterol — all of those things. Nevertheless, the incidence of steatohepatitis associated with metabolic function is pretty high. It’s about 5% to 14% of adults in the United States. That means there are about 9 million individuals.

Well, this is a drug called denifanstat. It inhibits fatty acid synthase. This is an enzyme that’s responsible for making a fatty acid called palmitate. It’s a saturated fatty acid. It’s deposited in the liver and it causes not only accumulation of fat, but it also causes death of the liver cells. It causes inflammation and it actually causes fibrosis. Potentially, if you could inhibit this enzyme, you could actually treat steatohepatitis.

That’s what this particular study addressed. It is a 2B trial about actually treating the disease and it should result in a larger clinical trial. They took 168 participants — they all had biopsy-proven steatohepatitis — and they randomized them to denifanstat 50 mg daily over a 2-year period or to placebo. At the end of it, did the steatohepatitis get better?

For those that received placebo, about 16% of them improved. For those that received denifanstat, 38%. We would like for 90% of people to respond, not 38%, but that’s still good. There was an interesting side effect and that’s about 1 in 5 people experienced hair loss, but other than that no serious side effects. So a new medication, a new pathway, which is potentially quite beneficial.

Elizabeth: It’s interesting that more of the folks in the denifanstat group became infected with COVID during this study period, 17% versus 11% of those in the placebo group.

Rick: This study was started before COVID. It continued through COVID and then finally ended afterwards. It’s hard to say that this particular thing increased the infection rate with COVID. There is a lot we don’t know about these patients: how many of them actually were exposed and how many got vaccinated, so you’re right. Statistically, there is a difference between the two. Interestingly enough, there were no other increased infections at all, either viral or bacterial infections. I just think it happened to be luck of the draw.

Elizabeth: I guess I would finally note that what we know is that this condition can largely be prevented.

Rick: A metabolic syndrome can be addressed in some individuals. In other individuals, it’s not a lifestyle choice. It’s either a genetic or metabolic condition that they don’t have any control over. But for many of us, we can — by making wise lifestyle choices — reduce steatohepatitis.

Elizabeth: 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 up and make healthy choices.

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