The role of multidetector computed tomography coronary angiography with calcium score and Framingham Risk Score in evaluation of rheumatoid arthritis patients with chest pain

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JICC-402; No. of Pages 8 Journal of Indian College of Cardiology xxx (2017) xxx–xxx

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Journal of Indian College of Cardiology journal homepage: www.elsevier.com/locate/jicc

Original article

The role of multidetector computed tomography coronary angiography with calcium score and Framingham Risk Score in evaluation of rheumatoid arthritis patients with chest pain Abdelaziz Mohamad Gomaa a,*, Ahmed Taha Omar Abou Ghonima b, Nashwa Abdelrahman Ibrahim c, Mohamad Foud Almaghraby d a

Zagazig University, Faculty of Medicine, Cardiology Department, Egypt Banha University, Faculty of Medicine, Rheumatology and Rehabilitation Department, Egypt c Ain Shams University, Faculty of Medicine, Rheumatology and Rehabilitation Department, Egypt d Banha University, Faculty of Medicine, Internal Medicine Department, Egypt b

A R T I C L E I N F O

A B S T R A C T

Article history: Received 2 March 2017 Accepted 24 March 2017 Available online xxx

Objectives: To evaluate diagnostic yield of coronary artery calcium (CAC) scoring using multidetector CT imaging in rheumatoid arthritis (RA) patients presented with chest pain. Patients and methods: Seventy RA patients evaluated using the 28 joint disease activity (DAS-28) score, Disability Index (DI) and radiologically for Larsen–Dale index. Patients underwent assessment for coronary artery disease (CAD) risk factors and coronary risk stratification using the Framingham Risk Score (FRS). Patients were clinically categorized according to criteria for typical anginal pain (TAP) and were scanned using a 64-row spiral CT scanner for CAC scoring and were stratified according Agatston CAC scores for calculation of total Agatston score (TAS). Results: Clinically, 32 patients had full criteria of TAP, 27 patients showed a picture of atypical anginal pain, while 11 patients had non-anginal chest pain. FRS predicted low, intermediate and high risk of CAD in 34, 18 and 18 patients, respectively. TAS defined no CAC in 4 patients, while mild, moderate and severe CAC was detected in 24, 36 and 6 patients, respectively. Regression analysis defined low HDL blood level, current smoking and high TAS, DAS-28 and FRS as significant predictor for TAP in decreasing order of significance. Receiver operating characteristic (ROC) curve analysis defined low HDL blood level and high TAS as the significant sensitive and specific tests, respectively. There was positive significant correlation between FRS and both of TAS scores and extent of coronary stenosis. However, FRS was the least significant predictor for TAP. Conclusion: Screening of RA patients with combination of clinical scoring using FRS and CAC using noninvasive multidetector CT could allow early detection of patients at risk for acute cardiovascular events. However, TAS acts better for the prediction of TAP. ß 2017 Indian College of Cardiology. All rights reserved.

Keywords: Rheumatoid arthritis Coronary artery calcium scoring Acute chest pain

1. Introduction Rheumatoid arthritis (RA) is a chronic systemic autoimmune inflammatory disease in which the peripheral joints are the primary sites of inflammation, often leading to destruction of these joints. RA is characterized by symmetrical synovitis, progressive joint damage, pain, fatigue, and disability.1

* Corresponding author. E-mail address: [email protected] (A.M. Gomaa).

The spectrum of RA ranges from benign remitting manifestations to rapidly progressive forms with increased mortality. About 10% of patients show an intractable rapidly progressive course associated with severe extra-articular manifestations. Within the first three years, 70% of the patients develop radiological erosions of the joints and 31% of patients had hand deformities.2 Cardiovascular disease (CVD) is also prevalent in patients with RA, with onset in early disease and subclinical involvement is higher than anticipated. Several disease-specific risk factors, like seropositivity, disease activity, and medications, are implicated in the pathogenesis of CVD in RA. Cardiovascular risk assessment in RA varies from the general population.3

http://dx.doi.org/10.1016/j.jicc.2017.03.004 1561-8811/ß 2017 Indian College of Cardiology. All rights reserved.

Please cite this article in press as: Gomaa AM, et al. The role of multidetector computed tomography coronary angiography with calcium score and Framingham Risk Score in evaluation of rheumatoid arthritis patients with chest pain, J Indian Coll Cardiol. (2017), http:// dx.doi.org/10.1016/j.jicc.2017.03.004

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RA can manifest in a variety of cardiac complications, including pericarditis, valvular disease, cardiomyopathy, and amyloidosis. There is an increased incidence of coronary artery disease (CAD) in RA. Patients with prevalent RA suffer more severe CAD compared to the general population and also have poorer outcomes4 with an increased risk of cardiovascular (CV) mortality attributed to a higher incidence of heart failure and ischemic heart disease.5 The elevated risk of ischemic heart disease in patients with RA has been linked to immune-mediated mechanisms, chronic inflammation and disease severity as evidenced by the lower risk of CAD in RA patients treated with tumor necrosis factor inhibitors compared with biologic-naı¨ve RA patients.6 Several imaging techniques may reveal vascular calcium deposits. Although calcifications may occur in small amounts in the earlier stages of atherosclerosis, they are usually seen in more advanced lesions. Vascular calcification is commonly used as a subclinical marker of atherosclerosis and has been linked to increased all-cause mortality, cardiovascular mortality and coronary events.7 Patients with RA are known to develop early-onset, diffuse calcification in various vascular beds compared to age and sexmatched controls, so they are at increased risk for morbidity and mortality from CVD.8 This is consistent with the concept whereby inflammation promotes atherosclerosis and vascular calcification. However, specific mediators such as proinflammatory cytokines and not global inflammation could be involved.9 Recent meta-analyses of the relationship between calcification and cardiovascular risk have focused exclusively on coronary artery calcium (CAC) scores.10 Thus, the current study aimed to evaluate the diagnostic yield of CAC scoring and CT coronary angiography using multidetector CT imaging in RA patients presented with chest pain.

2. Patients and methods The present prospective study was conducted at Departments of Rheumatology and Rehabilitation, Cardiology and Internal Medicine, Dallah Hospital, Riyadh KSA from June 2014 to February 2016. The study protocol was approved by the Local Ethical Committee and patients’ fully informed written consents were obtained prior to study participation. 2.1. Patient selection All enrolled patients had RA and required evaluation because of symptoms of chest pain and carrying one or more cardiovascular risk factor. All patients were fulfilled the 2010 American college of Rheumatology criteria for diagnosis of RA.11 Patients’ demographic data including gender, weight, height for calculation of body mass index (BMI) according to the equation: BMI = weight (kg)/height (m2)12 were determined. Patients with history of acute myocardial infarction (AMI), heart failure, coronary artery revascularization, stroke, peripheral vascular disease, abdominal aortic aneurysm, current atrial fibrillation, cardiomyopathy, valvular heart disease, congenital heart disease, weight exceeding 150 kg, inflammatory diseases other than RA were excluded from the study. 2.2. Assessment of RA disease activity and severity RA disease activity was assessed using the 28 joint disease activity score (DAS-28) and was categorized as follows: DAS28  3.2 means inactive, >3.2–5.1 means moderate activity and >5.1 means very active disease.13 Pain was assessed by a 0–100 mm

horizontal visual analog scale (VAS) with VAS score of 0–25 indicates mild pain, >25–50 indicates moderate pain, >50–75 indicates severe pain and >75 indicates intolerable pain.14 Functional disability was evaluated using the Swedish version of the Stanford health assessment questionnaire to calculate the Disability Index (DI). The eight categories assessed by DI are (1) dressing and grooming, (2) arising, (3) eating, (4) walking, (5) hygiene, (6) reach, (7) grip, and (8) common daily activities. The difficulty during each of these acts was assessed as follows: 0: without any difficulty, 1: with some difficulty, 2: with much difficulty and 3: unable to do, then the sum of the categories scores is calculated and divided by the number of categories. This gives a score in the 0–24 range.15 Laboratory assessment of RA disease activity included measurement of erythrocyte sedimentation rate (ESR; mm/h), Creactive protein (mg/l) and ELISA quantitation of Rheumatoid factor IgM isotype using standard laboratory methods were performed at hospital laboratory. Radiological assessment included postero-anterior radiographs of hands, wrists, and forefeet and joint destruction was classified by comparison with standard reference films according to the Larsen–Dale index.16 For the scored 32 joints; each joint is graded where grade 0 indicates no abnormality; grade I indicates slight abnormality with one or more of the following criteria: soft tissue swelling, juxta-articular osteoporosis, slight narrowing of the joint space; grades II–V indicate erosion and narrowing of the joint space of increasing severity. The degree of erosive damage is the most decisive criterion in grading and patient was considered having erosive disease if at least one definite erosion, on any of the hands or feet radiographs, was detected. 2.3. CAD risk factors assessment Patients were assessed for conventional coronary risk factors including obesity, cigarette smoking, hypertension, hypercholesterolemia, diabetes mellitus, and family history of CAD. Obesity was defined as BMI  30 kg/m2. Smoking was defined as any cigarette smoking within the last year. Hypertension was defined as a previously established diagnosis with systolic blood pressure  140 mmHg, diastolic blood pressure  90 mmHg, or maintenance antihypertensive medication use. Hypercholesterolemia was defined according to the National Cholesterol Education Panel guidelines17 or by the current use of lipid-lowering medication. Diabetes mellitus was defined as a previously established diagnosis, insulin or oral hypoglycemic therapy, fasting glucose of 126 mg/dl, or non-fasting glucose of 200 mg/dl. Family history of CAD was defined as MI, coronary revascularization, or sudden cardiac death for father <55 yearsof-age or mother <65 years-of-age. Typical angina was defined as a combination of: (1) discomfort in the anterior chest, neck, shoulders, jaw, or arms; (2) precipitated by physical exertion or emotional stress; and (3) relieved by rest or nitroglycerin within minutes. Atypical angina was defined as chest pain with 2 of these 3 factors, and non-anginal chest pain was defined as chest pain with <2 of these 3 factors.18 2.4. Cardiac risk stratification Coronary risk stratification was conducted using the Framingham Risk Score (FRS) calculated using age, sex, smoking status, serum total cholesterol and HDL cholesterol concentrations, blood pressure, and on antihypertensive therapy or not. FRS was used to assess the 10-year risk of developing heart disease or having a heart attack with low risk was defined as FRS < 10%, Moderate risk as FRS as 10–20% and sever risk as FRS > 20%.19

Please cite this article in press as: Gomaa AM, et al. The role of multidetector computed tomography coronary angiography with calcium score and Framingham Risk Score in evaluation of rheumatoid arthritis patients with chest pain, J Indian Coll Cardiol. (2017), http:// dx.doi.org/10.1016/j.jicc.2017.03.004

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2.5. CT coronary angiography 2.5.1. Data acquisition Scans were performed using a 128-row spiral CT scanner (Siemens, SOMATOM). Patients with a pre-scan heart rate of 70 beats/min or higher were given 25–50 mg of metoprolol orally 1 h before scanning. First, patients underwent non-enhanced prospective (ECG)-gated sequential scan to measure CAC Score. Thereafter, coronary CT angiography (CTA) was performed using retrospective ECG gating with ECG-based tube current modulation. A double-head power injector was used to inject contrast media through a 20G canula in an antecubital vein. A test bolus (10 ml contrast agent followed by a 20-ml saline flush) with injection rate of 5 ml/s was used to determine the timing of scan delay and image acquisition time. Depending on patient weight, iohexol 350 mgI/ ml (Omnipaque 350, GE Healthcare) or iopromide 370 mgI/ml (Ultravist 370, Bayer-Schering Pharma, Berlin, Germany) was injected at a speed of 5 ml/s. The main scanning parameters were as follows: 128 detectors; 0.625 mm individual detector width; 350 ms gantry rotation time; 120 kV tube voltage; ECG-modulated tube current ranged from 200 to 550 mA (the tube current was 550 mA during 40% to 80% RR interval when diagnostic image quality was required, and remained at 200 mA during the other phases of the RR interval); 0.16–0.22 pitch; 400 mm table feed/ rotation; 200–250 mm field of view. 2.5.2. Coronary calcification score calculation To determine the presence and quantity of coronary calcium, each of the 20 levels was evaluated sequentially. Calcific lesion was defined as the presence of at least 3 contiguous pixels with CT density of >130 Hounsfield units (HU) and this is the threshold for a calcific lesion and having an area 1 mm2. At each level, all pixels with CT density 130 HU were displayed. A ‘‘region of interest’’ was placed around all lesions found within a coronary artery. Automated measurements of the lesion area in square millimeters and the maximal CT number of each region of interest were recorded.20 A lesion score was determined based on the maximal CT number in the following manner: 1 = 130– 199, 2 = 200–299, 3 = 300–399, 4 = 400 HU. A score for each region of interest was calculated by multiplying the density score and the area (number of pixels). A total coronary calcium score was determined by adding up each of these scores for all 20 slices.21 Patients were stratified according to Agatston CAC scores where patients were considered as free of coronary artery calcification (CAC = 0), had mild calcification (CAC = 1–99), moderate calcification (CAC = 100–399) or had severe calcification (CAC  400).22 The coronary artery tree was segmented according to the modified American Heart Association classification, and these segments were investigated for the presence and characteristics of coronary plaques. The degree of stenosis was classified according to the percentage of lumen narrowing on the longitudinal image as <25% diameter indicated minimal stenosis, 25–49% indicated mild stenosis, 50–69% indicated moderate stenosis and 70% indicated severe stenosis and 100% indicated total occlusion.23 2.5.3. Statistical analysis Obtained data were presented as mean  SD, ranges, numbers and ratios. Results were analyzed using Wilcoxon; ranked test for unrelated data (Z-test) and Chi-square test (X2 test) for inter-group comparisons and paired t-test for intra-group comparisons. Possible relationships were investigated using Pearson linear regression. Sensitivity and specificity of estimated parameters as predictors were evaluated using the receiver operating characteristic (ROC) curve analysis judged by the area under the curve (AUC) compared versus the null hypothesis that AUC = 0.05. Statistical analysis was

3

conducted using the SPSS (Version 15, 2006) for Windows statistical package. P value <0.05 was considered statistically significant. 3. Results The study included 70 RA patients fulfilling the enrolment criteria and presented by chest pain. They were 18 (25.7%) males and 52 (74.3%) females, their mean age was 54.5  6.2 years, 16 patients (22.9%) were smokers while 54 (77.1%) were nonsmoker, their mean BMI was 29  6.1, family history of premature CAD was positive in 9 (12.8%) and negative in 61 (87.2%), the mean disease duration was 4.7  1.8 years, the mean VAS score was 38.4  14.7, the mean DAS-28 was 3.9  1.15 and the mean DI was 12.3  5.1, the mean ESR was 29.6  13.3 mm/h, the mean CRP was 16.6  10.2 mg/L, regarding the radiological finding erosive disease was detected in 21 patients (30%) and non-erosive disease in 49 patients (70%), the Anti-CCP was positive in 43 (61.5%) patients, 34 (48.6%) of them had erosive disease while 9 (12.9%) of them had non erosive disease, while negative in 27 (38.5%) patients, 15 (21.4%) of them had erosive disease and 12 (17.1%) had non-erosive disease. Rheumatoid factor was positive in 51 (72.8%) patients, 39 (55.7%) of them had erosive disease while 12 (17.1%) of them had non erosive disease and negative in 19 (27.2%) patients, 10 (14.3%) of them had erosive disease and 9 (12.9%) had non-erosive disease. Patients’ demographic, RA-related clinical, radiological and laboratory data are shown in Table 1. Clinical presentations were variable where 32 (45.7%) patients had full criteria of typical anginal pain (TAP), 27 (38.6%) patients had a picture of atypical anginal pain, while 11(15.7%) patients had non-anginal chest pain. 15 (21.4%) patients were diabetics with mean fasting blood glucose (FBG) of 210  46.8 mg/dl. 47 (67.1%) patients were hypertensive with mean systolic blood pressure (SBP) of 159.9  17.4 mmHg. Majority of patients were dyslipidemic with total cholesterol ?200 mg/dl in 47 (67.1%) patients and low HDL blood levels was detected in 49 (70%) patients of studied patients. Cardiac risk stratification of studied patients according to Framingham CHD risk score defined 34 (48.45%) patients with low risk, 18 (25.8%) patients were of moderate risk and another 18 (25.8%) patients were of sever risk. CAC as calculated by total Agatston score (TAS) defined only 4 (5.7%) patients with Zero CAC, 24 (34.3%) patients had mild CAC and 36 (51.4%) patients had moderate CAC, while only 6 (8.6%) patients had severe CAC. Angiographic studies detected 16 (22.9%) patient had minimal coronary artery stenosis, 22 patients (31.4%) had mild stenosis, 19 (27.1%) patients had moderate stenosis and 13(18.6%) patients had sever stenosis. Details of associated clinical manifestations, cardiovascular risk factors, lipid profile, cardiac risk stratification, CAC scoring and degree of coronary artery stenosis data of studied patients are shown in Table 2. There was positive significant correlation between clinical verification of type of chest pain according to the frequency of symptoms of TAP and age, male gender, being current smoker, BMI, SBP, FBG, total cholesterol level, DAS-28, DI, Framingham CHD risk Score (FRS) and TAS, while showed negative significant with HDL blood level (Table 3). Regression analysis for verification of clinical, laboratory data and TAS showed correlation with clinical type of chest pain defined low HDL level (p = 0.0009), high DAS-28 score (p = 0.0009), being current smoker (p = 0.001), high TAS (p = 0.002), and high FRS (p = 0.011) as the persistently significant predictors for TAP, while other parameters were excluded for being non-significant predictors. ROC curve analysis for parameters defined by Regression analysis as significant predictors for TAP defined low HDL level as

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Table 1 Patients’ demographic, RA-related clinical, radiological and laboratory data. Findings

Data Age

Gender

Strata

Total

21 (30%) 32 (45.7%) 17 (24.3%) 54.5  6.2

Male Female

18 (25.7%) 52 (74.3%)

Current smoking

BMI data

Yes No Weigh (kg) Height (cm) BMI (kg/m2)

Family history of CAD

RA clinical manifestations

40–49 50–59 60

Duration of disease (years)

Pain scoring (VAS score)

Disease activity score (DAS-28)

Disability Index (DI)

Radiological findings

Erosion

Laboratory findings

ESR (mm/h) CRP (mg/l) Anti CCP

Total

82.8  17.1 169.2  3.3 17 (24.3%) 20 (28.6%) 23 (32.9%) 7 (10%) 3 (4.2%) 29  6.1

Yes No

9 (12.8%) 61 (87.2%)

<5 5 Mean duration (SD) <25 =25–50 >50 Mean VAS score (SD) Inactive (<3.2) Moderate activity (>3.2–5.1) Very active (>5.1) Mean DAS-28 score (SD) 8 >8–16 >16 Mean DI (SD)

39 (55.7%) 31 (44.3%)

Strata

Underweight Average Overweight Obese Morbid obese

4.7  1.8 8 (11.4%) 45 (64.3%) 17 (24.3%) 38.4  14.7 9 (12.9%) 47 (67.1%) 14 (20%) 3.9  1.15 23 (32.9%) 31 (44.2%) 16 (22.9%) 12.3  5.1

Erosive disease Non-erosive

Positive Negative

Rheumatoid factor

16 (22.9%) 54 (77.1%)

Positive Negative

21 (30%) 49 (70%)

Erosive Non-erosive Erosive Non-erosive Erosive Non-erosive Erosive Non-erosive

29.6  13.3 16.6  10.2 34 (48.6%) 9 (12.9%) 15 (21.4%) 12 (17.1%) 39 (55.7%) 12 (17.1%) 10 (14.3%) 9 (12.9%)

Data are presented as numbers and mean  SD; percentages are in parenthesis; BMI: body mass index; RA: rheumatoid arthritis; CAD: coronary artery disease; VAS: visual analog scale; ESR: erythrocyte sedimentation rate; CRP: C-reactive protein.

the significant sensitive test with area under curve (AUC = 0.304, p = 0.005) and so could be used as a significant screening test, while TAS was the most significant specific test (AUC = 0.718, p = 0.002) and could be used as a good diagnostic test. High DAS-28 (AUC = 0.647) and being current smoker (AUC = 0.304) were specific predictors for TAP but were less significant (p = 0.035) than TAS (Fig. 1). ROC curve evaluation of the diagnostic ability of angiographic grading of coronary artery stenosis, CAC scoring and clinical FRS for discrimination of RA patients with TAP among those presenting with chest pain defined TAS as the most significant predictor with AUC = 0.718 (p = 0.002) followed by angiographic scoring with AUC = 0.704 (p = 0.004) and lastly FRS with AUC = 0.656 (p = 0.025) as shown in Fig. 2. Concerning the relation between FRS as clinical scoring and TAS as radiological scoring for discrimination of cases with TAP among RA patients with chest pain; there was positive significant correlation between both scoring systems (r = 0.380, p = 0.001) as shown in Fig. 3a.

There was also positive significant correlation (r = 0.263, p = 0.028) between extent of angiographic coronary stenosis and FRS (Fig. 3b). Despite detecting 34 patients had mild FRS indicating low-risk for having TAP; CAC scoring detected severe calcification in 4 patients, mild–moderate calcification in 29 patients and only one patient had CAC score of 0. 18 patients had moderate FRS indicating moderate risk of having TAP; however, CAC scoring detected severe calcification in 7 patients, mild-moderate calcification in 10 patients and one patient had (0) CAC score. The remaining 18 patients had severe FRS indicating high-risk for having TAP; however, CAC scoring detected no calcification in two patients, mild-moderate calcification in 8 patients and another 8 patients had severe calcification as shown in Table 4 and Fig. 4 4. Discussion The current selective study included RA patients presented by chest pain. According to clinical classification of chest discomfort18;

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Table 2 Clinical manifestations, cardiovascular risk factors, lipid profile, cardiac risk stratification, coronary artery calcification scoring and degree of coronary artery stenosis data of studied patients. Findings

Data Clinical presentation

Typical anginal pain Atypical anginal pain Non-anginal chest pain

Associated medical problems

Diabetic

32 (45.7%) 27 (38.6%) 11 (15.7%)

Hypertensive

Lipid profile

Total cholesterol (mg/dl)

HDL (mg/dl)

LDL (mg/dl)

Triglycerides (mg/dl)

Framingham CHD Risk Score

Low risk Moderate risk Sever risk

Total Agatston score

0 1–99 100–399 >400

Degree of coronary stenosis

Minimal stenosis Mild stenosis Moderate stenosis Severe stenosis

Number Mean FBG Number Mean SBP

15 (21.4%) 210  46.8 mg/dl 47 (67.1%) 159.9  17.4 mmHg

<200 200–239 >240 Mean level <40 40 Mean level 100–129 130–159 160–189 Mean level <150 150 Mean level

23 (32.9%) 28 (40%) 19 (27.1%) 225.5  42.5 49 (70%) 21 (30%) 37.2  4.4 29 (41.4%) 32 (45.7%) 9 (12.9%) 161.4  42.3 59 (84.3%) 11 (15.7%) 134.7  17.4

Frequency Mean score Frequency Mean score Frequency Mean score

34 (48.4%) 5.2  2 (2–9.2) 18 (25.8%) 14.7  3.1 (10.4–18.8) 18 (25.8%) 27  6.6 (20.5–41.8)

Frequency Frequency Mean score Frequency Mean score Frequency Mean score

4 (5.7%) 24 (34.3%) 81  13.6 36 (51.4%) 128.6  24.6 6 (8.6%) 421  8.8

16 22 19 13

22.9% 31.4% 27.1% 18.6%

Data are presented as numbers and mean  SD; percentages are in parenthesis; DM: diabetes mellitus; HDL: high-density lipoprotein; LDL: low-density lipoprotein CHD: chronic hear disease.

hypertension, triglyceride level, DAS28, extra-articular disease and use of corticosteroid or COX-2 inhibitors. Also, Gossec et al.26 using CV risk assessment evidenced that dyslipidemia and hypertension are the most frequent CV risk factors in RA patients. The present study detected a positive significant correlation between the presence of TAP and severity of RA manifested as high DAS-28 score and DI and high DAS-28 score acts as a positive predictor for presence of TAP. In line with these findings, Meek et al.27 reported that RA activity control decreased CV case fatality in low disease activity RA patients from 52.9% in 1998 to 6.9% nowadays. Arts et al.28 detected that the risk of CVE was significantly associated with DAS-28 not with RA disease duration that does not appear to independently affect the risk of CVE. Also, Solomon et al.29 showed that reduced time-averaged RA disease activity is associated with fewer CVE.

32 patients had criteria of TAP and 27 patients had atypical AP, while 11 patients had non-anginal chest pain; a finding indicating a close association between RA and the possibility for development of CAD. Also, hypertension, dyslipidemia and diabetes were detected by frequencies of 67.1%, 70% and 21.4%, respectively. Thus, these RA patients could be considered as cardiovascular high risk patients. In line with these findings Innala et al.24 reported that among 442 RA patients who reached 5-year follow-up period, treatment for hypertension significantly increased from 24.5% to 37.4%, diagnosis of DM from 7.1% to 9.5% and 10% of these patients had suffered a new CV event (CVE) of which 12 were fatal. Also, Chung et al.25 indicated that the risk of AMI is increased by 38% in RA patients compared to the general population. Moreover, Innala et al.24 reported that the hazard rate for a new CVE was increased with age at disease onset, male sex, a previous CVE, DM,

Table 3 Correlation coefficient between clinical type of chest pain (typical anginal pain) and other studied parameters.

r p

Age

Male gender

Smoker

BMI

SBP

FH

FBG

TC

HDL

DAS

Disease duration

Pain

DI

FRS

TAS

0.266 0.026

0.298 0.012

0.385 0.001

0.325 0.006

0.284 0.017

0.12 0.32

0.361 0.002

0.249 0.037

0.411 0.0008

0.388 0.001

0.149 0.219

0.136 0.477

0.289 0.012

0.320 0.007

0.359 0.002

BMI: body mass index; SBP: systolic blood pressure; FH: family history; FBG: fasting blood glucose; TC: total cholesterol; HDL: high density lipoprotein; DAS: RA disease activity score; DI: Disability Index; FRS: Framingham CHD risk Score; TAS: total Agatston score; p < 0.05: significant difference.

Please cite this article in press as: Gomaa AM, et al. The role of multidetector computed tomography coronary angiography with calcium score and Framingham Risk Score in evaluation of rheumatoid arthritis patients with chest pain, J Indian Coll Cardiol. (2017), http:// dx.doi.org/10.1016/j.jicc.2017.03.004

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Fig. 1. ROC curve analysis of significant predictors of typical anginal pain as defined by regression analysis.

1.0

TAS Angiography FRS

Sensitivity

0.8

0.6

0.4

0.2

0.0 0.0

0.2

0.4

0.6

0.8

1.0

1 - Specificity

Fig. 2. ROC curve analysis for the predictivity of TAS, angiographic stenosis grading and FRS as predictors for typical anginal pain in RA patients presented by chest pain.

The current study showed positive significant correlation between the frequency of patients had TAP and component items of Framingham CHD risk Score, but no single parameter or the score itself was found to be specific TAP predictor, thus indicating shortage of clinical evaluation alone to achieve diagnosis. In

support of these data; Davis et al.30 found the cardiovascular risk equations are not suitable for predicting CVD risk in patients with type 2 DM. Crowson et al.31 retrospectively assessed the predicted CVD risk using Framingham and Reynolds risk scores in RA patients and found both scores substantially underestimated CVD risk in patients with RA of both genders, especially in older ages and in patients with positive rheumatoid factor. Arts et al.32 assessed the predictive ability of 4 established CV risk models for the 10-year risk of fatal and non-fatal CVD in RA patients and concluded that Q.Risk II overestimates, while the other models, including FRS, underestimate CV risk in RA patients. Recently, in 2016, Tralha˜o et al.33 found the Systematic Coronary Risk Evaluation score calculator seems to be less discriminative than the atherosclerotic CVD score equation in identifying patients with high atherosclerotic burden. On contrary, CAC scoring did well as significant predictor for TAP against other parameters and as specific predictor with significantly high area under curve. In support for the specificity and possibility of reliance on CAC scoring as a proper diagnostic test especially for cases with intermediate or low FRS; Ellis et al.34 found that the percentage of Framingham ‘low-risk’ patients at zero and 5-year CVS risk was 78% and 58% respectively, however 10% and 8.8% of these patients had a calcium score of >400 units, indicating that they were actually at very high CVS risk, and 28% and 27% respectively had a calcium score of >100 units indicating that they were actually not at ‘low risk’. Also, Kawai et al.35 documented that clinical risk scores and standard risk prediction models used in general population do not adequately identify many RA patients with elevated CV risk. Moreover, Han et al.36 documented that in asymptomatic population, CAC improved prediction of allcause mortality over and above that of conventional risk tool. ROC curve evaluation of the diagnostic ability of angiographic grading of coronary vascular stenosis, TAS for CAC and clinical FRS for discrimination of RA patients with TAP among those presenting with chest pain arranged these parameters as TAS, angiographic scoring of coronary stenosis and FRS in decreasing order of significance. These data indicated that TAS for CAC using multidetector CT could be a powerful discriminative diagnostic tool for TAP. In support of these data, Budoff et al.37 found coronary CTA and conventional invasive coronary angiography exhibited similar diagnostic performance for the detection and exclusion of lesionspecific ischemia. Multiple recent studies tried to explore the underlying mechanism for the vicious cycle of RA, DM, dyslipidemia, hypertension ending at coronary heart attack and found the center of such cycle mostly is the inflammatory process where in Arida et al.38 documented that cumulative inflammatory burden

Fig. 3. Correlation between Framingham Risk Score and Total Agatston score (a) angiographic extent of coronary stenosis (b).

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Table 4 Patients’ distribution according to TAS grades and percentage of CA stenosis among FRS grades. Mild FRS (<10)

Moderate FRS (10–20)

Sever FRS (>20)

Normal (CAC = 0) Mild-moderate (CAC = 1–399) Severe (CAC > 400)

1 (1.4%) 29 (41.4%) 4 (5.8%)

1 (1.4%) 10 (14.3%) 7 (10%)

2 (2.9%) 8 (11.4%) 8 (11.4%)

Total

34 (48.6%)

18 (25.7%)

18 (25.7%)

Data are presented as numbers; percentages are in parenthesis; FRS: Framingham CHD risk score; CAC: coronary artery calcium.

Fig. 4. Patients’ distribution according to TAS grades and percentage of CA stenosis among FRS grades.

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Please cite this article in press as: Gomaa AM, et al. The role of multidetector computed tomography coronary angiography with calcium score and Framingham Risk Score in evaluation of rheumatoid arthritis patients with chest pain, J Indian Coll Cardiol. (2017), http:// dx.doi.org/10.1016/j.jicc.2017.03.004