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1
2
3
==Abstract==
4
5
====Background====
6
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The risk factors along with demographic and angiographic features associated with aorto-ostial atherosclerotic coronary artery disease usually differ from that of non-aorto-ostial atherosclerotic coronary artery disease.
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====Objectives====
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This study was designed to evaluate etiology of aorto-ostial atherosclerotic coronary artery disease involving left main coronary artery (LMCA), right coronary artery or both with consideration of clinical risk factors, demographic and angiographic features.
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====Methods====
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A total of 7356 angiograms over 2 years in continuation were analyzed.
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====Results====
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116 patients were found to have aorto-ostial coronary artery disease with prevalence of 1.5. A total of 95 patients who have complete data were analyzed. Mean age was 59 ± 10 years. Prevalence in males was 5.7 times greater than female. Isolated ostial LMCA was 2 times more prevalent than isolated ostial RCA. Hypertension, diabetes and smoking were the main risk factors. 34.7% of the patients had hypercholesterolemia (> 180 mg/dl) and 26.3% of the patients had hypertriglyceridemia (> 150 mg/dl). High TC/HDL (> 3.5) ratio was seen in 77.9% of the patients. When ostial LMCA group was compared with ostial RCA group hypertriglyceridemia (Odds ratio 9.8, 95% CI, 1.7–4.2, ''P''  < 0.001) and hypercholesterolemia (Odds ratio 7.05, 95% CI, 1.7–5.7, ''P''  < 0.001) emerged as independent risk factors for ostial LMCA disease.          
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====Conclusion====
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Overall there is 1.5% prevalence of atherosclerotic aorto-ostial disease of coronary arteries among patients of atherosclerotic coronary artery disease and higher proportions of patients are of male sex. Hypercholesterolemia, hypertriglyceridemia and high TC/HDL ratio can be considered as risk factors for aorto-ostial atherosclerotic coronary artery disease.
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==Keywords==
26
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Coronary artery disease ;                             Risk factors ;                             Aorto-ostial disease
28
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==1. Introduction==
30
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Atherosclerotic coronary artery disease is one of the leading causes of morbidity and mortality world-wide.
32
33
Patients of atherosclerotic coronary artery disease, have wide variations in their age and time of presentation, gender distribution, risk factor profile, invasive and non-invasive assessment and response to different treatment modalities.
34
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Coronary atherosclerosis could be a focal or diffuse disease. Similarly, it could be stenotic or ectatic. Why atherosclerosis affects certain regions of the coronary arteries preferentially and why clinical manifestations occur only at certain times, are still enigmas.
36
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The spatial heterogeneity of coronary atherosclerosis could be explained on the basis of the risk factors like lipoprotein and smoking, but these have global rather than local effect on arteries.
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It is well known that CAD is more common in males, as compared to females. Hypertension, diabetes, smoking and dyslipidemia are other established risk factors for CAD. Since CAD per se is more predominant in males, theoretically the same should be true for ostial CAD. However, an extensive literature review brought forward multiple studies which indicate that female sex is an independent risk factor for ostial CAD [[#bb0005|[1]]]  and [[#bb0010|[2]]] . LMCA narrowing mostly occurs beyond the ostium in the mid portion or at the bifurcation, where it can extend to both major branches [[#bb0015|[3]]]  and [[#bb0020|[4]]] .      
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The most frequent cause of LMCA stenosis, whether the ostium is affected or not, is atherosclerosis.
42
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There is a disagreement about whether ostial LMCA disease is different from the disease in the body of the LMCA. Studies have suggested that ostial LMCA stenosis is a distinct pathology in younger and female patients with fewer risk factors for cardiovascular diseases [[#bb0015|[3]]]  and [[#bb0025|[5]]] . The frequency of concomitant ostial right coronary artery (RCA) stenosis varies from 2.6% to 9% to 14% in patients with ostial LMCA stenosis [[#bb0005|[1]]] , [[#bb0010|[2]]]  and [[#bb0030|[6]]] .      
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Darabian et al. suggested that risk factors such as hypertriglyceridemia and female sex are independent risk factors for ostial lesions of both LMCA and RCA [[#bb0010|[2]]] .      
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In a study of 1254 patients with coronary artery disease who underwent cardiac catheterization studies from 1975 through 1977, 114 (9%) had significant (≥ 50%) stenosis of the left main coronary artery (LMCA). Thirty-four of the 114 (29.8%) had stenosis of the LMCA ostium (2.7% patients). Unstable angina was more frequent in these patients, most of whom were in functional classes III and IV, than those with other LMCA lesions [[#bb0035|[7]]] .      
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O. Yildirimturk et al. documented co-existence of both ostial left main and right coronary artery ostial stenosis. According to them, both female predominance and coexistence of ostial LMCA and ostial RCA stenosis suggest a different pathological ground for this disease. The frequency of concomitant ostial right coronary artery (RCA) stenosis varies from 9 to 14% in patients with ostial LMCA stenosis [[#bb0005|[1]]] .      
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The incidence of CAD is unequivocally rising. Since atherosclerosis is the chief underlying etiology of ostial coronary artery disease, multi-vessel coronary artery disease with involvement of ostium is becoming more common. This study is conducted to see the change in incidence and various presentations of ostial coronary disease as well as pattern of involvement of other coronary arteries.
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==2. Methods==
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===2.1. Study design===
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The present study was conducted in the Department of Cardiology, All India Institute of Medical Sciences, New Delhi. All patients undergoing invasive coronary angiography between July 2012 and December 2014 were screened for the presence of aorto-ostial coronary artery disease. Informed consent was taken after making the subjects aware of the purpose of the study. For patients, who underwent angiography prior to the start of study, records were extracted from in-patient hospital database and through telephonic contact with patients and OPD follow up. For patients who were analyzed prospectively, selective coronary angiography was performed by Judkins catheter via femoral route. Multiple views, including the right anterior oblique, left anterior oblique and anterior shallow caudal were recorded. In patients with ostial CAD, iv NTG was given to rule out coronary artery spasm and repeat angiography was performed. For the purpose of the study, ostial segment stenosis was defined as a proximal significant stenosis up to 3 mm from coronary origin [[#bb0035|[7]]] . Patients were considered to have significant ostial LMCA disease if the percent diameter stenosis exceeded 50% of the luminal diameter and ostial RCA disease if the per cent diameter stenosis exceeds 75% of the luminal diameter [[#bb0035|[7]]] . Of the 7356 coronary angiographies performed in the study period, 116 had significant ostial CAD (LMCA and RCA involvement). Of these, complete data was available in only 95 patients and these were included in the study.      
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==3. Study population==
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The study population comprised of all patients of age above 18 years, investigated with coronary angiography between July 2012 and December 2014 in the institute. Patients with the following conditions which predispose to non-atherosclerotic disease or aorto-ostial lesion of coronaries were excluded from participation in the study: (1) History of radiotherapy, (2) Syphilis, (3) Rheumatoid arthritis, (4) Takayasu arteritis, (5) Aortic valve disease, (6) Aortic valve replacement, (7) Kawasaki disease, (8) Injury following coronary intervention, (9) Bypass grafts of CABG, (10) Restenosis after percutaneous interventions of aorto-ostial coronary lesions.
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===3.1. Statistical analysis===
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Data was collected on structured proforma and managed on Microsoft Excel spread sheet. The correctness of entries was checked and mistakes and omissions were rectified. Statistical processing and analysis were performed using SPSS version 17. Descriptive statistics were conducted by frequency tables. Continuous variables were expressed as mean ± SD. The chi-squared test and Fishers exact test were used to check the association between categorical variables.
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===3.2. Ethical approval and consent for study===
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Ethical approval was obtained from the Institute Ethics Committee and a written informed consent was obtained from the patients at the time of their enrolment.
70
71
==4. Results==
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Total 116 patients had significant ostial disease (right or left coronary artery), out of this only 95 patients had full data that was required according to protocol. Hence the 21 patients were excluded from the study and the 95 patients with complete data were analyzed.
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==5. Demographic profile, risk factors, mode of presentation, echocardiographic parameters and lipid profile of the study group==
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[[#t0005|Table 1]]  is the summary of the characteristics of the patients with atherosclerotic aorto-ostial coronary artery disease that were included in the study. The study population had mean age of 59 ± 10 years and mean BMI of 26.4 ± 4. Obesity was seen in 29 patients (30.6%) and 16 patients (16.8%) were found overweight. About 2/3rd patients were hypertensive. A substantial proportion of patients (about 44%) presented with acute coronary syndrome. NYHA Class II angina was reported by two-thirds of the patient population. Graded lipid profile of the participants has been mentioned in [[#t0005|Table 1]] . Overall, 33 patients (34.7%) had total cholesterol ≥ 180 mg/dl. 25 patients (26.3%) had triglycerides ≥ 150 mg/dl. Low HDL (< 40 mg/dl in males and < 50 mg/dl in females) was seen in 49 patients (51.6%). Serum LDL ≥ 130 mg/dl was seen in 9 patients (9.5%). Serum LDL level < 100 mg/dl was seen in 53 patients (55.8%). High LDL/HDL ratio was present in 7 patients (7.4%). High TC/HDL ratio was seen in 74 patients (77.9%).
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<span id='t0005'></span>
80
81
{| class="wikitable" style="min-width: 60%;margin-left: auto; margin-right: auto;"
82
|+
83
84
Table 1.
85
86
Pt. characteristics.
87
88
|-
89
90
! 
91
! 
92
! No. of patients (N = 95)
93
! Percentage (%)
94
|-
95
96
! rowspan="2" | Age wise distribution
97
| <55years
98
| 32
99
| 34.0
100
|-
101
102
! ≥55years
103
| 63
104
| 66.0
105
|-
106
107
! rowspan="2" | Sex wise distribution
108
| Male
109
| 81
110
| 85.0
111
|-
112
113
! Female
114
| 14
115
| 15.0
116
|-
117
118
! rowspan="3" | BMI (kg/m2)
119
| <25
120
| 50
121
| 52.6
122
|-
123
124
! 25–29.9
125
| 16
126
| 16.8
127
|-
128
129
! ≥30
130
| 29
131
| 30.6
132
|-
133
134
! Diabetes
135
| 
136
| 35
137
| 36.8
138
|-
139
140
! Hypertension
141
| 
142
| 60
143
| 63.2
144
|-
145
146
! Smoking
147
| 
148
| 37
149
| 38.9
150
|-
151
152
! Positive family H/O CAD
153
| 
154
| 4
155
| 4.3
156
|-
157
158
! STEMI
159
| 
160
| 10
161
| 10.6
162
|-
163
164
! NSTEMI
165
| 
166
| 31
167
| 32.6
168
|-
169
170
! Non-ACS
171
| 
172
| 54
173
| 56.8
174
|-
175
176
! Angina NYHA Class II
177
| 
178
| 75
179
| 78.9
180
|-
181
182
! Angina NYHA Class III
183
| 
184
| 19
185
| 20.0
186
|-
187
188
! Angina NYHA Class IV
189
| 
190
| 1
191
| 1.1
192
|-
193
194
! LV EF<30%
195
| 
196
| 5
197
| 5.5
198
|-
199
200
! LV EF 30–45%
201
| 
202
| 20
203
| 21.1
204
|-
205
206
! LV EF 46–55%
207
| 
208
| 30
209
| 31.5
210
|-
211
212
! LV EF>55%
213
| 
214
| 40
215
| 42.1
216
|-
217
218
! rowspan="2" | Total cholesterol
219
| ≥180mg/dl
220
| 33
221
| 34.7
222
|-
223
224
! <180mg/dl
225
| 62
226
| 65.3
227
|-
228
229
! rowspan="2" | Triglycerides
230
| ≥150mg/dl
231
| 25
232
| 26.3
233
|-
234
235
! <150mg/dl
236
| 70
237
| 73.7
238
|-
239
240
! rowspan="2" | HDL
241
| Abnormal
242
| 49
243
| 51.6
244
|-
245
246
! Normal
247
| 46
248
| 48.4
249
|-
250
251
! rowspan="3" | LDL
252
| <100mg/dl
253
| 53
254
| 55.8
255
|-
256
257
! 100–129mg/dl
258
| 33
259
| 34.7
260
|-
261
262
! >130mg/dl
263
| 9
264
| 9.5
265
|-
266
267
! rowspan="2" | LDL/HDL
268
| ≥3
269
| 7
270
| 7.4
271
|-
272
273
! <3
274
| 88
275
| 92.6
276
|-
277
278
! rowspan="2" | TC/HDL
279
| <3.5
280
| 21
281
| 22.1
282
|-
283
284
! ≥3.5
285
| 74
286
| 77.9
287
|}
288
289
===5.1. Pattern of vessel involvement===
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291
LMCA was diseased in 55 patients (57.9%) out of which 47 patients had significant ostial disease. 40 patients (42.1%) had normal LMCA. RCA was diseased in 74 patients (77.9%) out of which 50 patients had significant ostial disease. 21 patients (22.1%) had normal RCA. Isolated ostial LMCA was involved in 10 patients. Isolated ostial RCA was involved in 5 patients. One patient had involvement of both ostial RCA and ostial LMCA without involvement of distal vessels. Ostial LMCA was associated with diseased LAD in 4 patients, diseased LCX in 2 patients and diseased non-ostial RCA in 4 patients. All vessels (LMCA, RCA, LAD and LCX) were involved together in 16 patients. The most common pattern of coronary vessel involvement was ostial RCA with simultaneous LCX and LAD disease and this was seen in 29 patients. Ostial RCA with LAD disease was seen in 9 patients and ostial RCA with LCX disease was seen in 4 patients ([[#t0010|Table 2]] , [[#f0005|Fig. 1]] A and B).
292
293
<span id='t0010'></span>
294
295
{| class="wikitable" style="min-width: 60%;margin-left: auto; margin-right: auto;"
296
|+
297
298
Table 2.
299
300
Pattern of vessel involvement.
301
302
|-
303
304
! colspan="2" | 
305
! No. of patients  N = 95                                                    
306
! Percentage  (%)                                                    
307
|-
308
309
| colspan="4" | LMCA involvement
310
|-
311
312
! Present
313
| Ostial
314
| 47
315
| 49.4
316
|-
317
318
! 
319
| Non-ostial
320
| 8
321
| 8.5
322
|-
323
324
! Absent
325
| 
326
| 40
327
| 42.1
328
|-
329
330
| colspan="4" | 
331
|-
332
333
| colspan="4" | RCA involvement
334
|-
335
336
! Present
337
| Ostial
338
| 50
339
| 52.6
340
|-
341
342
! 
343
| Non-ostial
344
| 24
345
| 25.3
346
|-
347
348
! Absent
349
| 
350
| 21
351
| 22.1
352
|-
353
354
| colspan="4" | 
355
|-
356
357
| colspan="4" | LAD involvement
358
|-
359
360
! Present
361
| Ostial
362
| 17
363
| 17.9
364
|-
365
366
! 
367
| Non-ostial
368
| 50
369
| 52.7
370
|-
371
372
! Absent
373
| 
374
| 28
375
| 29.4
376
|-
377
378
| colspan="4" | 
379
|-
380
381
| colspan="4" | LCx involvement
382
|-
383
384
! Present
385
| Ostial
386
| 13
387
| 13.7
388
|-
389
390
! 
391
| Non-ostial
392
| 44
393
| 46.3
394
|-
395
396
! Absent
397
| 
398
| 38
399
| 40.4
400
|}
401
402
<span id='f0005'></span>
403
404
{| style="text-align: center; border: 1px solid #BBB; margin: 1em auto; max-width: 100%;" 
405
|-
406
|
407
408
409
[[Image:draft_García_250547482-1-s2.0-S2352906716300252-gr1.jpg|center|379px|Fig. 1]]
410
411
412
|-
413
| <span style="text-align: center; font-size: 75%;">
414
415
Fig. 1.
416
417
A. Prevalence and pattern of vessel involvement in study population.
418
419
B. Distribution of vessel involvement in study population.
420
421
</span>
422
|}
423
424
===5.2. Demographics of study group according to individual vessel involvement===
425
426
With ostial LMCA disease, 42 (89%) patients were males. The mean age of patients with LMCA disease was 57 ± 11 years. 16 (34%) were diabetic, 25 (53%) were hypertensive and 18 (38%) were smokers. 15 patients (32%) were obese. ([[#t0015|Table 3]] , [[#f0010|Fig. 2]] A and B). In the sub group of patients with ostial RCA disease, 41 (82%) patients were males. The mean age was 60 ± 9 years. 36 (72%) were hypertensive and 19 (38%) were diabetic. 19 (38%) were smokers while 15 (30%) were obese ([[#t0015|Table 3]] , [[#f0010|Fig. 2]] A and B). In the subgroup of patients with isolated RCA or LMCA disease, 12 (75%) were males. The mean age of this subgroup was 59.2 ± 5 years. 12 (75%) were diabetic and 4 (25%) were hypertensive. 9 (56%) were smokers and 7 (44%) were obese ([[#t0015|Table 3]] ,[[#f0010|Fig. 2]] A and B).
427
428
<span id='t0015'></span>
429
430
{| class="wikitable" style="min-width: 60%;margin-left: auto; margin-right: auto;"
431
|+
432
433
Table 3.
434
435
Distribution of risk factors in study population.
436
437
|-
438
439
! 
440
! colspan="2" | Ostial LMCA
441
! colspan="2" | Ostial RCA
442
! colspan="2" | Isolated ostial LMCA or RCA
443
|-
444
445
! 
446
! N = 47
447
! %
448
! N = 50
449
! %
450
! N = 16
451
! %
452
|-
453
454
! Male
455
| 42
456
| 89
457
| 41
458
| 82
459
| 12
460
| 75
461
|-
462
463
! Female
464
| 5
465
| 11
466
| 9
467
| 18
468
| 4
469
| 25
470
|-
471
472
! Diabetes
473
| 16
474
| 34
475
| 19
476
| 38
477
| 12
478
| 75
479
|-
480
481
! Hypertension
482
| 25
483
| 53
484
| 36
485
| 72
486
| 9
487
| 56
488
|-
489
490
! Smoking
491
| 18
492
| 38
493
| 19
494
| 38
495
| 9
496
| 56
497
|-
498
499
! Family history
500
| 2
501
| 4
502
| 2
503
| 4
504
| 1
505
| 6
506
|-
507
508
! Obesity
509
| 15
510
| 32
511
| 15
512
| 30
513
| 7
514
| 44
515
|}
516
517
<span id='f0010'></span>
518
519
{| style="text-align: center; border: 1px solid #BBB; margin: 1em auto; max-width: 100%;" 
520
|-
521
|
522
523
524
[[Image:draft_García_250547482-1-s2.0-S2352906716300252-gr2.jpg|center|378px|Fig. 2]]
525
526
527
|-
528
| <span style="text-align: center; font-size: 75%;">
529
530
Fig. 2.
531
532
A. Sex distribution in three subgroups of patients.
533
534
B. Risk factor prevalence in three subgroups of patients.
535
536
</span>
537
|}
538
539
===5.3. Clinical presentation according to individual vessel involvement===
540
541
28 (60%) patients in ostial LMCA group, 48 (84%) patients in ostial RCA group and 13 (81%) patients in isolated ostial LMCA or RCA group do not have acute coronary syndrome as their first clinical presentation. [[#t0020|Table 4]]  and [[#f0015|Fig. 3]] A and B are providing cumulative representation of clinical presentation according to individual vessel involvement in each of the three groups of patients.
542
543
<span id='t0020'></span>
544
545
{| class="wikitable" style="min-width: 60%;margin-left: auto; margin-right: auto;"
546
|+
547
548
Table 4.
549
550
Distribution of clinical presentation in study population.
551
552
|-
553
554
! rowspan="2" | 
555
! rowspan="2" | 
556
! colspan="2" | Ostial LMCA
557
! colspan="2" | Ostial RCA
558
! colspan="2" | Isolated ostial LMCA or RCA
559
|-
560
561
! N = 47
562
! %
563
! N = 50
564
! %
565
! N = 16
566
! %
567
|-
568
569
! rowspan="3" | AOE
570
| NYHA II
571
| 35
572
| 75
573
| 41
574
| 82
575
| 14
576
| 88
577
|-
578
579
! NYHA III
580
| 11
581
| 23
582
| 9
583
| 18
584
| 2
585
| 12
586
|-
587
588
! NYHA IV
589
| 1
590
| 2
591
| 0
592
| 0
593
| 0
594
| 0
595
|-
596
597
! rowspan="3" | ACS
598
| None
599
| 28
600
| 60
601
| 42
602
| 84
603
| 13
604
| 81
605
|-
606
607
! NSTEMI
608
| 16
609
| 34
610
| 6
611
| 12
612
| 2
613
| 13
614
|-
615
616
! STEMI
617
| 3
618
| 6
619
| 2
620
| 4
621
| 1
622
| 6
623
|}
624
625
<span id='f0015'></span>
626
627
{| style="text-align: center; border: 1px solid #BBB; margin: 1em auto; max-width: 100%;" 
628
|-
629
|
630
631
632
[[Image:draft_García_250547482-1-s2.0-S2352906716300252-gr3.jpg|center|379px|Fig. 3]]
633
634
635
|-
636
| <span style="text-align: center; font-size: 75%;">
637
638
Fig. 3.
639
640
A. ACS as 1st presentation (in %) in three subgroups of patients.
641
642
B. Class of angina (% vice distribution) in three subgroups of patients.
643
644
</span>
645
|}
646
647
===5.4. Lipid profiles according to individual vessel involvement===
648
649
Hypercholestrolemia (total cholesterol ≥ 180 mg/dl) and hypertriglyceridemia (TG ≥ 150 mg/dl) were mainly observed in ostial LMCA group and not in other two groups ([[#t0025|Table 5]]  and [[#f0020|Fig. 4]] A, B). It was observed that serum hypertriglyceridemia and hypercholesterolemia were significantly more common in patients with ostial LMCA disease than in ostial RCA disease (''P''  < 0.001). High TC/HDL ratio (≥ 3.5) was seen in 34 (72%) patients in ostial LMCA group, 39 (78%) patients in ostial RCA group and 12 (75%) patients in isolated ostial LMCA or RCA group ([[#t0025|Table 5]]  and [[#f0020|Fig. 4]] C).
650
651
<span id='t0025'></span>
652
653
{| class="wikitable" style="min-width: 60%;margin-left: auto; margin-right: auto;"
654
|+
655
656
Table 5.
657
658
Lipid profile in study population.
659
660
|-
661
662
! rowspan="2" | 
663
! rowspan="2" | 
664
! colspan="2" | Ostial LMCA
665
! colspan="2" | Ostial RCA
666
! colspan="2" | Isolated ostial LMCA or RCA
667
|-
668
669
! N = 47
670
! %
671
! N = 50
672
! %
673
! N = 16
674
! %
675
|-
676
677
! rowspan="2" | Total cholesterol
678
| ≥180mg/dl
679
| 30
680
| 64
681
| 10
682
| 20
683
| 3
684
| 19
685
|-
686
687
! <180mg/dl
688
| 17
689
| 36
690
| 40
691
| 80
692
| 13
693
| 81
694
|-
695
696
! rowspan="2" | Triglycerides
697
| ≥150mg/dl
698
| 38
699
| 80
700
| 15
701
| 30
702
| 2
703
| 13
704
|-
705
706
! <150mg/dl
707
| 9
708
| 20
709
| 35
710
| 70
711
| 14
712
| 87
713
|-
714
715
! rowspan="2" | HDL
716
| Abnormal
717
| 19
718
| 40
719
| 29
720
| 58
721
| 8
722
| 50
723
|-
724
725
! Normal
726
| 28
727
| 60
728
| 21
729
| 42
730
| 8
731
| 50
732
|-
733
734
! rowspan="3" | LDL
735
| <100mg/dl
736
| 25
737
| 53
738
| 29
739
| 58
740
| 10
741
| 63
742
|-
743
744
! 100–129mg/dl
745
| 20
746
| 43
747
| 14
748
| 28
749
| 6
750
| 36
751
|-
752
753
! ≥130mg/dl
754
| 2
755
| 4
756
| 7
757
| 14
758
| 0
759
| 0
760
|-
761
762
! rowspan="2" | LDL/HDL
763
| <3
764
| 44
765
| 94
766
| 47
767
| 94
768
| 15
769
| 94
770
|-
771
772
! ≥3
773
| 3
774
| 6
775
| 3
776
| 6
777
| 1
778
| 6
779
|-
780
781
! rowspan="2" | TC/HDL
782
| <3.5
783
| 13
784
| 28
785
| 11
786
| 22
787
| 4
788
| 25
789
|-
790
791
! ≥3.5
792
| 34
793
| 72
794
| 39
795
| 78
796
| 12
797
| 75
798
|}
799
800
<span id='f0020'></span>
801
802
{| style="text-align: center; border: 1px solid #BBB; margin: 1em auto; max-width: 100%;" 
803
|-
804
|
805
806
807
[[Image:draft_García_250547482-1-s2.0-S2352906716300252-gr4.jpg|center|379px|Fig. 4]]
808
809
810
|-
811
| <span style="text-align: center; font-size: 75%;">
812
813
Fig. 4.
814
815
A. Serum total cholesterol levels in three subgroups of patients.
816
817
B. Serum triglyceride levels in three subgroups of patients.
818
819
C. TC/HDL cholesterol levels in three subgroups of patients.
820
821
</span>
822
|}
823
824
==6. Discussion==
825
826
According to the projections for 2020, cardiovascular disease will remain the leading cause of death and disability in industrial countries [[#bb0040|[8]]] . Coronary artery disease (CAD) currently accounts for very high mortality rates in developing countries. Among patients with CAD, it is widely accepted that significant LMCA disease is associated with an increased cardiac mortality; in addition, it is the most prognostically important single lesion involving the coronary arteries. Ostial lesions presenting as an obstructive disease proximal to the bifurcation of the main stem into the LAD and LCX jeopardize all but the inferior and posterior surfaces of the left ventricle. Ostial left main coronary artery disease is frequently accompanied by the concomitant involvement of 1 or more of other epicardial vessels [[#bb0045|[9]]] .      
827
828
The risk of CAD is associated with the extent and severity of atherosclerosis in adults. The concept that CAD can be prevented has increasingly become a driving force in cardiovascular medicine. At the core of primary prevention lies the concept of risk assessment. A general notion has evolved that the intensity of preventive efforts should be adjusted to a patients risk for developing CHD, that is, the higher the risk, the more aggressive the intervention should be.
829
830
In the current study, of the 7356 coronary angiographies performed in the said period, 116 patient had significant ostial CAD. The prevalence of ostial coronary artery disease was 1.5%. In a similar study conducted by Darabian et al. in 2008, the prevalence of significant coronary ostial disease was 2.6%. They defined significant LMCA and RCA as 50% luminal diameter stenosis [[#bb0010|[2]]] . In our study, the significant LMCA ostial disease is a decrease of > 50% luminal diameter and significant RCA ostial disease is a reduction of > 70% luminal diameter as per generally accepted definition. Therefore prevalence in our study may be lower due to strict criteria used that may differ from the generally accepted definition of ostial stenosis of RCA. In another study conducted by Yildirimturk et al., 87 patients had significant ostial left main coronary or significant right coronary artery disease in 2898 coronary angiographies with prevalence of 3.0% [[#bb0005|[1]]] .      
831
832
An observation of a few studies which have studied ostial CAD has been summarized in [[#t0030|Table 6]]  for comparison and contrast with present study.
833
834
<span id='t0030'></span>
835
836
{| class="wikitable" style="min-width: 60%;margin-left: auto; margin-right: auto;"
837
|+
838
839
Table 6.
840
841
Comparison of various studies with present study.
842
843
|-
844
845
! colspan="2" rowspan="2" | 
846
! colspan="3" | Darabian et al. 2008 [[#bb0010|[2]]]
847
! Mahajan et al. [[#bb0050|[10]]]
848
! colspan="3" | Yildirimturk et al. (2011) [[#bb0005|[1]]]
849
! colspan="3" | Present study (Verma et al)
850
|-
851
852
! Ostial LMCA
853
! Ostial RCA
854
! Ostial LMCA + RCA
855
! Ostial LMCA
856
! Ostial LMCA
857
! Ostial RCA
858
! Ostial LMCA + RCA
859
! Ostial LMCA
860
! Ostial RCA
861
! Ostial LMCA + RCA
862
|-
863
864
! colspan="2" | No of patients
865
| 66
866
| 65
867
| 36
868
| 46
869
| 53
870
| 19
871
| 15
872
| 47
873
| 50
874
| 16
875
|-
876
877
! colspan="2" | Mean age (years)
878
| 62.36±7.8
879
| 63.3±8.6
880
| 62.64±7.94
881
| 65±13
882
| 64±11
883
| 66±11.9
884
| 67±9.6
885
| 57±11
886
| 60±9
887
| 59.2±5
888
|-
889
890
! rowspan="2" | Sex
891
| Male
892
| 59.1% (39)
893
| 58.5% (38)
894
| 52.8% (19)
895
| 48% (22)
896
| 84.9% (45)
897
| 84.2% (16)
898
| 46.7% (7)
899
| 89% (42)
900
| 82% (41)
901
| 75% (12)
902
|-
903
904
! Female
905
| 40.9% (27)
906
| 41.5% (27)
907
| 47.2% (17)
908
| 52% (24)
909
| 15.1% (8)
910
| 15.8% (3)
911
| 53.3% (8)
912
| 11% (5)
913
| 18% (9)
914
| 25% (4)
915
|-
916
917
! colspan="2" | Hypercholesterolemia
918
| 
919
| 
920
| 
921
| 65% (30)
922
| 48% (24)
923
| 42.1% (8)
924
| 64.3% (9)
925
| 64% (30)
926
| 20% (10)
927
| 19% (3)
928
|-
929
930
! colspan="2" | Hypertension
931
| 63.1% (41)
932
| 60.9% (39)
933
| 65.7% (23)
934
| 72% (33)
935
| 64% (32)
936
| 63.2% (12)
937
| 85.7% (12)
938
| 53% (25)
939
| 72% (36)
940
| 56% (9)
941
|-
942
943
! colspan="2" | Diabetes
944
| 37.5% (24)
945
| 30.6% (19)
946
| 35.3% (12)
947
| 43% (20)
948
| 38% (19)
949
| 47.4% (9)
950
| 42.9% (6)
951
| 34% (16)
952
| 38% (19)
953
| 75% (12)
954
|-
955
956
! colspan="2" | Smoking
957
| 40.9% (27)
958
| 43% (28)
959
| 48.5 (17)
960
| 26% (12)
961
| 44% (22)
962
| 26% (5)
963
| 21% (3)
964
| 38% (18)
965
| 38% (19)
966
| 56% (9)
967
|-
968
969
! colspan="2" | Family history
970
| 21.9% (14)
971
| 27% (17)
972
| 28.6% (10)
973
| 39% (18)
974
| 14% (7)
975
| 10.5% (2)
976
| 14.3% (2)
977
| 4% (2)
978
| 4% (2)
979
| 6% (1)
980
|-
981
982
! colspan="2" | Obesity
983
| 
984
| 
985
| 
986
| 
987
| 14% (7)
988
| 26.3% (5)
989
| 21.4% (3)
990
| 32% (15)
991
| 30% (15)
992
| 44% (7)
993
|-
994
995
! colspan="2" | ACS
996
| 46.1% (47)
997
| 61.6% (40)
998
| 53% (20)
999
| 
1000
| 
1001
| 
1002
| 
1003
| 40% (19)
1004
| 16% (8)
1005
| 19% (3)
1006
|}
1007
1008
In our study, 95 patients with significant ostial coronary disease (left main and right) were selected. Mean age was 59 ± 10 years. Prevalence in males was 5.7 times greater than female (85% vs. 15%). When patients were subgrouped in ostial LMCA and ostial RCA disease, a similar pattern of male predominance was seen in both groups. Ostial LMCA was 8 times more prevalent and ostial RCA was 4 times more prevalent in males than females. When isolated ostial LMCA and ostial RCA disease group was considered, male prevalence was three times that of female (12 Vs 4, [[#t0015|Table 3]] ). These findings contradict finding in similar studies by Darabian et al. [[#bb0010|[2]]]  and Yildirimturk et al. [[#bb0005|[1]]]  which have observed greater female predominance in ostial CAD. In the study by Mahajan et al., there was a trend suggestive of a higher incidence of ostial lesions among women (63% vs. 31%; ''P''  = .06) [[#bb0050|[10]]] . Barner et al. reported that 43.5% of their left ostial group and 12% of their left main group were women (''P''  <.005) [[#bb0055|[11]]] . Sasaguri et al. noticed that 4 patients out of 5 cases (80%) in their ostial stenosis group were women, but there were only 10 women (9%) in the LMCA group [[#bb0015|[3]]] . Yamanaka and Hobbs reported that women were predominant among subjects with stenosis of 1 or both coronary ostial (64%) [[#bb0030|[6]]] . Miller et al. [[#bb0060|[12]]]  detected 5 (0.12%) women with isolated ostial Left main coronary artery disease among 4000 patients with CAD, and Welch et al. [[#bb0065|[13]]]  reported 10 (0.01%) women with isolated left main lesion among 1000 women in their study. However, these studies do not explain this higher prevalence of ostial CAD in females despite predominance of atherosclerotic risk factors in males.      
1009
1010
Prevalence of ostial CAD in the elderly (age ≥ 55 years) was twice the number of young patients (age < 55 years). There was no significant age difference between ostial LMCA group and ostial RCA group in our study.
1011
1012
Of the 95 patients, 16 patients had isolated significant ostial disease without involvement of distal part of coronary artery. Isolated ostial LMCA was involved in 10 patients. Isolated ostial RCA was seen in 5 patients. Ostial RCA disease was more common than ostial LMCA disease. This is similar to the findings by Rissanen et al. [[#bb0070|[14]]] .One patient had involvement of both ostial RCA and ostial LMCA without involvement of distal vessels. Ostial LMCA was associated with diseased LAD in 4 patients, diseased LCX in 2 patients and diseased non-ostial RCA in 4 patients. All vessels (LMCA, RCA, LAD and LCX) were involved concomitantly in 16 patients.      
1013
1014
The most common pattern of coronary vessel involvement was ostial RCA with simultaneous LCX and LAD disease and this was seen in 29 patients. Ostial RCA with LAD disease was seen in 9 patients and ostial RCA with LCX disease was seen in 4 patients. This signifies that atherosclerosis is a diffuse disease and involvement of multiple segment of coronary disease is common.
1015
1016
Among risk factors, hypertension emerged as the chief risk factor and was present in 63.2% of the study group. Similar results are seen in studies by Darabian et al. [[#bb0010|[2]]] , Yildirimturk et al. [[#bb0005|[1]]]  and Mahajan et al. [[#bb0050|[10]]]  ([[#t0030|Table 6]] ). In our study, diabetes was present in 36.8% and smoking 39.6% patients. This statistics are similar to the findings by Mahajan et al. [[#bb0050|[10]]]  and Yildirimturk et al. [[#bb0005|[1]]] . The prevalence of obesity in the study group was 30.6% of the patients. Significant family history for CAD was present in only 4% of our patients. This does not correlate with the higher prevalence of positive family history that was seen in other studies [[#bb0005|[1]]] , [[#bb0010|[2]]]  and [[#bb0050|[10]]] .      
1017
1018
In our study, there was no significant difference in terms of risk factors like diabetes, hypertension, smoking, family history, obesity, HDL, LDL, LDL/HDL, total cholesterol/HDL in ostial LMCA, ostial RCA and isolated ostial LMCA and RCA stenosis group.
1019
1020
The relationship between lipid profile and pattern of disease was studied diligently. 33 patients (34.7%) had hypercholesterolemia (≥ 180 mg/dl). 25 patients (26.3%) had hypertriglyceridemia (≥ 150 mg/dl). Low HDL (< 40 mg/dl in males and < 50 mg/dl in females) was seen in 49 patients (51.6%). Serum LDL ≥ 130 mg/dl was seen in 9 patients (9.5%). Serum LDL level ≤ 100 mg/dl was seen in 53 patients (55.8%). High LDL/HDL ratio was seen in 7 patients (7.4%). High TC/HDL ratio was seen in 74 patients (77.9%).
1021
1022
When subgroup analysis was done for ostial left main coronary artery disease 64% had hypercholesterolemia (≥ 180 mg/dl) and 80% had hypertriglyceridemia (≥ 150 mg/dl). Low HDL ( <40 mg/dl in males and <50 mg/dl in females) was seen in 19 patients (40%). Serum LDL ≥ 130 mg/dl was seen in 2 patients (4%). In sub group analysis of patients with ostial RCA involvement, 8% had hypercholesterolemia ( >180 mg/dl). 30% had hypertriglyceridemia (> 150 mg/dl).
1023
1024
When ostial LMCA group was compared with ostial RCA group hypertriglyceridemia (Odds ratio 9.8, 95% CI, 1.7–4.2, ''P''  < 0.001) and hypercholesterolemia (Odds ratio 7.05, 95% CI, 1.7–5.7, ''P''  < 0.001) emerged as independent risk factors for ostial LMCA disease.      
1025
1026
42% patients had acute coronary syndrome (ACS) as first clinical event of presentation, out of which NSTEMI was found in 32.6% and STEMI was found in 10.6% of the patients. ACS was significantly higher in ostial left main subgroup compared to ostial RCA subgroup, (''P''  < 0.05) while there was no significant difference in severity on angina in the two sub groups.      
1027
1028
Ostial coronary disease is one of the manifestations of atherosclerosis and atherosclerosis incidence is higher in male. In our study frequency of male is higher than female similar to non-ostial coronary atherosclerotic disease. Ostial coronary disease is influenced by hemodynamic at the ostium as there is increased turbulence which may lead to endothelial dysfunction, endothelial injury and plaque deposition that lead to atherosclerotic stenosis. Different studies that have mentioned female preponderance to ostial coronary artery disease have not mentioned a likely cause for this observation. The study has got limitation as the sample size is small. We need to evaluate risk factors other than diabetes, hypertension, smoking, family history and lipid profile also.
1029
1030
==7. Conclusion==
1031
1032
We concluded that prevalence of significant ostial coronary artery disease in this study was 1.5% and higher proportion of patient was of male sex. Hypertriglyceridemia and hypercholesterolemia can be considered as risk factors for ostial left main coronary artery disease. Prevalence of ACS was higher in ostial left coronary artery disease group compared to RCA subgroup. There was no difference in terms of risk factors other than hypertriglyceridemia and hypercholestrolemia in ostial LMCA and ostial RCA group.
1033
1034
==Conflict of interest==
1035
1036
The authors report no relationships that could be construed as a conflict of interest.
1037
1038
==References==
1039
1040
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1041
[[#bb0005|[1]]] O. Yildirimturk, M. Cansel, R. Erdim, E. Ozen, I.C.C. Demiroglu, V. Aytekin; Coexistence of left main and right coronary artery ostial stenosis: demographic and angiographic features; Int. J. Angiol., 20 (1) (Mar 2011), pp. 33–38</li>
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[[#bb0010|[2]]] S. Darabian, A.R. Amirzadegan, H. Sadeghian, S. Sadeghian, A. Abbasi, M. Raeesi; Ostial lesions of left main and right coronary arteries: demographic and angiographic features; Angiology, 59 (2008), pp. 682–687</li>
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[[#bb0015|[3]]] S. Sasaguri, Y. Honda, T. Kanou; Isolated coronary ostial stenosis compared with left main trunk disease; Jpn. Circ. J., 55 (1991), pp. 1187–1191</li>
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[[#bb0020|[4]]] C.L. Pritchard, J.G. Mudd, H.B. Barner; Coronary ostial stenosis; Circulation, 52 (1975), pp. 46–48</li>
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[[#bb0025|[5]]] K.K. Koh, H.K. Hwang, P.G. Kim,  ''et al.''; Isolated left main coronary ostial stenosis in oriental people: operative, histopathologic and clinical findings in six patients; J. Am. Coll. Cardiol., 21 (1993), pp. 369–373</li>
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[[#bb0030|[6]]] O. Yamanaka, R.E. Hobbs; Solitary ostial coronary artery stenosis; Jpn. Circ. J., 57 (1993), pp. 404–410</li>
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[[#bb0035|[7]]] B.L. Salem; Left main coronary artery ostial stenosis: clinical markers, angiographic recognition and distinction from left main disease; Catheter. Cardiovasc. Diagn., 5 (2) (1979), pp. 125–134</li>
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[[#bb0040|[8]]] C.J. Murray, A.D. Lopez; Alternative projections of mortality and disability by cause 1990–2020: global burden of disease study; Lancet, 349 (1997), pp. 1498–1504</li>
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[[#bb0045|[9]]] B.H. Bulkley, W.C. Roberts; Atherosclerotic narrowing of the left main coronary artery: a necropsy analysis of 152 patients with fatal coronary heart disease and varying degrees of left main narrowing; Circulation, 53 (1976), pp. 823–828</li>
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[[#bb0050|[10]]] N. Mahajan, M.B. Hollander,  ''et al.''; Isolated and significant LMCA disease, demographic, hemodynamic and angiographic features; Angiology, 57 (2006), pp. 464–477</li>
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[[#bb0055|[11]]] Barner HB, Reese J, Standeven J, McBride LR, Pennington DG, Willman VL. Left coronary ostial stenosis: comparison with left main coronary artery stenosis. Ann. Thorac. Surg.; 47(2):293–6.</li>
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[[#bb0060|[12]]] G.A. Miller, M. Honey, H. El-Sayed; Isolated coronary ostial stenosis; Catheter. Cardiovasc. Diagn., 12 (1986), pp. 30–33</li>
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[[#bb0065|[13]]] C.C. Welch, W.L. Proudfit, W.C. Sheldon; Coronary arteriographic findings in 1000 women under age 50; Am. J. Cardiol., 35 (2) (1975 Feb), pp. 211–215</li>
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[[#bb0070|[14]]] R. Viljo; Occurrence of coronary ostial stenosis in a necropsy series of myocardial sudden death and violent death; BHJ, 37 (2) (1975), pp. 182–191</li>
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</ol>
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