TOPIC SERIES: CVD PREVENTION IN RHEUMATIC DISEASE

Data derived from a large, well-characterized cohort of patients with psoriatic arthritis (PsA) followed prospectively for over 35 years in Canada suggest that PsA disease activity and systemic inflammation are independently predictive of cardiovascular event development. Traditional cardiovascular risk factors were also found to be highly predictive of cardiovascular disease (CVD), as expected, however findings further suggest that PsA disease itself and systemic inflammation are also independently associated with increased CVD risk.  These results were recently published in the Annals of the Rheumatic Diseases.

“While the independent effect of disease-related inflammation on cardiovascular risk is established in [rheumatoid arthritis], few studies have thus far attempted to elucidate the link between metabolic abnormalities and PsA-related factors to determine the independent effect of psoriatic disease activity on cardiovascular morbidity,” Dafna Gladman, MD, of the Centre for Prognosis Studies in the Rheumatic Diseases, Toronto Western Hospital, Ontario, Canada and colleagues stated. They therefore sought to clarify what factors are independent predictors of cardiovascular event development in patients with PsA, in addition to the cumulative incidence of these events.


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Prospective clinical data from a single PsA specialty clinic in Toronto was collated and a cohort analysis was performed.  Briefly, patients being treated at the University of Toronto PsA clinic were enrolled into the already ongoing prospective study, with assessments conducted every 6-12 months to evaluate demographics, pharmacotherapy, PsA-related outcomes, laboratory results, and lifestyle changes.  Any patient with a past medical history of any cardiovascular event prior to initial PsA diagnosis were not included in the data analysis.

Cardiovascular events linked to these patients were subsequently identified by using the clinic database, with 2 physicians agreeing upon a consensus diagnosis for each cardiovascular event. Researchers defined the primary composite end point at time of first major event, including myocardial infarction (MI), ischemic stroke, requirement for revascularization, or death from cardiovascular-related causes. 

High Yield Data Summary

  • Increased PsA disease activity (tender joint counts, dactylitic digits, disability scores) and traditional CV risk factors (hypertension, diabetes, hyperlipidemia) both appear to increase CV events in PsA

Researchers defined the secondary composite end point as the occurrence of the first cardiovascular event, including transient ischemic attack (TIA), angina, or congestive heart failure (CHF). 

When attempting to identify the risk factors for CVD development, researchers included both validated, traditional cardiac risk factors (diabetes mellitus, hypertension, hyperlipidemia, hypertriglyceridemia, and smoking) in addition to PsA disease-related potential risk factors.  

The PsA-related factors evaluated were disease duration, tender and swollen joint count, enthesitis count, clinically damaged joint count, psoriasis area and severity index [PASI], erythrocyte sedimentation rate [ESR)], leucocyte count, health assessment questionnaire [HAQ], Short form Health Survery-36 [SF-36] physical component score [PCS], and use of either nonsteroidal antiinflammatory drugs, corticosteroids, disease-modifying antirheumatic drugs, or tumor necrosis factor-alpha inhibitors.

A total of 19,649 person-years (PYs) of follow-up were analyzed (mean of 9.84 ± 8.61 years per person starting from clinic entry to the last CVD assessment), derived from 1091 patients with PsA.  One hundred four cardiovascular events occurred during the study observation period, including 57 MIs, 9 ischemic strokes, 19 requirements for revascularization, 2 deaths attributed to CVD, 10 episodes of angina, 1 noted TIA, and 6 cases of CHF. 

When analyzing the proportion of patients with PsA who had a cardiovascular event within the observation period, researchers found that 19.8% of patients ≥ 70 years old had a predefined cardiovascular composite event.  This number increased to 30.1% by the time patients were ≥ 80 years old.  No trends (either increase or decrease) were noted in the rate of development of cardiovascular events between January 1,1978 and November 20, 2013 (P = .73).

As expected, traditional cardiovascular risk factors including diabetes, hypertriglyceridemia, and hypertension were associated with cardiovascular event development in univariate analysis. PsA disease activity as measured by tender joint count, dactylitic digit count, leukocyte count, disability on the SF-36-PCS, increased ESR levels in women, and methotrexate pharmacotherapy were also predictive of cardiovascular events.  These factors remained independently associated with development of cardiovascular events even after adjustment for existence of traditional cardiac risk factors.

After multivariate analysis, several independent predictors of major cardiovascular events were identified and are represented below (table 1). Independent predictors for any cardiovascular event also included PsA-disease characteristics in addition to traditional cardiac risk factors (table 2).

These findings are clinically important because they suggest that tight PsA decrease control may mitigate the risk of future CVD development.

“The risk of developing cardiovascular events was explained in part by traditional cardiovascular risk factors; however, the level of [PsA] disease activity and the extent of systemic inflammation were independent predictors of cardiovascular events,” the authors stated.

Summary and Clinical Applicability

A significant percentage of patients with PsA will have a cardiovascular event, especially as they age. In addition to traditional cardiovascular risk factors, increased PsA disease activity also appears to increase cardiovascular risk.

“These results highlight the importance of screening and controlling all traditional cardiovascular risk factors as well as targeting for minimal disease activity that can potentially reduce cardiovascular risk,” the authors concluded.

Limitations and Disclosures

  • Lack of data on other potential predictors of CVD, including information on physical activity, family history of cardiovascular events, and body mass index
  • Cumulative PsA disease activity prior to study enrollment/first visit to outpatient clinic could not be accounted for due to study design

No conflicts of interest were disclosed by study authors.

 

Table 1. Variables Independently Predictive of Major Cardiovascular Events* in Psoriatic Arthritis After Multivariate Analysis 

Relative Risk (RR) 95% Confidence Interval (CI)
Diabetes Mellitus 2.72 1.60 to 4.62 
Elevated ESR** 1.83 1.12 to 2.99
Hypertension 1.81 1.11 to 2.92
Number of dactylitic digits 1.20 1.08 to 1.34

ESR = erythrocyte sedimentation rate 

* Major cardiovascular event was defined as occurrence of myocardial infarction, ischemic stroke, need for cardiac revascularization, or cardiovascular death

** ESR only amongst women with psoriatic arthritis

 

Table 2. Variables Independently Predictive of Any Cardiovascular Event* in Psoriatic Arthritis After Multivariate Analysis 

Relative Risk (RR) 95% Confidence Interval (CI)
Diabetes 2.53 1.54 to 4.16
Hypertension 1.71 1.11 to 2.64
Elevated ESR** 1.70 1.10 to 2.62
Number of dactylitic digits 1.18 1.06 to 1.32

*  Any cardiovascular event was defined as occurrence of angina pectoris, transient ischemic accident, or congestive heart failure 

** ESR only amongst women with psoriatic arthritis

    Reference

    Eder L, Wu Y, Chandran V, Cook R, Gladman DD. Incidence and predictors for cardiovascular events in patients with psoriatic arthritis. Ann Rheum Dis. 2016;75:1680-1686 doi:10.1136/annrheumdis-2015-207980

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