European Journal of Cardiovascular Medicine

Acute myocardial infarction (AMI) is defined by rapid development of myocardial necrosis  due to  imbalance between oxygen supply and demand of the myocardium. Myocardial infarction has become a significant problem in developed countries . It is becoming an increasingly significant problem in developing countries. (1 )  Cardiovascular disease (CVD) has become a major public health problem. South Asian countries, like India, Pakistan, Sri Lanka and Bangladesh  represent greatest number. They have increased mortality due to CVD at a younger age in comparison to the local population.  (2)They have the highest risk of developing coronary artery disease at a younger age in comparison to other countries . This also leads to socio economic burden of these countries. Heart diseases are rising in South-Asian countries  like in Indians 5–10 years earlier than in other countries around the world.The mean age for first presentation of acute coronary events  in Indians is 53 years which is earlier than other subgroups. Coronary artery disease  that manifests at a younger age can have devastating consequences for an individual .More importantly, the disease catches Indians young. The risks are explained on the basis of traditional and non-traditional risk factors. In Southeast Asia alone, 7,423,000 deaths were due to noncommunicable diseases as compared with 5,730,000 deaths related to communicable diseases in the year 2002.   With 6.8% and 5.0% of disability-adjusted life-years (DALYs) lost, coronary  artery disease and stroke were globally the second and third largest causes of disease burden in men aged 40 years and older in 2002 respectively . Even in women, CAD and stroke were the third and fourth main causes of DALYs lost worldwide respectively.  The average life expectancy at birth in India is 63.7 years( 63.1 for males and 64.4 for females)  (4 ),  Due to health care improvement . The number of increased old age population has increased from 19.61 million in 1950 to 75.93 million in 2000(5)and thereby increasing  Coronary artery disease. It has been observed that  CAD rates have increased in India during the last 30 years  (6).The exact prevalence of CAD in India is difficult to estimate.India  not only has a high prevalence of CVDs but also particular concern that productive  working groups aged 35-65 age are being affected most. Incidence of CAD in young age groups in India is about 12%–16%, which is higher than ethnic groups.  Nearly half of the CVD-related deaths (52% of CVDs) in India occur below the age of 50 years.  Studies reported about 25% of acute myocardial infarction (MI) in India occurs under the age of 40 years. (7)Studies reported that CADs are occurring in Indians five  to ten years earlier than in other populations around the world. (8 ) Infact, younger Asian women have worse survival at 28 days after acute MI . (9)In view of the above discussion, it is imperative to ascertain the causes of the rising prevalence and emergence of CAD earlier in the life of Indians.Risk factors for premature CAD in Indians are conventional modifiable risk factors and some non-modifiabke risk factors for MI.  The INTERHEART study showed hypertension and diabetes were more important risk factors in younger Indian females than male counterparts .It appears that North Indians manifest the disease at lower levels of total cholesterol ( 10,11,12 )Also, a greater role can be attributed to total cholesterol and LDL cholesterol in atherogenesis in the younger Indian population with age ≤40 years having angiographically proven CAD. Smoking and low physical activity in Indians have been found to be prevalent especially in 20–39 year-old urban adults.Family history is another independent  emerging risk factor observed in young Indian CAD study .     A substantial increase in the prevalence of obesity is being seen especially in young age groups  due to nutritional transition . Indian population develop CAD and  first myocardial infarction before the age of 40 years is 5 to 10 folds higher. (13) Cigarette smoking has been identified as the single factor very strongly associated with CAD in the young adult ( 14).  Hypertension , sedentary  habits and lack of exercise are firmly established risk factors for CAD in general, but they appear to contribute only marginally in young population. ( 15) .  In this study the risk factors, clinical presentation, biochemical parameters, angiographic profiles and short term outcome of myocardial infarction in patients less than 45 years has been studied and compared with the older patients.

AIM OF THE STUDY:

To compare the risk factors like smoking, diabetes mellitus, hyperlipidemia, obesity and hypertension in young patients ( ≤45 years ) with  myocardial infarction in >45 years of age.  To assess the angiographic features of coronary artery disease between the two groupsTo compare the presence of collaterals in patients with acute myocardial infarction between the younger and older age groups. To assess the Left ventricular function between the two groups. 

The approval of the ethics committee of IPGMER & SSKM Hospital, Kolkata  was obtained.We reviewed all cardiac catheterization and in-hospital records of the first 100 patients who underwent this procedure at SSKM  between 2020-2023. Of those 100 patients, 50 patients at or under the age of 45  years have been catheterized for evaluation after myocardial infarction These 50 young patients were compared to 50 randomly selected patients at or above 45 years of age catheterized for evaluation of coronary artery disease, all who had suffered a prior myocardial infarction. The patients were divided into two groups: Group 1 – Patients less than or equal to 45 years age with myocardial infarction (n = 50). Group 2 – Patients with 45 years or more than that with myocardial infarction (n = 50). The cut off age of less than or equal to 45 years for young MI group was assigned in accordance with various previous studies which use similar cut off age 45 The diagnosis of myocardial infarction was based on the  universe  definition of AMI criteria .Myocardial infarction was diagnosed if all of three of the following criteria were present. 1)Persistent  chest pain or discomfort typical of cardiac ischemia, lasting longer than 30 minutes which not relieved by sublingual nitroglycerin2) Initial ST elevation or depression of 1mm or more  in at least two consecutive inferior or   more than 2 mm ST elevation in at least two consecutive anterior chest leads 3) Elevation of serum troponin value more than 99 percentile .The data were  recorded as per the protocol and proforma sheet, which have  been previously formulated. In all the participants, details of the age, sex and occupation were recorded with the details of personal  habits like smoking, alcohol use. Medical history like diabetes mellitus , hypertension and a significant family history of ischaemic heart disease also took into account.Anthropometric measurements like Weight, height and waist and hip circumference were recorded for each person. Fasting blood glucose, fasting lipid profile, serial ECGs and the cardiac enzymes ( Troponin ) were evaluated.Echocardiography was done in all the patients. All these patients were taken up for coronary angiography which was performed by the standard Judkins technique after adequate preparation and anticoagulation. The risk factors which were studied were hypertension, diabetes mellitus, smoking habits, overweight (a BMI of > 25 kg/m2), the waist to hip ratio (a WHR of >0.91cms was considered as a risk factor), hyperlipidaemia (serum cholesterol of 200 mg%) and a family history of coronary artery disease .

Hyperlipidemia was defined as a fasting total cholesterol concentration concentration 220 mg/dl, a fasting triglyceride 150 mg/dl, or the use of antihyperlipidemic therapy.The patients who were currently smoking and those who claimed to have stopped smoking for one year were considered as smokers and others were considered as non-smokers. The coronary angiographic profile was studied in all these patients to determine the number of vessels involved and the type of the vessels which were involved.  All patients underwent catheterization within two weeks of their hospitalization. The coronary angiography was performed via the femoral artery route using standard sized sheaths and Judkins left and right coronary catheters.Multiple angulations and views were used. Lumen diameter narrowing was graded as minor ( <30%) , intermediate ( 40-70%) severe (>70%). The definition of a significant anatomical stenosis was >70 % localized luminal narrowing. 

STUDY GROUP SELECTION

Inclusion Criteria: Acute ST elevation myocardial infarction ,Non ST elevation myocardial infarction,Both sexes, Age Group <= 45 years and > 45 years. Both thrombolysed and non thrombolysed patients.

Exclusion Criteria:

Age group < 18 years ,Chronic stable angina, Unstable angina,Patients who underwent PCI / CABG. 5. Previous MI.

Statistical Analysis: 

Statistical testing will be conducted with the statistical package for the social science system version IBMSPSS@20 Continuous variables will be presented as mean(SD).  Categorical variables will be expressed as frequencies and percentages.  Chi square test will be used in categorical data whereas student 't'  will be used to compare mean  for two groups. For all statistical tests 'P' values less than 0.05 and 0 .01 will be taken to indicate a significant and highly significant respectively.

These risk factors are generally considered under the following two categories

Conventional risk factors: (16)

• Smoking
• Hypertension
• Diabetes mellitus
• Obesity
• Hyperlipidemia and Elevated Low-Density Lipoprotein Cholesterol
• High-Density Lipoprotein
• Cholesterol
• Triglyceride
• Metabolic Syndrome,
• Insulin Resistance and Diabetes
• Family history
• Mental Stress, Depression
• Chronic kidney disease
• Peripheral artery disease

Novel atherosclerotic risk factors:  

High-Sensitivity C - Reactive Protein

Homocysteine    

Fibrinogen and Fibrin D-Dimer 

Lipoprotein (a)

Over the period of 3 years , 50 random patients of each group ( less than 45yr and more than 45 yrs )  are selected according to their hospital admission.Angiography was done in the index hospital admission.All patients were admitted with acute coronary syndrome

We compared  the two groups with demographic, clinical features , risk factors and angiographic profiles.

Group 1 : Age ≤ 45 years

Group 2 : Age > 45 Years

Table 1.AGE DISTRIBUTION IN YOUNG AGE:

In younger group ( age < 45) , 36 ( 72%) patient belongs to ≥ 35 yr age  and 14 patients ( 28% ) belongs to < 35 years age group .

GENDER:

50 patients aged 45 or less (group 1) among them 44 were male and 6 were female.  In group 2 (more than  45 years) 36 were men and 14 were women. The gender distribution between two groups was significant with p value - 0.046, chi square value - 4

TABLE 2

*significant at 5% level   

SMOKING:   Risk factors analysis revealed smoking to be overwhelmingly present in both groups (64 % percent [n=32] in group 1 and 32% percent [n=16] in group 2).  There is a statistically significant difference between group 1 and group 2 with respect to smoking as a risk factor for CAD.  p value of <0.001 ,suggestive of highly significance.

TABLE  2

HYPERTENSION:

Hypertension was more frequent in group 2 patients [50%] than in group 1 [14%]. This is a statistically significant p value (p value <0.001) between two groups.

TABLE 3

DIABETES MELLITUS:

In group1 there were 7 patients [14%] with diabetes when compared with group 2 which had 22 patients [44%] . There is statistical significance between two groups (p value <0.001  , very high statistical significance) .

TABLE 4

OBESITY: 

In our study 15 patients [30.0%]  in group 1 and 20 [40 %] in group 2 were obese. There was no significant difference between the two groups with regard to obesity  ( p value 0.295) .  But , the prevalence of obesity is much higher in both this population

TABLE 5

FAMILY HISTORY

When compared in group 1 family history was statistically significant ( p value = 0.022) with group 2.  Group 1  population  ( age > 45) had  more frequent family history than group 2 (age < 45)  ( 52% vs 28% )

TABLE 6

Smoking and positive family history is more prevalent in younger age groups compared to Group 2. But, hypertension, diabetes and obesity are more common in age group more than 45 yr. 

NOVEL RISK FACTORS IN YOUNG GROUP:

Table:7 A.   LIPOPROTEIN A:

High Lipoprotein A level is present in 70% of patients in Group 1 { age ≤ 45)

1. HOMOCYSTEINE:

Figure 1

Apo B / Apo A1 ratio increased in 88 % of patients in age group ≤45 years . 66%  of them belong to the high risk category.

MI TYPES:

In our study,  group 1 patients had suffered 58% percent [n=29] anterior wall myocardial infarction(MI) , 30 percent [n=15]  inferior MI  ,6 percent  [3]  , 4% NST - ACS [2] while group 2,  42% percent [n=21] anterior wall myocardial infarction(MI) , 26 percent [n=13]  inferior MI  , 8 percent  [4] posterior  wall MI, 18 % NST - ACS [n=10] patients respectively. Small number of patients had Lateral wall MI  in both groups.  No statistical significant difference found between two groups.

TABLE 8

KILLIP CLASS - 

41 patients (82%)  in Group 1 and 33 patients ( 66%) in group 2 presented with killips class I. the difference is not statistically significant (P=0.290) .

TABLE 9

Table:10 ANGIOGRAPHY: NO OF VESSELS INVOLVED

Angiographically, the incidence of one vessel disease and normal coronary anatomy was much higher in patients from group 1. In group 2 there were 4% with normal coronary anatomy and 50% with one vessel disease involvement.. But  the incidence of significant double  ( 12% vs 30% ) and three-vessel (6 % vs 14%) disease  was statistically much lower in group 1 vs. group 2.  [ p value 0.024]

Table 11 VESSELS INVOLVED:

CORONARY INVOLVEMENT

Table 12 LMCA

The incidence of left main coronary artery disease was low in group 1 (2 percent) [1] when compared to group 2 which is 22 percent[11] which was statistically significant. ( p value 0.002)

Table 13 LAD: In group 1 there were 58 percent [29] of Left Anterior Descending Artery involvement when compared to 64 percent [ 32] in group 2 , which is statistically not significant ( p value 0.584)

Table 14 LCX:

In group 1 there were 26 percent [13] of Left circumflex Artery involvement when compared to 32 percent [ 16] in group 2 , which is statistically not significant ( p value 0.509)

Table 15 RCA:

In group 1 there were 28 percent [14] of Left circumflex Artery involvement when compared to 40 percent [ 20] in group 2 , which is statistically not significant ( p value 0.509)

Table:16 Mean comparison of Lipid Profile parameters between two groups

*Significant at 5% level, **Significant at 1% level

Mean total cholesterol , triglyceride, LDL,HDL levels are highly statistical significant  with p value 0.001      Comparison of Ejection fraction (%) and

No statistical difference noted between two groups in terms of ejection fraction and time of presentatons.

Table17

No statistical difference in BMI between two groups with p value 0.05 though prevalence of obesity is high in both groups.  ( 28% vs 36%)

Premature coronary  artery disease is a rapidly progressive form of atheromatous process . The risk factors and short term outcome of acute myocardial infarction in young adults varied from their elderly counterparts. Cigarette smoking has been the single factor most strongly associated with CAD especially in the young adult population . Diabetes and dyslipidemia are also frequently present in young CAD patients. Whereas the importance of these factors in the pathogenesis of CAD and their powerful relationship to rapid disease progression is well documented (81,82) their importance in this population is not characterized in detail. In a study done by Kanitz MG et al to define the risk factors and clinical presentation of patients under age 40  the major risk factor was tobacco use 81%, then family history 40%, hypertension 26%, and dyslipidemia 20%.In our study in patients under age 45 , tobacco use was present in 64 %, family history  52 %, hypertension 14 %,  obesity  30 %.

 In another study conducted by Hong  et all  conclusions were, occurrence of Acute myocardial infarction below  forty years was the predominant disease of men. Risk factor analysis revealed a history of cigarette smoking and hypercholesterolemia were more frequently found in the young patients, but a history of hypertension and diabetes were more frequently found in the elderly patients. (83)

In our study in the less than 40 years group,88%  were men, cigarette smoking was more common in younger patients, whereas hypercholesterolemia was present in both groups. Hypertension and diabetes were more frequent in the elderly group in our study .

In a prospective clinical study conducted by Fournier et al  the most common risk factors were cigarette smoking 94.5% and hypercholesterolemia 48% and that the short term prognosis was excellent.(84)

The short term outcome in the younger patients in our study was better than the older ones ( in hospital  mortality 14% vs 20 % though not statistically significant. Younger patients (≤45 Yrs)  had a lower in-hospital morbidity and mortality rate. These  young groups have a lower incidence of congestive heart failure and a shorter length of stay.

Stefanos Garoufalis et al conducted a study and found that  family history and smoking were the most common risk factors in patients ≤45 years old P<0.04, P<0.0001, respectively, and hypertension and diabetes mellitus were more prevalent in patients >45 years, P<0.00001 for both (58,85). In this study, we had similar results, with family history (52% vs 28%), smoking (64% vs 32%) being common in younger patients, but  hypertension (14 vs 50%) and diabetes (14 vs 44%) is more common in more than 40 yr age group.

The distribution of lesions in our patients, with a high incidence of normal coronary arteries (10% )and one vessel disease ( 72%) , is in accordance with previous studies(17,22)

Biswas PK et al in Journal of Indian Medical Association 1995 had documented the preponderance of one vessel disease in young MI patients.  Our study finding is similar to the above study .

Young patients with significant coronary obstruction have less extensive disease than older patients. The present findings  of predominantly single-vessel disease in young patients and multivessel disease in older patients is in accord with previous studies .

In our study, the left main coronary artery disease is higher (13.9 vs 1.8%) in patients with age more than 45 years than in young MI patients ( p value 0.002). In younger age groups (less than or equal to 45 years age group), there were 50.9 percent  of Left Anterior Descending Artery involvement when compared to 40.5 percent  in the more than or equal to 45 years group. The mean ejection fraction was 47.12 %  The p  value was 0.534 and there was no statistical significance between the two groups with respect to the ejection fraction.

When compared with younger age (less than or equal to 45 years) family history was statistically significant (p value = 0.002) in the more than 45 years group.  MI group (group 1) had more frequent family history than group 2. This is in correlation with the previous studies showing   family history of premature coronary heart disease was more common only in young men .

Obesity : Though prevalent in both groups ( 30% vs 40% ) , but not statistically significant . ( p value 0.295)

Anterior wall MI was more in both groups ( 58% vs 42% ) followed by Inferior wall MI and NST-ACS more common in the age > 45 group ( 4% vs 18%). Angiographically triple vessels involvement was more in group 2 ( >45 Yrs) .

Mean heart rate at the time of presentation was higher in the younger age group ( 81.44 vs 74.10 bpm) with p value of 0.028.

Mean systolic blood pressure and diastolic blood pressure were not statistically significant.Lipid profile shows significant p values. Mean values for total cholesterol, triglyceride and LDL were higher in more than 45 yr age groups. No significant difference in time of presentation in both groups. ( Mean 86 hrs vs 102 hrs)  ( p value of 0.296)

The large  burden of coronary artery disease among South Asians appears to be primarily due to dyslipidemia which is characterized by: high levels of ApoB, triglycerides, Lp(a), borderline high levels of LDL-C, low levels of HDL-C and Apo-A1. It has been observed that total levels  of cholesterol and LDL-C  are correlated with extent and severity of CAD in Asian Indians as in whites. However, at any given total cholesterol or LDL-C level, South  Asian countries have a greater CAD risk than whites.

Lp(a) appears to be a major risk factor in Asian Indians as compared to whites. A high level of Lp(a) is shown to the most prevalent dyslipidemia in our young patients with premature CAD. Lp(a) levels are governed almost exclusively by race, ethnicity, and genetics, unlike other lipids, where the levels are influenced by age, gender, diet, and other environmental factors. The effect of Lp(a) on the atherogenicity is not only additive but also multiplicative. It  is also regarded as a biological marker for familial CAD.

In our study, Lp(a) levels were above 30 mg/dl in 32% of the patients . Increased LP )a)  represents an important risk factor in young MI  patients . Our finding is similar to the previous study by Prajapati et al. ( 21.5% patients have increased LP (a) level. (91)]

Asian Indian have higher Homocysteine levels than others. In India, large proportion of people are vegetarian . Furthermore, in the study done by Arumalla and Reddy [,92)  hyperhomocysteinemia was found in 66% of the patients with AMI. The slightly lower prevalence of hyperhomocysteinemia in our patients might be due to increased fish consumption in the Bengali diet. Hence, we should encourage higher intake of fruits and avoid overcooking of vegetables to prevent hyperhomocysteinemia.                

LIMITATIONS Our study did not include all patients with a myocardial infarction to routinely undergo cardiac catheterization. Hence, the present analysis cannot claim to represent the findings for all patients early after myocardial infarction.

Coronary angiography was performed according to clinical indication for suspected coronary artery disease and was representative of clinical practice. Therefore, there is a potential for selection bias. 

No attempt was made to document the presence of coronary vasospasm in the patients with normal coronary arteries by ergonovine stimulation, due to the patients being catheterized during the period early after infarction.

No systemic questioning regarding the use of cocaine or other sympathomimetic drug was performed.

Young MI patients (age 45 years) patients who have had a myocardial infarction have less extensive coronary artery disease than older (more than or equal to 45 years) patients, with a significant incidence of angiographically normal vessels and with left main.

The risk factor analysis reveals that hypertension and hyperlipidemia were more common in older patients while smoking was common in both the groups being more frequent in younger age groups.

To slow the momentum of Coronary artery disease , particularly among the working-age population, major initiatives are needed to combat CAD, whether promotion of diet and physical activity, generation of awareness among both sexes, or development of guidelines for risk factors and therapeutic and surgical strategies.

ABBREVIATIONS

• ACC- American College of Cardiology
• ACEI- Angiotensin Converting Enzyme Inhibitor
• ACS- Acute coronary syndrome
• AHA- American Heart Association
• ARB- Angiotensin receptor blocker
• CAD- coronary artery disease
• CHD-coronary heart disease
• ECG- Electrocardiography
• EF- Ejection fraction
• ESC- European Society of Cardiology
• HDL- High Density Lipoprotein
• IHD- ischemic heart disease
• IWMI - Inferior Wall Myocardial Infarctions
• AWMI - Anterior Wall Myocardial Infarctions
• LAD-Left anterior descending artery
• LCA-Left Coronary Artery
• LCX -Left circumflex artery
• LDL- Low Density Lipoprotein
• STEMI- ST Elevation Myocardial Infarction

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