We divided our patients into 3 groups according to the coronary artery disease and culprit lesion:

LAD group: 305 patients with significant LAD lesion.

LCx group: 148 patients with significant LCx lesion.

RCA group: 181 patients with significant RCA lesion.

Statistical Analysis

All data were analyzed using SPSS software statistical package for social science version 19 (SPSS, Inc. Chicago, IL, USA). Results were presented as mean value ± SD for continuous variables and as frequency (%) for categorical variables. Data was tested for normality using the Kolmogorov-Smirnov test. Means were compared using ANOVA, Student t-test or Mann-Whitney test according to the number of groups in comparison. Categorical data were compared using chi-squared test. P value was set at <0.05 for significant results & <0.001 for highly significant results.

Results

166 (31.4%) of our patients had single vessel disease, 111 (21%) had 2 vessel disease, 83 (15.7%) with 3 vessel disease and 169 (31.9%) had non-significant lesion.

Demographic data of the patients are in Table 1, with significantly higher incidence of significant LAD lesion 305((57.5%), followed by RAC 181 (34.2%), while LCx showed the least incidence148 (27.9%).

LCx and RCA groups had older age (57.1±9.9& 57.7±9.9) compared to those in LAD group (55.7 ±10.6), with no significant difference; p>0.05.

Hypertension was significantly more prevalent in LCx 101 (68.2%) and RCA 117 (64.6%) groups compared to LAD group 156 (54.1%), P<0.05.

Significantly higher incidence of smoking in LCx 84 (56.8) group compared to LAD136 (44.4%) group, P<0.05.

Diabetes mellitus was significantly more prevalent in LCx group 75 (50.7%) compared to LAD group128 (42%), P<0.05.

Table 2 showed the angiographic characters of the groups:

Between single vessel disease, LAD was significantly more prevalent 41%, followed by RCA 27.1% (P<0.05) and LCx 13.3% (P<0.001).

52.4% of LAD lesions were proximal compared to 42.8% in LCx and 36.7% in RCA, P<0.05 to all.

Incidence of mid lesion was significantly more in RCA 50% compared to LCx42.9% P<0.05.

Distal lesion was significantly more prevalent in RCA 20.4 % compared to LCx 11.9 % (P<0.05) and LAD 9.5% (P<0.001).

Incidence of ectataic lesion was significantly higher in RCA 6.1% and LCx 7% compared to LAD 3.2%, P<0.05.

Incidence of multiple lesions was significantly more prevalent in LAD vessel 22.1% followed by LCx 7.2% and RCA2%, P<0.001.

Tables 3& 4 showed the demographic and angiographic characters of the culprit vessels:

Significantly higher incidence of culprit LAD lesion 27.6% compared to RCA 7% and LCx 5.9 % between all patients (p<0.001 to all).

LAD with significant lesion was significantly more prone to be the culprit vessel 47.5%, compared to LCx 21.1% and RCA 20.4%(p<0.001).

Patients with culprit LAD and those with culprit RCA showed significantly more male predominance (88.4% and 88.6% respectively) compared to those with LCx 77.4% culprit, (P<0.05).

Hypercholesterolemia was significantly more prevalent between those with culprit RCA 76.4% compared to those with LCx 61.3 % and LAD 64.4%, P<0.05.

Incidence of hypertension was significantly more in culprit LCx 80.6% followed by RCA 62.2% (p<0.05) compared to LAD 41.1%, P<0.001.

Incidence of smoking was significantly more in culprit LCx 71% and RCA 70.3% compared to LAD 42.5%, P<0.001.

Incidence of diabetes mellitus was significantly more in culprit LCx 58.1% compared to RCA 43.2 % (p<0.05) and LAD 35.6% (P<0.001), and showed significant differences in culprit RCA compared to LAD (P<0.05) .

Family history of CAD was significantly more in culprit LCx 54.8 % compared to RCA 43.2 % (P<0.05) and LAD 31.5% (P<0.001), and showed significant differences in culprit RCA compared to LAD(P<0.05) .

Proximal culprit LAD 63.5% and RCA 55.6% had significantly higher incidence compared to LCx38.5%, p<0.05.

Mid culprit LCx 53.9% had significantly higher incidence compared to RCA 38.9% and LAD 36.2%, p<0.05.

Distal culprit LCx 7.7% had significantly higher incidence compared to RCA 3%, p<0.05.

STE-ACS was significantly more prevalent in culprit LAD 76.7% compared to RCA 44.4% and LCx 43.5%., P<0.001

NSTE-ACS was significantly more prevalent in culprit LCx 56.5% and RCA 55.6% compared to LAD 23.3%, P<0.001.

Troponin level was significantly higher in those with culprit LAD 6.1±7.2 vs, 0.17±0.2 in RCA and 0.01 in LCx, P<0.001.

Discussion

Atherosclerosis is a complex, involving endothelial cells, smooth muscle cells and arterial extracellular matrix macromolecules, which undergo a phenotypic switch from their normal physiological function to a pathological one under the effect of local flow hemodynamics and inflammatory mechanisms [15].

The identification and control of coronary risk factors, such as diabetes, smoking, arterial hypertension and hyperlipidemia, is the cornerstone of preventative strategies [1].

Local and systemic factors coexist to initiate atherosclerosis and allow its progress; atherosclerotic lesions tend to form at certain arterial segments despite the systemic effect of risk factors on all arteries.

Several studies have now validated the low shear stress hypothesis of atherosclerosis [15,16]. Low/oscillatory endothelial shear stress is an important key factor in atherosclerosis initiation and progression as it is implicated in the critical switch from normal physiological to a pathological one. Laminar flow and unidirectional high shear stress are athero-protective [17].

These observations highlight the importance of local hemodynamic conditions in susceptible individuals with CAD risk factors.

There were no difference regarding age and gender among all groups with significant coronary lesion. There were male predominance in all groups regarding presence of culprit lesions, in agreement with Ozaki et al, [10] with fewer females in LAD and RCA compared to LCx while Halim SA , et al [16] found fewer women among patients with a culprit LCx compared with those with a culprit LAD or RCA as he studied those with NSTE-ACS only.

LAD lesion was more prevalent, it tends to carry multiple lesions mainly proximal that were more prone to be sites of culprit lesions and to be presented as STE-ACS than the other vessels, in agreement with Katritsis et al, [18] and with Wang et al, [19].

RCA significant lesions were more frequent in the mid segments followed by the proximal one, but the proximal segment was more prone to be the site of culprit lesion.

LCx was the least vessel to carry significant lesion which were equally distributed between proximal and mid segments, the mid segments were more prone to have culprit lesions this was in agreement with Katritsis DG, et al, [18] while Wang et al, [19] detected that LCx thrombosis was more frequent in the proximal segment. Culprit LCx presented in most cases as NSTE-ACS, these results were in correlation with Antoni ML et al, [9], From et al, [20] and Ghanim, et al, [21] this could be due to lesser LCx longitudinal strain that makes the plaque less prone to rupture, with lesser transmural ischemia.

The LAD, most of the RCA, and the mid to distal LCx and its branches pass along the LV longitudinal axis. The proximal-to-mid LCx, pass in the atrioventricular groove along the circumferential axis of the base of the heart. This anatomy can explain why there is a higher shear stress on the proximal LAD and RCA with predominance of the culprit lesions in their proximal segments and a lower incidence of the proximal LCx as a site of culprit lesion due to higher RCA and LAD systolic shortening [8].

In our studytroponin level was significantly higher in those with culprit LAD than RCA and was the least in LCx, this was in disagreement with Halim SA, et al, study [16] and Antoni ML et al, [9] who demonstrated that patients with a culprit lesion in the LAD and LCx had significantly higher-peak cardiac enzymes compared with patients with culprit lesions in the RCA this discrepancy may be due to their selection of patients with NSTE-ACS only. In our study, LCx as a culprit had a higher incidence of NSTE-ACS which incorporated those with unstable angina who had no enzyme elevation. LAD as an artery (more prone to carry culprit lesion) supplies a larger area of the heart, with a higher incidence of STE-ACS with a higher enzyme release.

Study Limitations

Our analysis depended on the two-dimensional coronary angiogram, that lakes good assessment of spatial anatomic relationships and not study the characters of the vulnerable plaques. We did not study the TIMI flow or the SYNTAX score.

Conclusion

LAD tends to carry more than one culprit lesion more to be proximal. Risk factors responsible for instability and sheer stress (uncontrolled DM, uncontrolled hypertension, heavy smoking) were more prevalent between patients with LCx as a culprit followed by RCA in Egyptian; this may draw the attention for aggressive control of these risk factors to reduce vulnerability in these patients.

Recommendations

Further studies of human coronary anatomy using IVUS, as well as in-depth analysis of coronary hemodynamics with study of the coronary flow reserve, TIMI and myocardial blush, are necessary for characterization and identification of coronary lesions.

References

1. Laslett LJ, Alagona P Jr, Clark BA 3rd, Drozda JP Jr, Saldivar F, Wilson SR, Poe C, et al. The worldwide environment of cardiovascular disease: prevalence, diagnosis, therapy, and policy issues: a report from the American College of Cardiology. Journal of the American College of Cardiology. 2012; 60: S1-S49.
2. Malek AM, Alper SL, Izumo S. Hemodynamic shear stress and its role in atherosclerosis. JAMA. 1999; 282: 2035-2042.
3. Chatzizisis YS, Jonas M, Coskun AU, Beigel R, Stone BV, Maynard C, et al. Prediction of the localization of high-risk coronary atherosclerotic plaques on the basis of low endothelial shear stress: an intravascular ultrasound and histopathology natural history study. Circulation. 2008; 117: 993-1002.
4. Falk E, Shah PK, Fuster V. Coronary plaque disruption. Circulation. 1995; 92: 657-671.
5. Katritsis DG, Pantos J, Efstathopoulos E. Hemodynamic factors and atherosclerotic plaque rupture in the coronary arteries: From vulnerable plaque to vulnerable coronary segment. Coron Artery Dis. 2007; 18: 229-237.
6. Stein PD, Hamid MS, Shivkumar K, Davis TP, Khaja F, Henry JW. Effects of cyclic flexion of coronary arteries on progression of atherosclerosis. Am J Cardiol. 1994; 73:431-437.
7. el Fawal MA, Berg GA, Wheatley DJ, Harland WA. Sudden coronary death in Glasgow: Nature and frequency of acute coronary lesions. Br Heart J. 1987; 57: 329–335.
8. Virmani R, Burke AP, Farb A, Kolodgie FD. Pathology of the vulnerable plaque. J Am Coll Cardiol. 2006; 47: C13-C8.
9. Antoni ML, Yiu KH, Atary JZ, Delgado V, Holman ER, van der Wall EE, et al. Distribution of culprit lesions in patients with ST-segment elevation acute myocardial infarction treated with primary percutaneous coronary intervention. Coron Artery Dis. 2011; 22: 533-536.
10. Ozaki Y, Okumura M, Ismail TF, Naruse H, Hattori K, Kawai H, et al. Coronary CT angiographic characteristics of culprit lesions in acute coronary syndromes not related to plaque rupture as defined by optical coherence tomography and angioscopy. Eur Heart J. 2011; 32: 2814-2823.
11. Zimetbaum PJ, Josephson ME. Use of the electrocardiogram in acute myocardial infarction. N Engl J Med. 2003; 348: 933-940.
12. Levine GN, Bates ER, Blankenship JC, Bailey SR, Bittl JA, Cercek B, Chambers CE, et al. 2015 ACC/AHA/SCAI focused update on primary percutaneous coronary intervention for patients with ST-elevation myocardial infarction: an update of the 2011 ACCF/AHA/SCAI guideline for percutaneous coronary intervention and the 2013 ACCF/AHA guideline for the management of ST-elevation myocardial infarction: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Society for Cardiovascular Angiography and Interventions. Endorsed by the Latin American Society of Interventional Cardiology; PCI WRITING COMMITTEE, Catheter Cardiovasc Interv. 2016; 87: 1001-1019.
13. Lang RM, Badano LP, Mor-Avi V, Afilalo J, Armstrong A, Ernande L, Flachskampf FA, et al. Recommendations for cardiac chamber quantification by echocardiography in adults: an update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging. J Am SocEchocardiogr. 2015; 28: 1-39.e14.
14. Serruys PW, Onuma Y, Garg S, Sarno G, van den Brand M, Kappetein AP, Van Dyck N, et al. Assessment of the SYNTAX score in the Syntax study. EuroIntervention. 2009; 5: 50-56.
15. Zaromytidou M, Siasos G, Coskun AU, Lucier M, Antoniadis AP, Papafaklis MI, et al. Intravascular hemodynamics and coronary artery disease: New insights and clinical implications. Hellenic J Cardiol. 2016; 57: 389-400.
16. Halim SA, Clare RM, Newby LK, Lokhnygina Y, Schweiger MJ, Hof AW, Hochman JS, et al. Frequency, clinical and angiographic characteristics, and outcomes of high-risk non-ST-segment elevation acute coronary syndromes patients with left circumflex culprit lesions. Int J Cardiol. 2016; 203: 708-713 d.
17. Wong CK, White HD. Patients with circumflex occlusions miss out on reperfusion: how to recognize and manage them. Curr Opin Cardiol. 2012 Jul; 27: 327-330.
18. Wang JC, Normand SL, Mauri L, Kuntz RE. Coronary artery spatial distribution of acute myocardial infarction occlusions. Circulation. 2004; 110: 278-284.
19. Katritsis DG, Efstathopoulos EP, Pantos J, Korovesis S, Kourlaba G, Kazantzidis S, et al. Anatomic Characteristics of Culprit Sites in Acute Coronary Syndromes. J Interv Cardiol. 2008; 21: 140-150.
20. From AM, Best PJ, Lennon RJ, Rihal CS, Prasad A. Acute myocardial infarction due to left circumflex artery occlusion and significance of ST-segment elevation. Am J Cardiol. 2010; 106: 1081-1085.
21. Ghanim D, Kusniec F, Kinany W, Qarawani D, Meerkin D, Taha K, et al. Left Circumflex Coronary Artery as the Culprit Vessel in ST-Segment-Elevation Myocardial Infarction. Tex Heart Inst J. 2017; 44: 320-325.