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 semaglutide and mortality, beta-blockers after myocardial infarction (MI), comparing fecal immunochemical tests (FITs), and 30-year cardiovascular disease (CVD) prediction with a blood test in women.
Program notes:
0:41 A single blood test for CVD in women over 30 years
1:40 Each biomarker provided additive information
2:41 Every quintile increase
3:31 Semaglutide and infectious disease risk
4:31 COVID emerged during study
5:32 Reduced all cause mortality by 19%
6:34 Stopping beta-blockers after heart attack
7:35 Increased risk of chest pain
8:35 Should be looked at earlier?
8:57 Comparing FITs
9:57 Huge variation in the tests
10:57 Will require more colonoscopies
11:52 Repeated testing improves sensitivity
12:48 End
Transcript:
Elizabeth: The many benefits of semaglutide.
Rick: Should you stop beta-blocker medications after a heart attack?
Elizabeth: What’s the difference between all of those fecal immunochemical tests?
Rick: Using a single blood test to predict 30-year cardiovascular outcomes in women.
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: I’m Rick Lange, president of Texas Tech University Health Sciences Center in El Paso, where I’m also dean of the Foster School of Medicine.
Elizabeth: Rick, in genuflection to the European [Society] of Cardiology [ESC] meeting, which was just concluded, why don’t we turn first to the New England Journal of Medicine? Can a single blood test predict anything about 30-year cardiovascular risk in women?
Rick: There appear to be certain biomarkers or blood tests that may be particularly useful. Everybody knows how useful cholesterol can be — specifically LDL [low-density lipoprotein] cholesterol. We also know there are multiple pathways that contribute to cardiovascular disease, one of them being inflammation and another one being an unusual molecule called lipoprotein(a). It’s usually genetically determined. It seems to predict cardiovascular risk as well.
We have a unique opportunity in that there is the Women’s Health Study, which is a prospective cohort of almost 28,000 initially healthy U.S. women who had LDL cholesterol, high-sensitivity C-reactive protein, and lipoprotein(a). They followed them for 30 years to see whether this single blood test can provide any information about their cardiovascular risk.
These women were an average age of 55 at baseline. Each of these measurements predicted cardiovascular risk over the subsequent 30 years, but each biomarker also provided additive information to the other two such that the combination of all three provided the greatest magnitude for the long-term cardiovascular risk.
The 30-year risk rose with each quintile elevation. You say, well, that’s kind of somewhat interesting, but we knew that these contributed to 10-year risk. What we want to do is we want to actually try to lower the risk as early as possible and it seems like this single blood test was predictive.
Elizabeth: Talk to me right now about the status of lipoprotein(a), and, of course, C-reactive protein is something that isn’t just routinely measured.
Rick: LDL cholesterol is routinely measured. Recently, markers of inflammation, C-reactive protein being one of them, have been added to the armamentarium of things that we measure. Now, the lipoprotein(a) is genetically determined and to date we don’t have any way of lowering it. However, there are a number of studies ongoing that show some very promising medications that in the future will likely lower lipoprotein(a). Now, for LDL cholesterol and C-reactive protein, every quintile increase contributed to cardiovascular risk. But for lipoprotein(a) it was just the very top one.
Elizabeth: There are a number of confounders that I would also be interested in exploring. Those would be, of course, BMI [body mass index] and sedentary lifestyle, other markers of inflammation. I absolutely agree with you that taking a look at all of those things early in life and prescribing interventions — which I would start with weight loss, exercise, and a change in diet — before I would go to any meds, and certainly before I went to anything for lipoprotein(a); that’s where I would go with this information.
Rick: Well, you’re right. The other lifestyle change you didn’t mention was smoking cessation. For individuals that have a genetically determined high lipoprotein(a), those lifestyle changes don’t drastically affect that, so it’s going to require pharmaceuticals.
Elizabeth: I’m going to agree with you, and we’re going to see what happens.
Let’s turn to the Journal of the American College of Cardiology. This is an article in press and was also at the [ESC] meeting. This is looking at the effect of semaglutide on mortality and COVID-19-related death. We knew, of course, that semaglutide was starting to look like our latest and greatest; maybe we ought to be adding this to the water.
There is a study that was begun called the Semaglutide Effects on Heart Disease and Stroke in Patients with Overweight or Obesity (SELECT) trial. It enrolled over 17,000 participants who were older than 45 years of age with a BMI that was greater than or equal to 27 kg/m2 with established cardiovascular disease, but without diabetes, to either once-weekly subcutaneous semaglutide 2.4 mg or placebo. This went on for a mean of 3.3 years.
During that time period, of course, a very noteworthy event happened: that was that COVID emerged. During that time, they had 833 deaths, 58% of them were cardiovascular deaths with 42% non-cardiovascular deaths. Those folks who had received the semaglutide had lower rates of all-cause death, cardiovascular death. and non-cardiovascular death.
The most common cause of the non-cardiovascular death was infection. In those folks who were taking the semaglutide, that occurred at a lower rate than it did in those with the placebo. They broke out COVID, of course. Fewer participants treated with semaglutide had COVID-19 related serious adverse events or died of COVID-19 in this time period.
Once again, it’s sure looking like semaglutide has a multitude of benefits, and reducing infection risk, including infection risk with COVID-19, appears to be one of them.
Rick: Over 17,000 patients had established cardiovascular disease, but they did not have diabetes. They were overweight. Semaglutide reduced all-cause mortality by 19%, cardiovascular death by 15%, and non-cardiovascular death by 23%, predominantly because of fewer infectious deaths — in particular, COVID-19 related deaths.
This is the first randomized study to show that a specific therapy that acts through multiple metabolic pathways and also induces meaningful weight loss also reduces all-cause death.
Elizabeth: However, the authors say that this does not appear to have been mediated through weight loss, that they think there is another pathway that’s involved — at least one.
Rick: It looks like the results with regard to mortality were independent of those related to weight loss. I mentioned that this medication has multiple pathways — one is weight loss, but it also has a bunch of metabolic or hormonal pathways as well.
Elizabeth: Well, it’s sure sounding like as we quipped a while ago that we’re going to start seeing a whole lot more use of this medication.
Rick: I think you’re right, Elizabeth.
Elizabeth: Returning to the New England Journal of Medicine …
Rick: I teed this up, should you stop beta-blocker therapy after your heart attack? For decades now, when people have had a heart attack, one of the medicines they are sent home with is beta-blocker therapy, and over 90% of individuals that have had a heart attack are sent home on beta-blocker therapy based upon data that was gathered really decades ago. This was before we were routinely opening arteries.
As a result of these therapies, we have less heart failure, dysfunction of the heart, and lower mortality. The question is, do people still need to remain on beta-blockers? It’s been recommended that after a year you stop beta-blocker therapy.
These investigators did an open-label, randomized, noninferiority trial at 49 different sites in France. Over 3,700 individuals who had had a heart attack were randomized to either continue beta-blocker therapy or after they had been on it for at least a year to stop.
What they discovered is that stopping beta-blocker therapy was not non-inferior. There was an increased risk of complications — specifically, death was the same, heart attack was the same, but there was an increased risk of hospitalizations for recurring chest pain or other cardiovascular reasons. By the way, beta-blocker therapy interruption did not seem to improve the quality of life.
Elizabeth: One of the things that I still remember when beta-blockers lo these many years ago kind of emerged in my consciousness was this upregulation of the receptors. It makes sense to me that if you withdraw them you’re going to end up symptomatic.
Rick: Where receptors end up being a particularly important role is in people that have heart failure. What wasn’t clear is if you’ve had your heart attack and your heart function looks relatively good. Is beta-blocker therapy helpful in those particular individuals? All they do is reduce the risk of having angina — i.e., chest pain — following the heart attack that would result in hospitalization. That’s a relatively soft outcome. The investigators said, well it’s really left to the discretion of the patient and the physician.
Elizabeth: Does this suggest to you that this is an issue that should be examined earlier after someone has an MI and is put on beta-blockers?
Rick: Well, in fact, there is going to be some additional studies coming up that we’re doing right now.
Elizabeth: I would finally note that when I talk to people who are on beta-blockers they do complain of sluggishness.
Rick: But, Elizabeth, you would have predicted that stopping a beta-blocker would improve the quality of life, but it really didn’t do so.
Elizabeth: Finally, let’s turn to Annals of Internal Medicine and this is a three-institution study, one of which is Texas Tech Health Sciences Center in El Paso. It’s a comparative performance of common fecal immunochemical tests, so-called FIT tests, and that’s what I will use.
The authors put forward this idea that, gosh, there is an awful lot of those tests out there. People are selecting them versus colonoscopy or sigmoidoscopy as a screening mechanism for colorectal cancer. Gosh, do we know anything about these multitude of tests?
They decided to compare the performance characteristics of five commonly used FITs and then they used colonoscopy as their reference standard. Their participants were those age 50 to 85 years who were already undergoing screening or surveillance colonoscopy. I have got to give kudos to these participants. They completed all of these five different FIT tests before their colonoscopy, including four qualitative tests and one quantitative test.
What they basically found was that there was a huge variation in these tests looking at the brand of FIT test that you are going to use is really pretty important, clearly pointing to the need to compare these tests and to see, gosh, what do we really need to employ when we’re using them?
Rick: What the FIT tests do is they detect human hemoglobin, red blood cells, in the stool samples. Although colonoscopy accounts for about 60% of colorectal cancer screening in the United States, it obviously requires resources and it carries higher risk than stool testing. But many individuals don’t want to undergo it, so FIT testing is used. It’s a primary screening program for many colorectal cancer screening programs.
There are 26 different FIT tests approved by the FDA and what we have highlighted is they are not all the same. There are implications for the benefits and the cost-effectiveness of using colorectal cancer screening using FIT. For example, tests that have lower sensitivity are going to miss more patients and tests with very high sensitivity will have lower predictive values. They require more colonoscopies to detect patients with actionable findings. Knowing what the sensitivity and specificity is for each of these tests has important implications.
Elizabeth: Among these five tests that they assessed is that sensitivity for advanced colorectal neoplasia for these polyps varied from 10% approximately to 37%, which is a pretty wide range. Similarly, their specificity varied from 86% to 97%. This is a huge range that’s represented just in these five. What would happen if we did all 26 of these tests?
Rick: You’re right, Elizabeth. But even for those with lower sensitivities, the FIT test thing is recommended on an annual basis, whereas the colonoscopy is recommended every 5 to 7 to 10 years. Even if FIT testing has lower sensitivity if you repeatedly do it over the course of time, additively the sensitivity — which goes, for example, from 30% for a single test — could reach 81% after five rounds of screening. Nevertheless, not all testing is the same.
Elizabeth: It’s still disconcerting to note that only 60% of U.S. adults who are eligible for screening get screened.
Rick: Correct. Regardless of what screening technique the patient prefers, unfortunately, many patients don’t get screened at all. Colorectal cancer is preventable and it oftentimes starts as polyps that take years to develop. Removal of those polyps can prevent colorectal cancer and improve colorectal cancer survival.
Elizabeth: On that note then, that’s a look at this week’s medical headlines from Texas Tech. I’m Elizabeth Tracey.
Rick: I’m Rick Lange. Y’all listen up and make healthy choices.
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