Cardiovascular Risk and Psoriasis

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Patients with moderate to severe psoriasis die about 5 years younger than they should based on their risk factors for mortality, with the majority due to cardiovascular disease. If we could eliminate the excess risk of cardiovascular events that our patients are facing, we would narrow the gap they are experiencing in life expectancy. That is why we are undertaking the National Psoriasis Foundation (NPF)-funded Prevention of Cardiovascular Disease and Mortality in Patients with Psoriasis or Psoriatic Arthritis(CP3) study.¹ In this article, I will answer frequently asked questions about the link between psoriasis and cardiovascular disease and give an update on the preliminary results of the CP3 study.

What Is the Clinical Significance of Cardiovascular Risk in Patients with Psoriasis?

There are a few different ways that clinicians and patients with psoriasis can think about the issue of cardiovascular risk. In general, if you compare psoriasis to other major diseases that promote cardiovascular risk, such as rheumatoid arthritis (RA), there is a similarity. For example, a patient with moderate to severe psoriasis has a similar increased risk of having cardiovascular events and premature mortality compared to someone with moderate to severe RA.

Another way to think about cardiovascular risk in patients with psoriasis is compared to their risk of developing a melanoma, for example. The excess risk of developing a cardiovascular event related to psoriasis above and beyond the patient’s risk factors for cardiovascular disease is about 30 times higher than their risk of developing a melanoma in the upcoming year. There is a much higher risk of a cardiovascular event for the patient than what we are typically worried about in melanoma.

Lastly, we know from some of the earlier studies we have done, and others have since confirmed, that there is a pattern of accelerated cardiovascular risk. We see measures of association (relative risks) that are substantially higher in young people with psoriasis. A young person in their 30s or 40s may have a doubling to tripling of their risk of having a cardiovascular event compared to someone without psoriasis. The relative risk seems to get smaller overtime because age dominates the risk of heart disease over time, but the absolute extra risk people face from psoriasis goes up exponentially as they age. The risk they are facing for heart disease related to psoriasis is higher when they are 50, 60, 70, and so on.

As clinicians, we must think about this problem across the whole lifespan. When patients are young, their relative risk is high, but their absolute risk is low because they are young. This is an important time for the patient to shift behaviors to have a better cardiovascular profile over time, such as consuming a healthy diet, exercising, and quitting smoking. Some patients need to be screened for diabetes, hyperlipidemia, and hypertension because they tend to have more risk factors and have not been treated appropriately. Then when they are older, their risk is increasing and, therefore, there is more emphasis on preventing heart disease. When patients are in their 40s to mid-70s, prevention techniques such as using statins play a big role in lowering their risk of having a heart attack or stroke and premature mortality.

What Is the Impact of Psoriasis Treatment on Cardiovascular Risk?

We know from a variety of work that the more severe the skin disease, the higher the risk of having a cardiovascular event, as well as the higher the risk of having coronary disease. This begs the logical question: Can controlling skin inflammation alone be enough to lower a patient’s risk of heart disease and stroke? Studies to date have been indeterminate in that respect. We have done a whole series of randomized placebo-controlled trials of tumor necrosis factor (TNF) inhibitors, IL-12/23 inhibitors, IL-17 inhibitors, phototherapy, and the phosphodiesterase-4 inhibitor apremilast.

These therapies have varying benefits on different cardiovascular pathways, but nothing clearly stands out as definitively lowering cardiovascular risk. TNF inhibitors seem to have the strongest signal so far. They seem to lower the pathways of inflammation that are most important to developing cardiovascular disease compared to placebo. There are some observational data to support that people who go on TNF inhibitors have lower rates of cardiovascular events over time. However, we need randomized controlled trials to prove this because things could be counterintuitive. We know that TNF inhibitors treat psoriasis well, but they could cause a psoriasis-like reaction in the skin. Or, as another example, IL-17 inhibitors are anti-inflammatory in the skin, but they could be pro-inflammatory in the gut and cause inflammatory bowel disease.

Emerging data also suggest that the arrow may go both ways in terms of causality. The genetics of having coronary artery disease seems to be causally related to developing psoriasis. It may be that patients have atherosclerotic disease triggering what we see as psoriasis in the clinic. It is such a multifactorial process that just treating the skin disease alone is unlikely to fully eradicate the risk we are seeing in our patients.

What Are the Current Guidelines of Care?

In 2019, the American Academy of Dermatology (AAD) and NPF, and then the American College of Cardiology (ACC) and American Heart Association (AHA) published guidelines on cardiovascular risk in psoriasis. The AAD/NPF guidelines were the first time that our specialty came out with a recommendation for dermatologists to screen for comorbidities in one of our diseases. Number one, the guidelines recommend that we educate our patients. If you have a patient with psoriasis, you need to make them aware that having this skin disease is predictive of having a higher risk of cardiovascular risk factors and events. Second, either we as dermatologists should be initiating the age-appropriate screening for traditional cardiovascular risk factors in these patients, or we should be encouraging patients to see their primary care doctor to have these screenings done. We should be more intensive about this when the patient’s psoriasis is more severe (more than 10% body surface area) or if they are a candidate for systemic phototherapy. These are the patients we are most likely to impact with preventive efforts.

In general, screening for risk factors is based on a person's age. In terms of the standard guidelines that come out from other societies, you are looking at checking cholesterol every 4 to 6 years or so, screening for diabetes with a hemoglobin A1C at least once and then maybe every 3 to 5 years thereafter, and doing a blood pressure at least once a year. That is what should be typical for most people with psoriasis, and then you individualize it.

If a patient’s labs are completely normal and they are young, healthy, and have no family history of cardiovascular disease, they may not get checked again for 5 or 6 years, but what you will often see in clinical practice is that these labs are abnormal. The hemoglobin A1C is going to be in a prediabetes range, or the lipids are going to be abnormal. The patient is going to need to see their primary care doctor. There are a variety of treatments that can be used if necessary, or at least the primary care doctor is going to say, "Try to exercise more and have a healthier diet, and then we will recheck in 6 months or a year to see how you are doing."

Once people are in the 40 to 75 range, their risk of having a cardiovascular event starts getting significant enough that the standard of care in primary care or preventive cardiology is gathering the patient’s cholesterol levels, blood pressure, whether they smoke, and their age and sex and using a formula to predict their 10-year risk of a heart attack or stroke. This is where the ACC/AHA guidelines come in. They now define psoriasis as being a cardiovascular risk enhancer, similar to someone who has RA or HIV infection. Again, this is a powerful finding and one of the first times another specialty has come out and said, "We need to pay attention to a skin disease." Basically, if a patient’s predicted risk is above 5% or they are in what we call the borderline category of a 5% to 7.5% 10-year risk of having a cardiovascular event and they have psoriasis, they should talk to their doctor about how to lower their risk of having a heart attack or stroke.

In most cases, these patients should probably go on a statin because independent of what their cholesterol is, it will lower their risk of having a cardiovascular event. Some patients will say, "You know what? I don't want to take another medication.” In that case, a coronary artery calcium score is often recommended because that can help refine their risk. What I find in my own practice is that many patients in this situation get their coronary artery calcium score, and it is abnormal. Now they know they have coronary disease. At that point, they usually say, "Give me the statin.” At the end of the day, people do not want to die of a heart attack or stroke. It is as simple as that. A lot of this is helping patients understand what their risk is and what should be done, but it is powerful information when you get a coronary calcium scan, and you see a vessel lighting up. That is usually compelling for patients.

One of the problems is that we are not doing a good job of identifying cardiovascular risk in our patients or educating them about it. We published a paper in the Journal of Investigative Dermatology within the last year showing that when people in the prime age group for cardiovascular prevention (ages 40 to 75) see a dermatologist for psoriasis, only 3% of the time are they getting cholesterol or blood glucose checked.2 About 10% of the time, they are getting a blood pressure check. This is well below what we need to be doing.

When we interviewed patients, we learned they often do not know that psoriasis is related to cardiovascular disease.^3,4 Even in my own practice, when we tell patients and then interview them later, they do not recall it, so they need repeated education. They really do want to hear it from us as dermatologists in the context of psoriatic disease care. When we say to them, "You see that rash on your skin? It puts you at higher risk of having heart disease," it is powerful to them. Then when we talked to our colleagues, overwhelmingly, they feel it is completely doable to order cholesterol and hemoglobin A1C because we are often drawing labs anyway, for example, if we are going to put a patient on a biologic.^3,4 The biggest challenge our colleagues feel is what to do with this information. Many do not want to be involved in managing abnormal results, which is perfectly understandable.

There are a couple of things that I always recommend to my colleagues. Number one, just as you should have a close relationship with a rheumatologist if you are caring for patients with psoriasis because many of them may have psoriatic arthritis, you should have a colleague in the community who is a preventive cardiologist or primary care doctor interested in this topic and willing to see these patients. The other thing is, in my own practice, I pick up a ton of coronary disease because I have a colleague who I collaborate with on these things. All I have to do is order a test. I have 2 phrases I use in my electronic medical record. If everything is normal, I say, "Things look good." I have a stock phrase I use from the AHA with a link to diet and exercise recommendations for a heart healthy lifestyle. If the results are abnormal, the patient gets a message saying, "You have a higher risk of cardiovascular disease. I recommend you see your primary care doctor or my colleague who is a preventive cardiologist." I also pick up a ton of undiagnosed diabetes and a lot of undiagnosed hypertension. These patients are incredibly grateful when we pick this up for them because it is potentially lifesaving, and I do not find it burdensome at all.

To make things easier for our colleagues, we are working on the CP3 study funded by the NPF and their Psoriasis Prevention Initiative with one of the largest research grants the NPF has ever given.¹ We have developed, and now we are testing, a centralized care coordinator. The idea is that the dermatologist would follow the guidelines by ordering the labs. If the results are abnormal, we would have the patient virtually see the care coordinator at the NPF. That person would then educate the patient, calculate their risk of heart disease based on the available formulas, and then print out what is supposed to be done, giving it to the patient and sending it to their primary care doctor or the doctor who is going to manage this, with a copy back to the referring dermatologist so they are aware of what is going on.

We have done a highly successful pilot study in 85 patients. Now we are doing a study in around 500 patients to definitively test this model. If we can show that having dermatologists around the country provide this education to their patients, screen them for cardiovascular risk factors, and refer them to the care coordinator when results are abnormal and this helps patients get better control of their cardiovascular risk factors, then we would hope to make this available nationwide to dermatologists.

How Can Dermatologists Identify and Manage Cardiovascular Risk in Psoriasis?

The first step is you want to educate the patient about the relationship between psoriasis and cardiovascular disease. Many patients will realize it makes sense that inflammation on their skin may portend something internally. As dermatologists, we have the advantage of treating a chronic disease. We know our patients for a long period of time. The first time you see them, or when you see them at the first follow up, you are fixing the skin disease. But when you see them back in 3 or 4 months and they are doing well, then that may be the time to focus on cardiovascular risk.

Again, in general, many patients have not had cardiovascular risk screening in the last couple of years. It is likely they are due for it. This is especially going to be true as people get older, and they are anywhere between their 40s and 70s. So there, you want to get a cholesterol panel and a hemoglobin A1C test. These do not have to be done fasting. If done nonfasting, the triglycerides may be abnormal, but the result should not be so crazy abnormal that you cannot interpret it. If the triglycerides are severely abnormal, you did the patient a favor because that means something is wrong.

Hemoglobin A1C will tell you what the patient’s glucose has been for the last 3 months on average, and you will get back 1 of 3 results. Either it is going to be normal, in a prediabetes range, or in a diabetes range. In my practice, probably 30% to 40% of patients have prediabetes. If those patients lose weight through diet and exercise, they will lower their risk of diabetes. Increasingly, people go on the new glucagon-like peptide-1 agonists or weight loss drugs, and they make a huge difference, or they can go on metformin to prevent the development of full-blown diabetes.

You will also want to take a blood pressure in the office. Often, I find that a patient’s blood pressure is elevated. I think a lot of people with psoriasis have “white coat” hypertension. The standard of care now is that they must do their blood pressure monitoring at home to diagnose and manage high blood pressure. If it is abnormal in the office, they should see their primary care doctor, who will usually instruct them to buy a home blood pressure cuff if blood pressure is abnormal in their office.

Our job is to alert the patient about the impact their skin disease has on their overall health, which hopefully motivates them to go to their primary care doctor. However, in my practice, I find that many of my patients either do not have a primary care doctor or they may not have a great relationship with their primary care doctor, so they are looking for someone else to help them. That is why it is important for dermatologists to have a relationship with a community colleague who is interested in cardiovascular risk assessment.

Disclosure: Dr Gelfand has served as a consultant for AbbVie, BMS, Boehringer Ingelheim, FIDE (which is sponsored by multiple pharmaceutical companies), GSK, Janssen Biologics, and Novartis Corp and receives research grants (to the Trustees of the University of Pennsylvania) from Amgen, BMS, and Pfizer, Inc. Dr Gelfand is a deputy editor for the Journal of Investigative Dermatology (receiving honoraria from the Society for Investigative Dermatology), chief medical editor for Healio Dermatology (receiving honoraria), and a member of the board of directors for the International Psoriasis Council and the Medical Dermatology Society (receiving no honoraria).

References

1. Prevention of cardiovascular disease and mortality in patients with psoriasis or psoriatic arthritis (CP3): translating guidelines of care to better outcomes for patients with psoriatic disease study. National Psoriasis Foundation. Accessed September 25, 2023. https://www.psoriasis.org/prevention-of-cardiovascular- disease-and-mortality

2. Neopaney A, Wang S, Shin DB, et al. Prevention of cardiovascular disease and mortality in patients with psoriasis or psoriatic arthritis (CP3) study: preliminary results. J Invest Dermatol. 2023;143(5 Suppl):S115. https://doi.org/10.1016/j. jid.2023.03.676

3. Barbieri JS, Beidas RS, Gondo GC, et al. Analysis of specialist and patient perspectives on strategies to improve cardiovascular disease prevention among persons with psoriatic disease. JAMA Dermatol. 2022;158(3):252-259. doi:10.1001/ jamadermatol.2021.4467

4. Gustafson AC, Gelfand JM, Davies J, et al. Specialist and patient perspectives on strategies to improve cardiovascular disease prevention among persons living with psoriatic disease. J Psoriasis Psoriatic Arthritis. 2022;7(4)174-186. https://doi. org/10.1177/24755303221101848