Objective Calcium score carotid IMT hs-crp

Transcription

1 P3952 Role of coronary calcium score, carotid intima-media thickness and C-reactive protein in predicting extent of coronary artery disease in young patients. Bedside Poster P3952 Role of coronary calcium score, carotid intima-media thickness and C-reactive protein in predicting extent of coronary artery disease in young patients. A. A. M. Farrag (Giza/EG), N. Abdel Razek (Cairo/EG), H. Yehia (Cairo/EG), S. A. Salama (Cairo/EG), Y. Baghdady (Cairo/EG), A. Rizk (Cairo/EG) 1

2 Objective Despite the availability of effective preventive therapies, cardiovascular disease remains the leading cause of morbidity and mortality (1). Risk factor assessment, the first step in primary prevention, guides the therapeutic strategy, because the intensity of preventive effort is tailored to the patient s CAD risk status (2). Recently, technological advances in cardiac imaging modalities and novel serum markers have expanded our understanding of the atherosclerotic process and facilitating non-invasive assessment of the coronary vasculature (3). The presence of any calcium in the coronary tree is diagnostic of coronary atherosclerosis. Calcium score directly correlated with the risk of cardiac events. A useful aspect of a high positive calcium score is to move an intermediate risk patient with suspected CAD into a high-risk category. The introduction of electrocardiogram gated imaging of the heart with the more recently developed multislice spiral computed tomography (MSCT) showed promising results in this field. It permits high resolution examination of the heart during one phase of a cardiac cycle in a single breath hold and so can quickly scan the heart with a very high resolution in a very short period of time (4-6). In addition, many studies have demonstrated that carotid IMT measured by B-mode ultrasound correlates with the presence of coronary atherosclerosis and represents an independent risk factor for CAD events. Impressive data showed that the higher the IMT, the greater the risk of myocardial infarction (7, 8). On the other hand, laboratory and experimental evidences indicate that atherosclerosis in addition to being a disease of lipid accumulation, also represent a chronic inflammatory process (9, 10). Researchers have hypothesized that inflammatory markers such as hs-crp provide an adjunctive method for assessment of cardiovascular risk. In support to this hypothesis, several studies have shown that plasma level of CRP is a strong predictor of risk of future myocardial infarction, stroke, peripheral vascular disease and vascular death among individuals without clinically recognized cardiovascular disease (11). Based on these findings, we designed our study to test the role of three novel risk factors for atherosclerosis; coronary calcium score, carotid intima-media thickness and high sensitivity C-reactive protein in predicting the extent of CAD in young patients. 2

3 Methods and Materials Study population: One hundred and six patients below age of 60 (12) (68 males, mean age 51 ± 7) with suspected CAD (typical anginal pain in a male or positive stress testing) were studied. We exclude patients who were already known to have ischemic heart, cerebrovascular or peripheral arterial disease. Patients with systemic, inflammatory or infectious disease or neoplasia and those with major surgery within the previous 6 months were also excluded. Coronary calcium score: Coronary calcium score was measured using multislice spiral computed tomography (MSCT) (4-slice GE medical system with a dedicated cardiac package smartscan-software). The study was a non-contrast electrocardiogram-gated with each slice triggered at 80% of the patient s R-R interval, so that the images were obtained at the same point of diastole. The images were taken at mm section thickness. Usually slices were obtained. Each slice was examined for calcium deposits and when a focus of calcium was detected, a region of interest was drawn around. The area of calcium and its peak density were then determined and added to calculate the selective and total score. The system automatically used the Agatston scores (1990) methodology for calcium quantification (13). According to Calcium Score Interpretation Guide, Mayo Clinic 1999 (14), normal score for any age is ideally zero. One-10 indicates minimal plaque burden, mild plaque burden, moderate plaque burden and >400 indicates extensive plaque burden. 3

4 Carotid intima-media thickness: Ultrasound examination was performed with a 7.5 MHz linear-array transducer and imaging system (HP Sonos 4500) by a single trained cardiologist. Right and left distal centimeter of the common carotid arteries, carotid bifurcation and the proximal centimeter of internal carotid arteries in three different projections (anterior, lateral and posterior) were scanned. Intima-media thickness values for the three different projections and for the right and left carotid arteries were averaged to obtain the mean IMT. Measurement of hs-crp: Venous blood samples were collected prior to coronary angiography and stored at -20 o c before analysis. C-reactive protein was measured in the serum using enzyme linked immunosorbent assay (ELISA). Testing was performed by the laboratory staff who were blinded to all clinical, MSCT or carotid duplex data. Coronary angiography: Selective coronary angiography was performed in all patients by the Judkins approach. We considered a vessel diseased if any of its segments contained a stenosis 50% by the use of quantitative coronary angiography (QCA). Accordingly, patients were classified into four groups as regards to extent of CAD: group 1 ; normal coronary arteries, group 2 ; single vessel disease, group 3 ; two vessel disease and group 4 ; three vessel disease. The four main coronary branches (left main, left anterior descending, left circumflex and right coronary artery) were assessed. 4

5 Results Table 1: Baseline clinical characteristics Variable Group 1 Group 2 Group 3 Group 4 Age 51 ± 6 50 ± 7 44 ± 8 54 ± 7 Male (%) 8 (31) 23 (70) 10 (83) 27 (77) Hypertension (%) 20 (77) 22 (67) 7 (58) 21 (60) Diabetes mellitus (%) 12 (46) 15 (46) 4 (33) 13 (37) Smoking (%) 6 (23) 15 (46) 8 (67) 33 (66) Family history of CAD (%) 2 (8) 12 (36) 4 (33) 4 (11) Total cholesterol 182 ± ± ± ± 41 LDL 106 ± ± ± ± 38 HDL 39 ± 4 41 ± 5 41 ± 9 40 ± 7 Figure 1: Mean coronary calcium score for different patient groups. Table 2: Coronary calcium score in different groups Group CCS= 0-10 CCS= CCS= CCS= >400 1 (n= 26) 18 (69%) 6 (23%) 2 (8%) 0 (0%) 2 (n= 33) 9 (27%) 20 (61%) 4 (12%) 0 (0%) 3 (n= 12) 5 (42%) 2 (17%) 2 (17%) 3 (25%) 4 (n= 35) 2 (6%) 6 (17%) 18 (51%) 9 (26%) Compared to group 1, there was a statistically significant correlation between CCS and the extent of CAD (p= 0.001, p= and p= ) for group 2, 3 and 4 respectively. Figure 2: Mean carotid IMT for different patient groups. 5

6 Greater mean IMT values were encountered in group 4 patients as compared to patients with normal coronaries (p= 0.013). Figure 3: Mean hs-crp in different patient groups. There was a statistically significant positive correlation between hs-crp and age (p= 0.001, r=0.314). Higher hs-crp values were encountered in patients with elevated serum total cholesterol (p= 0.026, r= 0.216). Compared to group 1, patients in group 2, 3 and 4 had a significantly higher hs-crp values (p= 0.005, p= and p= ) respectively. By multivariate logistic regression analysis we found that diabetes mellitus and serum LDL cholesterol can predict higher values of CCS (p= 0.037, r= and p= 0.05, r= 0.461) respectively. As regards both carotid IMT and hs-crp, age and serum total cholesterol can predict higher values (p= 0.017, r= and p= 0.05, r= 0.440) respectively for the IMT and (p= 0.001, r= and p= 0.002, r= 0.709) respectively for the hs-crp. On the other hand, when controlling for age, hypertension, diabetes mellitus, family history, smoking and serum cholesterol level, it was found that both CCS and hs-crp were significant independent predictors for extent of CAD (p= , r= and p= , r= ) respectively. 6

7 Conclusion Conclusion: Non invasive imaging techniques and novel serum markers have the potential to directly or indirectly measure and monitor atherosclerosis. This study conclude that combining non-invasive imaging techniques for coronary calcium scoring and carotid intima-media thickness measurement together with serum markers like high sensitivity C-reactive protein can provide an assessment of the presence, extent and stability of potential coronary atherosclerosis. 7

8 Illustrations & Figures 8

9 References References: 1. Robert Park, Robert Detrano, Min Xiang, Youhanna Ibrahim, Laurie LaBree and Stanley Azen. Combined use of computed tomography coronary calcium scoring and C-reactive protein levels in predicting cardiovascular events in non-diabetic individuals. Circulation, 2002; 106: Expert Panel on Detection, Evaluation and Treatment of High Blood Cholesterol in Adults. Summary of the third report of the National Cholesterol Education Program (NECP) Expert Panel on Detection, Evaluation and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). JAMA, 2001; 285: Greenland P, Abrams J et al. Prevention conference V: Beyond secondary prevention: Identifying the high risk patient for primary prevention: Noninvasive test of atherosclerotic burden: Writing group III. Circulation, 2000; 101: e16-e22 4. Obuchowski NA, Modic MT. Calcium scoring: Criteria for evaluating its effectivness. Semin Ultrasound CT MR, 2003; Feb 24 (1): Ulzheimer S, Kalender WA. Assessment of calcium scoring performance in cardiac computed tomography. Eur Radiol, 2003; Mar 13 (3): Jakobs TF, Wintersperger BJ, et al. Ultra-low-dose coronary artery calcium screening using multislice CT with retrospective ECG gating. Eur Radiol, 2003; may Chambless LE, Heiss G, Folsom AR et al. Association of coronary heart disease incidence with carotid arterial wall thickness and major risk factors: The Atherosclerosis Risk in Communities (ARIC) study, Am J Epidemiol, 1997; 146: O Leary DH, Polak JF, et al. Carotid intima media thickness as a risk factor for myocardial infarction and stroke in older adults: Cardiovascular Health Study. N Engl J Med, 1999; 340: Rader DJ. Inflammatory markers of coronary risk. N Engl J Med, 2000; 343: Danesh J, Whincup P, Walker M, et al. Low grade inflammation and coronary heart disease: Prospective study and updated meta-analysis. BMJ, 2000; 321: Svati H, Kristin L. C-reactive protein: A novel marker of cardiovascular risk. Cardiology in Review, 2003; 11 (4): Grundy SM. Coronary plaque as a replacement for age as a risk factor in global risk assessment. Am J Cardiol, 2001; 88: 8E-11E 13. Agatston AS, Janowitz WR, Hildner FJ, et al. Quantification of coronary artery calcium using ultrafast computed tomography. J Am Coll Cardiol 1990; 15: Calcium Score Interpretation Guides, Mayo Clinic Mayo Clin Proc, 1999; 74:

10 The Authors Azza Farrag, Cardiology Department, Cairo University, Egypt Naglaa Abdel Razek, Radiology Department, Cairo University, Egypt Hisham Yehia, Cardiology Department, Cairo University, Egypt Sameh Salama, Cardiology Department, Cairo University, Egypt Yasser Baghdady, Cardiology Department, Cairo University, Egypt Amal Rizk, Critical Care Department, Cairo University, Egypt 10

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