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Table of Contents
ORIGINAL ARTICLE
Year : 2019  |  Volume : 9  |  Issue : 4  |  Page : 216-222

Female predominant coronary tortuosity is related to significant coronary artery disease. A prospective observational study


Department of Cardiology, Faculty of Medicine, Assiut University, Assiut, Egypt

Date of Web Publication11-Mar-2020

Correspondence Address:
Dr. Ayman K M. Hassan
Department of Cardiology, Faculty of Medicine, Assiut Univeristy, Assiut
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/JICC.JICC_27_19

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  Abstract 


Background: Coronary tortuosity (CT), quantified by our new tortuosity severity index (TSI), strongly predicts anginal pain in patients with normal coronary angiography (CA). The connection between CT and coronary arteriosclerosis is still imprecise. Objectives: The objective was to study CT in patients with coronary artery disease (CAD). Patients and Methods: This is a prospective study at university hospitals between May 2016 and January 2017. We included 331 consecutive patients who underwent CA due to typical chest pain and showed CAD with a lesion >30%. Patients were prospectively divided into two groups based on the presence (n = 186) or absence (n = 145) of significant CAD (≥70%) and compared for clinical, echocardiographic, and CA characteristics. The TSI was either significant (mild/moderate CT with >4 curvatures in total or severe/extreme CT with any number of curvatures) or not significant TSI (mild/moderate CT with curvatures ≤4 curvatures in total). Results: Patients with significant CAD had the highest rate of CT (66% vs. 17%, P ≤ 0.001) and significant TSI (69% vs. 20%, P < 0.001) compared to those without. CT affects the left anterior descending coronary artery in middle and distal segments as a single vessel in 80% of patients. Patients with CT were more commonly females and hypertensives with small body surface area. Multivariate logistic regression analysis identified female gender (odds ratio [OR] = 4.7, confidence interval [CI] = 2.4–8.9) and CT as the main predictors of significant CAD (OR = 6.7, CI = 3.2–14.2). Conclusions: CT with significant TSI is positively related with significant CAD. This finding is more pronounced among hypertensive females with small body surface area.

Keywords: Chest pain, coronary tortuosity, female gender, significant coronary artery disease


How to cite this article:
M. Hassan AK, Mohamed EA, N. Ahmed TA, Hasan-Ali H, Demitry SR. Female predominant coronary tortuosity is related to significant coronary artery disease. A prospective observational study. J Indian coll cardiol 2019;9:216-22

How to cite this URL:
M. Hassan AK, Mohamed EA, N. Ahmed TA, Hasan-Ali H, Demitry SR. Female predominant coronary tortuosity is related to significant coronary artery disease. A prospective observational study. J Indian coll cardiol [serial online] 2019 [cited 2020 Jul 10];9:216-22. Available from: http://www.joicc.org/text.asp?2019/9/4/216/280344




  Introduction Top


Tortuous coronary arteries with turns and loops had been a frequent angiographic finding in many studies and clinical researches.[1] The importance of coronary tortuosity (CT) comes from the possibility of reducing the coronary blood flow, through diminishing coronary perfusion pressure distal to the tortuous point of the artery, as a result to this kinking and tortuosity, which may lead to ischemia.[2] There might be a compensatory pathway of the tortuous coronary structure which will compensate for the reduction in perfusion pressure at rest;[3],[4],[5] however, during exercise, it lacks the capacity to preserve adequate blood supply.[6] Coronary artery tortuosity has been reported in patients who presented with myocardial infarction.[2],[7],[8],[9] This correlation between CT and acute coronary syndromes can be explained by increased possibility of acute coronary artery obstruction[10] and higher incidence of diabetes.[8],[11] Furthermore, CT was associated in most of the cases with reversible myocardial perfusion defects and chronic stable anginal presentation.[2],[4],[12],[13],[14] The connection between CT and coronary arteriosclerosis is still imprecise.

In our previous report on CT, we found that it is a strong predictor of anginal pain in patients with normal coronary angiography (CA) in spite of positive stress study. This observation was more noticed among elderly and hypertensive female patients.[15]

This study hypothesizes that patients with significant coronary artery disease (CAD) (defined by invasive CA as >50% stenosis of the left main stem or ≥70% stenosis in a major coronary artery[16]) would have a higher prevalence of significant tortuosity severity index (TSI) compared to patients without significant CAD. We are validating our previously published TSI used to standardize the CT analysis[15] in this report.


  Patients And Methods Top


Study design and patients' selection

This is an observational prospective study done to evaluate adult patients who underwent CA due to typical chest pain with or without significant electrocardiogram (ECG) changes. Inclusion criteria are patients with typical anginal pain and having obstructive coronary disease on their angiography with >30% diameter stenosis. We excluded patients with normal coronary arteries (normal CA was defined as the absence of plaques or presence of a lesion ≤30% stenosis), myocardial bridge, coronary ectasia, spasm or fistula, renal insufficiency (serum creatinine >1.5 mg/dl), peripheral arterial disease, or the presence of another explanation of chest pain such as myocarditis, hypertrophic cardiomyopathy, pulmonary hypertension, or valvular heart disease. Assiut University Institutional Review Board approved the study which complies with the Declaration of Helsinki. An informed written consent was obtained from all patients explaining the purpose and conduction of this research study.

Among 675 patients who presented with typical chest pain and scheduled for CA in the period between May 2016 and January 2017, 144 patients refused to be included in the study, 200 patients had normal coronary arteries (this group was analyzed in our previous report in details[15]), and the remaining 331 patients were included in this study [Figure 1].
Figure 1: Flowchart of the study. Significant CAD = defined by invasive coronary angiography as >50% stenosis in the left main and/or >70% stenosis in a major coronary vessel; **patients with normal coronary angiography had been analyzed extensively in our previous article;[15] #excluded patients were based on the exclusion criteria presented previously. CAD: Coronary artery disease, CA: Coronary angiography, CT: Coronary tortuosity, pts: Patients, TSI: Tortuosity severity index

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Study groups

Our study patients were prospectively classified according to the presence or absence of significant CAD (defined by invasive CA as >50% stenosis of the left main stem and/or ≥70% stenosis in a major coronary vessel[16]) into two groups and were compared for their baseline demographic, electrocardiographic, and echocardiographic characteristics.

Electrocardiographic analysis

It was done during precatheterization to identify significant ST-segment or T-wave changes and other ECG changes in correlation to chest pain.

Echocardiographic assessment

Detailed two-dimensional echocardiography assessment including segmental wall motion assessment, left ventricular (LV) mass, LV mass index, and ejection fraction was calculated for all included patients day before CA.[17]

Coronary angiographic assessment

As reported in our previous report,[15] standard femoral approach was used. The left anterior descending coronary artery (LAD), left circumflex coronary artery (LCX), and right coronary artery were observed and evaluated by an experienced cardiologist in different angulations for the presence of significant stenosis in major epicardial coronary arteries or their branches (vessel diameter >2.5 mm). Offline analysis of the maximum lumen narrowing percent was determined for any coronary lesion using standard quantitative software.[18] CA of all patients included in the study should show CAD with a lesion >30% diameter stenosis at quantitative assessment. Coronary artery assessment by SYNTAX score segmentation was used to describe CT.[19],[20]

Coronary tortuosity and angulation diagnostic algorism

This part has been explained in details in our previous study.[15] In summary, CT is identified by the presence of ≥3 curvatures with ≥45° change in vessel direction along the main trunk of one artery or more, only in vessels >2.5 mm in diameter, present both in systole and diastole [Figure 2]. Offline assessment of all patients' angiograms was done by two experienced operators (A.H. and H.H.) blinded to the admission groups. CT was diagnosed using consistent predefined rules with the same view angles for every artery. Weighted kappa statistics was used to calculate the interobserver agreement revealing good settlement (k = 0.95, P = 0.001).
Figure 2: Consist of four portions labeling the diagnosis of coronary tortuosity. The arbitrary line drawn with arrows showing the points of bending (a) ramus branch in AP caudal view, shows mild CT (degree of the angle of deviation between 45 and <90°) with 4 bends; (b) LAD branch in LAO cranial view shows moderate CT (angle between 90 and 180°) with 3 bends; (c) RCA coronary artery in LAO view shows extreme tortuosity with one coronary loop; (d) LAD branch in RAO cranial view shows severe CT (angle >180°) with >5 bends. LAD: Left anterior descending coronary artery, LCX: Left circumflex coronary artery, RCA: Right coronary artery

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Tortuosity severity index calculation

This index was discussed in details previously.[15] The TSI was specified either significant TSI or nonsignificant TSI, depending on the sum of scores for each artery using the number of curvatures and the degree of angulation from a virtual straight line, as showed in details in [Figure 2].

Clinical follow-up

All study patients were followed up in a dedicated outpatient clinic at 1 and 3 months after CA. Clinical follow-up included routine clinical evaluation and assessment of the revascularization strategy used in all patients (either percutaneous coronary intervention [PCI] or coronary artery bypass graft [CABG]).

Statistical analysis

Categorical variables were presented as counts and proportions (percentages) and compared by Pearson's Chi-square analysis or Fisher's exact test. Normal distribution of continuous data was tested using a Kolmogorov–Smirnov test. Continuous and normally distributed data are presented as mean ± standard deviation and were compared by unpaired t-test. Not-normally distributed data are expressed as median with interquartile range, and the Mann–Whitney U-test was used to compare differences between two groups. The interobserver agreement was calculated with weighted kappa statistics. Correlations were done by Spearman's correlation coefficient test. Univariate and multivariate logistic regression analyses were performed using all potentially relevant variables to identify baseline-independent predictors of significant CAD. All P values are two-tailed, and statistical significance was defined if P < 0.05. All analyses were performed with SPSS version 22.0 statistical software (SPSS Inc., Chicago, IL, USA).


  Results Top


The main demographic, clinical, echocardiographic, and angiographic characteristics of the study groups are listed in [Table 1]. Patients were divided into two groups based on the presence (Group I) or absence (Group II) of significant CAD; there were significantly higher prevalence of female gender, hypertension, less smokers, and severe LV hypertrophy (LVH) in Group I compared to Group II. All patients with significant CAD underwent revascularization either by PCI or CABG within 3 months of follow-up. Patients in Group I had the highest rate of CT (66.1% vs. 17.2%, P < 0.001) and significant TSI (69% vs. 20%, P < 0.001) compared to Group II [Table 1].
Table 1: Demographic data of study group based on the presence or absence of significant coronary artery disease

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The same 331 patients were reclassified into groups based on the presence or absence of CT [Table 2]. There were 148 patients (44.71%) with CT in the study group. 73.6% of this CT were in the LAD especially in segments 7 and 8 according to SYNTAX score segmentation, furthermore 81.8% of CT was in single vessel as shown in [Figure 3]. Patients with CT were more commonly females, hypertensives, and less smokers with small body surface area. Furthermore, LVH was observed more frequently in those patients. By further analysis of the degree of LVH, patients with CT had the severest degree of LVH compared with those without CT [Table 2]. None of our patients died at 3 months of clinical follow-up.
Table 2: Demographic data of study population based on the presence or absence of coronary tortuosity

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Figure 3: Consist of four portions evaluating the anatomical difference of coronary tortuosity. (a) The percentage of patients with CT that was more common in LAD compared with LCX or RCA in patients with CAD. (b) The percentage of single vessel with CT that was more common compared with multivessel CT. (c) The higher incidence of significant tortuosity severity index in patients with significant CAD compared with nonsignificant group. (d) Elucidate which segment of the coronary artery, based on SYNTAX score segmentation, had more frequently CT. Segments 7 and 8 in LAD were more affected than other segments followed by segments 13 and 14 in LCX. LAD: Left anterior descending coronary artery, LCX: Left circumflex coronary artery, RCA: Right coronary arter

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Univariate logistic regression analysis identified several factors for prediction of significant CAD including female gender, hypertension, small body surface area, LVH, and CT. However, when putting all risk factors together in the multivariate logistic regression model, female gender (odds ratio [OR] = 4.7, 95% confidence interval [CI] = 2.4–8.9, P < 0.001) and CT (OR = 6.7, 95% CI = 3.2–14.2, P < 0.001) were the only independent predictors of significant CAD [Table 3]. The presence of significant TSI was associated with an 11-fold increase in the odds of having significant CAD by further analysis (OR = 11, CI = 2.41–50.37, P = 0.002). There is a clear interaction between the effect of CT and LV mass/index, as the CT effect reduced to six folds, instead of nine folds, with addition of LV mass to the regression model. This interaction confirms the correlation between CT and hypertension in our study.
Table 3: Logistic regression analysis for prediction of significant coronary artery disease

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  Discussion Top


The main finding of our study is that CT with significant TSI is positively associated with significant CAD. Patients with CT were more frequently females and hypertensives with small body surface area. Our study demonstrates that female gender and CT were independent predictors of significant CAD.

Previous studies demonstrated that CT may constitute as a risk factor for atherosclerosis since it can lead to the appearance of a segment with low wavering shear stress in the internal wall of the curve's descent when the angle of the curve is >120°.[2],[5],[21],[22],[23],[24],[25],[26] Even more, Levent and Zeynep[26] showed that there was a statistically significant positive correlation between CT and SYNTAX score in patients who underwent CABG surgery. This comes in agreement with our study where patients with significant CAD demonstrate almost 7-fold higher frequency of CT compared to patients with nonsignificant coronary lesions. Furthermore, two-thirds of patients with CT and significant CAD had significant TSI. On the other hand, Li et al.[27] reported that CT was negatively correlated with coronary atherosclerosis, and the incidence of major adverse events on 4-year follow-up was not affected by the presence or absence of CT. This difference can be explained on the basis of different study designs and the definition used for CAD (>50% stenosis); however, in our study, we used a definition >30% stenosis for CAD this is why the prevalence in our study was higher. Furthermore, 71% of patients in the study by Li et al. had a significant CAD either in one or two vessels which still considered significantly high percentage in patients with CT, in accordance with this study.

The pathophysiology of anginal pain due to CT has been studied lately.[1],[2],[5],[6],[28],[29] It is suggested that CT leads to a decrease in filling pressures in the distal vessel and thereby microcirculation. This is supposed to be due to the substantial hemodynamic shearing powers and reformed flow dynamics that occur in tortuous arteries.[2],[5] CT may represent greater resistance to blood flow during exercise, in such a way that compensatory tools of flow adjustment may not be sufficient to maintain an adequate flow and so lead to myocardial ischemia.[30] Furthermore, CT was associated in another study[31] with increased mean platelet volume, platelet-to-large cell ratio, platelet-to-lymphocyte ratio, and neutrophil-to-lymphocyte ratio even in the absence of CAD, which may elucidate its relation with atherosclerosis.

In accordance with our study regarding higher incidence of CT in female gender, Li et al.[27] carried out a retrospective analysis on 1010 patients who had undergone CA due to anginal complaint, and patients were divided into four groups according to the presence or absence of CT and the presence or absence of coronary obstructions and did a 2–4-year follow-up with these patients. The CT prevalence was 39.1% in the study groups and was significantly higher in women and in hypertensive patients. Other studies including our previous report on patients with angina and normal CA; female gender was also predominant in patients with CT.[15],[32] It was reported previously that the frequency of tortuosity increases as the heart size and mass decreases in females.[7] This was in agreement with our study results where patients with low body surface area had a higher rate of CT.

As regard age, we did not find any relationship between aging and CT in agreement with Groves et al.[13] However, several other researchers have reported a relationship between advanced aging and CT.[2],[15],[33]

For less smoking in groups with CT reported in our study, this can be attributed to the predominance of female gender in this group with less smoking habit in our locality. This comes in agreement with Li et al.[12] who described the same finding in Chinese patients.

There are several determinants for CT including the differences in tortuosity between circumferentially and longitudinally leaning coronary arteries and also between systole and diastole. It has been found that tortuosity increases during systole and is more pronounced in circumferentially (LCX) than in longitudinally (LAD) oriented arteries in patients with hypertension.[33] In the present study, the LAD was the most common vessel with CT, this comes in agreement with our previous report[15] and Gaibazzi et al,[14] but dissimilar from other studies which found that circumflex artery was most often affected.[27],[33] This difference can be clarified on the basis that we diagnose CT only if present both in systole and diastole involving only the vessels with a diameter >2.5 mm in our analysis.

In our study, we revealed that CT was more frequent in patients with LVH and higher LV mass index. Several studies had linked hypertension to CT. Turgut et al.[24] showed that compromised LV relaxation could increase CT. Dagianti et al.[30] and Jakob et al.[33] showed in subsequent studies that LV geometry changes as a result of chronic LV pressure and volume overload affect the tortuosity of coronary arteries, so that concentric hypertrophy seems to increase CT through abnormal LV relaxation. Myocardial hypertrophy increases CT probably due to angiogenetic factors, mediated through growth factors, wall stress or blood flow.[34],[35] More recently, Li et al.[27] showed that CT was more frequent in hypertensive patients in agreement with our results.

Concerning the prevalence of CT, the work by Li et al.[27] identified CT in 34% of patients with CAD, and the incidence of CT was more in non-CAD patients than in CAD patients (45.1% vs. 34.4%, P = 0. 001). This is different from our study where the incidence was 46% in patients with normal CA (our previous report[15]) and 44% in this study on patients with CAD. This difference can be explained on the basis of different definitions of CAD used by Lie et al. Alternatively, Levent and Zeynep[26] described a higher prevalence of CT (51.8%) as the definition used was in agreement with our definition, but they included vessels <2.0 mm in diameter which explain the higher prevalence compared to ours. No internationally accepted clear definition of CT in the literature but only few previous reports addressed this issue.[2],[13],[14],[27],[30] We defined CT by the presence of >3 curvatures with >45° angulation in vessel direction along the main trunk of at least one artery present both in systole and diastole including only vessels >2.5 mm in diameter.[15] Regarding our definition, it is by some means similar to the definition chosen by Li et al.[27] (≥3 bends with an angle ≥45° change in vessel direction along the main trunk of at least one artery in systole and in diastole). From our viewpoint, the proposed TSI model (significant TSI [demarcated as mild/moderate CT with >4 bends in total or sever/extreme CT with at least one bend] or else nonsignificant TSI)[15] is more clinically relevant in patients with CAD compared to previously reported TSI.[33] In this study, we validated this TSI model in a large number of patients revealing its accuracy in describing CT; therefore, we recommend adding this TSI model to all CA report results.

Limitations of our study include: (1) We did not investigate the shear stress and flow dynamics or other hemodynamic features that affect artery tortuosity, and these factors need further studies to clarify related issues. (2) Tortuous coronary arteries were not further examined with fractional flow reserve (FFR) or intra vascular ultrasound (IVUS), which may provide insight on whether arterial remodeling is present in the tortuous segment shown by angiography or not. Further prospective studies with large cohort and long follow-up time are needed to clarify this point.


  Conclusions Top


CT with significant TSI is positively related with significant CAD. This finding is more pronounced among hypertensive females with small body surface area.

Acknowledgment

We would like to thank Prof. Amr Yousef and professors of cardiovascular medicine at Assiut University for clinical guidance and scientific enthusiasm who support our work and enriched the discussion and application of our TSI new definition.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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    Figures

  [Figure 1], [Figure 2], [Figure 3]
 
 
    Tables

  [Table 1], [Table 2], [Table 3]



 

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