Multiple Chronic Conditions and Death; Diabetes Treatment for Gout

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 the impact of lipoprotein(a), or Lp(a), frailty as a predictor of dementia, a diabetes medicine in kidney stones and gout, and the impact of multiple chronic medical conditions on hospitalization and death.

Program notes:

0:40 Diabetes treatment, kidney stones, gout

1:40 To prevent kidney stones need to treat 20

2:40 How do other diabetes meds compare?

3:42 Multimorbidity, hospital admission, and death

4:42 Sort combinations to calculate risk

5:42 Inadequate resources in the winter

6:44 Person centered approach needed

7:10 LDL not the whole story

8:10 Risk related to both LDL and Lp(a)

9:10 Recommend Lp(a) measurement

9:36 Frailty as a predictor of dementia

10:39 Risk varied from 20-75% increased risk

11:42 Number of factors to assess frailty

13:09 End

Transcript:

Elizabeth: Can frailty help us determine who is at risk to develop dementia?

Rick: Using diabetes treatment to prevent kidney stones.

Elizabeth: Looking at combinations of multiple long-term conditions and the risk of hospital admission or death.

Rick: And LDL cholesterol isn’t the whole story.

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, I’m going to toss the ball to you. Which of these would you like to start with?

Rick: Let’s talk about diabetes treatment and the possibility that it can actually prevent kidney stones and may help prevent gout as well.

Elizabeth: And that is in the BMJ.

Rick: We have talked recently about the many benefits of what’s called an SGLT2 inhibitor. It’s a medicine that’s been found to be very useful in individuals that have hyperglycemia due to type 2 diabetes. Not only does it lower the sugar, but it also helps prevent heart failure, for example.

Here is what we noticed in individuals that use it. It tends to lower their serum uric acid levels. Now, uric acid when elevated is what causes gout. The uric acid crystallizes in the joint and it causes gout. That same uric acid can crystallize to cause kidney stones.

They looked at over 20,000 patients that had kidney stones and type 2 diabetes, some of whom had gout. What they discovered is if you did use an SGLT2 inhibitor it did significantly decrease the risk of kidney stones and the risk of gout. To prevent a kidney stone, you needed to treat 20 individuals. For people that have recently had a kidney stone attack, you only needed to treat five of them to prevent a subsequent event. This may influence individuals or influence providers in prescribing this particular medication, especially in individuals that are known to have kidney stones or in individuals that are known to have gout.

Elizabeth: You didn’t mention what was the impact on the gout, the gout attacks, and the folks who were on the SGLT2 inhibitors.

Rick: It lowered the gout rate by about 28%.

Elizabeth: That’s really significant for folks who have gout because, goodness, that is just such a painful condition and just so troubling and disabling, honestly.

Rick: Yeah. Whenever we see results like this, we want to know, is there a biologic plausibility? In fact, the SGLT2 inhibitors do a couple of things. One is they increase urine volume. We know that that can reduce the risk of recurrent kidney stones.

Elizabeth: I wonder about long-term cardiovascular disease risk in folks with type 2 diabetes who are being treated, and we know that there is efficacy with some of these other medicines with that.

Rick: The SGLT2 inhibitors are used to prevent heart failure or heart failure readmissions in individuals that have diabetes. Whenever we try to decide what medicines we’re going to treat somebody with, we look at the primary effect, and the other is, can we get secondary benefits from it?

Elizabeth: Once again, let’s go to some of the other literature looking at the impact on obesity. Even today, I saw a study that I didn’t pick for us to talk about, but this notion that somehow substance use disorder might be impacted by the use of some of these agents, and those are not the SGLT2 inhibitors.

Rick: Right. You have the primary effect. You say, is there a secondary effect I’d like to take advantage of? Is somebody obese and that may sway more towards one medication, or does someone have a substance abuse disorder? We know that these particular agents can help in that as well.

Let’s put this in our back pocket. It’s knowing that the SGLT2 inhibitors can prevent kidney stones and gout in individuals that have those and that may sway individuals to take these particular agents.

Elizabeth: Okay. Remaining in the BMJ, this is a really enormous study. It feels to me like — and I don’t know if this is true, if it feels like this to you too — those folks in the U.K. are doing these really enormous studies with these giant data sets.

They are looking at the combinations of multiple long-term conditions and the risk of hospital admission or deaths during the winter in ’21 to ’22 in England. They had data for 48 million+ adults, of whom 15 million, or 31.2% of their population, had multiple long-term health conditions. If you had multiples, what was your overall risk of hospitalization and death?

What they determined was that overall, your risk of hospital admission was 11 times that of folks who did not have multiple chronic conditions. Then they broke those out into various combinations of cancer, chronic kidney disease, cardiovascular disease, and type 2 diabetes, and were able to sort them to determine these combinations were all deleterious. All of them increased somebody’s risk of hospitalization and death in orders of tens magnitude.

They did find that the one condition that was at every single one of the combinations was cardiovascular disease. Cardiovascular disease combined with dementia appeared in all of the top five combinations of long-term conditions that would predict mortality.

The authors then conclude that this is all really interesting. It might help us to highlight groups that we know that are at a special risk to be targeted for interventions that might help to keep them out of the hospital and keep them not developing respiratory conditions, which, of course, is what is the proximal cause of death for many of them.

Rick: Yep. The reason why they picked the winter months is in the United Kingdom, that’s when the pattern of increased hospital admissions really hits them. They don’t have adequate resources during that particular time, so they are trying to identify those high-risk individuals.

As you mentioned, Elizabeth, 31% of their population — of their 48 million individuals — had multiple comorbidities. Most of the hospitalizations occur because of respiratory diseases, things like pulmonary infections and asthma. There were other things as well, though: falls, atrial fibrillation, heart failure, pulmonary embolism, and stroke. Those things rounded it out.

Hopefully, this information will allow them to target those individuals’ chronic conditions and co-manage them to try to minimize the risk a patient will need hospitalization during the winter months.

Elizabeth: They do mention, of course, that when anxiety or depression is added to these combinations, it also results in an increased risk. Then when they survey the literature, they say that in the past, this prevalence of multiple long-term conditions in diverse populations varies between 37% and almost 40% across Europe.

Finally, they trot out this notion that we have talked about so many times. They call on a person-centered approach that focuses on personalized care planning, shared decision-making, and coordinated management, which we would love to see that just globally, wouldn’t we?

Rick: Yeah. Here, I am as a cardiovascular specialist. It’s easy for specialists not to see the whole picture and not to manage their chronic kidney disease or the cancer, or the depression, or the osteoarthritis. We need a quarterback that’s actually looking at all of those things.

Elizabeth: Indeed. Let’s turn to Circulation and you saying LDL is not the whole story.

Rick: No. For our listeners that may not be aware, LDL stands for low-density lipoprotein. It’s a type of cholesterol. We want to lower as much as possible. But there are other types of lipoproteins and one of those being lipoprotein (a) or what’s called Lp(a).

Now, one of the reasons we focus on LDL cholesterol is we’ve clearly associated them with heart disease and we’ve shown that by lowering the LDL cholesterol we reduce the risk of heart attacks. Lp(a) is incredibly important when predicting the risk as well.

What these investigators did was they looked at the contribution of lipoprotein (a) and LDL cholesterol in cardiovascular risk. They looked at that among almost 28,000 participants who were in six different placebo-controlled statin trials. These are individuals that have high LDL and we’re going to lower it with a statin. They looked at the risk of coronary heart disease events.

What they discovered is that even in statin-treated individuals, the risk of these events was related not only to the level of LDL, but also to the level of Lp(a). If your Lp(a) was elevated to the highest quartile, your risk of cardiovascular events was still increased almost 40%. If both LDL and lipoprotein (a) were elevated, it elevated your risk by 90%.

We really don’t have many good ways to lower Lp(a), yet. There are ongoing clinical trials in which we’re going to be able to significantly lower it. The Lp(a) is genetically determined. You can’t really change it with your diet. You can’t change it with your lifestyle. We’re only going to be able to modify the pharmacologic agents and the only one we have now that does that are the PCSK9 inhibitors that are usually reserved for those individuals that have an elevated LDL that isn’t lowered with a statin.

Elizabeth: What’s interesting to me about this is this has been emerging on the horizon for quite some time. Talk to me about measurement of this and routine measurement of this.

Rick: Well, because it’s genetically determined, you only need to measure it one time and you don’t have to be fasting for it.

Elizabeth: For this moment, would you recommend that people have that measured?

Rick: I would. First of all, it’s inexpensive. It’s easy to do. That result that we have now will still be valid for a year or two when these treatments become available. But I also think it helps to drive therapies. Everything I can control we’re going to be very strict about.

Elizabeth: Finally, let’s turn to JAMA. Can we use a frailty trajectory to predict dementia?

That’s something, of course, that is a bit of a Holy Grail. How can we determine if you’re at risk to develop dementia? If and when we have agents that are effective, this would help us to identify who might benefit from those.

They look at data from four prospective cohort studies: the English Longitudinal Study of Ageing, the Health and Retirement Study, the Rush Memory and Aging Project domestically, and the National Alzheimer Coordinating Center. From 1997 through 2024, this included individuals who were 60 years or older without cognitive impairment at baseline. They ultimately looked at data from just shy of 30,000 participants with a mean age of 71.6 years, the majority of whom were female. They ended up with 3100+ cases of incident dementia and they also looked at this frailty trajectory.

Frailty, especially as it accelerates, we can take a look at that 4 to 9 years in advance or identify it before incident dementia. Actual risk that was associated with it varied between about a 20% increased risk to about a 75% increased risk.

They say, “Frailty — maybe we can identify this early and it will tip us off that someone’s at risk for dementia.” They do opine that there are interventions for frailty that might end up intervening with regard to the development of dementia.

Rick: But first I’d ask is, how do you determine if someone’s frail or not? In this study, there were 52 different things that compose the frailty index. Anything from, do they have any comorbid conditions, how quickly they’re able to walk, or can they climb upstairs, or can they reach or pull or lift pounds. Those kinds of things. It can indicate advanced biologic aging. Some people age faster than others, and that’s what the frailty index is meant to identify.

It is interesting that this frailty index precedes dementia. If you can somehow treat the frailty, maybe we can reduce the incidence of dementia. That’s a great hypothesis. It’s going to take a while to determine whether we can do that.

Elizabeth: I agree. I too was totally impressed by the number of factors they included to assess frailty. They do say that their interventions involve both exercise, delivered in group settings, nutritional supplementation, this increased notion of socialization, kind of getting people out and about.

Once again, we have taken a look at those interventions that try to employ a multitude of factors and sometimes we have seen a positive outcome and sometimes we haven’t. The flip side is also intriguing to me. The data on hearing aids and on then the development of dementia does seem to determine that if we ameliorate that particular disability we can impact on the development of dementia, so I at least am hopeful.

Rick: All the things that you mentioned, all those lifestyle changes, positively impact frailty, pretty much every comorbid condition, and also can positively impact the development of dementia. It’s interesting. I have many patients in their 70s, 80s, and some in their 90s that said, “If I knew if I was going to live this long, I would have lived a little bit differently when I was younger.” That’s probably good advice.

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.