Aug 2, 2021
This week's episode features author Shih-Chuan Chou and editorialist Alexander Sandhu discuss the article "Impact of High-Deductible Health Plans on Emergency Department Patients With Nonspecific Chest Pain and Their Subsequent Care."
Dr. Carolyn Lam:
Welcome to Circulation on the Run, your weekly podcast summary and backstage pass to the Journal and its editors. We are your co-hosts, I'm Dr. Carolyn Lam Associate Editor from the National Heart Center and Duke National University of Singapore.
Dr. Greg Hundley:
And I'm Dr. Greg Hundley Associate Editor, Director of the Pauley Heart center at VCU health in Richmond, Virginia.
Dr. Carolyn Lam:
Greg, I am so excited about today's feature discussion that's going to be about high deductible health plans and their impact on emergency department patients with chest pain and their subsequent care. Now, I can tell you as coming from outside of US, I learned so much from this discussion so everybody's going to want to hear it. But before we go there, let's discuss the other papers in today's issue. Greg, do you have a paper?
Dr. Greg Hundley:
You bet. Thanks Carolyn. So my paper is going to really evaluate a very interesting question about the role of measuring lipoproteins and their subfractions in patients, not with coronary disease, but peripheral arterial disease. And it comes to us from Dr. Scott Damrauer from the University of Pennsylvania School of Medicine. So Carolyn lipoprotein related traits have been consistently identified as risk factors for atherosclerotic cardiovascular disease, just like we said. Largely based on their role in progression of coronary artery disease, but the relative contributions of these lipoproteins to those with peripheral arterial disease really haven't been as well defined. So these authors leveraged a large scale genetic association data to investigate the effects of circulating lipoprotein related traits on peripheral arterial disease risk.
Dr. Carolyn Lam:
Interesting. So what did they find, Greg?
Dr. Greg Hundley:
Right, Carolyn. So ApoB was prioritized as the major lipoprotein fraction usually or almost causally responsible for both peripheral and coronary artery disease risk. Extra small VLDL particle concentration, we'll call that excess VLDLP was identified as the most likely subfraction associated with peripheral arterial disease risk while large LDL particle concentration was most likely the sub fraction associated with coronary artery disease risk. And genes associated with excess VLDLP and large LDL particle concentration included canonical ApoB pathway components although gene specific effects were quite variable. And then finally Carolyn, lipoprotein A was associated with increased risk of peripheral arterial disease, independent of Apo protein B. So therefore Carolyn, I think the take home message from this study is that ApoB lowering drug targets and ApoB containing lipoprotein subfractions had really diverse associations with atherosclerotic cardiovascular disease and distinct subfraction associated genes suggested that possible differences in the role of these lipoproteins really are involved in the pathogenesis of peripheral arterial as opposed to coronary arterial disease.
Dr. Carolyn Lam:
Wow. Thanks Greg. Hey, it struck me that we haven't had a quiz in a long time. Okay, but we're not going to do it now. Don't choke because this one's kind of tough. I don't think I could even answer it. What is phospholamban?
Dr. Greg Hundley:
Well, let me guess. I remember having this, I think. Let's just... Carolyn I do not know what phospholamban is.
Dr. Carolyn Lam:
Let me just tell us all. Phospholamban is a critical regulator of calcium cycling and contractility in the heart. The loss of arginine at position 14 in phosphate lanvin is associated with dilated cardiomyopathy and a high prevalence of ventricular arrhythmias. But how this deletion causes dilated cardiomyopathy is still poorly understood. And there are no disease specific therapies. And hence today's paper, which comes from Dr. Karakikes and colleagues from Stanford university school of medicine. What they did is they employed human induced pluripotent stem cells and CRISPR Cas9 gene editing technologies to create an in vitro model of dilated cardiomyopathy associated with this phosphate lanvin 14 deletion mutation. Single cell RNA sequencing revealed the activation of an unfolded protein response pathway, which was also evident by significant up-regulation of marker genes in the hearts of patients with the deletion. Pharmacological and molecular modulation of this unfolded protein response pathways suggest a compensatory role in this type of dilated cardiomyopathy. Augmentation of the unfolded protein response by the small molecule BIP protein inducer X Millia rated contractile dysfunction.
Dr. Greg Hundley:
So Carolyn, tell me what are the clinical implications?
Dr. Carolyn Lam:
Well, these findings suggest a mechanistic link between proteostasis and the phospholamban 14 deletion induce pathophysiology that could be exploited to develop a therapeutic strategy for this kind of cardiomyopathy. The study also highlights how human induced pluripotent stem cells and cardiomyocyte modeling could be combined with small molecule testing as a paradigm for studying genotype, phenotype associations in heart disease.
Dr. Greg Hundley:
Very nice Carolyn. Well, my next paper comes to us also from the world of preclinical science. And it's from Dr. Philip Marsden from the University of Toronto. And Carolyn endothelial nitric oxide synthase or eNOS is an endothelial cell specific gene predominantly expressed in medium to large size arteries where endothelial cells experience athero-protective laminar flow with high shear stress. Now disturbed flow with lower average shear stress decreases eNOS transcription, which leads to the development of atherosclerosis especially at bifurcations and in the curvatures of arteries. So the prototypical arterial endothelial cell gene contains two distinct flow responsive SIS DNA elements in the promoter. The shear stress response element and the Kruppel-like factor or KLF element. Previous in vitro studies suggested there're positive regulatory functions on flow induce transcription of the endothelial genes, including eNOS. However, the in-vivo function of these SIS DNA elements remains unknown.
Dr. Carolyn Lam:
Wow. So what did these investigators do, Greg?
Dr. Greg Hundley:
Right. So Carolyn the authors report for the first time that the shear stress response element and the KLF elements are critical flow sensors necessary for a transcriptionally permissive hypo methylated eNOS promoter in endothelial cells under chronic shear stress in vivo. Moreover endothelial nitric oxide synthase expression is regulated by flow dependent epigenetic mechanisms, which offers novel mechanistic insight on eNOS gene regulation in atherogenesis.
Dr. Carolyn Lam:
Nice. Thanks Greg. Well, let's go through what else is in this week's issue. In a cardiovascular case series, Dr. Ribeiro discusses the Platypnea-Orthodeoxia Syndrome, a case of persistent hypoxemia in an elderly patient. In ECG challenge, Dr. Challenge shows a case of diffuse St. Segment elevation with idiopathic malignant ventricular arrhythmias. There's an exchange of letters between doctors Wang and Sattler regarding the article cross priming dendritic cells exacerbate immunopathology after ischemic tissue damage in the heart. And there's an On My Mind article by Dr. Mullasari Sankardas on of occlusions, inclusions and exclusions time to reclassify infarctions. So interesting.
Dr. Greg Hundley:
Very nice, Carolyn. So I've got a couple of things in the mail bag. There is from Professor Kunfu a Research Letter entitled PTP MT-1 is required for embryonic cardio lipid biosynthesis to regulate mitochondrial morphogenesis and heart development. And then finally our own Bridget Kuhn has a cardiology news entitled vegan diets that are culturally aligned with traditional soul food gained popularity among black individuals. Well Carolyn, I can't wait to get to your feature discussion today.
Dr. Carolyn Lam:
Me too. Today's feature paper is about the impact of high deductible health plans on emergency department patients with non-specific chest pain and their subsequent care. I'm so pleased to have with us the first author Dr. Andrew Chou from Brigham and Women's hospital, as well as the editorialist Dr. Alexander Sandhu from Stanford university. Welcome gentlemen, please tell us about your current study.
Dr. Andrew Chou:
Yeah, so I think the reason we did this study was really obviously aware of the context, but also me working as an emergency decision. So anybody in the ED will now that, there's all kinds of versions of chest discomfort that comes through the ED and they always are worried about heart attack. And we do this testing kind of day in day out, it gets kind of inundated. So a lot of people have put thought into what we should do in the emergency room. We should get ECG, we should care cardiac enzymes when we're worried about it. But what really quite remains uncertain is really what to do afterwards. We get this patient, we test them, we didn't really find heart attacks, but there's a lot of uncertainty about what to do after. Do we do stress test, do we hospitalize them to get the stress test or other testing.
Dr. Andrew Chou:
As a result, there's a lot of variation in care. And I think partly because of that, they're kind of the shared decision making came out of that. As a part of the solution was to involve patient via, Hey, here are your risks. Let's talk about whether or not this would make sense for you to stay, get testing among other decisions. But what's always interesting to me is that even though we have this push towards having patients have kind of needing to make these decisions because of money, we don't really talk about costs and even their sort of sense of pride about, oh, we don't want to talk about costs. We just want to be the best medical treatment for you, but cost is such a reality for the patients. So, that's kind of the motivation behind getting this study done. So the way we wanted to test it was to set it up as closely as possible to run my trial but knowing that it's not really possible in the real world to do something like that.
Dr. Andrew Chou:
So we had to be pretty selective about who we include as a study population. So the first thing we did was we took essentially a large national insurer and their claims database. We look at only the people who enrolled in insurance products through their employer. So employers in the US can choose what type of plan they want to offer patients. And we only chose employers that offer only one type of insurance at a time within each year of a plan. So what we did is we chose people who had essentially two years of enrollment. And in the first year, they all have to have loaded up full plans.
Dr. Andrew Chou:
Meaning deductibles are less than $500. It's still a lot of money, but it's less compared to... The second year either they still have low deductible plan or the experimental group is going to be a group of people who employer only offer high deductible plan, which we define as having deductible greater than $1,000. So that sort of set up a control and experimental group with a similar baseline and then a different followup period of a year. And then we also did additional matching by employer characteristics and their own, the member characteristics to kind of make them as close as possible in terms of compabilities, age, as well as employer size, which we find to be a really big factor. Because large employers tend to have lower deductibles because they can risk care a lot better among their employees where a small employers like companies with five, 10 employees tend to have high deductible plans. So we use that population to compare essentially what happens after a certain company switch to kind of calculate the effect of the high deductible plan.
Dr. Carolyn Lam:
Great. Very novel design. But could you please tell us your results?
Dr. Andrew Chou:
Yeah, so we found is that once the employees from the companies that switch, there were less ED visits that ended up with a diagnosis of chest pain. This is important to bring in also the nuance here, which is that these are ED visits that effectively are not have been seen and test it. And they don't have a severe diagnosis like a heart attack or other significant cardiac issues that were found at least during the initial ED stay. And that decreased, which sort of makes the question whether or not these decreased visits or either where they just another chest visit without really other diagnoses or are they visits that actually have diagnosis. The other thing we found was also that there's a decrease in admissions from these ED visits actually. And majority of it, even though when we did our study, we actually were looking at admissions through the 30 days after these ED visits.
Dr. Andrew Chou:
But we found that the majority of difference is actually the admissions directly from these initial ED visits with time is just horrible. Two more things we found was that the amount of testing that was done after the ED visits, or not really consistently decreased because of high deductible, some tests really didn't have a difference and some more invasive and expensive tests did have some differences. But if you account for the decrease in the chest pain ED visits, then they're not really that notable. But the last finding, which perhaps is the most interesting of which is that there seems to be an increase in heart attack diagnosis and admissions after these visits for chest pain and our statistics for the entire study population actually wasn't significant. But we decided to look at the subgroup patients from poor communities who presumably have lower income and found that the same findings in this group was actually statistically consistent and so we felt comfortable reporting that. So I think that was probably the most interesting finding from our study.
Dr. Carolyn Lam:
Right. Thanks Andrew. Alex, I have to bring you in here. I really love the editorial love that you said to go or not to go as the title. But could you put these findings in context, please?
Dr. Alexander Sandhu:
Yes. Happy to and thank you for having me. I think studies like this study by Andrew and colleagues are incredibly important as we make health policy decisions that have large impacts on clinical decision-making for both patients and clinicians. It's important that we study them to understand how they impact patient decision-making clinical outcomes and costs, because obviously that can have important ramifications for future design at the end detecting unintended consequences. I think this study adds to a large body of work done by Andrew and his colleagues, really helping us to understand the implications of high deductible health plans on patient decision-making and subsequent outcomes. This is an incredibly important topic because of the proliferation of high deductible health plans over time and then potentially since the advent of the Affordable Care Act with fixed premiums leading to more and more cost sharing for patients. And it's really critical that we understand how that cost sharing impacts patients.
Dr. Alexander Sandhu:
And I think that chest pain is a wonderful test because chest pain can be something very serious. It's almost universal that when patients have acute onset chest pain, that a clinician asks them to go to the emergency department for further evaluation. However, we also have a large body of evidence that suggests that the large majority of chest pain episodes are not serious and don't end up needing additional treatment. So it's an area that I think both you could imagine decreased utilization once you applied cost sharing to patients. But what were you very much worried about the unintended consequences of people not going to the emergency department, if it's a serious condition. I think this was a well-designed quasi experimental analysis to look at the lower risk, but majority of episodes of chest pain where they're non-specific and not resulting in acute coronary syndrome and to try to demonstrate it that the high deductible health plans do lead to reductions in those episodes.
Dr. Alexander Sandhu:
I think as Andrew said, one of the most fascinating findings was this increase in acute MI's it was consistently significant amongst the low-income patients, but was not related to patients that were discharged because of potentially the effects of the high deductible and then came back in with acute MI's but were actually acute MI's during the initial admission. I was wondering if Andrew could maybe both explain that nuance a little bit more, which you get into the discussion of that paper, and then also walk us through maybe some thoughts that you and your study team had for causes for that potential finding.
Dr. Andrew Chou:
Yeah, absolutely. Thanks for raising that. So I think going into it initially, our hypothesis was really that, but when we first saw it, our initial thought was that, oh, maybe perhaps after they're discharged, they're supposed to get testing and patients or then follow up with their doctors. So they have increased poor outcomes. And so after that thought, that's when we did the kind of subgroup analysis looking at just patients who were discharged versus those who were admitted when they were diagnosed with chest pain at their initial ED visits. And exactly what we found is that the difference is really among people who were admitted initially, which is surprising to us. So I think what that signals to us is that our initial thought was not correct in the sense that this is not really a result of lack of followup or didn't intend to the testing that they were scheduled or didn't go see their doctor afterwards. But really like patients who are showing up in the ED already are more prone to perhaps having a heart attack.
Dr. Andrew Chou:
And so it really points to which is what you mentioned at your program, which we totally agree as well, that more upstream factors is affecting this. Could it be that they don't tend to take their medications as they should, or they didn't go to their doctors for checkups as they should, or they could have had earlier identification of heart problems if they have more perhaps milder symptoms beforehand until before the ED visits that could have presented certain things. So, that's hard to say. I do think that there is a... One of my mentors in this paper, Dr. Wareham, who has done a ton of work in the space of high deductible plan with kind of chronic disease management, they have definitely shown a lot of differences when patients have higher cost sharing. They'd certainly defer a lot of carriers, especially in diabetics have more complications and it might be a similar scenario here that which would make the most sense and fits the best with our findings here.
Dr. Carolyn Lam:
So that's a great question Alex and great insight Andrew. I think at this point, I need to ask you both. So what overall do you think is the clinical implication or there'd be any practical next step that you think should follow from this? Maybe I'll let Andrew start and then Alex finish?
Dr. Andrew Chou:
Sure. Thank you. I think there's kind of... I think two aspects to this one is really broader policy changes. I think if anything, it's quite uncertain whether or not the reduction in ED visits for chest pain is something detrimental. It's unsure whether or not the reduce admission is detrimental. But what is certain is that especially in lower income population certainly feels the higher out-of-pocket costs a lot more. And if there is an unintended consequence, it will certainly be magnified in this population. And in fact, I think a couple of past studies who having compared really high income versus low income population has found that really, high income patients tend to do okay and they're able to pick and choose appropriately of type of care they need. Whereas low-income patients tend to have really unanticipated changes. So, really trying to minimize the impact for low-income patients is going to be important policy direction.
Dr. Andrew Chou:
And there are a number of ways of doing it. I think there certainly is an increasing trend for companies to fund the health savings account, which is actually a tax deferred almost like investment accounts or certain fund to help them offset some of their healthcare out-of-pocket costs. But the other aspect of it, which I think is all a bit harder to push for is really for employers and insurance to just keeping their account patient's income when they're kind of pushing forward products for a high deductible plan. So low-income patients should just not have quite as big of a deductible as the high income earners do. But a different aspect it's really clinically for clinicians. It's tough because I think insurance put this forward because they want to influence patient decisions before they even see the clinician. But after they decide to come visit clinician, I think the clinician should be aware of the financial reality for the patient when making these decisions.
Dr. Andrew Chou:
But it's really hard for me to think about whether or not this is going to be a good thing for the patient or not. And one of the biggest concerns for really my colleagues in the department is really whether or not if we are really talking poor patients out of certain care by reviewing their financial reality with them and by through that are we essentially discriminating against other patients. So that's really a big unknown. I think that's definitely an area that we should definitely heavily invest in research because we're just pushing forward with price discussion for care to encourage price discussion at the clinic here without really knowing what's going to happen.
Dr. Carolyn Lam:
Yeah. Wow. Alex?
Dr. Alexander Sandhu:
Yeah, I definitely agree with Andrew. I think if we want to make decisions based on cost and we want patients to make those decisions and we as clinicians, obviously should be helping them. We need more transparency around costs, current deductible status, and that has to be available at the point of care so it actually can be integrated in decision-making. But I think that's likely not enough. I mean, even for clinicians, it's hard to determine how clinically necessary it is to get emergency evaluation before you see the patient when you get a phone call. So I think, if it's hard for clinicians with all of our years of experience, it's hard to understand how we can really expect that from our patients.
Dr. Alexander Sandhu:
I wholly agree with Andrew that I think a critical step is it's going to be important to reduce the risk of cost sharing for low-income patients with a number of potential interventions to do that, which I think are the real policy implications here. And then more generally, I think we should make sure that deductibles aren't discouraging utilization of high value cost effective intervention. There are currently safeguards in the Affordable Care Act about that. But I think we need to think about those closely and probably expand that so we don't see high deductible health plans leading to lower stat rates or worse diabetes prevention.
Dr. Carolyn Lam:
Wow. Words of wisdom. I just cannot thank you both enough for publishing such a beautiful paper, important findings, as well as just a very lovely editorial in Circulation. Thank you. Learned a lot. I'm sure the audience did too. Please remember you're listening to Circulation on the Run. Please tune in again next week with Greg and I.
Dr. Greg Hundley:
This program is copyright of the American heart association, 2021. The opinions expressed by speakers in this podcast are their own and not necessarily those of the editors or of the American heart association. For more visit ahajournals.org.