Kerala Heart Journal -Arumugan


Original article

Kerala Heart J  2016; 6(2):xx-xx. 
 


CLINICAL  AND ANGIOGRAPHIC PROFILE OF CORONARY ARTERY DISEASE AMONG  YOUNG SOUTH INDIAN MALES


Arumugam Chandrakasu1, Avinash Jayachandran1, Chokkalingam Meyyappan1, Ganesh Narayan1, Pradeep Gopinath Nayar1,Ahamed Basha Abdul Bari2

Department of Cardiology1, Department of Physiology2,Chettinad Hospital and Research Institute, Rajiv Gandhi Salai, Kelambakkam, Chennai 603103, India.

Corresponding Author:
Dr Arumugam C,
Department of Cardiology,Chettinad Hospital and Research Institute,
Rajiv Gandhi Salai, Kelambakkam, Chennai 603103, India.Email: arumugamcardio@yahoo.com

 

Abstract

Background : Incidence of Coronary artery disease (CAD) among young adults has been rising across the globe.  However, very few data are available regarding CAD in South Indian population.  Hence, the present study was aimed to analyze clinical profile of CAD in young South Indian males.

Methods: Retrospective study was done in 874 males under 50 years of age who underwent coronary angiography between 2009 to 2013.  Age (Group I - < 40 years, Group II- 40 to 49 years), clinical presentation, risk factors for CAD, angiographic findings and management strategy were analyzed.

Results: Group I patients represented 26.9 % (235) of the population and 73.1% (639) were group II.  All the risk factors except diabetes were more frequently present in group II: family history (p = 0.002), smoking (p <0.0001), alcohol consumption (p < 0.0001), hypertension (p = 0.006), dyslipidemia (p < 0.0001) and diabetes (p =0.07).  There was no significant difference in the clinical presentation between the two groups.  Group I were more often advised for coronary artery bypass surgery whereas group II patients required percutaneous coronary interventions frequently.      

Conclusions: Risk factors for CAD have increased among young males in South India with more extensive disease at a younger age with frequent need for revascularization procedures.  Screening for risk factors should start at an earlier age, and smoking cessation, promotion of physical activities and healthy dietary pattern have to be strongly encouraged to this vulnerable group.

Key Words: Coronary Artery Disease, Young Males, Clinical Profile

Introduction

Incidence of coronary Artery Disease (CAD) is more common in old age,   however, it is frequently observed in young adults in the present day scenario.  Around 10% of documented CAD patients are below 45 years of age (1).  Patients from the Indian subcontinent present relatively at a younger age and have more severe CAD when compared to young patients from other ethnic groups (2-5).

CAD in young males is devastating and needs special attention because the death and disability during the productive years of life without warning leads to tragic consequences.  It has an implication on the financial status as in many Indian families, males are the sole bread winners.  Indians are more prone as a community to CAD at a much younger age (6, 7).  Indians also have shown higher incidence of morbidity and mortality due to CAD than other ethnic population (8).

            Several risk factors contribute to the increase in prevalence of CAD in different age groups. The traditional risk factors like hypertension (HT), diabetes mellitus(DM), high levels of triglycerides, low density lipoprotein cholesterol (LDL - C) and low levels of high density lipoprotein cholesterol (HDL-C), stressful and sedentary lifestyle changes are suggested as additional risk factors for CAD(9).  Previous data from different studies have shown that in young individuals smoking, hypertension and dyslipidemia play an important role in the development of premature coronary artery disease (6, 10).  Smoking can increase the risk of CAD by 3-5 times and a modest increase in central obesity increases the risk further(10). Nearly 50% of young males had no risk factors and this should prompt one to evaluate for other non-traditional risk factors like Lp(a), homocysteine and other prothrombotic conditions.  There is a definite need to identify and correct the conventional risk factors for coronary artery disease at a younger age.

            There is  paucity of  comparative data with regard to CAD among young and older males in the Indian population. The present study was an attempt to evaluate the clinical profile, risk factors & angiographic pattern of CAD in young males (<40 years of age) undergoing coronary angiography (CAG) and compare it with that of  older males (40- 49 years of age).

 

Materials and Methods

 

 A retrospective study was done in the Chettinad Academy of Research and Education /Chettinad Super Speciality Hospital between  the years 2009 to 2013 in males below the age of 50 years who underwent coronary angiography(CAG) for the evaluation of coronary artery disease(CAD).  Institutional Ethics committee approval was obtained and all the case reports of all eligible patients were meticulously screened for collection of data like age, sex, clinical presentation and presence of conventional risk factors for CAD namely hypertension(HT), diabetes mellitus(DM), dyslipidemia, smoking, alcohol intake and family history.  The coronary angiographic findings and the management strategy advised by the consultant cardiologist were recorded.

Male patients aged > 50 years and all the All females were excluded from the study. Patients admitted for CAD, in whom coronary angiogram was not done or patients with inadequate clinical or angiographic details were not included in the analysis.  On the basis of age, patients were divided into two groups: Group I (young males) - males < 40 years of age, Group II(older males) - males aged between 40 - 49 years.  The clinical presentation and indication for CAG was divided into the following subsets: Unstable Angina(UA), Non-ST  Elevation Myocardial Infarction(NSTEMI, ST Elevation Myocardial Infarction(STEMI), Atypical chest pain, Typical effort angina or its equivalent and/ or positive TMT and others i.e. which is not fitting into any of the above category.  The others category mainly consisted of CAG done as a part of pre-operative evaluation for  cardiac valve surgeries and non-cardiac surgeries.   Coronary angiogram findings were evaluated for the presence of  lesion in each major epicardial coronary arteries - left anterior descending artery(LAD), left circumflex artery(LCX), right coronary artery(RCA) and if present, Ramus intermedius (RI).  Angiographic videos were reviewed again if details were inadequate or unclear.  In this study, significant CAD was defined as presence of at least >70% stenosis of luminal diameter in atleast one of the major epicardial coronary arteries in CAG.  Further, based on the number of vessels involved, they were classified as having single vessel disease(SVD), double vessel disease(DVD) and triple vessel disease(TVD).  Patients having less than 70% stenosis were categorized as having non-obstructive CAD/minimal CAD.  If CAG showed no lesion and had less than TIMI III (Thrombolysis in myocardial infarction)flow, they were said to have microvascular dysfunction(MVD).  Presence of Left main (LM) coronary artery disease was noted with specific attention and significant  LM disease was defined as at least >50% stenosis of luminal diameter by visual assessment in the LM vessel.  The management advised by the consultant cardiologist was also recorded.

 All statistical analyses were performed using SPSS 17.0 software. A  p-value <0.05 was considered to be statistically significant.

 

Results

A   total   of   874  male  patients were included in the study and 235(26.9%) were below the age of 40 years (Group I) and 639(73.1%) were between 40 - 49 years (Group II) (Table 1).    All the risk factors studied except diabetes were more frequently present in older males(Group II) than younger males(Group I) : family history of CAD(8.6% Vs 2.6%, p 0.002),smoking (24.4% Vs 8.5 %,p <0.0001),alcohol consumption (18.9% Vs 7.7%,p<0.0001) hypertension(40% Vs 29.8%,p 0.006), dyslipidemia (19.7% Vs 9.4%, p< 0.0001).(Table 1).  Though the prevalence of diabetes was higher in older males, it was not statistically significant(35.2% vs 28.5%, p =0.07).  It was observed that more number of patients in Group I  had no risk factors when compared to Group II (45.1% Vs 27.8%, p <0.0001).

 

Age group

Group

Age

No. of patients

I

< 40 years

235 (26.9%)

II

40 49 years

639 (73.1%)

 

Total

874

 

Risk factor

Parameters

Group I

Group II

χ 2

p value

Family history

6(2.6)

55(8.6)

9.671

0.002

Smoking

20(8.5)

156(24.4)

26.922

<0.0001

Alcohol

18(7.7)

121(18.9)

16.271

<0.0001

Diabetes Mellitus

67(28.5)

225(35.2)

3.414

0.065

Hypertension

70(29.8)

256(40)

7.669

0.006

Dyslipidemia

22(9.4)

126(19.7)

13.041

<0.0001

No risk factors

106(45.1)

178(27.8)

23.450

<0.0001

Clinical presentation

Unstable angina

17(7.2)

51(8)

6.796

0.340

STEMI

74(31.5)

240(37.5)

NSTEMI

10(4.3)

26(4.1)

CSA/ Positive TMT

51(21.7)

127(19.8)

Atypical chest pain

59(25.1)

118(18.4)

Others

24(10.2)

77(12)

Angiographic presentation

Normal coronaries/ microvascular disease

38(16.2)

133(20.8)

 

 

 

16.971

 

 

 

0.005

Minimal CAD/recanalised coronaries

54(23)

165(25.8)

Single vessel disease

24(10.2)

90(14.1)

Double vessel disease

26(11.1)

87(13.6)

Triple vessel disease

93(39.6)

164(25.6)

Involvement of coronary arteries

LAD

97(41.3)

310(48.4)

3.543

0.060

LCX

72(30.6)

225(35.2)

1.565

0.211

RI

39(16.6)

133(20.8)

1.907

0.167

RCA

79(33.6)

254(39.7)

2.697

0.101

Management

Medical

151(64.3)

357(55.9)

 

9.291

 

0.026

PCI

42(17.9)

175(27.4)

CABG

42(17.9)

105(16.4)

Medical

151(64.3)

357(55.9)

Table 1: Baseline characteristics, clinical and angiographic profile of study population
Data are expressed as number of patients. Numbers in parentheses indicate percentage
**Comparison of  various risk factors  between the two groups. Datas are expressed as number of patients. Numbers in parentheses indicate percentage. A p value < 0.05 is considered significant
***STEMI-ST elevation MI,NSTEMI-Non ST elevation MI,CSA-Chronic stable angina,TMT-TreadMill Test
Clinical presentation indicates the  diagnosis made during admission or indication for coronary angiography. Others denote indication other than above mentioned problems which include pre-op coronary evaluation for valve surgeries
****Comparison of angiographic data between the two groups based on the number of diseased coronary arteries
Significant CAD was defined as  >70% stenosis in major epicardial coronaries. Fractional Flow Reserve  was not done in this study.
LAD-Left Anterior Descending Artery,  LCX-Left Circumflex Artery,  RI-Ramus Intermedius,  RCA-Right Coronary Artery
Comparison of individual  coronary  arteries  involved between the two groups.  A p value < 0.05 is considered significant
PCI- Percutaneous Coronary Intervention, CABG- Coronary Artery Bypass Surgery
These were the treatment strategy adviced by  the treating cardiologist after analysing  the coronary angiogram
 



There was no statistically significant differences observed between the two groups in the  clinical presentations (Table 1).  NSTEMI, chronic stable angina and atypical chest pain were more common in Group I( 4.3% Vs 4.1%,21.7% Vs 19.8%, 25.1% Vs 18.4% respectively ) while Unstable angina and STEMI patients were higher in Group II (7.2% Vs 8%, 31.5% Vs 37.5%  respectively).  However, the differences observed were not statistically significant (Chi square 6.7; p value = 0.3).

The angiographic findings of the two groups were compared on the basis of the number  of coronary arteries involved (Table.1).  Single vessel disease(SVD) and double vessel disease (DVD) were more commonly observed in Group II than Group I (SVD-14.1% Vs 10.2%, DVD-13.6% Vs 11.1%, p=0.005).  Further, triple vessel disease was significantly higher in Group I than Group II(39.6% vs 25.6%, p=0.005).  A significant number of patients in Group II had normal coronaries and insignificant lesions when compared to Group I.  Among the coronary arteries involved, there was no statistically significant difference between two groups.  LAD was the most commonly affected vessel followed by RCA and then LCX (Table 1).

With regard to the management advised to the patient by the consultant cardiologist after the coronary angiogram, it was observed that medical management and CABG were more the frequently suggested options in Group I whereas Group II patients required more of percutaneous coronary interventions (PCI) (Table 1). Death occurred in 6(0.9%) patients of the Group II whereas no mortality was observed in the Group I.  Of the total 874 patients studied, 292(33.4%) were diabetics and 582(66.6%) were non diabetics.  No significant difference was noted in the clinical presentation among these Groups (Table 2).  Angiographic findings in diabetics were compared to the non-diabetics (Table 2).  Triple vessel disease was found to be more frequently present in non-diabetics while SVD and DVD were more common in diabetics.  While studying the trend of risk factors from 2009 to 2014, it was observed that except hypertension, all other risk factors had progressively increased in the subsequent years (Table 3).

 

 

 

Clinical presentation

Parameters

Non diabetic

Diabetic

χ 2

p value

Unstable angina

43(7.4)

25(8.6)

 

 

8.313

 

 

0.216*

STEMI

218(37.4)

96(32.9)

NSTEMI

20(3.4)

16(5.5)

CSA Positive TMT

111(19)

67(22.9)

Atypical chest pain

127(21.8)

50(17.1)

Others

63(10.8)

38(13)

 

 

Angiographic pattern

Normal coronaries/ microvascular disease

108(18.5)

63(21.6)

 

 

22.106

<0.0001**

Minimal CAD/ recanalised coronaries

145(24.9)

74(25.3)

Single vessel disease

66(11.3)

48(16.4)

Double vessel disease

65(11.1)

48(16.4)

Triple vessel disease

198(34)

59(20.2)


Table 2: Clinical and angiographic findings of diabetics and non diabetics

This table compares the clinical diagnosis and angiographic findings  between diabetics and non-diabetics irrespective of the age
*No significant difference was noted in the clinical presentation between diabetics and non-diabetics
**Angiography showed significant difference between diabetics and non-diabetics


Risk factor

2009

2010

2011

2012

2013

2014

χ 2

p value

Family History

5(4.1)

2(1.4)

9(7.2)

4(2.4)

3(1.8)

38(25.3)

98.735

<0.0001

Smoking

24(19.7)

17(12.2)

19(15.2)

15(8.9)

21(12.4)

80(53.3)

129.9

<0.0001

Alcohol

14(11.5)

11(7.9)

14(11.2)

15(8.9)

13(7.6)

72(48)

141.1

<0.0001

Diabetes

27(22.1)

49(35.3)

47(37.6)

56(33.1)

51(30)

62(41.3)

13.308

0.021

HTN

42(34.4)

44(31.7)

51(40.8)

64(37.9)

75(44.1)

50(33.3)

7.394

0.193

DLP

14(11.5)

17(12.2)

16(12.8)

19(11.2)

20(11.8)

62(41.3)

76.966

<0.0001

No RF

48(39.3)

58(41.7)

36(28.8)

67(39.6)

56(32.9)

19(12.7)

39.65

<0.0001


Table 3: Risk factor profile trend over the time( 2009 to 2013)

RF- risk factor,HTN- hypertension,DLP-dyslipidemia
Comparison of  prevalence of  risk factors  for CAD- trends over the years


Discussion

            Coronary artery disease (CAD) is the most common cause of death in adults globally, including India.  Although CAD mainly occurs in patients older than 45 years, young men or women can also suffer from Myocardial Infarction (MI).  The incidence of CAD in younger age group has been rising in India, especially in the males (5).  The disease is associated with considerable morbidity, psychological changes and financial burden for the individual and the family, especially when it affects the young individual. Male sex is more prone to CAD when compared to their pre-menopausal female counterparts.  It was observed in the INTERHEART study that South Asian men encountering AMI were 5.6 years younger than women (11). 

            There are no universal definition/criteria for young CAD.  Further, there are no guidelines to describe the cut-off age.  Various authors defined different age limits for young CAD.  In 1966, Frederick T defined patients below 45 yrs of age as those having young MI  in his study (12). Noeman A et al described myocardial infarction in patients below 40 years as young MI (10)(11).   Hoit DB  described  young age as below 45 years, middle age as 45 to 70 years and elderly as more than 70 years (13).  Most of the studies  defined the same age limit for both sexes while few studies had given higher cut-off ages for females. Young patients were defined as men aged 45 and women 50 years by Abreu M et al in his study of Young Patients with Acute Coronary Syndrome (14).   In coronary artery surgery study (CASS) registry, Zimmerman defined young men as below 35 years and young women as below 45 years of age (15).

We included only males in the present study and defined young males as below the age of 40 years and older males as between 40 to 49 years.  Literature search revealed few studies in CAD which included only males.  Also, most of them had evaluated only MI patients.  In the present study, 27% of males were below 40 years which was higher than the 16% reported  by Awan et al who had included both sexes below 40 years in his study (16).   Fournier et al  analyzed patients with documented MI aged 40 years which represent only 4.1% of total MI admissions and they observed majority were males in the study (17).  The probable reasons for this difference might be the following (a) selection of cases from cathlab where angiogram was done for various indications,  not only for acute myocardial infarctions in the current study (b) first MI develop in  south Asians at a relatively younger age than persons  in other countries (18).

 

There is a strong association between Cigarette smoking and CAD in young males and it was noted that smoking was found more commonly in young adults than older individuals with MI(76-90 % Vs 40%)(2, 15) .  Hoit BD observed only 8% of MI were not smokers in his study of  CAD in patients below the age of 45 years(13).  Smoking increases the platelet aggregation, fibrinogen levels and coronary vasospasm, and decreases the fibrinolytic activity and coronary flow reserve. Repeated smoking causes  catecholamine surge with resultant damage to endothelium and thrombus formation.  Current smoking history was present  in majority of  patients with young MI (14).  Cessation of  the smoking at anypoint of time is beneficial  and  no difference was noted in the long-term mortality between former smokers and non-smokers. Autopsy studies in the  coronary arteries of young population  have shown smokers have more extensive fatty streak lesions and develop at an earlier age than non-smokers (19).  There were more smokers in older males when compared to younger males in the current study.

 There is an existing controversy as to whether moderate alcohol consumption played a protective role while high alcohol intake increased the risk of CAD. From the substudy of the Indian patients in the INTERHEART trial, regular alcohol consumption was not reported to be protective for AMI in South Asians. In the present study, alcohol consumption was significantly higher in older males. Jayachandra et al al had also observed higher alcohol consumption in patients aged more than 45 years compared to younger patients, although it was not statistically significant (20).

            Authors observed Diabetes was present equally in both the groups and Hypertension was found to be more common in older males in the present study, but  Awan et al (16) and Chen et al (2) observed both HT and DM were equally present in the in both the groups. However, elderly males (60 years ) were compared to young (45 years) in the analysis by Chen et al.  In an another study in patients with documented MIs by Zimmerman et al  noticed  both DM and HT were more common in older patients (15).  A similar study by Neoman showed that both HT and DM were more common in older adults (10).  These findings implies that diabetes starts at a younger age in Indians.  Dyslipidemia  was significantly frequent in older males than young males in the present study,  But Chen et al observed that hypertriglyceridemia and low HDL levels were commoner in younger  patients (2).  Also, Mohammed et al (21) found that hyperlipidemia was more often seen in younger persons.  On the other hand, Zimmerman et al  observed triglycerides and mean cholesterol levels to be similar in young and older men(15).

 

            With regard to the clinical presentation, the authors observed no significant difference between young and older males, even in diabetics. This was contrary to the study reports of Chen et al (2) where stable angina was more common in older patients and acute coronary syndromes were commoner in young group. Further, in his study only patients with documented CAD were included for analysis and older males were more than 60 years of age.

            Normal angiogram or non-obstructive lesions   have been observed more often in young patients with myocardial infarction. In the current  study, older males were found to have  higher incidence of non-obstructive lesions, SVD and DVD.  Also young males were noted to have higher incidence of  Triple vessel disease , which was an unusual finding compared to many studies (22-25) where SVD was more common in young patients. Zimmermann et al. demonstrated that both in young men and women, normal coronaries, minimal lesions,SVD and DVD were more common than their older counterparts(15).   Mohammed et al also observed that SVD was more common in young population and TVD was common in older people(21). Young patients in most studies presented with less number vessels involved than the older persons, (22-25). But, the present study showed more extensive disease in younger patients. This finding might indicate that Indians males have an earlier occurrence of the disease process .

                Cole and his colleagues noticed revascularisation procedures(CABG and PCI) improved the prognosis in  patients with  coronary artery disease. There was no difference between the groups for the treatment advised (PCI and CABG) in the present study. Equal number of patients in both groups were advised medical management in the current study and this might be attributed to the fact that patients who had undergone CAG as part of pre-operative coronary evaluation prior to valve surgeries or non-cardiac surgeries were also included in the analysis. In patients with multivessel disease,  CABG was adviced more often  than PCI because of financial constraints as multivessel PCI with drug eluting stents is costlier than CABG in India.

 

Based on the observations from the present study, authors suggest screening of risk factors for CAD should start at an earlier age in Indian males, and cessation of smoking, promotion of physical activities and avoidance of high fat diets have to be strongly encouraged to this vulnerable group. Since atypical presentations were common in young  patients, high index of suspicion is necessary for early diagnosis. As nearly half of the young males had no risk factors in the current study, they should evaluated for  non-conventional risk factors like Lp(a) and  homocysteine.

The  limitation of the study was that Fractional Flow Reserve(FFR)  was not used in borderline lesions and only conventional risk factors for CAD for were evaluated.

   

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