Psoriatic Arthritis and Cardiovascular Disease Intertwined?

Patients with psoriasis and psoriatic arthritis (PsA) have a higher rate of cardiovascular disease. Part of that is because they have a higher rate of the usual risk factors for cardiovascular disease. But after those risk factors are accounted for, the psoriatic arthritis itself is associated with an additional increase in cardiovascular disease (CVD), according to several recent studies. One hypothesis is that rheumatic diseases and atherosclerosis may be related because they both have an inflammatory mechanism.  Those traditional risk factors include metabolic syndrome, type 2 diabetes mellitus, cholesterol and other lipids, hypertension, and obesity. Some of that is due to the drugs used to treat inflammatory diseases, like corticosteroids. Some of it is due to the difficulty that people with arthritis have in being active and exercising.  Framingham in Olmsted County  “There is an association between rheumatoid arthritis (and cardiovascular disease) due to traditional and nontraditional cardiovascular risk factors (i.e., elevated inflammatory markers, rheumatoid factor seropositivity, corticosteroid use),” wrote F.C. Ernste of the Mayo Clinic in Rochester, Minn., and colleagues in the July 2015 Arthritis Care & Research. Cardiovascular risk in patients with psoriatic arthritis “is less well understood, and available studies may be limited by selection bias, heterogenous patient groups, and definition of outcome assessments. Yet, the consequences of underestimating (cardiovascular disease) risk in the (psoriatic arthritis) population in clinical practice may result in a missed opportunity to intervene early.” Ernste and colleagues used the Framingham Risk Score to see what effect psoriatic arthritis had on cardiovascular disease. The Framingham Risk Score uses age, sex, smoking status, hypertension, diabetes mellitus, total cholesterol and high-density lipoprotein cholesterol to calculate the risk of a person having cardiovascular disease over the next 10 years.  Starting in 1989, Ernste and colleagues recruited 158 patients with psoriatic arthritis in Olmsted County, Minn. Thirty-two patients already had cardiovascular disease; 126 did not. They calculated the Framingham Risk Score from their medical records and followed them for 10 years. The patients were more likely to be smokers and more likely to be obese. Obesity and smoking are risk factors for both psoriatic arthritis and cardiovascular disease.  “The aims of our study were to assess the prevalence of CVD risk factors at the onset of PsA, examine the incidence of CVD among patients newly diagnosed with PsA, and compare the observed incidence of CVD events with CVD events predicted by the (Framingham Risk Score) to determine its applicability in this patient population,” wrote Ernste and colleagues.  The Framingham Risk Score predicted that over 10 years, of the 126 patients without cardiovascular disease, 10 patients would develop cardiovascular disease. Actually, 18 patients developed cardiovascular disease.  Ernst and colleagues concluded that the Framingham Risk Score underestimated the true risk of cardiovascular disease in patients newly diagnosed with psoriatic arthritis. The observed 10-year risk was twice as high as the risk predicted by the Framingham Risk Score beginning after age 40 years. The 10-year cumulative incidence of cardiovascular events was 17. The majority of newly diagnosed psoriatic arthritis patients had a greater than 10% risk of cardiovascular disease.  Some of the laboratory tests, particularly the erythrocyte sedimentation rate and C-reactive proteins, were not associated with an increased risk of cardiovascular disease. This is in contrast to rheumatoid arthritis, where these markers do predict higher risks of cardiovascular disease. This may be because psoriatic arthritis has relatively low levels of chronic inflammation.  The Framingham Risk Score may underestimate the extent of cardiac risk in psoriatic arthritis patients, they wrote, “because chronic system inflammation may lead to endothelial dysfunction, atherosclerosis and other downstream effects not accounted for by risk assessment scoring systems.”  Traditional risk factors outweigh inflammatory markers A study of psoriatic arthritis in Toronto used a different method to examine that chronic system inflammation, and their result was different in some ways. Their endpoint was atherosclerotic plaque area on the carotid arteries, as measured by vascular ultrasound. They found that traditional cardiovascular risk factors did account for most of the atherosclerosis, and were more significant than traditional inflammatory markers, they wrote in the May 14, 1014 Annals of Rheumatic Diseases. Dafna Gladman and colleagues of Toronto Western Hospital, Ontario, Canada, recruited 235 patients with psoriatic arthritis at the University of Toronto psoriatic arthritis clinic, who were also part of an ongoing prospective cohort study and had been enrolled in the clinic for a median of seven years. The investigators measured clinical and laboratory variables. The laboratory tests included erythrocyte sedimentation rate, C-reactive protein, and white blood cell count. Current psoriasis activity was scored by the Psoriasis Area and Severity Index (PASI), and by two psoriasis-specific composite measures, Disease Activity Index for PsA (DAPSA) and Psoriatic Arthritis Disease Activity Score (PASDAS), which include physical assessments such as joint counts, and C-reactive protein.  In a regression analysis, more severe atherosclerosis was associated with higher erytherocyte sedimentation rate, a higher white blood cell count, and a higher DAPSA. However, after adjustment for traditional cardiovascular risk factors, these associations were no longer statistically significant.  Patients with more severe athrosclerosis were more likely to be older, obese, smokers, have hypertension diabetes and dyslipidemia. The researchers noted that traditional cardiovascular risk factors are prevalent in patients with psoriatic arthritis. In rheumatoid arthritis and lupus, the cardiovascular risk increases with the duration of the disease. Gladman and colleagues also hypothesized that psoriatic arthritis would do the same. They were surprised to find that this was not true for their psoriatic arthritis patients.  Elevated erythrocyte sedimentation rate and white blood cells, both markers of systemic inflammation, were associated with more severe atherosclerosis. “Leukocytes play a key role in the inflammatory responses involved in atherogenesis,” wrote Gladman and colleagues. “Blood monocytes and T cells cross the endothelial layer into the intima, where they produce proinflammatory cytokines that upregulate cell-mediated immunity and promote vascular endothelial dysfunction, which results in plaque formation. Activated neutrophils and their products have been linked with vulnerable plaques.”  Statins lower DAS28 too Conventional treatment of cardiovascular disease includes statins. As previously reported in Rheumatology Network, the Rosuvastatin in Rheumatoid Arthritis, Ankylosing Spondylitis and other inflammatory joint diseases study (RORA-AS) treated 86 patients, who had carotid plaques and inflammatory joint disease, with rosuvastatin to attain the recommended low-density lipoprotein cholesterol level of ≤70 mg/dl, S. Rollefstad of the Diakonhjemmet Hospital, Oslo, Norway and colleagues wrote in the July 2015 Arthritis & Rheumatology. After 18 months of treatment, the primary endpoint, carotid plaque height, was reduced by 0.19 mm. Mean low-density lipoprotein, 155 mg/dl at baseline, was reduced by 89 mg/dl. Interestingly, disease activity scores in 28 joints were lower among those with the greatest plaque size reduction. 

References:

Nurmohamed MT, Heslinga M, Kitas GD. Cardiovascular comorbidity in rheumatic diseases. Nat Rev Rheumatol. 2015 Aug 18. doi: 10.1038/nrrheum.2015.112. [Epub ahead of print] Review.

Eder L, Thavaneswaran A, Chandran V, Cook R, Gladman DD. Increased burden of inflammation over time is associated with the extent of atherosclerotic plaques in patients with psoriatic arthritis. Ann Rheum Dis. 2015 Oct;74(10):1830-5. doi: 10.1136/annrheumdis-2014-205267. Epub 2014 May 14.

Chiu HY, Chang WL, Huang WF, et al. Increased risk of arrhythmia in patients with psoriatic disease: A nationwide population-based matched cohort study. J Am Acad Dermatol. 2015 Sep;73(3):429-38. doi: 10.1016/j.jaad.2015.06.023. Epub 2015 Jul 15.

Rollefstad S, Ikdahl E, Hisdal J, et al. Rosuvastatin-Induced Carotid Plaque Regression in Patients With Inflammatory Joint Diseases: The Rosuvastatin in Rheumatoid Arthritis, Ankylosing Spondylitis and Other Inflammatory Joint Diseases Study. Arthritis Rheumatol. 2015 Jul;67(7):1718-28. doi: 10.1002/art.39114.

Ernste FC, Sánchez-Menéndez M, Wilton KM, et al. Cardiovascular risk profile at the onset of psoriatic arthritis: a population-based cohort study. Arthritis Care Res (Hoboken). 2015 Jul;67(7):1015-21. doi: 10.1002/acr.22536.