Psoriatic Arthritis Podcast

Cardiovascular Risk in Patients With Psoriatic Arthritis

Stanley Cohen, MD; Atul Deodhar, MD


September 20, 2022

This transcript has been edited for clarity.

Stanley Cohen, MD: I am Dr Stanley Cohen and welcome to Medscape's InDiscussion series on psoriatic arthritis. This is episode four of the second season. Today, we'll be discussing cardiovascular risk in psoriatic arthritis and the impact of effective treatment. And I have one of my good friends here today — Dr Atul Deodhar who is professor of medicine, Division of Arthritis and Rheumatic Diseases in the School of Medicine at Oregon Health & Science University. He is also medical director of the Rheumatology Clinics Immunology Infusion Center in the Home Infusion Program in the Division of Arthritis and Rheumatic Diseases at Oregon. He has a special interest in psoriatic arthritis and spondyloarthropathies, has been well published, and has participated in multiple clinical trials. It's our pleasure to have you here today, Atul. Thank you for joining us. I look forward to talking with you about this issue.

Atul Deodhar, MD: I'm delighted to be here.

Cohen: Great to have you. I understand you've put a case together. Why don't we just present the case, and then we'll try to talk about cardiovascular risk in psoriatic arthritis and spondyloarthropathies.

Deodhar: This is a patient I saw earlier this week since I was thinking about this podcast we are doing today — there isn't anything special about the case. It was a routine visit for a patient with psoriatic arthritis. He's a 57-year-old gentleman whom I have seen for some time. And in the past, he has failed methotrexate, he has failed etanercept, he has failed adalimumab, and I've seen him for about a couple of years. He's a typical psoriatic arthritis patient in that he has obesity, a history of hypertension, hyperlipidemia, diabetes, and uncontrolled psoriatic arthritis. I put him on ustekinumab for some time, and he came to see me. He still had significant arthritis when I examined him. He had 12 swollen joints and about a similar number of tender joints. He had reduced shoulder abduction. He was also tender on his lateral epicondyle. While talking to him, it occurred to me as a rheumatologist, of course — how am I going to control his psoriasis? How am I going to control his psoriatic arthritis?

But then we are internists, and we should also always consider the other comorbidities. Psoriatic arthritis in some ways is even worse in this situation than rheumatoid arthritis when it comes to obesity, hyperlipidemia, diabetes, hypertension, etc. This gentleman I picked particularly for today's discussion has a very good primary care physician, and he is already receiving treatment for hypertension, hyperlipidemia, etc., but despite that, his blood pressure when I saw him was 170 over 90. His cholesterol was done by his primary care physician, his LDL was high, and he was on atorvastatin. He was also on an ACE inhibitor. I was thinking that this was something for which I probably need to get help from my cardiology friends. We have a preventive cardiology department that is very good. This is something that is beyond us as rheumatologists — we should be taking care of all these problems because we are internists, but at the same time, we don't keep up with treatment of diabetes or hypertension and hyperlipidemia. There are so many advances in these areas, and beyond a certain stage, we should not hesitate to take help from our colleagues in other divisions such as cardiology. We do comanage patients with dermatology. Sometimes we comanage patients with gastroenterology if they've got inflammatory bowel disease–associated problems. Sometimes we comanage patients with ophthalmologists if they get uveitis. We should really be dealing with these kinds of situations, especially with psoriasis or psoriatic arthritis, with cardiologists, preventive cardiology, and endocrinologists if we have difficulty in bringing patients' lipids under control.

Cohen: This is a typical patient with multiple comorbidities associated with increased cardiovascular risk. First question: Do you think or are there any data showing there is an increased prevalence of comorbidities with psoriatic arthritis compared to something like rheumatoid arthritis? Is there an increase in metabolic syndrome, obesity, hypertension, or hyperlipidemia in patients with psoriatic arthritis compared to patients with rheumatoid arthritis. Are there any data? Tell me about that.

Deodhar: There are several systematic literature reviews and meta-analyses that have looked at this, and we know that there is an increased prevalence of metabolic syndrome in patients with psoriasis or psoriatic arthritis, just like in rheumatoid arthritis. This depends on how you define metabolic syndrome. There are different definitions in the literature, but in general, there is definitely an increased risk for metabolic syndrome in patients with psoriasis and psoriatic arthritis. To your specific question, the risk may be even higher in psoriatic arthritis compared to rheumatoid arthritis. There was a recently a metabolic syndrome prevalence published from Spain, and they looked at the CARMA (Spanish Cardiovascular in Rheumatology) cohort. What they found out was that compared to patients with rheumatoid arthritis, there was an increased risk of obesity especially, and with this, hyperlipidemia and hypertension in patients with psoriatic arthritis even more than what we find in patients with rheumatoid arthritis. And when, of course, you compare this with the general population, there is an increased risk of hyperglycemia, hypertriglyceridemia, hypercholesterolemia, obesity, hypertension, etc. It's interesting that if a patient goes to a diabetologist because they have diabetes, the diabetologist treats their diabetes but the patient also comes out of the appointment with a prescription for aspirin, a prescription for a statin, a prescription for, of course, their diabetes, and a prescription for their hypertension. Diabetologists do a great job taking care of this. Rheumatologists, because we are internists, we can do only so much. But then we should certainly be cognizant to the fact that all these features do play a role in the patient's overall health. And we should then, if we cannot treat them, get help from our cardiology or endocrinology friends.

Cohen: I agree with you 100%. This has been a difficult sell even with my associates in my clinical practice to get them to provide more global care. We need to do a team approach with our primary care or cardiology colleagues. Let me ask you a question. What's the role of the disease activity in cardiovascular risk? Are there studies to suggest that the degree of psoriasis might be associated with cardiovascular risk, or that poorly controlled disease activity is associated with cardiovascular risk in psoriatic arthritis or spondyloarthropathies?

Deodhar: It's curious. There are several cardiovascular risk prediction algorithms, and probably the most popular or the most famous would be the Framingham Risk Score. But there are others. There are the American College of Cardiology/American Heart Association pooled cohort equations. Then there is something called QRISK 2. Then there is something called SCORE, which is Systematic Coronary Risk Evaluation. There are several of these scores available that predict cardiovascular risk, and they take into account the usual cardiovascular risk factors we learn in medical school and as residents, which are hypertension, hyperlipidemia, male sex, smoking, obesity, diabetes, etc. When you apply these to patients with psoriatic arthritis, you find that these risk prediction algorithms underestimate the risk of cardiovascular risk in these patients. And the same thing was found in rheumatoid arthritis and in axial spondyloarthritis or ankylosing spondylitis. That brings us to the question: What is the extra thing these typical Framingham Risk Score algorithms, etc., are not measuring? The answer is, of course, the systemic inflammation. With psoriasis and psoriatic arthritis, like rheumatoid arthritis and axial spondyloarthritis, the systemic inflammation adds to the conventional risk factors that we all know about, which are hypertension, hyperlipidemia, obesity, and smoking. We know this. But there are additional risks, and several people have come up with multiplication factors. You can do it with your Framingham Risk Score or your American College of Cardiology/American Heart Association score — whichever score you use — but then multiply it by 1.8 or 1.5. There are people who have come up with different numbers, but the basic idea is that these algorithms underestimate, and inflammation definitely plays a role. There was a paper, as you may remember, about controlling the inflammation with, interestingly, I think it was the IL-1 inhibitor, in The New England Journal of Medicine to see whether it reduced the risk for cardiovascular disease. It did actually reduce the risk to a small extent. Colchicine also was used to reduce the risk of cardiovascular disease by reducing the inflammation. Inflammation definitely plays a role in the cardiovascular risk of these patients.

Cohen: We know that inflammation and disease activity play a role. What about the impact of our treatments? We have multiple therapies now looking at different pathways of inflammation that are very effective in psoriasis and psoriatic arthritis. What hard data do we have to show that any of these therapies reduce cardiovascular risk?

Deodhar: That's a great question. We know that in rheumatoid arthritis, both methotrexate and tumor necrosis factor (TNF) inhibitors reduce the cardiovascular risk. I have been searching for this specifically for psoriatic arthritis. There was one article I found way back in 2015. They did, again, a meta-analysis and a systematic literature review, and they looked specifically for the effects of TNF inhibitors, methotrexate, and nonsteroidal anti-inflammatory drugs, and also corticosteroids on cardiovascular events in patients with rheumatoid arthritis, psoriasis, and psoriatic arthritis. This was a meta-analysis by doing a systematic literature review, and most of the studies they found were also on rheumatoid arthritis. This was a large undertaking. They used Medline, Embase, Cochrane Database, etc., from 1962 to 2014. This article was published in 2015, and most of the studies they found were in rheumatoid arthritis. Their meta-analysis showed what we already knew — that in rheumatoid arthritis, the TNF inhibitors and methotrexate do reduce the cardiovascular risk. Nonsteroidal anti-inflammatory drugs increase the risk. Most of that in those days was because of rofecoxib. We don't use rofecoxib anymore. Corticosteroids increase the cardiovascular risk as well. Now in psoriasis and psoriatic arthritis, the systemic therapy with these agents did reduce the risk of all cardiovascular events, and the relative risk was 0.75 to 1.6, and it was still a statistically significant result. The TNF inhibitors and methotrexate both again showed the same signal when they took systemic therapy together. Then they could get a significant P value. But when they started teasing out whether it was methotrexate or whether it was anti-TNF therapy, they did not have the statistical power to look at this. Most of the data we have come from rheumatoid arthritis — that reducing inflammation reduces the risk. In psoriatic arthritis, this was one of the attempts, and they found that there is certainly a signal in the same direction. If you take all the systemic therapy together, it does become statistically significant. This brings into the discussion that things like nonsteroidal anti-inflammatory drugs and prednisone certainly increase the risk of cardiovascular disease.

Cohen: The data are somewhat limited. Certainly the data we have are promising but really don't address whether it's IL-17 inhibition or IL-23 inhibition, or IL-12/23 inhibition — it's just that the data are limited. We just don't know. We presume based on the flip side that reducing inflammation should be a good thing, but the data don't exist at this point.

Deodhar: That's right. I think we need to treat many, many patients. And these types of data require national-level databases or large databases in Europe. As you know, Stan, any patient who gets a biologic generally gets into some kind of data bank that the National Health Service mandates rheumatologists to put their patients into. These types of data banks or cohorts, at the national level, are very useful for looking back on the population level at whether IL-17 inhibitors, IL-12/23 inhibitors, IL-23 inhibitors would be in the same category as TNF inhibitors when it comes to reducing the cardiovascular risk. Currently, these data are not available.

Cohen: So we have two JAK inhibitors that are approved, and we're going to have a TYK2 inhibitor, another JK isoform inhibitor, which will probably be approved. Do we have the same concerns that have been raised by the regulatory agencies? We do have the restriction, and we shouldn't use them until after TNF failures at this point. You agree with that. Obviously we're going to follow the restrictions. But what are your thoughts about the JAK inhibitors? The good news about psoriasis patients is that they're a little younger than our patients in rheumatoid arthritis, so we can probably get away with JAK inhibitors in the younger patients. I am just curious what you think about the role of the JAK inhibitors at this point in patients who do have cardiovascular risk factors and have psoriatic arthritis or psoriasis?

Deodhar: I'd like to get back to my patient, and I'll tell you exactly what happened with this patient earlier this week — the 57-year-old gentleman I was looking at. I had to change his current biologic to something else. He had tried two anti-TNFs and one IL-12/23 inhibitor. We went into this long discussion, and I was telling him about his hypertension, hyperlipidemia, and diabetes when I told him I was also going to refer him to our endocrinology department. Endocrinology, in fact, works in preventive cardiology because we need to get these things under control better.

One more quick point I want to make is about obesity. We sometimes hesitate to discuss this with the patient because it's a touchy subject and it's shared decision-making. But you always kind of ask permission — at least I do. I ask them if we can talk about their weight, and if it is okay for me to discuss it. Because it does impact how I treat their psoriatic arthritis. Patients who are overweight or obese have problems other than that — it reduces their functional ability. It's linked with greater psoriasis severity. It is linked with greater disease activity and even reduced response to the treatments we use as rheumatologists. Weight loss or maintenance of their weight helps our biologics work. The other thing of course, with obesity, is that these people also have increased risk of fatty liver and methotrexate use, so these kinds of drugs again become problematic with obesity. Getting back to this patient, I did think about a JAK inhibitor, and we did discuss an IL-17 inhibitor that he had never tried, an IL-23 inhibitor, and a JAK inhibitor. He was 57 years old. He doesn't have rheumatoid arthritis, but he has all these risk factors, and I would worry about the similar risk in patients with psoriatic arthritis we know with the oral surveillance study — that trial you mentioned — which actually gave the JAK inhibitor a black box warning. Yes, in a younger patient, in an ankylosing spondylitis patient who was maybe 30 or 35 years old, or if my patient was younger and not obese and didn't have the cardiovascular risk factors, I probably would go with the JAK inhibitor. But for somebody who's 57 already with these risk factors, I would be concerned about using a JAK inhibitor. He ultimately decided to go with the IL-17 inhibitor after telling him about all the issues. That concern is in the back of my mind when patients have cardiovascular risk already known because of their conventional risk factors.

Cohen: Thankfully, we have alternative therapies we can choose from, and I think is a relative contraindication in that population as well. Atul, this has been terrific. I appreciate your time with us, and I hope you found this fun as well. Thank you for giving us some insight on cardiovascular risk in psoriatic arthritis patients.

Deodhar: Thank you so much, Stan, I enjoyed it.

Cohen: Thank you so much for joining us for episode four, and I look forward to another great discussion in episode 5. This is Dr Stanley Cohen for InDiscussion.

Listen to additional seasons of this podcast.


Prevalence of Metabolic Syndrome in Psoriatic Arthritis: Systematic Literature Review and Results From the CARMA Cohort

Metabolic Syndrome

What Is the Framingham Risk Score (FRS)?

2013 ACC/AHA Guideline on the Assessment of Cardiovascular Risk: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines

What Is the Systematic Coronary Risk Evaluation (SCORE)?

Anti-inflammatory Therapy With Canakinumab for Atherosclerotic Disease

Colchicine in Patients With Chronic Coronary Disease

The Effects of Tumour Necrosis Factor Inhibitors, Methotrexate, Non-steroidal Anti-inflammatory Drugs and Corticosteroids on Cardiovascular Events in Rheumatoid Arthritis, Psoriasis and Psoriatic Arthritis: A Systematic Review and Meta-analysis

Psoriatic Arthritis Medication

Efficacy and Safety of Selective TYK2 Inhibitor, Deucravacitinib, in a Phase II Trial in Psoriatic Arthritis

FDA Requires Warnings About Increased Risk of Serious Heart-Related Events, Cancer, Blood Clots, and Death for JAK Inhibitors That Treat Certain Chronic Inflammatory Conditions

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