In this podcast, George Karpouzas, MD, talks about his research on highly sensitive cardiac troponin-I and IgA antibodies against β-2 glycoprotein 1 in the setting of coronary atherosclerosis among patients with rheumatoid arthritis.
Additional Resource:
- Karpouzas GA, Ormseth SR, Hernandez E, Budoff MJ. Highly-sensitive cardiac troponin-I and beta-2-glycoprotein-I IgA antibodies inform the utility of screening and follow-up non-invasive coronary atherosclerosis evaluation and optimize cardiovascular risk assessment in rheumatoid arthritis. Paper presented at: American College of Rheumatology 2019; Atlanta, GA; November 8-11, 2019. https://acrabstracts.org/abstract/highly-sensitive-cardiac-troponin-i-and-beta-2-glycoprotein-i-iga-antibodies-inform-the-utility-of-screening-and-follow-up-non-invasive-coronary-atherosclerosis-evaluation-and-optimize-cardiovascular/
George A. Karpouzas, MD, is a professor of medicine at the University of California, Los Angeles, and chief of rheumatology at The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center in Los Angeles, California.
TRANSCRIPT:
Amanda Balbi: Hello everyone, and welcome to another installment of Podcasts360—your go-to resource for medical news and clinical updates. I’m your moderator Amanda Balbi with Consultant360 Specialty Network.
A new study evaluated highly sensitive cardiac troponin-I and IgA antibodies against β-2 glycoprotein 1 in the setting of coronary atherosclerosis among patients with rheumatoid arthritis.
Today I’m speaking with the lead author of the study, Dr George A. Karpouzas, MD, who is a professor of medicine at UCLA and chief of rheumatology at Harbor-UCLA Medical Center in Los Angeles, California.
Thank you for joining us today, Dr Karpouzas. Let’s dive into your study.
To start, can you tell us more about these biomarkers, and why you chose to focus on them?
George Karpouzas: Sure. Cardiovascular risk calculators that are in use for general patients underperform in rheumatoid arthritis risk estimations Attempts at RA-specific cardiovascular risk calculators also failed to improve risk prediction in this disease.
We recently reported that serum levels of highly sensitive cardiac troponin I, which is a cardiac-specific structural biomarker, associated with occult coronary plaque burden and cardiovascular events in RA at 5 years, beyond traditional cardiac risk factors or cardiac risk scores.
Additionally, we found that antibodies against β-2 glycoprotein 1 of the IgA subclass promoted coronary plaque progression and moderated the effect of inflammation on incident cardiovascular events in rheumatoid arthritis.
Specifically, patients without coronary plaque at baseline evaluation had no ischemic cardiovascular events at 5 years. By contrast, 45% of patients with obstructive or extensive disease suffer cardiovascular events at that time mark, 5 years.
And those patients that have nonobstructive or nonextensive disease—so they’re in between the 2 others—had about 3% to 4% incidence of ischemic cardiovascular events over the same period of time. What is unclear, however, is when to recommend coronary atherosclerosis evaluation with cardiac computed tomography angiography in RA patients who do not have symptoms or diagnosis of cardiovascular disease.
Additionally, it's even less well known whether such an assessment should be repeated in the future. So, within the context of this study, we tried to ask 2 questions.
First, whether highly sensitive cardiac troponin I or anti-β-2 glycoprotein 1 IgA alone or in combination could in fact improve prediction of coronary plaque presence, upon a screening study beyond clinical risk scores.
Next we asked whether either biomarker or their combination can predict progression to extensive or obstructive plaque on follow-up evaluation, which, as I mentioned, is associated with such profoundly higher risk of cardiovascular events in both short and long term.
Amanda Balbi: Does either biomarker alone or in combination best predict plaque or coronary artery calcium presence on an initial coronary CT angiogram?
George Karpouzas: We previously reported that patients who have high cardiac troponin I have higher prevalence of coronary plaque at baseline. And they also have enrichment of different plaque severities across higher tertiles of this biomarker.
Also, they have significantly higher expensive or obstructive disease compared to those with low cardiac troponin I. By contrast, there is no significant difference in total plaque presence at baseline at least, based on β-2 glycoprotein 1 IgA presence.
When highly sensitive cardiac troponin I information is added to a baseline prediction model for cardiovascular events that contains only traditional cardiac risk factors, it most certainly significantly improved the prediction accuracy for baseline plaque presence.
In contrast, addition of anti-β-2 glycoprotein 1 IgA status information did not contribute to this. And the combination of β-2 glycoprotein 1 to highly sensitive cardiac troponin I offered no added benefit to the highly sensitive cardiac troponin I model alone.
What all this means is that the presence of highly sensitive cardiac troponin I high levels at baseline may prompt the initial consideration for a screening CTA.
Amanda Balbi: Does either biomarker predict progression to extensive or obstructive plaque on a follow-up evaluation?
George Karpouzas: As I mentioned, we previously reported that if you don't have coronary plaque at baseline—these patients had no ischemic cardiovascular events at 5 or 8 years, respectively.
By contrast, 45% of those with obstructive or expensive disease suffered ischemic cardiovascular events at 5 years. So, notably though, only 3% of patients who had no plaque at baseline developed new obstructive lesions at follow-up.
Therefore, repeat coronary angiography in the first 2 groups would obviously be not necessary, arguably. However, 18% of patients who had nonextensive known obstructive disease developed extensive or obstructive disease on follow-up CTA.
And as I mentioned earlier, this carries a dramatic difference in cardiovascular risk. So, it would be important to further understand who of those patients may actually be at risk for such progression and may, therefore, benefit from a follow-up CTA evaluation to confirm it.
Also, we recently reported that β-2 glycoprotein 1 IgA presence at baseline independently associated with coronary plaque progression, whereas CTA alone did not. So, we evaluated whether β-2 glycoprotein 1 IgA presence was associated with an increased risk of nonobstructive disease to extensive obstructive disease. And we did find in fact that this was the case.
43% of patients who had β-2 glycoprotein 1 positivity with known extensive and obstructive disease proceeded to develop extensive obstructive disease, compared to 8% of those without, and that was specifically true for patients who had an initial CTA based on a high cardiac troponin I level.
In that case, 71% of double-positive patients, meaning β-2 glycoprotein 1 IgA and highly sensitive cardiac troponin I patients, had this transition, compared to only 7.7% of those who were negative for β-2 glycoprotein 1 IgA.
So when you add the information of β-2 glycoprotein 1 IgA to this baseline model, again of all the traditional cardiac risk factors, then this β-2 glycoprotein 1 information significantly again improved the prediction accuracy of developing extensive obstructive disease at follow-up.
Amanda Balbi: And you and your colleagues ultimately conducted this study to better understand when to proceed with coronary atherosclerosis evaluation in asymptomatic patients with RA and whether such an assessment should be repeated in the future. Do your findings suggest screening asymptomatic patients with RA?
George Karpouzas: I think in order to answer the importance of this is to just say that the clinical manifestations of cardiovascular disease in patients with rheumatoid arthritis is quite different than the ones that do not have this disease. So, patients with rheumatoid arthritis are much less likely to have typical symptoms of chest pain and angina, and actually are much more likely are 5 times more likely to present with either sudden cardiac death or an asymptomatic myocardial infarction.
If we just decide to wait until the people become symptomatic, we may have missed a big chunk of patients that actually are already at risk and have plaque that is very high risk.
Remember the premise of our study—what we showed at baseline, and this is a cohort of fully asymptomatic patients—is that in asymptomatic patients who have extensive or obstructive disease, 45% of them will develop ischemic cardiovascular events within 5 years, which would suggest a 2-step approach.
What we would suggest is that above and beyond the clinical cardiovascular risk stratification we do for our patients in rheumatology clinic, perhaps an evaluation of cardiac troponin I in everybody may be a starting step. So, for those who have a high cardiac troponin I at baseline, regardless of their cardiovascular risk bracket, we would advise is that a CCTA screening procedure gets done.
And based on what we find there, we can proceed. If we find that there is no plaque at all, the coronaries are clean, and that suggests that these patients are very low risk, and we can proceed with lifestyle modification. If patients are very high risk by virtue of having obstructive plaque, then obviously we should immediately start aggressive therapy for prevention of those patients.
We do know that this therapy works for a randomized controlled trial, a multicenter one with many, many thousands of patients that was done in Scotland recently.
However, for patients who are in between—they have plaque, but it's not obstructive, it's not extensive—if those patients are positive for β-2 glycoprotein 1, they deserve a second look, because if they are, about 40% of them will have a chance of developing obstructive plaque at follow-up.
As I mentioned earlier, this is associated with a much higher risk of cardiovascular events and massive change in therapeutic approach.
Amanda Balbi: So, what would you say is the overall key take-home message from your study?
George Karpouzas: I think that these biomarkers can basically inform the utility of a baseline screening study and can certainly help us understand which patients may require repetition of this study in our quest to optimize cardiovascular risk assessments in rheumatoid arthritis.
Amanda Balbi: Absolutely. Thank you so much for speaking with me today, Dr Karpouzas.
George Karpouzas: Amanda, thank you so very much for the opportunity to communicate to the greater rheumatology community, what the key messages of our findings are.
