Carotid ultrasound has been the most extensively studied imaging modality for CVD risk assessment in RA. In a cohort of 599 RA patients with no history of ACS, rates of ACS were nearly 4 times higher in RA patients with bilateral carotid plaque on carotid ultrasound, and the association with ACS was independent of other traditional and RA-related risk factors.41 Presence of bilateral carotid plaques was similarly associated with an increased risk of overall CVD events (hazard ratio [HR], 3.34 [95% CI, 1.21-9.22]), ACS alone (HR, 6.31 [95% CI, 1.27-31.40]), and a lower mean CVD event-free survival (13.9 versus 15.2 years, P = 0.01) in a separate inception cohort of 105 RA patients with no prior history of CVD.42 The most useful application of carotid ultrasound may be in conjunction with clinical CVD risk models. Use of carotid ultrasound improved CVD risk stratification among RA patients who were considered at moderate risk by the EULAR-modified SCORE calculator.43 Beyond carotid ultrasound, measurement of arterial stiffness through ultrasound could also aid in CVD risk stratification. Aortic pulse wave velocity and augmentation index, measures of arterial stiffness, are predictive of CVD in the general population as well as RA patients and improve with reduction in RA disease activity.44,45 Peripheral arterial stiffness (brachial-ankle elasticity index) is impaired in RA patients and predictive of CVD morbidity and mortality in the general population.46,47
CT coronary angiography and coronary artery calcium (CAC) scores are reliable measures of coronary artery atherosclerosis and have been validated for CVD risk assessment in the general population.48-52 While the association between RA and CT-related findings of atherosclerosis is well established, assessment of CT-mediated evaluation as a prognostic tool for CVD in RA is limited. In one cohort study, CAC predicted higher rates of CVD events in Chinese patients with RA and systemic lupus erythematosus in a pooled analysis, although results were limited by low event rates and the absence of RA-only subanalyses.53
While the aforementioned imaging modalities have focused on enhancing the identification of atherosclerosis, echocardiography or cardiac magnetic resonance imaging (MRI) may be useful for detecting subclinical structural and/or functional abnormalities that predispose to CHF. Structural abnormalities including increased left ventricular mass and hypertrophy are more prevalent in RA patients and predict incident CHF in the general population.54-56 MRI measures of myocardial inflammation, including T1 mapping and extracellular volume, are associated with higher mortality rates and also appear to be elevated in RA patients.57,58 Whether identification of these imaging findings influences the cost-effective clinical management of RA patients needs further study.
Biomarkers
Serum biomarkers, such as the anti-CCP antibody, have become crucial to the evaluation of patients suspected to have RA. With the growing understanding of the role pro-inflammatory mediators play in CVD pathogenesis and the relative ease with which they can be measured, serum biomarkers have potential to inform CVD risk assessment. In the general population, hsCRP concentrations are predictive of CVD and are included in the Reynolds Risk Score.27 In RA, CRP concentrations are typically much higher than those observed among individuals in the general population solely at increased CVD risk, yet elevated levels remain predictive of CVD death independent of RA disease activity and traditional CVD risk factors.59 Several additional cytokines, chemokines, and adhesion molecules have been associated with surrogate markers of CVD in RA patients, although further study is needed to elucidate thresholds that signify increased CVD risk in a population characterized by the presence of systemic inflammation.60
Cardiac biomarkers used frequently in the general population may be useful to assess CVD risk in RA patients. N-terminal-pro brain natriuretic peptide (NT-pro BNP) is a biomarker typically used to evaluate CHF severity, but it may also predict long-term mortality in patients with coronary heart disease.61,62 Circulating NT-pro BNP concentrations are elevated in RA independent of prevalent CHF and may serve as a useful tool to identify subclinical cardiac disease in RA patients.63 High-sensitivity cardiac troponin I (HS-cTnI) assays are capable of detecting levels of cardiac troponin below the threshold typically used to diagnose ACS. HS-cTnI levels are increased in RA patients independent of additional CVD risk factors, and elevated levels (> 1.5 pg/mL) were associated with more severe CT angiography findings of coronary plaque as well as increased risk of CVD events.64,65
