Original Article Acta Medica Anatolia Volume 2 Issue 3 2014

The relationship between gated myocardial perfusion findings and risk factors for coronary artery disease

Ayse Nurdan Korkmaz1, Billur Caliskan1, Melih Engin Erkan2, Huri Tilla Ilce2, Mustafa Yıldırım2, Ahmet Semih Dogan2 1 Department of Nuclear , Abant Izzet Baysal University, Faculty of Medicine, Bolu, Turkey. 2 Department of , Duzce University, Faculty of Medicine, Duzce, Turkey.

Abstract

Objectives: Coronary artery disease risk factors to be considered are one of the important approaches in terms of early diagnosis and treatment. Gated SPECT provides important diagnostic and prognostic information for coronary artery disease. The aim of this retrospective study is to investigate the relationship between these risk factors for coronary artery disease and gated myocardial perfusion scintigraphy findings. Methods: Two hundred fifty-three (144 women, 109 men) referred to our clinic without a previously known coronary artery disease were included to this study. The mean age of the patients was 57.42 ± 10.71 years. Major cardiovascular risk factors (age, gender, hypertension, diabetes mellitus, hyperlipidemia, smoking, family history) were investigated. Statistical analysis of the relationship between risk factors for coronary artery disease and myocardial perfusion scintigraphy findings was performed using SPSS 15.0. Results: A mild correlation was found between the myocardial perfusion findings and risk factors of the evaluated 253 patients. Significantly negative results were found in ischemia/scar findings (p=0.01), wall movement disorder (p=0.004), left ventricular ejection fractions (p=0.002), end-systolic volume and end-diastolic volume (p=0.001), total thickening and movement scores (p=0.001, p=0.002, respectively) in the group with more than 2 risk factors. Conclusions: Increased number of risk factors for coronary artery disease was found to be associated with more frequent positive findings in gated myocardial perfusion scintigraphy. Our findings show that accuracy of myocardial perfusion scintigraphy may increase with appropriate assessment of risk factors.

Keywords: Myocardial perfusion scintigraphy, coronary artery disease, risk factors.

Received: 19.05.2014 Accepted: 16.06.2014 Acta Medica Anatolia Introduction

Coronary artery diseases (CAD) and related investigate the relationship between the risk factors complications are among the leading causes of death for coronary artery disease and Gated SPECT (Single (1, 2). The number of patients with CADs is increased Photon Emission Computerized Tomography) MPS by 6.4% each year and many patients die due to CAD findings (presence of defect, localization of defect, (3). and functional parameters such as wall movement, and left ventricle volume (LV). Classical risk factors include age, gender, family history, hypertension, hyperlipidemia, diabetes Materials and Methods mellitus and smoking (4). Several risk factors have been defined to identify risk groups and to early Data of a total of 253 patients (109 males and 144 diagnose this disease, which leads to serious females) aged between 24-83 years, who presented economic and social losses. to Duzce University Medical Faculty Training and Research Hospital, Department of Nuclear Medicine Ventricle wall movement is impaired and diastolic between January 2008 and March 2009 for and systolic dysfunction occurs along with myocardial perfusion scintigraphy, who had atypical progression of CAD, which causes decrease in blood chest pain, dyspnea and positive ECG signs, who had flow and impairment in myocardial perfusion (5). It is not been diagnosed with CAD or had been suspected important to diagnose ischemia prior to the for CAD, were retrospectively investigated. Detailed occurrence of these changes. anamnesis, physical examination findings and biochemical parameters of the patients were Myocardial perfusion scintigraphy (MPS) is a reliable evaluated. Risk factors of the patients including age, method used to detect myocardial ischemia and total cholesterol and triglyceride levels, smoking scars, evaluate the localization and extensiveness, status, blood pressure values, glucose concentrations and to assess physiological importance of and family history had been recorded based on the obstructions. The aim of this retrospective study is to

Correspondence: Ayse Nurdan Korkmaz MD, Department of Nuclear Medicine, Bolu, Turkey. 97 [email protected]

Original Article Korkmaz AN et al.

anamnesis or measurements. Gated SPECT MPS scans Visual data obtained from Gated myocardial of these patients were reevaluated. perfusion SPECT images were divided into four groups as normal and three other, according to the vascular Table 1: Results of correlation analysis between MPS localization. Group without defect was considered as findings and number of risk factors Group 1 (normal), whereas LAD area was considered as Group 2 (anterior, septum, anteroseptal, apical), rho p* RCA area was considered as Group 3 (inferior, SEF - 0.187 0.003 inferobasal, inferoseptal), and LCx area was REF - 0.173 0.006 considered as Group 4 (lateral, inferolateral, SSTS 0.207 0.001 anterolateral). Relation between these groups, as RSTS 0.169 0.007 well as other MPS findings (gated parameters, some SSMS 0.195 0.002 data obtained by exercise test) and coronary artery RSMS 0.194 0.002 disease risk factors, was explored. SESV 0.203 0.001 RESV 0.208 0.001 Patients were divided into two groups based on the SEDV 0.189 0.002 number of risk factors: those having two or less risk REDV 0.194 0.002 factors and those having more than two risk factors. *Spearman’s correlation analysis; SEF: Stress Ejection Fraction, REF: Resting Ejection Fraction. STS: Sum Tablo 2: Comparison of MPS findings between risk Thickness Scores, SMS: Sum Movement Score, ESV: factor groups (Mean± SD) End-Systolic Volume, EDV: End-Diastolic Volume. MPS Risk Risk p* Patients diagnosed with CAD, patients underwent findings factor ≤ 2 factor > 2 PTCA or coronary artery bypass surgery, as well as the patients whose general status has been impaired SEF 57.48 ± 53.01 ± 0.002 during procedure (due to arrhythmia, hypertension or 9.99 13.10 acute coronary syndrome), and whose recordings REF 57.81 ± 53.69 ± 0.007 were incomplete, were excluded from the study. 10.11 13.72 Gated SPECT MPS was performed by using one day SSTS 4.34 ± 6.3 8.11 ± <0.001 stress-rest protocol with Tc-99m Sestamibi (MIBI) for 9.56 all patients in the study group. Stress study was RSTS 3.93 ± 6.45 ± 0.012 performed via pharmacological stress (dipyridamole 6.27 9.42 infusion) in 38 patients, in who exercise test was SSMS 7.11 ± 11.79 ± 0.001 contraindicated, or via physiological stress on 9.48 13.42 treadmill according to the Bruce or modified Bruce RSMS 6.30 ± 10.68 ± 0.003 protocol in 215 patients. MIBI was administered via 8.90 14.02 intravenous route at a dose of 296-370 MBq (8-10 SESV 39.11 ± 52.66 ± 0.001 mCi) during stress scan and 814-925 MBq (22-25 mCi) 19 39.21 during resting scan. Scanning was performed by RESV 38.96 ± 51.01 ± 0.001 single-head (Siemens, E.CAM) 19.44 36.99 synchronous with ECG. Images were processed on SEDV 87.30 ± 102.21 ± 0.001 Siemens e.soft computer system using QGS 24.06 44.56 (Quantitative Gated SPECT) package program. Left REDV 87.92 ± 100.97 ± 0.004 ventricular volumetric and functional parameters, 27.20 42.14 QGS software package and semiquantitative visual *Student t test, p<0.05 was considered significant. analysis method were obtained from the stress and SEF: Stress Ejection Fraction, REF: Resting Ejection rest images. These parameters are stress left Fraction, STS: Sum Thickness Score, SMS: Sum ventricular ejection fraction (SEF), resting left Movement Score, ESV: End-systolic volume, EDV: ventricular ejection fraction (REF), stress end-systolic End-diastolic volume. volume (SESV), stress end-diastolic volume (SEDV), rest end-systolic volume (RESV), rest end-diastolic volume (REDV), stress sum thickness score (SSTS), resting sum thickness score (RSTS), stress sum movement score (SSMS) and rest sum movement score (RSMS) contained.

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Table 3: Comparison between defect localizations and numerical variables Group 1 Group 2 Group 3 Group 4 P (normal) (LAD) (RCA) (LCx) (n=97) (n=101) (n=43) (n=12)

Age 55 ± 9 57 ± 11 59 ± 10 65 ± 10 0.012* SKB 133 ± 18 132 ± 18 138 ± 23 145 ± 24 0.071 DKB 82±13 82 ± 13 87 ± 10 85 ± 9 0.13 LDL 110 ± 32 120 ± 47 151 ± 52 125 ± 9 0.152 HDL 46 ± 12 47 ± 14 45 ± 9 57 ± 7 0.652 Triglycerides 198 ± 134 200 ± 158 200 ± 100 131 ± 41 0.924 Cholesterol 191 ± 29 200 ± 57 232 ± 69 209 ± 10 0.261 Glucose 111 ± 39 106 ± 21 110 ± 17 140 ± 28 0.518

One Way ANOVA test, posthoc sceffe*: significant age difference between group 1 and group 4. SBP: Systolic Blood Pressure, DBP: Diastolic blood pressure, LDL: Low Density Lipoprotein, HDL: High Density Lipoprotein Statistical Analysis Results

Data were analyzed using SPSS 15.0 program. This study included 253 patients (the mean age 57 ± Correlation between wall thickness and movement 10 years, 144 (57%) females and 109 (43%) males). Of scores on stress and resting images obtained by using the patients underwent Gated SPECT MPS, 111 have QGS package program and the number of risk factors presented with typical chest pain, 107 have presented was analyzed by Spearman’s correlation analysis. with atypical chest pain, 33 have presented with dyspnea, and 2 have presented with positive ECG signs Table 4: Comparison of wall movement for CAD. characteristics between risk factor groups Normal Slightly severe Spearman’s correlation analysis performed for stress (n=168) hypokinetic hypokinetic and resting MPS signs; given risk factors revealed a (n=78) or akinetic negative correlation between increase in the number (n=7) of risk factors and SEF and REF of the patients, but a Risk 91 31 0 positive correlation between increase in the number factor of risk factors and SSTS, RSTS, SSMS, RSMS, SESV, ≤ 2 RESV, SEDV, and REDV values. That is to say, SEF and Risk 77 47 7 REF values are decreased but SSTS, RSTS, SSMS, RSMS, factor SESV, RESV, SEDV and REDV values are increased as > 2 the number of risk factors is increased (Table 1). Patients were divided into two groups based on the The patients were divided into two groups based on number of risk factors: those having two or less risk the number of positive risk factors for CAD: those factors and those having more than two risk factors. having two or less risk factors (n=122) and those Visual findings of the MPS and gated parameters, having more than two risk factors (n=131) (Table 2). categorical data were compared by chi-square test, whereas numerical data were compared by student-t Comparing quantitative risk factors between the test. Significant values were evaluated by regression patients divided into four groups according to the analysis. In addition, defect localizations obtained by involvement areas on MPS, significant age difference MPS for each risk factor were separately evaluated by was observed between group 4 (circumflex area) and chi-square test. One- Way ANOVA test was used to group 1 (normal), whereas other factors were similar compare the mean number of risk factors in the in all groups (Table 3). patients, who have been divided into four groups according to the visual signs on MPS. A p value <0.05 was considered significant.

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Table 5: Relation between risk factors and defect characteristics. Risk factor Normal İschemia (n=134) Scar (n=25) p* (n=94)

Gender (F / M) 59(%63)/35(%37) 78(%58)/56(%42) 7(%28)/18(%72) 0.007 Age (F ≥ 55, M ≥ 45) 54 (%30.9) 97 (%55.4) 24 (%13.7) 0.001 Hypertension 54 (%34.4) 87 (%55.4) 16 (10.2) 0.507 Hyperlipidaemia 36 (%30.5) 66 (%55.9) 16 (%13.6) 0.049 Diabetes Mellitus 19 (%36.5) 29 (%55.8) 4 (%7.7) 0.810 Cigarette (+) 31 (%33.0) 49 (%52.1) 14 (%14.9) 0.104 Family history (+) 18 (%30.5) 30 (%50.8) 11 (%18.6) 0.031 Chi-square test, p=0.01 Patients were evaluated in three groups according to Discussion the wall movement characteristics obtained by MPS: those with normal wall movement (n=168), slightly CAD remains as the leading cause of death in hypokinetic (n=78) and severe hypokinetic or akinetic developed countries. Approaches for early diagnosis (n=7). How wall movement characteristics have been and treatment gain importance as the incidence of the affected in the risk groups was evaluated by chi- disease is increased. For this purpose, risk factors for square test. Accordingly, likelihood of detecting wall CAD development were identified and reported that movement defect and severity of lesions were they could be clinically used in detecting priority increased as the number of risk factors was increased patient group to make early diagnosis (4). Whilst (p=0.004). Interestingly, severe hypokinesia or akinesia coronary (CAG), which is the gold has not been detected in the group having 2 or less standard among methods used for the diagnosis of risk factors (Table 4). CAD, gives anatomic information, it does not give information about metabolic determination of Patients were divided into three groups according to myocardial ischemia. However, MPS offers important the defect characteristics detected by MPS: normal information about coronary artery stenosis based on (n=94), ischemia (n=134) and scar (n=25). Comparisons functional parameters (6). between risk factors and defect characteristics were done by chi-square test. These comparisons revealed This study found that prevalence of positive Gated that ischemia and scar were more prevalent in risky SPECT MPS findings is increased as the number of age group; scar was more prevalent in males and in positive factors among given classical CAD risk factors the patients with hyperlipidaemia; and ischemia was (age, gender, family history, hypertension, more prevalent in females. Moreover, interestingly, hyperlipidaemia, diabetes mellitus and smoking) is ischemia and scar were less prevalent in those with increased. In addition to these poor prognostic factors, positive family history. No relation was found between severity of Gated SPECT MPS findings is also increased other risk factors and defect characteristics. These with the number of risk factors. results are demonstrated in Table 5. Various studies have shown that LVEF and LV volumes With regard to defect characteristics, ischemia and obtained by Gated SPECT MPS are important for the scar were found to be more prevalent in the patients diagnosis and to predict the prognosis of CAD (7-9). having more than two risk factors as compared to Both parameters have been demonstrated to be those having two or less risk factors (Table 6). important indicators of cardiac death (8, 9). Moreover, it has been reported that LVEF is correlated with wall Table 6: Comparison of defect characteristics in risk movement and thickness (10) and that stress and factor groups resting scores of wall thickness and wall movement Risk factor Normal İschemia Scar evaluated by Gated SPECT MPS are higher in CAD groups (n=94) (n=134) (n=25) cases (11). The present study demonstrated significant decrease in stress and resting LVEF scores and Risk factor 54 62 9 significant increase in LV movement scores and wall ≤ 2 thickness as the number of risk factors is increased Risk factor 40 72 16 (particularly if more than 2) in the patients without > 2 CAD. It was found that increase in the number of risk Chi-square test, p=0.01 factors unfavorably influences quantitative MPS measurement.

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Studies performed with Gated SPECT MPS have shown movement obtained by Gated SPECT MPS and the risk a linear correlation between increase in CAD and factors. It has been demonstrated that, higher the outcomes and increase in LV EDV and ESV (12, 13). The number of risk factors higher the wall movement present study as well, determined significant increase impairment. in SESV, RESV, SEDV and REDV values as the number of risk factors is increased, and showed that these values Many studies have demonstrated the relation are remarkably high particularly in patients having between development and severity of CAD and the more than 2 risk factors. risk factors (18, 19). Gimelli et al. (19) reported stress- related MPS abnormalities to be associated with Sanlı et al. (15) evaluated Gated SPECT MPS images by cardiovascular risk factors in the patients with angina- dividing ischemic changes into 3 groups according to like chest pain and without significant coronary coronary artery areas (LAD, RCA and LCx) and reported stenosis. The present study found that CAD-related LCx lesions to be associated with HT, whereas RCA ischemia and scar on MPS are more prevalent in the lesions to be associated with male gender among CAD patients having more than 2 risk factors and that risk factors. On the other hand, they reported no ischemia is more prevalent in females whereas scar is association between localization of perfusion defects more prevalent in males. Moreover, both defects were on MPS and DM and hyperlipidaemia, which are significantly more prevalent in risky age group. among classical risk factors of CAD. Likewise, the present study found that RCA defects are more Demonstrating ischemia on MPS is one of the most common in male gender and there was no association important approaches in the diagnosis and between any of defect localizations and DM, management of CAD (4). The degree and hyperlipidaemia and, unlikely, with HT as well. On the extensiveness of CAD, left ventricle functions, and other hand, more and severer involvement has been number of concomitant risk factors have been detected in all defect localizations in the risky age reported to be the most important indicators of one- group. year prognosis in a patient diagnosed with CAD (20). The present study found the number of risk factors to Sag et al. (16) investigated coronary risk coefficient be higher in the patients having defect. and coronary angiographic vascular involvement and risk factors and reported that LDL, HDL, diastolic BP Limitations of the study and height have a role on vascular distribution of the disease. Although the present study evaluated Gated Although specificity and sensitivity of Gated SPECT SPECT MPS findings, overall defect findings have been MPS method are high in the diagnosis of CAD, the found to be more prevalent only in the patients in results not having been verified by CAG, which is the risky age group as compared to low-risk group. LCx gold standard in the diagnosis of CAD, is the most defects in particular were more prevalent in risky age important limitation. This reduces the reliability of group. There was no relation between presence of risk results. Besides, not evaluating newly identified risk factors such as smoking, DM, HT, family history for factors (homocysteine, hCRP elevation, etc.) in CAD, and hyperlipidaemia and defect localization. addition to the classical risk factors is the important Moreover, no relation was found also between blood limitation of the study. pressure, HDL and LDL cholesterol levels and defect localization. Among defect localization groups, it was Conclusion observed that the number of risk factors was significantly higher in the patients with defect in RCA It has been demonstrated many Gated SPECT MPS areas as compared to the patients with normal MPS findings were unfavorably influenced as the number of findings. coronary artery disease risk factors is increased in the patients not diagnosed with CAD or suspected for Wall movement and thickness obtained by Gated CAD. The present study exposed the significant SPECT MPS are of diagnostic value in interpreting fixed relation between abnormal Gated SPECT MPS findings perfusion defects. Bavelaar et al. (17) investigated and some risk factors and total number of risk factors. contribution of Gated SPECT MPS to fixed perfusion Although MPS findings have not been verified by CAG, lesions. It has been reported that, quantitative Gated we think that inquiring risk factors of the patients in SPECT MPS gives important information about detail and considering them while interpreting the differentiation of MI-related scar tissue and artifact- images would help enhancing the accuracy of MPS. related fixed lesions. The present study compared wall

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