JCDR - Register at Journal of Clinical and Diagnostic Research
Journal of Clinical and Diagnostic Research, ISSN - 0973 - 709X
Internal Medicine Section DOI : 10.7860/JCDR/2020/45770.14269
Year : 2020 | Month : Dec | Volume : 14 | Issue : 12 Full Version Page : OC01 - OC05

Peripheral Artery Disease in Patients Presenting with Acute Coronary Syndrome in Hill Population of Northern India

Nagaraju Naik Banavath1, Mohd Iqbal Dar2, Mohd Iqbal Wani3, Aamir Rashid4, Khursheed A Khan5

1 Senior Resident, Department of Cardiology, SKIMS, Soura, Srinagar, Jammu and Kashmir, India.
2 Senior Resident, Department of Cardiology, SKIMS, Soura, Srinagar, Jammu and Kashmir, India.
3 Senior Resident, Department of Cardiology, SKIMS, Soura, Srinagar, Jammu and Kashmir, India.
4 Assistant Professor, Department of Cardiology, SKIMS, Soura, Srinagar, Jammu and Kashmir, India.
5 Professor, Department of Cardiology, SKIMS, Soura, Srinagar, Jammu and Kashmir, India.


NAME, ADDRESS, E-MAIL ID OF THE CORRESPONDING AUTHOR: Mohd Iqbal Dar, Room No. f04, Old Sr Hostal, SKIMS, Soura, Srinagar, Jammu and Kashmir, India.
E-mail: darmohdiqbal@yahoo.in
Abstract

Introduction

Acute Coronary Syndrome (ACS) and Peripheral Artery Disease (PAD) represent the serious presentations of the atherosclerotic disease spectrum. PAD due to atherosclerotic disease can lead to significant morbidity and mortality with significant medical and economic burden.

Aim

To study the prevalence of PAD in patients presenting with ACS in the Hill population of Northern India.

Materials and Methods

Patients presenting with ACS, with acute chest pain, Electrocardiogram (ECG) changes and elevated troponins were enrolled in the study. The presence of PAD was assessed with MESI Ankle Branchial Measuring Device (MESI ABPI MD® Slovenia EU) system which uses plethysmographic sensors with an inbuilt software that automatically calculates ABI with accuracy. Patients with ABI <0.91 were further evaluated by Computed Tomography (CT) Angiography of lower limb vessels.

Results

A total of 288 patients were included in the study. There were 238 (82.6%) males and 50 (17.4%) females. Majority of patients had hypertension (214, 74.3%) as the risk factor. ST-Elevation Myocardial Infarction (STEMI) was seen in 197 (68.4%) and Non-ST Elevation Myocardial Infarction (NSTEMI) in 91 (31.6%). Coronary angiography was done in 240 patients. Single vessel disease was seen in 135 (56.2%), double vessel disease in 69 (28.8%) and triple vessel disease in 36 (15%) cases. Out of overall 288 patients 9 (3.12%) had borderline ABI (ABI- >0.9 and ≤1.0) and 4 (1.38%) had abnormal ABI (ABI <0.9). CT angiography of 3 out of 4 patients with ABI <0.9 showed significant atherosclerosis of lower limb vessels.

Conclusion

There was very low prevalence of PAD with ACS in this study population.

Keywords

Introduction

The Peripheral Artery Disease (PAD) generally refers to the vascular disease of an upper or lower extremity associated with decreased blood supply leading to symptoms like claudication and gangrene [1]. Atherosclerosis is the most common aetiology, but other conditions presenting with similar complaints are vasculitis, vasospasm, venous thrombosis, venous insufficiency and lymphatic disorders [2]. This disorder is most commonly asymptomatic and some patients present for the first time with a threatened ischemic limb or a nonhealing ulcer [3].

PAD is one of the most underreported diseases among the spectrum of atherosclerosis because of the low prevalence of the symptomatic disease or atypical nature of presenting symptoms and most commonly affecting elderly population with other comorbidities [4].

ACS represents the acute catastrophic presentation of the coronary atherosclerotic disease process. PAD has been found to be associated with increased risk of coronary, cerebral and carotid atherosclerotic disease which is independent of traditional atherosclerotic risk factors like smoking, diabetes and hypertension [5-7]. Additionally, impaired mobility in PAD masks the signs of early coronary artery disease like angina pectoris and patients usually present with advanced coronary atherosclerosis, adversely affecting the outcome of the ACS as depicted by multiple studies [8,9].

There are wide geographical and racial variations in the prevalence and outcome of PAD worldwide. High prevalence of PAD is seen in western population with poor outcomes in the black population than in white population [10]. Low PAD prevalence was seen in Middle Eastern population [11]. Data on Indian population is scarce with one study from southern India showing a high prevalence of PAD in the study population [12]. Hence, this study was aimed to understand the prevalence of PAD in patients presenting with ACS in a hill population of Northern India.

Materials and Methods

Study Design

This study was an observational cross-sectional study conducted over a period of two years at Sheir-i-Kashmir Institute of Medical Sciences Srinagar, which is the lone Tertiary Care Centre of Kashmir. The ethical clearance for the study design was sought and granted by the Institutional Ethical Committee (IEC) and informed consent was obtained from patients/relatives for utilisation of data for research purposes (Ref no. IEC/SKIMS protocol101/2020).

Participants

The recruitment of patients for this study took place between February 2018 to January 2020. Patients reporting to this centre with a diagnosis of an ACS (STEMI, NSTEMI and Unstable Angina) based on American College of Cardiology (ACC)/American Heart Association (AHA) diagnostic criteria were considered for this study [13,14]. The acceptable sample size for this study with a confidence interval of 99% and a margin of error 10% was 166.

Inclusion criteria: All consenting patients presenting as ACS were included in the study.

Exclusion criteria: Patients with deranged Kidney Function Tests, contrast allergy, denying consent for participation or coronary angiography, known PAD and patients presenting with cardiogenic shock or other structural complication were excluded from the study.

Patient Evaluation

1. Basic and coronary evaluation

Patients were evaluated for the presence of risk factors of atherosclerosis. History of smoking, diabetes mellitus, PAD and family history of coronary artery disease was noted. Patients were screened for the presence of dyslipidemia and diabetes mellitus by lipid profile testing and fasting blood sugars/HbA1c respectively according to ADA guidelines [15]. Blood sample for Lipid profile was taken on admission or within 48 hours of admission and prior to initiation of high dose statin therapy, as both of these factors (postinfraction duration >48 hours and high dose statins) cause significant alteration in lipid metabolism [16].

Definitions of risk factors:

Diabetes- A fasting glucose of >126 mg/dL (>7 mmol/L) or an HbA1c of >6.5%, or with a RBG >200 mg/dL and with symptoms of hyperglycaemia [15].

Hypertension- A Systolic Blood Pressure (SBP) >140 mmHg and Diastolic Blood Pressure (DBP) >90 mmHg and or already on treatment for the same [17].

Dyslipidemia- defined as any one of the following: serum total cholesterol ≤200 mg/dL, serum LDL cholesterol ≤130 mg/dL, serum HDL cholesterol <40 mg/dL, in men or <50 mg/dL in women, or serum triglycerides ≤150 mg/dL [18].

Body Mass Index (BMI)- defined as: normal (18.0-22.9 kg/m2), overweight (23.0-24.9 kg/m2), or obesity (≤25 kg/m2) [19].

Patients included in the study underwent baseline 2D Echocardiography and coronary angiography if no contraindication to coronary angiography was present. Patients were subsequently revascularised as per ACC/AHA recommendation.

2. Evaluation of PAD

Ankle Brachial Index (ABI) assessment was performed during hospitalisation. ABI assessment was done using MESI ABPI MD® Slovenia EU. This device has three cuffs that are to be attached to the patient’s extremities all at the same time and the device uses a PADsenseTM algorithm which controls the inflation and deflation process of the cuffs. It works on plethysmographic sensors with an inbuilt software that automatically calculates ABI with accuracy. This device allows the operator to assess both the limbs simultaneously with no time delay contrast to handheld Doppler probe machines which takes longer duration for assessment of the same in one limb. This device was studied in various studies which have given an overall sensitivity of 85% and a specificity of 95% with good reproducibility to this device [20]. An ABI value >1.0 and ≤1.4 was considered normal, Abnormal high ABI >1.4, Borderline ABI >0.9 and ≤1.0, Abnormal low ABI ≤0.9.

All patients with an ABI <0.9 were subjected to CT angiography after 3 weeks for the assessment of PAD. Those patients found to have significant obstructive disease amenable for revascularisation were treated as per the ACC/AHA guidelines for the management of PAD.

Statistical Analysis

All the data was initially compiled in Microsoft Excel and then exported to SPSS. Baseline categorical data was described using numbers and percentages, continuous data was described using mean and standard deviation. Student’s Independent t-test was employed for comparing continuous variables. The p-value ≤0.05 was considered significant. Statistical analysis was done using SPSS Version 23.0.

Results

A total of 288 patients were included in the study. Baseline demographics and clinical features of the study population are given in [Table/Fig-1].

Clinical features of the study population. Continuous data was described using Mean and Standard Deviation and Student’s Independent t-test was employed for comparing continuous variables.

ParameterACS (n=288) (%)STEMI (n=197) (68.4%)NST-ACS (n=91) (31.6%)p-value
Age (Years)<60 years141 (49.0%)90 (45.7%)51 (56.0%)0.461
≤60 years147 (51.0%)107 (54.3%)40 (44.0%)
Mean±SD57.4±11.3657.9±11.3256.4±11.41
GenderMale238 (82.6%)168 (85.3%)70 (76.9%)0.210
Female50 (17.4%)29 (14.7%)21 (23.1%)
BMI (kg/m2)18-22.981 (28.1%)58 (29.4%)23 (25.3%)0.582
23-24.996 (33.3%)63 (32.0%)33 (36.3%)
≤25111 (38.5%)76 (38.6%)35 (38.5%)
Mean±SD24.53±2.7524.51±2.6724.57±2.93
Smoking statusSmoker207 (71.9%)143 (72.6%)64 (70.3%)0.761
Non-smoker81 (28.1%)54 (27.4%)27 (29.7%)
Diabetes mellitusPresent101 (35.1%)68 (34.5%)33 (36.3%)0.482
Absent187 (64.9%)129 (65.5%)58 (63.7%)
HypertensionPresent214 (74.3%)141 (71.6%)73 (80.2%)0.118
Absent74 (25.7%)56 (28.4%)18 (19.8%)
Dyslipidemia (n=204)Present194 (95.1%)133 (96.4%)61 (92.4%)0.363
Absent10 (4.9%)5 (3.6%)5 (7.6%)
Family history of CADPresent26 (9.0%)18 (9.1%)8 (8.8%)0.289
Absent262 (91.0%)179 (90.9%)83 (91.2%)

NST-ACS: Non ST elevation-acute coronary syndrome; CAD: Coronary artery disease


Lipid profile on admission or within 24 hours of myocardial infarction and prior to high dose statin therapy was done in 204 patients. Fifty four patients had received high dose statin therapy in peripheral centres prior to referral to this centre and 30 patients presented more than 48 hours after myocardial infarction and lipid profile of these patients was not considered in the final lipid data analysis. Out of 204 patients with lipid profile considered in the study, 95.1% (n=194) had at least one form of dyslipidemia as shown in [Table/Fig-2].

Lipid profile of the study population.

ParameterLevelsN (%)
TC>200 mg/dL30 (14.7)
<200 mg/dL174 (85.3)
LDL>130 mg/dL26 (12.7)
<130 mg/dL178 (87.3)
HDL<40 mg/dL (M) + <50 mg/dL (F)176 (86.3)
>40 mg/dL (M) + >50 mg/dL (F)28 (13.7)
TG>150 mg/dL70 (34.3)
<150 mg/dL134 (65.7)

TC: Total cholesterol; LDL: Low density lipoprotein; HDL: High density lipoprotein; TG: Triglycerides; M: Males; F: Females


Out of 138 patients of STEMI with lipid profile, dyslipidemia was noted in 96.4% (n=133) and out of 66 patients of NST-ACS with lipid profile, 92.4% (n=61) patients were having dyslipidemia.

Coronary Angiogram (CAG) could be done in only 240 patients due to financial constraints and other contraindications. The CAG profile, syntax score and echocardiographic features of the study population are given in [Table/Fig-3].

Coronary angiographic profile, Echo (EF) and syntax score of the patient population.

ParameterACSSTEMINSTEMI
Echo (EF) Mean±SD52.5±11.28 (n=288)50.2±10.03 (n=197)57.4±12.24 (n=91)
Syntax score Mean±SD7.87±7.8 (n=241)7.09±6.49 (n=167)9.62±9.97 (n=74)
CAG done24016674
SVD135 (56.2%)99 (73.3%)36 (26.7%)
DVD69 (28.8%)48 (69.5%)21 (30.5%)
TVD36 (15%)19 (52.8%)17 (47.2%)

ACS: Acute coronary syndrome; STEMI: ST-elevation myocardial infarction; NSTEMI: Non-ST elevation myocardial infarction; SVD: Single vessel disease; TVD: Triple vessel disease


Of the 288 patient population, 13 (4.5%) patients had an abnormal ABI value on presentation. Of this 4 (1.38%) had an ABI <0.9 suggestive of definitive PAD and 9 (3.12%) had ABI value between 0.9 and 1.0 suggestive of borderline PAD disease. Percentage of the elderly population (age group ≤60 years) with an abnormal ABI value was 3.4% (5 out of 147) (p=0.391). Of the 238 male population 9 (3.7%, n=238) patients had abnormal ABI values and out of 50 female population 4 (8%, n=50) had abnormal ABI values with a male to female ratio of 2.25:1 for abnormal ABI value (p=0.192). The clinical and biochemical profile of patients with and without PAD is given in the [Table/Fig-4].

Clinical and biochemical profile of patients with and without PAD.

Demographic variablesNon-PAD (n=275) (%)PAD (n=13) (%)p-value
Age (Years)(n=288)<60133 (48.4)8 (61.5)0.391
≤60142 (51.6)5 (38.5)
Mean±SD57.5±11.3554.8±11.49
Gender(n=288)Male229 (83.3)9 (69.2)0.192
Female46 (16.7)4 (30.8)
BMI(n=288)18-22.976 (27.6)5 (38.5)0.688
23-24.993 (33.8)3 (23.1)
≤25106 (38.5)5 (38.5)
Mean±SD24.54±2.7424.23±3.06
Smoking status(n=288)Smoker198 (72.0)9 (69.2)0.828
Non-smoker77 (28.0)4 (30.8)
Hypertension(n=288)Present205 (74.5)9 (69.2)0.668
Absent70 (25.5)4 (30.8)
Diabetes(n=288)Present94 (34.2)7 (53.8)0.149
Absent181 (65.8)6 (46.2)
Dyslipidemia(n=204)Present184 (94.8)10 (100)0.462
Absent10 (5.2)0 (0)
Type of ACS(n=288)STEMI185 (67.3)12 (92.3)0.058
NSTEMI ACS90 (32.7)1 (7.7)
Family history of CAD(n=288)Present25 (9.1)1 (7.7)0.863
Absent250 (90.9)12 (92.3)
Echo (EF)(n=288)Mean±SD52.4±11.1953.5±13.430.743
Syntax score(n=288)Mean±SD7.83±7.868.54±6.890.751
Lipid profile Mean±SD(n=204)Cholesterol150.5±47.34152.1±72.270.921
LDL64.8±50.2373.7±61.460.534
HDL32.5±8.9328.2±5.590.137
Triglycerides (TG)151.4±114.81198.1±167.010.221
CAG(n=240)SVD128 (56.4)7 (53.8)0.783
DVD68 (30)1 (7.7)0.476
TVD31 (13.7)5 (38.5)0.028

Of the 13 patients with abnormal ABI, 3 patients with an ABI <0.9 undergone CT angiography of both lower limbs and rest of the patients were kept on medical follow-up for symptoms and progression of the disease. The fourth patient with ABI <0.9 was lost to follow-up and could not turn up for lower limb CT angiography. The CT angiography and the baseline profile of the patients with ABI <0.9 is given in [Table/Fig-5].

Profile of patients with ABI <0.91.

ParameterPatient 1Patient 2Patient 3Patient 4
Age (Years)50495065
SexMaleMaleFemalemale
SmokingYesYesYesYes
HTNNoYesYesYes
DMNoYes (on treatment)Yes (on treatment)No
DyslipidaemiaYesyes-Yes
BMI28.226.421.820.4
Family history of CADNoNoNoNo
TC (mg/dL)200119-137
LDL (mg/dL)13879-96
HDL (mg/dL)4023-26
TG (mg/dL)19090-117
Type of ACSIWMIAWMIAWMIIWMI
EF50%40%40%77%
CAG patternSVDSVDSVDSVD
Syntax11552
ABI (right/left)1.02/0.710.68/1.020.89/1.050.80/1.16
CT angio lower limbsComplete occlusion of distal SFA with distal collateral formation, CA++, calcified plaques in bilateral EIA and origins of profunda femorisDiffuse atherosclerotic narrowing of right popliteal artery and right posterior tibial artery with atherosclerotic disease without narrowing in B/L CFA/SFA.Not doneRight CFA showing discrete Plaque, with distal diffuse plaguing bilaterally with narrowing

HTN: Hypertension; DM: Diabetes mellitus; BMI: Body mass index; EF: Ejection fraction; TC: Total cholesterol; LDL: Low density lipoprotein; HDL: High density lipoprotein; TG: Triglycerides


Discussion

This study, conducted at this tertiary care center of the state was designed to evaluate the presence of peripheral artery in patients presenting as ACS. A total of 288 patients were includes in the study. Males constituted the majority of the study population. Dyslipidemia was the commonest risk factor identified followed by hypertension, smoking and diabetes. More than 2/3rd of the patients of ACS in the study presented as STEMI and the rest presented as NST-ACS.

Demographics and Risk Factors

The baseline characteristics of the study population were very similar to the characteristics of the study group from CREATE [21] registry, India, except for the higher prevalence of HTN and smoking habit among this study population. Compared to western data from GRACE registry [22], this study population had lower mean age group for occurrence of ACS, lower mean BMI values, higher prevalence of smoking, HTN, diabetes and higher occurrence of STEMI compared to NST-ACS. Similarly, the current study population compared to Gulf RACE registry [23], had lower mean BMI values, higher prevalence of smoking, HTN, diabetes and higher occurrence of STEMI compared to NST-ACS despite having similar mean ages for the occurrence of ACS.

In this study population, the occurrence of STEMI ACS was found to be higher compared to NST-ACS. The mean age of these groups of the population was 57.9 and 56.4 years, respectively. Males were predominant in both STEMI and NST-ACS groups. The mean BMI values of both groups were also similar. Population with obesity were also similar in both groups. Both the groups had the similar number of patients with a history of smoking, diabetes, dyslipidemia, family history of CAD but with more number of patients with hypertension (71.6% vs 80.2%; p=0.118) in NST-ACS group compared to STEMI group.

This baseline risk profile of STEMI and NST-ACS populations is similar to CREATE registry population, except for higher smoker and hypertensive patients in the current study. Prevalence of diabetes was higher in this STEMI population than in CREATE registry but are similar in NST-ACS group. This study data when compared to western Global Registry of Acute Coronary Events (GRACE) [22] and Manejo del Síndrome Coronario Agudo. Registro Actualizado (MASCARA) [24] registries had more STEMI patients than NST-ACS, lower mean age for occurrence of ACS, more smokers, more hypertensives and lower mean BMI values for both STEMI and NST-ACS groups. STEMI population in this study had more diabetic population compared to western registries. When compared to middle-east Gulf RACE registry [23], STEMI and NST-ACS groups in the current study population had more smoker and hypertensive patients and a lower mean BMI values but had similar mean age at presentation of ACS.

Dyslipidemia in the current study was noted in >90% of study subjects. The most common abnormality noted was low HDL followed by elevated TG, elevated total cholesterol levels and elevated LDL levels. This is in contrast to western data [25] where TC and LDL were found to be independent factors for CV events.

Coronary Status

In this study, CAG of the STEMI population had a higher percentage of SVD and DVD compared to NST-ACS group, but there was not much difference for the occurrence of TVD in both the groups. One of the registry data from Spain, MASCARA [24], compared the angiographic profiles of patients of ACS and had shown more prevalence for all the three profiles in STEMI compared to NST-ACS.

Coronary Artery Disease with vs without PAD

The mean age of the patient population of ACS with PAD in this study population was the same as the mean of ACS population without a PAD. This is in contrast with other registry data available [22], where the mean age of patients with PAD was higher than those without a PAD on presentation. The male population was higher in this study similar to other registry data but its incidence was equally higher in ACS group suggestive of no statistical significance. BMI values were similar in both groups of PAD and nonPAD, similar to other studies [22,26] suggestive of no clinical influence of it on the association of PAD in an ACS.

Tobacco abuse was also similar in both groups and similar to other registry [22] suggesting no statistical significance. The occurrence of HTN was similar in both groups in this study suggestive of no statistical significance which contrasts the western data [27] where there was a higher occurrence of HTN in patients with concomitant PAD. However, the Chinese registry data [28] also has a similar occurrence of HTN in both groups of PAD and nonPAD, similar to the current study. There was a higher occurrence of diabetes in patients with PAD compared to those without a PAD (though not statistically significant) similar to all other registries where there was a significant association of DM for the occurrence of PAD [26,27].

There was no association between family history of CAD and incidence of PAD and this characteristic was the least to be reported even for ACS in this study. The definition of dyslipidemia was different for different registries with most of them addressing it for abnormal higher levels of lipid profile [21-23]. Role of HDL was assessed less in most of these registries. In this study, a low HDL level was also considered as part of dyslipidemia, which increased the number of patients having any one of this abnormality to more than 90% for both the groups. When assessed individually, there was no independent association for any of the lipid parameter for the occurrence of PAD in an ACS patient, in contrast to other data that have shown an independent association between total cholesterol and LDL levels [27,28]. However, there was an occurrence of lower levels of HDL cholesterol among patients with PAD than patients without a PAD, though there was no statistically significant association with it.

Association

In this study, the authors tried to understand the association of pattern of coronary artery disease in presence of associated PAD among patients of ACS. In this study we could establish an association between the pattern of triple vessel disease and PAD (p=0.028) similar to multiple other studies across the world [29,30]. However, a Japanese study has shown a higher association of TVD with the increasing number of extra-cardiovascular lesions [30]. This study, first of its kind in this study population showed an overall low prevalence of PAD associated with ACS.

Limitation(s)

The main limitation of the study is that it was a single centre study. A multicenter study with larger sample size is needed to validate the findings.

Conclusion(s)

This study concludes that in this study population STEMI is more common than NSTEMI. In this study, population of ACS, significant lower ABI values (<0.9) for a definite PAD were very low compared to many studies across the globe done in the same scenario of ACS presentation. Furthermore, PAD is associated with triple vessel disease and overall incidence of PAD with ACS is very low in this study population.

NST-ACS: Non ST elevation-acute coronary syndrome; CAD: Coronary artery diseaseTC: Total cholesterol; LDL: Low density lipoprotein; HDL: High density lipoprotein; TG: Triglycerides; M: Males; F: FemalesACS: Acute coronary syndrome; STEMI: ST-elevation myocardial infarction; NSTEMI: Non-ST elevation myocardial infarction; SVD: Single vessel disease; TVD: Triple vessel diseaseHTN: Hypertension; DM: Diabetes mellitus; BMI: Body mass index; EF: Ejection fraction; TC: Total cholesterol; LDL: Low density lipoprotein; HDL: High density lipoprotein; TG: Triglycerides

References

[1]Criqui MH, Langer RD, Fronek A, Feigelson HS, Klauber MR, McCann TJ, Mortality over a period of 10 years in patients with peripheral arterial disease N Engl J Med 1992 326:381-86.10.1056/NEJM1992020632606051729621  [Google Scholar]  [CrossRef]  [PubMed]

[2]Carman TL, Fernandez BB, A primary care approach to the patient with claudication Am Fam Physician 2000 61(4):1027-32.  [Google Scholar]

[3]Smith GD, Shipley MJ, Rose G, Intermittent claudication, heart disease risk factors, and mortality: The Whitehall Study Circulation 1990 82:1925-31.10.1161/01.CIR.82.6.19252242518  [Google Scholar]  [CrossRef]  [PubMed]

[4]Newman AB, Sutton-Tyrrell K, Vogt MT, Kuller LH, Morbidity and mortality in hypertensive adults with a low ankle/arm blood pressure index JAMA 1993 270:487-89.10.1001/jama.1993.035100400910358147959  [Google Scholar]  [CrossRef]  [PubMed]

[5]Shah AM, Banerjee T, Mukherjee D, Coronary, peripheral and cerebrovascular disease: A complex relationship Journal of the Indian Medical Association 2010 108(5):292-96.  [Google Scholar]

[6]Newman AB, Shemanski L, Manolio TA, Anklearm index as a predictor of cardiovascular disease and mortality in the cardiovascular health study: The cardiovascular health study group Arteriosclerosis, Thrombosis, and Vascular Biology 1999 19:538-45.10.1161/01.ATV.19.3.53810073955  [Google Scholar]  [CrossRef]  [PubMed]

[7]Huelmos A, Jiménez J, Guijarro C, Belinchon JC, Puras E, Sanchez C, Underrecognized peripheral arterial disease in patients with acute coronary syndrome: Prevalence of traditional and emergent cardiovascular risk factors Revista Espanola de Cardiologia 2005 58(12):1403-10.10.1016/S1885-5857(06)60747-0  [Google Scholar]  [CrossRef]

[8]Bhatt DL, Peterson ED, Harrington RA, Ou FS, Cannon CP, Gibson CM, Prior polyvascular disease: Risk factor for adverse ischaemic outcomes in acute coronary syndromes European Heart Journal 2009 30(10):1195-202.10.1093/eurheartj/ehp09919339264  [Google Scholar]  [CrossRef]  [PubMed]

[9]Saboureta P, Cacoubb P, Dallongevillec J, Krempfd M, Mase JL, Pinel JF, REACH: International prospective observational registry in patients at risk of atherothrombotic events Results for the French arm at baseline and one year Archives of Cardiovascular Diseases 2008 101:81-88.10.1016/S1875-2136(08)70263-8  [Google Scholar]  [CrossRef]

[10]O’Donell TFX, Powel C, Deery S, Darling JD, Hughes K, Giles K, Regional variation in racial disparities among patients with peripheral artery disease J Vasc Surg 2018 68(2):519-26.10.1016/j.jvs.2017.10.09029459014  [Google Scholar]  [CrossRef]  [PubMed]

[11]Al-Thani HA, El-Menyar A, Zubaid M, Rashed WA, Ridha M, Almahmeed W, Peripheral arterial disease in patients presenting with acute coronary syndrome in six middle eastern countries Int J Vascu Med 2011 2011:81590210.1155/2011/81590222220279  [Google Scholar]  [CrossRef]  [PubMed]

[12]Krishnana MN, Geevarb Z, Mohanan PP, Venugopald K, Devika S, Prevalence of peripheral artery disease and risk factors in the elderly: A community based cross-sectional study from northern Kerala, India Indian Heart J 2018 70(6):808-15.10.1016/j.ihj.2017.11.00130580849  [Google Scholar]  [CrossRef]  [PubMed]

[13]Thygesen K, Alpert JS, Jaffe AS, Chaitman BR, Bax JJ, Morrow DA, Fourth universal definition of myocardial infarction Journal of the American College of Cardiology 2018 72(18)10.1016/j.jacc.2018.08.103830153967  [Google Scholar]  [CrossRef]  [PubMed]

[14]Amsterdam EA, Wenger NK, Brindis RG, Casey Jr DE, Ganiats TG, Holmes Jr DR, AHA/ACC guideline for the management of patients with Non-ST-Elevation Acute Coronary Syndromes. A report of the American College of Cardiology/American Heart Association task force on practice guidelines Journal of the American College of Cardiology 2014 64(24)10.1161/CIR.0000000000000134  [Google Scholar]  [CrossRef]

[15]American Diabetes AssociationClassification and diagnosis of diabetes: Standards of Medical Care in Diabetes-2019 Diabetes Care 2019 42(Suppl. 1):S13-28.10.2337/dc19-S00230559228  [Google Scholar]  [CrossRef]  [PubMed]

[16]Aubiniere-Robb L, Dickerson JE, Lipid testing and treatment after acute myocardial infarction: No flags for the flagship Br J Cardiol 2019 26:141-44.10.5837/bjc.2019.04131109735  [Google Scholar]  [CrossRef]  [PubMed]

[17]Chobanian AV, Bakris GL, Black HR, Cushman WC, Green LA, Izzo JL, The Seventh report of the Joint National Committee on prevention, detection, evaluation, and treatment of high blood pressure: The JNC 7 Report JAMA 2003 289:2560-72.10.1001/jama.289.19.256012748199  [Google Scholar]  [CrossRef]  [PubMed]

[18]Executive Summary of The Third Report of The National Cholesterol Education Program (NCEP) Expert Panel on detection, evaluation, and treatment of high blood cholesterol in Adults (Adult Treatment Panel III) JAMA 2001 285:2486-97.10.1001/jama.285.19.248611368702  [Google Scholar]  [CrossRef]  [PubMed]

[19]Misra A, Chowbey P, Makkar BM, Vikram NK, Wasir JS, Chadha D, for Consensus GroupConsensus Statement for diagnosis of obesity, abdominal obesity and the metabolic syndrome for Asian Indians and recommendations for physical activity, medical and surgical management J Assoc Phys India 2009 57:163-70.  [Google Scholar]

[20]Špan M, Geršak G, Millasseau SC, Meža M, Košir A, Detection of peripheral arterial disease with an improved automated device: Comparison of a new oscillometric device and standard Doppler method Vasc Health Risk Manag 2016 12:305-11.10.2147/VHRM.S10653427536125  [Google Scholar]  [CrossRef]  [PubMed]

[21]Xavier D, Pais P, Devereaux PJ, Xie C, Prabhakaran D, Reddy KS, Treatment and outcomes of acute coronary syndromes in India (CREATE): A prospective analysis of registry data Lancet 2008 371(9622):1435-42.10.1016/S0140-6736(08)60623-6  [Google Scholar]  [CrossRef]

[22]Froehlich JB, Mukherjee D, Avezum A, Budaj A, Kline-Rogers EM, López-Sendón J, Association of peripheral artery disease with treatment and outcomes in acute coronary syndromes. The Global Registry of Acute Coronary Events (GRACE) Am Heart J 2006 151(5):1123-28.10.1016/j.ahj.2005.11.00516644349  [Google Scholar]  [CrossRef]  [PubMed]

[23]Zubaid M, Rashed WA, Al-Khaja N, Almahmeed W, Al-Lawati J, Sulaiman K, Clinical presentation and outcomes of acute coronary syndrome in the gulf registry of acute coronary events (Gulf RACE) Saudi Med J 2008 29:251-55.  [Google Scholar]

[24]Ferreira-González I, Permanyer-Miralda G, Marrugat J, Heras M, Cunat J, Civeira E, MASCARA (Manejo del Síndrome Coronario Agudo. Registro Actualizado) study. General finding [published correction appears in Rev Esp Cardiol. 2008;61(11):1228] Rev Esp Cardiol 2008 61(8):803-16.10.1157/1312499118684363  [Google Scholar]  [CrossRef]  [PubMed]

[25]Upadhyay RK, Emerging risk biomarkers in cardiovascular diseases and disorders J Lipids 2015 2015:97145310.1155/2015/97145325949827  [Google Scholar]  [CrossRef]  [PubMed]

[26]Bertomeu V, Morillas P, Gonzalez-Juanatey JR, Prevalence of peripheral arterial disease in patients with acute coronary síndrome (PAMISCA) Investigators. Prevalence and prognostic influence of peripheral arterial disease in patients ≤40 years old admitted into hospital following an acute coronary event Eu J Vasc Endovasc Surg 2008 36(2):189-96.10.1016/j.ejvs.2008.02.00418375154  [Google Scholar]  [CrossRef]  [PubMed]

[27]Inohara T, Piper K, WoJdyla DM, Patel MR, Jones WS, Tricoci P, Incidence, timing and type of first and recurrent ischemic events in patients with and without peripheral artery disease after an acute coronary syndrome Am Heart J 2018 201:25-32.10.1016/j.ahj.2018.03.01329910052  [Google Scholar]  [CrossRef]  [PubMed]

[28]Kang YP, Chen LY, Kang TD, Liu WX, Clinical characteristics and adverse events in acute coronary syndrome patients with a history of peripheral arterial disease Arq Bras Cardiol 2019 113(3):367-72.10.5935/abc.2019015031482945  [Google Scholar]  [CrossRef]  [PubMed]

[29]Morillas P, Quiles J, Cordero A, Impact of clinical and subclinical peripheral arterial disease in mid-term prognosis of patients with acute coronary syndrome Am J Cardiol 2009 104(11):1494-98.10.1016/j.amjcard.2009.07.01419932781  [Google Scholar]  [CrossRef]  [PubMed]

[30]Kodaira M, Sawano M, Kuno T, Numasawa Y, Noma S, Suzuki M, Outcomes of acute coronary syndrome patients with concurrent extra-cardiac vascular disease in the era of transradial coronary intervention: A retrospective multicentre cohort study PLoS One 2019 14(10):e022321510.1371/journal.pone.022321531618228  [Google Scholar]  [CrossRef]  [PubMed]