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 a new agent for high triglycerides, the impact of low testosterone on mortality in men, ultraprocessed foods and mortality, and cardiovascular risk assessment improvement.
Program notes:
0:40 Improving assessment of cardiovascular risk
1:40 Trip through electronic medical record
2:40 Some cost and side effects
3:00 Association of ultraprocessed foods with mortality
4:00 4% higher all cause mortality
5:00 Surprised that cancer and CVD mortality not increased
6:00 Evidence in other studies for demyelinization
6:36 New treatment for high triglycerides
7:40 Injected medication
8:40 Doesn't lower cholesterol
9:00 Low testosterone in men and mortality
10:00 Low testosterone increased mortality
11:04 Less binding globulin?
12:55 End
Transcript:
Elizabeth: Ultra-processed foods and mortality.
Rick: A new therapy for individuals with high triglycerides.
Elizabeth: What's the impact of low testosterone on mortality for men?
Rick: And can cardiovascular risk assessment be improved?
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: Rick, as a cardiologist, I'm going to kick the ball right to you and turn straight to JAMA, looking at improving assessment of cardiovascular risk.
Rick: When we talk about preventing cardiovascular disease, the first thing we have to do is assess somebody's risk and then we try to target those risk factors. Well, we have traditional risk factors and they predict about 70% to 80% of the variability of the cardiovascular risk that we see in the general population. Can we actually improve our cardiovascular risk assessment?
What these investigators did is they looked at the incremental value of several biomarkers. These are blood tests that are commercially available: troponins, natriuretic peptides, and high-sensitivity C-reactive protein (hs-CRP). Those are biomarkers that either look at inflammation or cardiac injury, or some response to stress on the heart. When they used these in addition to the traditional risk factors, in fact they did improve risk assessment. But it was really very modest.
How could you use these? For most individuals, just the routine risk factors, it doesn't require anything special. You could actually do a trip to the electronic medical record and get most of the risk factors without drawing any blood. If you're already high-risk, then these biomarkers probably don't help. If you're low-risk, they probably don't help. But in that intermediate risk, when you're trying to decide how aggressive to be with therapy, these biomarkers may tip you into being more aggressive or less aggressive with regard to the medical therapy you prescribe for somebody.
Elizabeth: This has been somewhat of a Holy Grail, hasn't it? I know that we have talked about somehow improving this cardiovascular risk profile for folks many times. Specifically, we've also talked about sex differences, since so many of the studies and assessments previously have been done in men. Tell me, in your opinion, how important is it really to capture that additional part of the curve when you're trying to decide if somebody needs some kind of coping strategies for managing their risk?
Rick: It really only pertains to the people that are just kind of on the edge, and you say, "Am I going to be aggressive or not?" Because there are some costs associated with the medications, and side effects associated with the medications. If they are not going to significantly change your risk, then I probably wouldn't start them. I think it's going to be a fairly narrow part of the population that we see that this is going to apply to.
Elizabeth: Right, and keep people from taking medicines that they may not need, which is always a great outcome.
Let's turn to The BMJ and this study got a lot of attention. It was the "Association of ultra-processed food consumption with all-cause and cause-specific mortality." They used in this study one of our usual suspects, the Nurses' Health Study, and the Health Professionals Follow-up Study -- both nurses and physicians in the United States that were recruited to this and followed for quite a long time. In this case, they had 74,000+ women and almost 40,000 men with no history of cancer, cardiovascular disease, or diabetes at baseline.
What they looked at was the association of ultra-processed food intake, measured by semi-quantitative food frequency questionnaires every 4 years with all-cause mortality and cause-specific mortality due to cancer, cardiovascular, or other causes, including respiratory and neurodegenerative causes. What they ultimately determined was that compared with those in the lowest quartile of ultra-processed food consumption, participants in the highest quartile had a 4% higher all-cause mortality and a 9% higher mortality from causes other than cancer or cardiovascular disease, which I thought was a real curiosity that there were no associations found for either cancer or cardiovascular mortality in this analysis. What are your thoughts?
Rick: First of all, I think it's a very well-done study, as you said, with a long-term follow-up of over 30 years.
A couple of caveats. One is these are relatively healthy people, primarily a Caucasian population, so I'm not sure that this answers that question just across the globe. It is nice to know that the increased mortality is really fairly modest. They did note that the associations varied across different types of ultra-processed foods and the meat, poultry, seafood-based, ready-to-eat products showed particularly strong associations. Those are the ultra-processed foods that we really want to try to avoid. There are contaminants, additives, things of that nature, as well.
I was again surprised that cancer and cardiovascular mortality wasn't increased. Nevertheless, if we can avoid them, I think that's helpful. Also, they don't have the same nutritional value as other types of non-processed foods.
Elizabeth: I think your point is really well taken that this is a relatively healthy and educated population with few of the social pressures that might be experienced in other populations where there might be a more robust association. I would also note that they cite these statistics in their introduction, saying that ultra-processed food consumption accounts for 57% of daily energy intake among adults and 67% among youth in the United States. That's high consumption and I'm wondering how we're going to get our arms around that.
The other thing is that their association was most robust for neurodegenerative diseases. I, for one, would sure like to know what mechanism might account for that association.
Rick: There is evidence -- not in this study, but in others -- that the ultra-processed food is linked to a higher risk of demyelinization, that's a precursor to multiple sclerosis, decreased cognitive function, and even dementia. In fact, there are studies that show that ultra-processed diets that are high in ultra-processed foods may drive neuroinflammation and actually impair the blood-brain barrier. The inflammation involves not just the body, but also the brain as well.
Elizabeth: More to come on this one, no doubt. But it's sure sounding like for one thing, giving up on ultra-processed meats is probably a good idea even in the short term. Let's turn to the New England Journal of Medicine.
Rick: A new treatment for high triglycerides. It's a me-too drug because this is not the first in kind, but it's an improvement over another therapy for high triglycerides. A normal triglyceride is below 150, that's the blood level, and we consider it elevated at 150 to 450. There are people that have this familial type that is genetic, that is the highest, 500 to over 1,000 or 1,100. It increases cardiovascular disease, but it also increases the risk of pancreatitis.
The medications we have are only modestly effective. This is a therapy -- it's a genetic-type therapy that is called an [antisense oligonucleotide]. Typically what happens is the building block is DNA for a protein and the intermediate is what's called messenger RNA. This particular medication is called Olezarsen. It is an injectable once monthly that binds to the messenger RNA (mRNA) to prevent the protein from being manufactured. This particular protein is one that's associated with increasing or decreasing triglyceride levels.
In this particular study, they took 154 patients that had elevated triglycerides and a single monthly injection could decrease the triglyceride levels by 50%. There were very few side effects, mildly elevated liver function tests, but overall well-tolerated. It's an improvement over the other medication because this one actually binds to the liver and the liver is the source of the protein that we're trying to address.
The downside is it's an injection. It's going to be expensive. The proof of the pudding is we know we can lower triglycerides, but does it really lower cardiovascular events? We've done other things that have lowered triglycerides and it really hasn't. Now that we know that this can lower triglycerides, now we need to be able to say, "In people at high risk for cardiovascular events, if we give them this medication, does it prevent heart attacks, strokes, and heart failure?" That's where the follow-up studies will focus.
Elizabeth: Clearly, before we go authorizing a medication that's going to be expensive and inconvenient to take, we need to discern whether or not it actually helps.
Rick: Right. This medication, although it lowers triglycerides, it doesn't lower LDL cholesterol and we know that that's also a risk factor. It's nice to know that people who have very high triglycerides and develop pancreatitis as a result, we can lower their triglycerides substantially and we know it decreases the risk of pancreatitis.
Elizabeth: Avoiding pancreatitis, of course, is a very good outcome.
Finally, let's turn to the Annals of Internal Medicine. This is another question I feel like we have been talking about ad nauseam: what about levels of testosterone in men and all-cause cardiovascular mortality and incident cardiovascular disease?
This study purports to be the first one that actually is using a different method for assessing the levels of testosterone versus all the rest of them. This is a meta-analysis. They look not just at testosterone, but also sex hormone-binding globulin (SHBG), luteinizing hormone (LH), dihydrotestosterone (DHT), and estradiol. Their primary outcomes are all-cause mortality, cardiovascular death, and incident cardiovascular disease events. They also attempt to correct for all kinds of things: BMI, age, marital status, alcohol, smoking, physical activity, and comorbidities.
What they find -- they used mass spectrometry to assess this. At the end of the day, they find that men with low testosterone, high luteinizing hormone, or very low estradiol concentrations had increased all-cause mortality. Sex hormone-binding globulin concentration was positively associated, and the other metabolite of testosterone was non-linearly associated with all-cause and cardiovascular disease mortality. The ultimate question is, "OK, and if we give exogenous testosterone, is that going to ameliorate any of this?"
Rick: Yeah. When we talk about low testosterone, we're talking about concentrations below 213. That low testosterone can be due to either hypogonadism -- that is, we're producing less. Keep in mind that testosterone binds to this sex-binding globulin. It's a protein and it can also be low because that protein is low.
By the way, in the former instance when there is hypogonadism -- low testosterone and high LH -- that is associated with increased cardiovascular mortality. But if the testosterone was low just because you have less binding globulin, that doesn't affect mortality at all. If men have low T, then it needs to be followed up by assessing the sex-binding globulin. If that's low too, they probably don't need to do anything different. If it's low T because of hypogonadism, they probably should receive some supplement to improve cardiovascular mortality.
Elizabeth: What's the genesis of this? The authors even write, whether due to underlying testicular cause or centrally mediated -- and that's because of all these hormone pathways -- they are able to see that there is this association with all-cause mortality. That would argue, at least for me, for administering testosterone via patch.
Rick: I would agree with you. It makes the case for treating individuals that have testosterone levels below 213 or below 200.
Elizabeth: My last question for you would be, would you employ mass spectrometry in order to assess this while administering exogenous testosterone and then look at long-term outcomes to really answer this question?
Rick: Your point is well taken because one of the virtues of this particular study is they used a more precise way of measuring this. It's more accurate. If you're going to assess this, then one should say, "Is the lab assessing it by mass spectrometry?" That's the most accurate way of doing so. You surely don't want to treat somebody with medication based upon inaccurate results, or avoid treatment because of inaccurate results as well. It's one of the few times that you need to dig a little bit under the hood and find out exactly how they are measuring the testosterone levels.
Elizabeth: Very good. 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.