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Clinical Profile of Patients with Coronary Tortuosity and its Relation with Coronary Artery Disease
IJCCR
Clinical Profile of Patients with Coronary Tortuosity and
its Relation with Coronary Artery Disease
*Ankush Gupta1, Prashant Panda2, Yash P. Sharma3, Ashwin Mahesh4, Prafull Sharma5, Nalin
K. Mahesh6
1
Assistant professor, Department of Medicine & Cardiology, Base Hospital Delhi Cantt, New Delhi-10, India
2
Assistant professor, Department of cardiology, Advanced Cardiac Center, PGIMER Chandigarh, India
3
Head of the Department, Department of cardiology, Advanced Cardiac Center, PGIMER Chandigarh, India
4
Resident, Department of Medicine, Jaipur Golden Hospital, New Delhi, India
5
Associate professor, Department of Medicine & Cardiology, Base Hospital Delhi Cantt, New Delhi-10, India
6
Head of the Department, Department of Medicine & Cardiology, Base Hospital Delhi Cantt, New Delhi-10, India
Coronary tortuosity is a common angiographic finding. This study was done to observe the
clinical profile of patients with coronary tortuosity (CT) and its relation with coronary artery
disease (CAD). Method: A total 224 patients undergoing angiography for suspected CAD were
included in the study. Coronary tortuosity was defined by the presence of ≥3 consecutive bends
of > 45 degree, measured at end-diastole in an epicardial artery ≥2 mm in diameter. Coronary
tortuosity was present in 45(20.1%) patients (CT group) in the study and another 45 patients
without coronary tortuosity was randomly selected as control (NCT group). Clinical profile of CT
and NCT group was compared. Results: Incidence of coronary tortuosity was significantly higher
in females (p=0.000) and hypertensives (p=0.001) patients. Coronary tortuosity was most
commonly seen in Left circumflex coronary artery. Incidence of CAD was significantly lower in
CT group as compare to NCT group (0.02). Risk factors for CAD was associated with reduced
incidence of Coronary tortuosity. Majority (88.5%) patient with CT without CAD presented with
chronic stable angina out of which (65.2%) had an objective evidence of myocardial ischemia.
Conclusion: Coronary tortuosity is more commonly seen females and hypertensive patients. It
has negative correlation with CAD but can lead to myocardial ischemia. Risk factors of CAD do
not predict CT.
Keywords: coronary tortuosity; myocardial ischemia; coronary artery disease; chronic stable angina.
INTRODUCTION
Coronary artery disease (CAD) is the leading cause of
mortality and morbidity worldwide (Lloyd-Jones D et al,
2010; Zhang XH et al, 2008). The gold standard for
diagnosis of CAD is coronary angiography. Coronary
tortuosity (CT) is a common angiographic finding
encountered by cardiologists. Its association with chronic
pressure load and impaired left ventricular relaxation and
possibly coronary ischemia has been suggested by some
studies (Zegers ES et al, 2007; Turgut O et al, 2007; Jakob
M et al, 1996; Gaibazzi N, 2011; Gaibazzi N et al, 2011).
Tortuous coronaries could hamper the ventricular function.
They have been proposed as an indicator of the ventricular
dysfunction (Turgut O et al, 2007). CT is also associated
with reversible myocardial perfusion defects and chronic
*Corresponding author: Ankush Gupta, Department of
Medicine & Cardiology, Base Hospital Delhi Cantt, New
Delhi-10, India. E-mail: drankushgupta@gmail.com; Tel.:
+919592903488
International Journal of Cardiology and Cardiovascular Research
Vol. 4(2), pp. 066-071, September, 2018. © www.premierpublishers.org, ISSN: 3102-9869
Research Article
Clinical Profile of Patients with Coronary Tortuosity and its Relation with Coronary Artery Disease
Gupta et al. 067
stable angina (Gaibazzi N et al, 2011; Yang LI et al, 2012).
Patients with CT often suffer exercise-induced chest pain
that typically disappears at rest (Zegers ES et al, 2007).
These clinical findings indicate that CT may hinder
coronary blood supply. However, no clinical data directly
supports it. Whether CT leads to a significant decrease in
the coronary blood supply is still unknown. Isolated
coronary tortuosity in patients with chronic stable angina is
often ignored and is labeled as normal coronaries. These
patients remain symptomatic with angina with multiple
health care visits, affecting their quality of life. The
relationship between CT and CAD is still debatable. Only
limited data is available in the literature on clinical profile
of patients having CT, either in isolation or with CAD. This
study was done to observe the prevalence of CT in
patients undergoing coronary angiography. This study also
compared the clinical profile of patients having coronary
tortuosity with or without CAD.
MATERIALS AND METHODS
This is a prospective observational study conducted at
department of Cardiology, Advanced Cardiac Center,
Postgraduate Institution of Medical Education and
Research (Chandigarh), a tertiary care center in North
India. Patients undergoing coronary angiography from
January 2015 to December 2015 for suspected coronary
artery disease (CAD), were enrolled in the study. Patients
below the age of 18 years, patients with congenital heart
disease and with slow flow on coronary angiography were
excluded from the study. Suspected CAD patients were
those who presented with acute coronary syndrome,
chronic stable angina or asymptomatic patients
undergoing angiography to rule out CAD, like prior to valve
surgery. Detailed history and examination was done in all
the patients. All patients underwent biochemical
investigations which included fasting blood sugar, lipid
profile, serum uric acid, and renal function test. 12 lead
electrocardiography and detailed transthoracic
echocardiography was carried in all patients. All patients
underwent elective coronary angiography according to the
Judkins technique. CAD was defined as more than 50%
luminal narrowing in at least one main coronary artery. CT
was evaluated on special angulations, left anterior
descending artery (LAD) was assessed in right anterior
oblique with cranial angulations, left circumflex artery
(LCX) in left anterior oblique with caudal angulations and
right coronary artery (RCA) in right anterior oblique. CT
was defined by the presence of ≥3 consecutive
curvatures of more than 45 degree measured at end-
diastole in a major epicardial coronary artery ≥2 mm in
diameter (Figure 1). Coronary flow was objectively
quantified by using the corrected thrombolysis in
myocardial infarction (TIMI) frame count method. Patients
with a corrected TIMI frame count greater than two
standard deviations from the normal range for the
particular vessel were considered as having slow coronary
flow, while those who had a corrected TIMI frame count
within two standard deviations of the normal range were
classified as having normal coronary flow.
Figure 1: Images from two different patients showing
coronary tortuosity with more than 45-degree bend.
STATISTICAL ANALYSIS
Statistical analysis was done using SPSS version 17.
Normally distributed measurable data was compared
using Student’s t-test; whereas non-normally distributed or
ordinal data using the Mann–Whitney test. The
measurable data was presented as Mean± SD; whereas
the skewed data was presented as their Median. In
addition, Logistic regression was applied to find the
independent factors which are associated with the groups.
The association of all the Categorical /Classified data with
the two groups was analyzed with Chi-Square test or the
Fisher’s exact test, whichever is applicable. P value < 0.05
was taken as the level of significance.
RESULTS
A total of 224 patients underwent angiography over a
period of one year from January 2015 to December 2015.
Out of which 45 patients had coronary tortuosity (20.1%)
(CT group), 45 more patients were randomly selected as
control (NCT) group. In CT group 19(42.2%) patients had
CAD and 26 were without CAD (CT only). In NCT group
30((66.7%)) patient had CAD and 15 patients had normal
coronaries (Figure 2). The mean age of patients in the CT
and NCT group was 57.38+9.43 and 56.64+11.13 years
respectively. The number of male and female patients in
the CT group was 16(35.6%) and 29(64.4%) respectively.
The number of male and female patients in NCT group was
37(82.2%) and 08(17.8%) respectively. Hypertension was
present in 32 (71%) patients in CT group and in 16 (35.6%)
patients in NCT group. The distribution of risk factors in CT
and NCT group is shown in Table 1. CT incidence was
significantly higher in females, hypertensive patients and
patients with raised LDL. Incidence of CAD was
significantly lower in CT group. Table 2 shows multivariate
regression analysis using sex, hypertension (HTN),
diabetes mellitus (DM), smoking, LDL and CAD to predict
Clinical Profile of Patients with Coronary Tortuosity and its Relation with Coronary Artery Disease
Int. J. Cardiol. Cardiovasc. Res. 068
CT and NCT which was 87% and 91% respectively. So
female gender, hypertension raised LDL were associated
higher incidence of CT while diabetes, male sex, smoking,
peripheral vascular disease (PVD), low HDL, reduced
ejection fraction (EF) and CAD were linked with reduced
incidence of CT. Left circumflex (LCX) was the most
common single artery having CT. Out of 45 patients in CT
group, 39(86.7%) patients had CT in LCX artery either
alone or in combination with other coronary artery,
26(57.8%) had CT in left anterior descending (LAD) artery
and 06(13.3%) patients had CT in RCA (Table 3 ).
Table 1 shows Clinical profile of patients in coronary
tortuosity (CT) and non-coronary tortuosity group (NCT).
Parameter CT Group NCT Group p
value
AGE 57.38 ± 9.43 56.64 ± 11.13 0.737
Female 29 ( 64.4 ) 8(17.8) 0.000
Male 16(35.6) 37(82.2) 0.001
CAD 19(42.22) 30(66.67) 0.02
HTN 32 ( 71.1 ) 16(35.6) 0.001
DM 10(22.2) 26 ( 57.8 ) 0.001
DL 16 ( 35.6 ) 18(40) 0.664
Smoking 7(15.6) 15 ( 33.3 ) 0.050
PVD 0(0) 9 ( 20 ) 0.002
Family
History
3 ( 6.7 ) 0(0) 0.078
CVA 0 ( 0 ) 0 ( 0 ) -
HF 6 ( 13.3 ) 6 ( 13.3 ) 1.000
Prior PCI 1 ( 2.2 ) 2 ( 4.4 ) 0.557
Prior
CABG
0 ( 0 ) 0 ( 0 ) -
SBP 127.47 ± 15.33 117.73 ± 22.6 0.019
DBP 80.71 ± 8.18 73.49 ± 13.56 0.003
Hb 13.02 ± 1.4 12.79 ± 0.92 0.375
Creatinine 0.89 ± 0.25 0.84 ± 0.22 0.350
LDL 150.16 ± 29.7 126.53 ± 39.25 0.002
HDL 49.22 ± 8.24 44.98 ± 4.65 0.004
TG 164.91 ± 37.58 160.62 ± 46.16 0.630
FBS 103.67 ± 26.61 126.73 ± 37.26 0.001
EF% 56.76 ± 9.57 45.04 ± 13.37 0.000
Abnormal
ECG
22(48.9% 35(77.8%) 0.004
CAD- coronary artery disease, HTN-hypertension, DM-
diabetes mellitus, DL dyslipidemia, PVD- peripheral
vascular disease, CVA- cerebrovascular accident, HF-
heart failure, PCI- percutaneous coronary intervention,
CABG- coronary artery bypass graft, SBP- systolic blood
pressure, DBP- diastolic blood pressure, Hb- hemoglobin,
LDL- low density lipoprotein, HDL- high density lipoprotein,
TG- triglycerides, FBS- fasting blood sugar, EF- ejection
fraction.
Table 2: Multivariate Logistic regression of selected
variable for prediction of coronary tortuosity.
B S.E. Wald Df Sig. Exp
(B)
95% C.I
Male -1.274 .939 1.840 1 .175 .280 .044 - 1.762
HTN
absent
-1.445 .815 3.142 1 .076 .236 .048 - 1.165
Non
Diabetic
2.373 .959 6.120 1 .013 10.7
32
1.637 – 70.344
Non
smoker
2.401 1.222 3.861 1 .049 11.0
36
1.006 – 121.054
Raised
LDL
.070 .021 11.723 1 .001 1.07
3
1.031 – 1.117
CAD
absent
1.380 1.244 1.232 1 .267 3.97
7
.348 – 45.506
HTN- hypertension, LDL- low density lipoprotein, CAD-
coronary artery disease.
Table 3: shows Distribution of Tortuosity in coronary
arteries.
ARTERY FREQUENCY (n=45)
LAD 03(6.6%)
LCX 16(35.5%)
LAD & LCX 19(42.2%)
RCA 01(2.2%)
LAD & RCA 01(2.2%)
LCX & RCA 01(2.2%)
LAD,LCX & RCA 03(6.6%)
LAD- left anterior descending, LCX- left circumflex, RCA-
right coronary artery.
Figure 2: Flow chart showing distribution of study group
patients into CT and NCT group and their further four
subgroups. CAG- coronary angiography, CT- coronary
tortuosity, NCT- noncoronary tortuosity, CAD- coronary
artery disease.
Clinical Profile of Patients with Coronary Tortuosity and its Relation with Coronary Artery Disease
Gupta et al. 069
DISCUSSION
The prevalence of coronary tortuosity in the present study
was 20.1%. Study done by Li Y et al. (2011) and El Tahlawi
M et al (2016) showed prevalence of 39.1% and 37.3%
respectively. This difference is likely due to higher mean
age in these studies as compared to present study.
Advanced age has been associated with increased
incidence of CT (Pancera P et al, 2000). In the present
study the mean age of patients in CT group was 57.38 ±
9.43 years and females dominated the group with a
prevalence of 64.4%. While in the NCT group the mean
age was 56.64 ± 11.13 years and males constituted 82.3%
of this group. Female sex, hypertension and raised LDL
was associated with increased incidence of CT.
Hemodynamic forces have key role in modulation of
vascular structure. Arteries may become tortuous due to
increased pressure and reduced axial strain in an elastic
cylindrical arterial model (Han HC, 2012). So close
association between hypertension and CT is expected and
CT might be one of the forms of arterial remodeling
response to hypertension due to increased coronary
pressure and blood flow. Increased incidence of CT in
females as compared to males may be due to smaller
cardiac size in females and coronary tortuosity decreases
with cardiac enlargement (Hutchins GM et al, 1977). Yang
Li et al. (2011) and Groves SS et al. (2009) also found
increased incidence of CT in females and hypertensive
patients.
There have been conflicting reports regarding the
correlation of coronary tortuosity and coronary artery
disease. Previous studies have shown both negative (Li Y
et al, 2011; Groves SS et al, 2009; Serdar Turkmen et al,
2013) and positive (El Tahlawi M et al, 2016; Cunningham
KS et al, 2005; Davutoglu V et, 2012) correlation between
CT and CAD. In the present study we observed that in CT
group, 42.2% patients had CAD, whereas in NCT group
66.7% patients had CAD (p=0.002). So, we observed a
negative correlation between CT and CAD. Local
hemodynamic factors like low shear stress plays an
important role in the development of atherosclerosis and
plaque stability through modulation of endothelial cell
function and gene expression, while high shear stress is
associated with protection from atherosclerosis
(Chatzizisis YS et al, 2007). So, the negative relationship
between CT and CAD may be explained by the protective
effect of high shear stress caused by CT. This may be one
of the causes for lower incidence of CAD in female. In a
study of coronary tortuosity by Serdar Turkmen et al.
(2013), a negative correlation between CT and severity of
CAD was found. They used a novel numeric scoring
system for quantitative assessment of CT. They defined
the CT score as the sum of all bends on the main shafts of
the major epicardial arteries. They found less CT in the
males, smokers, diabetics and CAD patients. In a study by
El Tahlawi M et al. (2016), frequency of coronary tortuosity
and coronary artery calcium (CAC) scoring was observed
in patients with chronic stable angina using computed
tomography coronary angiography. Definition used for CT
was similar to the present study. They found higher CAC
score in the CT group (p value < 0.05) as compare to NCT
group revealing that, CT may be associated with
subclinical atherosclerosis in the absence of obstructive
CAD.
CT may be associated with the non- atherosclerotic cause
of CAD like spontaneous coronary artery dissection
(SCAD), especially in females. In a study of 246 patients
of SCAD by Eleid MF et al. (2014), tortuosity was a
common finding in patients presenting with their first SCAD
episode. Tortuosity was most commonly observed in the
left circumflex artery (LCX), followed by the left anterior
descending (LAD), and the right coronary artery (RCA). In
the present study also, most patients had CT in left
circumflex artery followed by LAD and RCA. Possible
explanation for this higher prevalence of coronary
tortuosity in LCX could be because of its natural course
and higher hemodynamic stress being tackled by this
artery.
In our study, 26 patients had only coronary tortuosity (CT
only group). The mean age of patients in CT only group
was 55.31+ 8.8 years. In this CT only group, 69.2% were
females and 73.2% patients were having hypertension.
This is in agreement with previous studies which showed
increased incidence of CT in females and hypertensive
patients (Li Y et al, 2011; Groves SS et al, 2009; Davutoglu
V et al, 2012). Prevalence of diabetes mellitus,
dyslipidemia, smokers and patients with heart failure was
very low. Out of these 26 patients, 23(88.5%) patients
presented with chronic stable angina (CSA), one patient
had unstable angina and 12(46.1%) patients had abnormal
ECG at presentation. Out of 23 patients, who presented
with chronic stable angina, 11 patients had positive
treadmill test (TMT) for inducible ischemia, 2 patients
showed reversible myocardial perfusion defect on stress
myocardial perfusion imaging and 2 patients had abnormal
regional wall motion abnormality on transthoracic
echocardiography. So out of 23 patients presenting with
chronic stable angina, we had 15 patients with objective
evidence of myocardial ischemia but angiography showed
only CT without significant coronary artery stenosis. There
are few case reports in literature about coronary tortuosity
as a cause of myocardial ischemia in patients with chronic
stable angina. Zegers ES et al. (2007) reported three
cases of angina with abnormal stress test and angiography
showing CT without fixed stenosis. They put forward the
hypothesis that coronary tortuosity leads to increase in
energy loss, resulting in a reduction in coronary perfusion
pressure distal to CT segment, ultimately leading to
ischemia (Gijsen FJ et al, 1999). Abdar Esfahani M et al.
(2012) reported that CT can cause CSA and found that its
severity increases with severity of CT. DÖRTLEMEZ Ö et
al. (1993) found significant decrease in systolic and
diastolic coronary flow velocity distal to CT segment using
intracoronary Doppler tipped guide wire. Li Y et al. (2012)
Clinical Profile of Patients with Coronary Tortuosity and its Relation with Coronary Artery Disease
Int. J. Cardiol. Cardiovasc. Res. 070
found that, CT results in significant decrease in coronary
blood pressure as compare to NCT group. They found
more decrease in coronary pressure with increasing CT
angle and number of CT curves. Xie X et al. (2013) did a
computational fluid dynamics (CFD) study to evaluate the
impact of CT on the coronary blood supply. They
concluded that CT has minor impact on coronary blood
flow at rest; while during exercise, patients with CT had
ineffective coronary auto-regulation, leading to myocardial
ischemia. One patient in CT only group presented with
unstable angina, Chesnutt JK et al. (2013) found that
tortuosity of microvessel triggers platelet activation and
thrombus formation. This may be responsible for acute
coronary syndrome in CT only patient.
It is clear from the present study that CT without significant
CAD can produce clinical symptom like chronic stable
angina with objective evidence of myocardial ischemia.
Present study showed negative correlation between CT
and CAD. Previous studies have shown that CT may be
associated with subclinical atherosclerosis (El Tahlawi M
et al, 2016; Davutoglu V et al, 2012). We propose that
patient with chronic stable angina and coronary tortuosity
without significant CAD should be treated as CAD patients
with antiplatelets, statins and antianginal drugs.
CONCLUSIONS
Coronary tortuosity is a common angiographic finding. Left
circumflex is the most common coronary artery with
tortuosity. Coronary tortuosity is commonly found in
females and hypertensive patients. Patients with coronary
tortuosity have low incidence of CAD but, can present with
chronic stable angina and objective evidence of
myocardial ischemia in the absence of significant
obstructive coronary artery disease. Isolated coronary
tortuosity in patients with chronic stable angina is often
ignored and is labeled as normal coronaries. These
patients remain symptomatic with angina with multiple
health care visits, affecting their quality of life. These
patients should be offered treatment with antiplatelets,
statins and antianginal drugs to improve their quality of life.
Clinical Implication
Coronary artery tortuosity without significant obstructive
coronary artery disease should be recognized as a cause
of chronic stable angina. These patients should be given
treatment with anteplatelets, statins and antianginals,
which may result in marked improvement in symptoms,
thereby improving the quality of life.
Funding: None.
Conflicts of Interest: The authors declare no conflict of
interest.
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Accepted 18 August 2018
Citation: Gupta A, Panda P, Sharma YP, Mahesh A,
Sharma P, Mahesh NK (2018). Clinical Profile of Patients
with Coronary Tortuosity and its Relation with Coronary
Artery Disease. International Journal of Cardiology and
Cardiovascular Research, 4(2): 066-071.
Copyright: © 2018 Gupta et al. This is an open-access
article distributed under the terms of the Creative
Commons Attribution License, which permits unrestricted
use, distribution, and reproduction in any medium,
provided the original author and source are cited.

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Clinical Profile of Patients with Coronary Tortuosity and its Relation with Coronary Artery Disease

  • 1. Clinical Profile of Patients with Coronary Tortuosity and its Relation with Coronary Artery Disease IJCCR Clinical Profile of Patients with Coronary Tortuosity and its Relation with Coronary Artery Disease *Ankush Gupta1, Prashant Panda2, Yash P. Sharma3, Ashwin Mahesh4, Prafull Sharma5, Nalin K. Mahesh6 1 Assistant professor, Department of Medicine & Cardiology, Base Hospital Delhi Cantt, New Delhi-10, India 2 Assistant professor, Department of cardiology, Advanced Cardiac Center, PGIMER Chandigarh, India 3 Head of the Department, Department of cardiology, Advanced Cardiac Center, PGIMER Chandigarh, India 4 Resident, Department of Medicine, Jaipur Golden Hospital, New Delhi, India 5 Associate professor, Department of Medicine & Cardiology, Base Hospital Delhi Cantt, New Delhi-10, India 6 Head of the Department, Department of Medicine & Cardiology, Base Hospital Delhi Cantt, New Delhi-10, India Coronary tortuosity is a common angiographic finding. This study was done to observe the clinical profile of patients with coronary tortuosity (CT) and its relation with coronary artery disease (CAD). Method: A total 224 patients undergoing angiography for suspected CAD were included in the study. Coronary tortuosity was defined by the presence of ≥3 consecutive bends of > 45 degree, measured at end-diastole in an epicardial artery ≥2 mm in diameter. Coronary tortuosity was present in 45(20.1%) patients (CT group) in the study and another 45 patients without coronary tortuosity was randomly selected as control (NCT group). Clinical profile of CT and NCT group was compared. Results: Incidence of coronary tortuosity was significantly higher in females (p=0.000) and hypertensives (p=0.001) patients. Coronary tortuosity was most commonly seen in Left circumflex coronary artery. Incidence of CAD was significantly lower in CT group as compare to NCT group (0.02). Risk factors for CAD was associated with reduced incidence of Coronary tortuosity. Majority (88.5%) patient with CT without CAD presented with chronic stable angina out of which (65.2%) had an objective evidence of myocardial ischemia. Conclusion: Coronary tortuosity is more commonly seen females and hypertensive patients. It has negative correlation with CAD but can lead to myocardial ischemia. Risk factors of CAD do not predict CT. Keywords: coronary tortuosity; myocardial ischemia; coronary artery disease; chronic stable angina. INTRODUCTION Coronary artery disease (CAD) is the leading cause of mortality and morbidity worldwide (Lloyd-Jones D et al, 2010; Zhang XH et al, 2008). The gold standard for diagnosis of CAD is coronary angiography. Coronary tortuosity (CT) is a common angiographic finding encountered by cardiologists. Its association with chronic pressure load and impaired left ventricular relaxation and possibly coronary ischemia has been suggested by some studies (Zegers ES et al, 2007; Turgut O et al, 2007; Jakob M et al, 1996; Gaibazzi N, 2011; Gaibazzi N et al, 2011). Tortuous coronaries could hamper the ventricular function. They have been proposed as an indicator of the ventricular dysfunction (Turgut O et al, 2007). CT is also associated with reversible myocardial perfusion defects and chronic *Corresponding author: Ankush Gupta, Department of Medicine & Cardiology, Base Hospital Delhi Cantt, New Delhi-10, India. E-mail: drankushgupta@gmail.com; Tel.: +919592903488 International Journal of Cardiology and Cardiovascular Research Vol. 4(2), pp. 066-071, September, 2018. © www.premierpublishers.org, ISSN: 3102-9869 Research Article
  • 2. Clinical Profile of Patients with Coronary Tortuosity and its Relation with Coronary Artery Disease Gupta et al. 067 stable angina (Gaibazzi N et al, 2011; Yang LI et al, 2012). Patients with CT often suffer exercise-induced chest pain that typically disappears at rest (Zegers ES et al, 2007). These clinical findings indicate that CT may hinder coronary blood supply. However, no clinical data directly supports it. Whether CT leads to a significant decrease in the coronary blood supply is still unknown. Isolated coronary tortuosity in patients with chronic stable angina is often ignored and is labeled as normal coronaries. These patients remain symptomatic with angina with multiple health care visits, affecting their quality of life. The relationship between CT and CAD is still debatable. Only limited data is available in the literature on clinical profile of patients having CT, either in isolation or with CAD. This study was done to observe the prevalence of CT in patients undergoing coronary angiography. This study also compared the clinical profile of patients having coronary tortuosity with or without CAD. MATERIALS AND METHODS This is a prospective observational study conducted at department of Cardiology, Advanced Cardiac Center, Postgraduate Institution of Medical Education and Research (Chandigarh), a tertiary care center in North India. Patients undergoing coronary angiography from January 2015 to December 2015 for suspected coronary artery disease (CAD), were enrolled in the study. Patients below the age of 18 years, patients with congenital heart disease and with slow flow on coronary angiography were excluded from the study. Suspected CAD patients were those who presented with acute coronary syndrome, chronic stable angina or asymptomatic patients undergoing angiography to rule out CAD, like prior to valve surgery. Detailed history and examination was done in all the patients. All patients underwent biochemical investigations which included fasting blood sugar, lipid profile, serum uric acid, and renal function test. 12 lead electrocardiography and detailed transthoracic echocardiography was carried in all patients. All patients underwent elective coronary angiography according to the Judkins technique. CAD was defined as more than 50% luminal narrowing in at least one main coronary artery. CT was evaluated on special angulations, left anterior descending artery (LAD) was assessed in right anterior oblique with cranial angulations, left circumflex artery (LCX) in left anterior oblique with caudal angulations and right coronary artery (RCA) in right anterior oblique. CT was defined by the presence of ≥3 consecutive curvatures of more than 45 degree measured at end- diastole in a major epicardial coronary artery ≥2 mm in diameter (Figure 1). Coronary flow was objectively quantified by using the corrected thrombolysis in myocardial infarction (TIMI) frame count method. Patients with a corrected TIMI frame count greater than two standard deviations from the normal range for the particular vessel were considered as having slow coronary flow, while those who had a corrected TIMI frame count within two standard deviations of the normal range were classified as having normal coronary flow. Figure 1: Images from two different patients showing coronary tortuosity with more than 45-degree bend. STATISTICAL ANALYSIS Statistical analysis was done using SPSS version 17. Normally distributed measurable data was compared using Student’s t-test; whereas non-normally distributed or ordinal data using the Mann–Whitney test. The measurable data was presented as Mean± SD; whereas the skewed data was presented as their Median. In addition, Logistic regression was applied to find the independent factors which are associated with the groups. The association of all the Categorical /Classified data with the two groups was analyzed with Chi-Square test or the Fisher’s exact test, whichever is applicable. P value < 0.05 was taken as the level of significance. RESULTS A total of 224 patients underwent angiography over a period of one year from January 2015 to December 2015. Out of which 45 patients had coronary tortuosity (20.1%) (CT group), 45 more patients were randomly selected as control (NCT) group. In CT group 19(42.2%) patients had CAD and 26 were without CAD (CT only). In NCT group 30((66.7%)) patient had CAD and 15 patients had normal coronaries (Figure 2). The mean age of patients in the CT and NCT group was 57.38+9.43 and 56.64+11.13 years respectively. The number of male and female patients in the CT group was 16(35.6%) and 29(64.4%) respectively. The number of male and female patients in NCT group was 37(82.2%) and 08(17.8%) respectively. Hypertension was present in 32 (71%) patients in CT group and in 16 (35.6%) patients in NCT group. The distribution of risk factors in CT and NCT group is shown in Table 1. CT incidence was significantly higher in females, hypertensive patients and patients with raised LDL. Incidence of CAD was significantly lower in CT group. Table 2 shows multivariate regression analysis using sex, hypertension (HTN), diabetes mellitus (DM), smoking, LDL and CAD to predict
  • 3. Clinical Profile of Patients with Coronary Tortuosity and its Relation with Coronary Artery Disease Int. J. Cardiol. Cardiovasc. Res. 068 CT and NCT which was 87% and 91% respectively. So female gender, hypertension raised LDL were associated higher incidence of CT while diabetes, male sex, smoking, peripheral vascular disease (PVD), low HDL, reduced ejection fraction (EF) and CAD were linked with reduced incidence of CT. Left circumflex (LCX) was the most common single artery having CT. Out of 45 patients in CT group, 39(86.7%) patients had CT in LCX artery either alone or in combination with other coronary artery, 26(57.8%) had CT in left anterior descending (LAD) artery and 06(13.3%) patients had CT in RCA (Table 3 ). Table 1 shows Clinical profile of patients in coronary tortuosity (CT) and non-coronary tortuosity group (NCT). Parameter CT Group NCT Group p value AGE 57.38 ± 9.43 56.64 ± 11.13 0.737 Female 29 ( 64.4 ) 8(17.8) 0.000 Male 16(35.6) 37(82.2) 0.001 CAD 19(42.22) 30(66.67) 0.02 HTN 32 ( 71.1 ) 16(35.6) 0.001 DM 10(22.2) 26 ( 57.8 ) 0.001 DL 16 ( 35.6 ) 18(40) 0.664 Smoking 7(15.6) 15 ( 33.3 ) 0.050 PVD 0(0) 9 ( 20 ) 0.002 Family History 3 ( 6.7 ) 0(0) 0.078 CVA 0 ( 0 ) 0 ( 0 ) - HF 6 ( 13.3 ) 6 ( 13.3 ) 1.000 Prior PCI 1 ( 2.2 ) 2 ( 4.4 ) 0.557 Prior CABG 0 ( 0 ) 0 ( 0 ) - SBP 127.47 ± 15.33 117.73 ± 22.6 0.019 DBP 80.71 ± 8.18 73.49 ± 13.56 0.003 Hb 13.02 ± 1.4 12.79 ± 0.92 0.375 Creatinine 0.89 ± 0.25 0.84 ± 0.22 0.350 LDL 150.16 ± 29.7 126.53 ± 39.25 0.002 HDL 49.22 ± 8.24 44.98 ± 4.65 0.004 TG 164.91 ± 37.58 160.62 ± 46.16 0.630 FBS 103.67 ± 26.61 126.73 ± 37.26 0.001 EF% 56.76 ± 9.57 45.04 ± 13.37 0.000 Abnormal ECG 22(48.9% 35(77.8%) 0.004 CAD- coronary artery disease, HTN-hypertension, DM- diabetes mellitus, DL dyslipidemia, PVD- peripheral vascular disease, CVA- cerebrovascular accident, HF- heart failure, PCI- percutaneous coronary intervention, CABG- coronary artery bypass graft, SBP- systolic blood pressure, DBP- diastolic blood pressure, Hb- hemoglobin, LDL- low density lipoprotein, HDL- high density lipoprotein, TG- triglycerides, FBS- fasting blood sugar, EF- ejection fraction. Table 2: Multivariate Logistic regression of selected variable for prediction of coronary tortuosity. B S.E. Wald Df Sig. Exp (B) 95% C.I Male -1.274 .939 1.840 1 .175 .280 .044 - 1.762 HTN absent -1.445 .815 3.142 1 .076 .236 .048 - 1.165 Non Diabetic 2.373 .959 6.120 1 .013 10.7 32 1.637 – 70.344 Non smoker 2.401 1.222 3.861 1 .049 11.0 36 1.006 – 121.054 Raised LDL .070 .021 11.723 1 .001 1.07 3 1.031 – 1.117 CAD absent 1.380 1.244 1.232 1 .267 3.97 7 .348 – 45.506 HTN- hypertension, LDL- low density lipoprotein, CAD- coronary artery disease. Table 3: shows Distribution of Tortuosity in coronary arteries. ARTERY FREQUENCY (n=45) LAD 03(6.6%) LCX 16(35.5%) LAD & LCX 19(42.2%) RCA 01(2.2%) LAD & RCA 01(2.2%) LCX & RCA 01(2.2%) LAD,LCX & RCA 03(6.6%) LAD- left anterior descending, LCX- left circumflex, RCA- right coronary artery. Figure 2: Flow chart showing distribution of study group patients into CT and NCT group and their further four subgroups. CAG- coronary angiography, CT- coronary tortuosity, NCT- noncoronary tortuosity, CAD- coronary artery disease.
  • 4. Clinical Profile of Patients with Coronary Tortuosity and its Relation with Coronary Artery Disease Gupta et al. 069 DISCUSSION The prevalence of coronary tortuosity in the present study was 20.1%. Study done by Li Y et al. (2011) and El Tahlawi M et al (2016) showed prevalence of 39.1% and 37.3% respectively. This difference is likely due to higher mean age in these studies as compared to present study. Advanced age has been associated with increased incidence of CT (Pancera P et al, 2000). In the present study the mean age of patients in CT group was 57.38 ± 9.43 years and females dominated the group with a prevalence of 64.4%. While in the NCT group the mean age was 56.64 ± 11.13 years and males constituted 82.3% of this group. Female sex, hypertension and raised LDL was associated with increased incidence of CT. Hemodynamic forces have key role in modulation of vascular structure. Arteries may become tortuous due to increased pressure and reduced axial strain in an elastic cylindrical arterial model (Han HC, 2012). So close association between hypertension and CT is expected and CT might be one of the forms of arterial remodeling response to hypertension due to increased coronary pressure and blood flow. Increased incidence of CT in females as compared to males may be due to smaller cardiac size in females and coronary tortuosity decreases with cardiac enlargement (Hutchins GM et al, 1977). Yang Li et al. (2011) and Groves SS et al. (2009) also found increased incidence of CT in females and hypertensive patients. There have been conflicting reports regarding the correlation of coronary tortuosity and coronary artery disease. Previous studies have shown both negative (Li Y et al, 2011; Groves SS et al, 2009; Serdar Turkmen et al, 2013) and positive (El Tahlawi M et al, 2016; Cunningham KS et al, 2005; Davutoglu V et, 2012) correlation between CT and CAD. In the present study we observed that in CT group, 42.2% patients had CAD, whereas in NCT group 66.7% patients had CAD (p=0.002). So, we observed a negative correlation between CT and CAD. Local hemodynamic factors like low shear stress plays an important role in the development of atherosclerosis and plaque stability through modulation of endothelial cell function and gene expression, while high shear stress is associated with protection from atherosclerosis (Chatzizisis YS et al, 2007). So, the negative relationship between CT and CAD may be explained by the protective effect of high shear stress caused by CT. This may be one of the causes for lower incidence of CAD in female. In a study of coronary tortuosity by Serdar Turkmen et al. (2013), a negative correlation between CT and severity of CAD was found. They used a novel numeric scoring system for quantitative assessment of CT. They defined the CT score as the sum of all bends on the main shafts of the major epicardial arteries. They found less CT in the males, smokers, diabetics and CAD patients. In a study by El Tahlawi M et al. (2016), frequency of coronary tortuosity and coronary artery calcium (CAC) scoring was observed in patients with chronic stable angina using computed tomography coronary angiography. Definition used for CT was similar to the present study. They found higher CAC score in the CT group (p value < 0.05) as compare to NCT group revealing that, CT may be associated with subclinical atherosclerosis in the absence of obstructive CAD. CT may be associated with the non- atherosclerotic cause of CAD like spontaneous coronary artery dissection (SCAD), especially in females. In a study of 246 patients of SCAD by Eleid MF et al. (2014), tortuosity was a common finding in patients presenting with their first SCAD episode. Tortuosity was most commonly observed in the left circumflex artery (LCX), followed by the left anterior descending (LAD), and the right coronary artery (RCA). In the present study also, most patients had CT in left circumflex artery followed by LAD and RCA. Possible explanation for this higher prevalence of coronary tortuosity in LCX could be because of its natural course and higher hemodynamic stress being tackled by this artery. In our study, 26 patients had only coronary tortuosity (CT only group). The mean age of patients in CT only group was 55.31+ 8.8 years. In this CT only group, 69.2% were females and 73.2% patients were having hypertension. This is in agreement with previous studies which showed increased incidence of CT in females and hypertensive patients (Li Y et al, 2011; Groves SS et al, 2009; Davutoglu V et al, 2012). Prevalence of diabetes mellitus, dyslipidemia, smokers and patients with heart failure was very low. Out of these 26 patients, 23(88.5%) patients presented with chronic stable angina (CSA), one patient had unstable angina and 12(46.1%) patients had abnormal ECG at presentation. Out of 23 patients, who presented with chronic stable angina, 11 patients had positive treadmill test (TMT) for inducible ischemia, 2 patients showed reversible myocardial perfusion defect on stress myocardial perfusion imaging and 2 patients had abnormal regional wall motion abnormality on transthoracic echocardiography. So out of 23 patients presenting with chronic stable angina, we had 15 patients with objective evidence of myocardial ischemia but angiography showed only CT without significant coronary artery stenosis. There are few case reports in literature about coronary tortuosity as a cause of myocardial ischemia in patients with chronic stable angina. Zegers ES et al. (2007) reported three cases of angina with abnormal stress test and angiography showing CT without fixed stenosis. They put forward the hypothesis that coronary tortuosity leads to increase in energy loss, resulting in a reduction in coronary perfusion pressure distal to CT segment, ultimately leading to ischemia (Gijsen FJ et al, 1999). Abdar Esfahani M et al. (2012) reported that CT can cause CSA and found that its severity increases with severity of CT. DÖRTLEMEZ Ö et al. (1993) found significant decrease in systolic and diastolic coronary flow velocity distal to CT segment using intracoronary Doppler tipped guide wire. Li Y et al. (2012)
  • 5. Clinical Profile of Patients with Coronary Tortuosity and its Relation with Coronary Artery Disease Int. J. Cardiol. Cardiovasc. Res. 070 found that, CT results in significant decrease in coronary blood pressure as compare to NCT group. They found more decrease in coronary pressure with increasing CT angle and number of CT curves. Xie X et al. (2013) did a computational fluid dynamics (CFD) study to evaluate the impact of CT on the coronary blood supply. They concluded that CT has minor impact on coronary blood flow at rest; while during exercise, patients with CT had ineffective coronary auto-regulation, leading to myocardial ischemia. One patient in CT only group presented with unstable angina, Chesnutt JK et al. (2013) found that tortuosity of microvessel triggers platelet activation and thrombus formation. This may be responsible for acute coronary syndrome in CT only patient. It is clear from the present study that CT without significant CAD can produce clinical symptom like chronic stable angina with objective evidence of myocardial ischemia. Present study showed negative correlation between CT and CAD. Previous studies have shown that CT may be associated with subclinical atherosclerosis (El Tahlawi M et al, 2016; Davutoglu V et al, 2012). We propose that patient with chronic stable angina and coronary tortuosity without significant CAD should be treated as CAD patients with antiplatelets, statins and antianginal drugs. CONCLUSIONS Coronary tortuosity is a common angiographic finding. Left circumflex is the most common coronary artery with tortuosity. Coronary tortuosity is commonly found in females and hypertensive patients. Patients with coronary tortuosity have low incidence of CAD but, can present with chronic stable angina and objective evidence of myocardial ischemia in the absence of significant obstructive coronary artery disease. Isolated coronary tortuosity in patients with chronic stable angina is often ignored and is labeled as normal coronaries. These patients remain symptomatic with angina with multiple health care visits, affecting their quality of life. These patients should be offered treatment with antiplatelets, statins and antianginal drugs to improve their quality of life. Clinical Implication Coronary artery tortuosity without significant obstructive coronary artery disease should be recognized as a cause of chronic stable angina. These patients should be given treatment with anteplatelets, statins and antianginals, which may result in marked improvement in symptoms, thereby improving the quality of life. Funding: None. Conflicts of Interest: The authors declare no conflict of interest. REFERENCES Abdar Esfahani M, Farzamnia H, Nezarat N. Chronic stable angina patients with tortuous coronary arteries: Clinical symptoms and risk factors. ARYA Atheroscler. 2012;7: S115-8. Cunningham KS, Gotlieb AI. 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  • 6. Clinical Profile of Patients with Coronary Tortuosity and its Relation with Coronary Artery Disease Gupta et al. 071 caliber of normal human coronary arteries. American heart journal. 1977;94(2):196-202. Jakob M, Spasojevic D, Krogmann ON, Wiher H, Hug R, Hess OM. Tortuosity of coronary arteries in chronic pressure and volume overload. Catheterization and cardiovascular diagnosis. 1996;38(1):25-31. Lloyd-Jones D, Adams RJ, Brown TM, et al. Heart disease and stroke statistics—2010 update A report from the American Heart Association. Circulation. 2010; 121(7): e46-215. Li Y, Shen C, Ji Y, Feng Y, Ma G, Liu N. Clinical implication of coronary tortuosity in patients with coronary artery disease. PloS one. 2011;6(8): e24232. Li Y, Shi Z, Cai Y, et al. Impact of coronary tortuosity on coronary pressure: numerical simulation study. PloS one. 2012;7(8): e42558. Pancera P, Ribul M, Presciuttini B, Lechi A. Prevalence of carotid artery kinking in 590 consecutive subjects evaluated by Echo color doppler. Is there a correlation with arterial hypertension? Journal of internal medicine. 2000;248(1):7-12. Serdar Turkmen, Zekeriya Kucukdurmaz, Caglar E Cagliyan, et al. Total tortuosity score: correlation with coronary artery disease and novel evaluation of possible risk factor. TGKD Cilt 17, Sayi kasim 2013:115-121. Turgut O, Yilmaz A, Yalta K, et al. Tortuosity of coronary arteries: an indicator for impaired left ventricular relaxation? The international journal of cardiovascular imaging. 2007;23(6):671-7. Xie X, Wang Y, Zhu H, Zhou H, Zhou J. Impact of coronary tortuosity on coronary blood supply: a patient-specific study. PloS one. 2013;8(5): e64564. Yang LI, Nai-feng LI, Zhong-ze GU, et al. Coronary tortuosity is associated with reversible myocardial perfusion defects in patients without coronary artery disease. Chin Med J. 2012;125(19):3581-3. Zhang XH, Lu ZL, Liu L. Coronary heart disease in China. Heart. 2008;94(9):1126-31. Zegers ES, Meursing BT, Zegers EB, Ophuis AO. Coronary tortuosity: a long and winding road. Netherlands Heart Journal. 2007;15(5):191-5. Accepted 18 August 2018 Citation: Gupta A, Panda P, Sharma YP, Mahesh A, Sharma P, Mahesh NK (2018). Clinical Profile of Patients with Coronary Tortuosity and its Relation with Coronary Artery Disease. International Journal of Cardiology and Cardiovascular Research, 4(2): 066-071. Copyright: © 2018 Gupta et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are cited.