Recognizing and managing cardiovascular risk in PsA patients
Patients with psoriatic arthritis (PsA) have a higher incidence of cardiovascular disease (CVD) than the general population for a variety of reasons. medwireNews speaks to Dr Lihi Eder (Women’s College Research Institute, University of Toronto, Ontario, Canada), a rheumatologist who specializes in cardiovascular comorbidities in patients with rheumatic diseases, about why PsA patients have elevated cardiovascular risk, and what can be done to mitigate it.
“Cardiovascular risk compared to the general population is about 40% higher in patients with PsA,” says Eder. She notes that PsA patients, as well as those with psoriasis, are at particularly high risk for developing heart attacks, angina, and heart failure, as well as “other types of cardiac diseases like atrial fibrillation.”
Indeed, as a result of this increased risk, the EULAR recommendations for the management of PsA emphasize the importance of considering comorbidities, especially CVD and metabolic syndrome, when deciding on a treatment strategy.
Why PsA patients have elevated CVD risk
“The reasons are complex,” notes Eder, adding that “it is a combination of traditional risk factors” as well as “the fact that [PsA patients] have systemic inflammation in their skin and in their joints.”
She explains that “a cluster of cardiovascular risk factors,” including diabetes, high blood pressure, and elevated cholesterol, which are associated with overweight and obesity, “tend to be more prevalent in people with PsA compared with the general population, [so] just by having these conditions people with PsA have high risk of developing CVD.”
Moreover, studies have demonstrated that inflammation is associated with CVD risk “independent of these other traditional risk factors,” says Eder. For example, a meta-analysis published in the Annals of the Rheumatic Diseases in 2017 showed that arthritis patients had a significantly increased risk for incident myocardial infarction relative to the general population after adjustment for age and sex, and this increased risk was attenuated, but still statistically significant for the majority of arthritis subtypes, after further adjustment for traditional CVD risk factors.
One population-based cohort study looked specifically at PsA patients, and demonstrated that patients not treated with DMARDs had a significant 24% increased risk for major adverse cardiovascular events compared with the general population after adjustment for factors including diabetes, hyperlipidemia, and smoking, while the risk was numerically, but not statistically significantly, increased for DMARD-treated patients.
“So all this means that we need to address both the traditional risk factors and the disease activity; we need to control both of them,” remarks Eder.
The impact of PsA therapies on CVD risk
Eder says the association between inflammation and CVD risk “raises the question of if we suppress the inflammation whether we can reduce the cardiovascular risk.” She notes, however, that “there is very little information about this in PsA,” although more is known in rheumatoid arthritis.
“We know that some medications that we use like NSAIDs [nonsteroidal anti-inflammatory drugs] tend to increase blood pressure and they may also be associated with a higher risk of developing cardiovascular diseases,” says Eder.
A 2017 meta-analysis of 34 randomized trials and observational studies – 28 involving RA patients and six involving PsA or psoriasis patients – found that NSAID use was associated with a significant 18% increased risk for cardiovascular events (myocardial infarction, heart failure, stroke and/or major adverse cardiac events), while corticosteroids were associated with a significant 47% increased risk. However, the authors of the meta-analysis demonstrated that the use of tumor necrosis factor (TNF) inhibitors and methotrexate was associated with a significant 30% and 28% reduction, respectively, in the risk for cardiovascular events.
TNF inhibitors are “the most investigated drug class,” and the evidence to-date suggests that “these medications may have a protective effect,” notes Eder. She explains that “by suppressing the inflammation they may reduce the risk of developing [cardiovascular] conditions.”
However, she cautions that all of studies investigating cardiovascular risk associated with TNF inhibitors in arthritis patients are observational, and therefore “the level of evidence is still not high.”
Taking these factors into account, Eder nevertheless believes that TNF inhibitors “probably don't increase [cardiovascular] risk,” and “they may be protective.”
How patients can reduce their CVD risk
“There are several things that patients can do” to lessen their CVD risk, says Eder. She says that “there are many physicians, family physicians, and even cardiologists, who are unaware that people with PsA have an increased risk beyond their traditional risk factors, and so many patients are underdiagnosed” and are not treated for risk factors such as high blood pressure and cholesterol.
She therefore suggests that if patients are aware of their elevated cardiovascular risk, “they need to try to raise this issue with their family physicians.”
Moreover, “patients can help themselves by trying to be more active if possible,” Eder says. She points out, however, that people with joint disease may do less physical activity than those without. A number of studies have demonstrated that individuals with rheumatoid arthritis, axial spondyloarthritis, and osteoarthritis are less active in general than healthy controls, despite evidence demonstrating that exercise has beneficial effects on symptoms and disease activity in patients with inflammatory arthritis. The authors of the 2018 EULAR recommendations for physical activity in arthritis patients suggest that the lower levels of exercise among these people could be due to patients or healthcare providers fearing flare-up or joint damage as a result of exercise.
Nonetheless, these guidelines, as well as the ACR recommendations, advocate physical activity as an important component of disease management in patients with arthritis, emphasizing the importance of discussions between healthcare providers and patients to establish people’s individual capabilities, preferences, and resources.
Eder remarks that weight loss – for those who are overweight – “is another way to control blood pressure and to improve cholesterol abnormalities,” and stresses that “people that smoke definitely need to stop smoking.”
Managing CVD in patients with PsA
Eder explains that when people with PsA develop CVD, they are typically managed by rheumatologists and cardiologists in separate clinics, but “[w]e need to think about ways to improve collaboration between specialties which will hopefully lead to better care for patients.”
She gives the example of a combined rheumatology–cardiology clinic that she and her cardiology colleagues from Women’s College Hospital in Toronto established “to address some of the needs and gaps in care.” One year after starting the combined clinic, the team had changed treatment in over half of the patients who attended.
There were significant proportions of untreated patients with high blood pressure, high cholesterol, so there is a need for better treatment
Among patients who were thought to be asymptomatic in terms of their heart conditions, “we discovered a lot of things that are not managed well,” she says.
“Some patients had really serious conditions, some needed angioplasty and had blockages in their arteries that were misdiagnosed; some of them had atrial fibrillation that was not [previously] treated nor diagnosed.”
Eder stresses that “you cannot be a specialist in every field,” and collaboration is especially important for these “complex patients with complex diseases.”
Looking to the future, Eder feels that there are a number of avenues for future research to better understand and manage CVD in patients with PsA.
“We still don’t completely understand what the underlying mechanisms are,” and although inflammation is important, “we don’t know the exact underlying mechanisms that are involved in the development of these cardiovascular conditions in rheumatic patients,” she says.
She believes that “we need more research that combines both clinical and epidemiologic tools, as well as more laboratory work like metabolomic and proteomic analysis to understand more about what mechanisms are important.” In turn, greater understanding of the pathophysiologic processes “may help us target the right drugs for the right patient because at the moment there is little information about the optimal approach for selection of medications in patients with arthritis or psoriasis and cardiovascular disease,” she adds.
Eder also thinks that further research into other types of cardiac manifestations in patients with psoriatic disease is needed. She highlights that in addition to “the development of atherosclerotic plaques and blockage of arteries,” other conditions may be important. For example, “there are very, very little data about arrhythmia, valve problems, and myocardial problems,” she says.
“So these are some of the areas of unmet need.”
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