In recent years coronary artery disease (CAD) is emerging as a new epidemic afflicting people of Indian subcontinent at relatively young age [1]. Acute Coronary Syndrome (ACS) Which is considered to be disease of older people over 45 yrs of age but is being observed in an increasing number of younger patients. On an average, people here develop Myocardial Infarction (MI) about 10 years earlier than other populations and its occurrence in patient less than 45 years is 5-10 folds higher [2].

As per literature, Acute Coronary Syndrome (ACS) in young is defined as being ACS occurring at age less than 40-45 years. Studies suggest that South Asians are at an increased risk of MI at a younger age (<45 yrs). It accounts for 3-12% of total AMI events. Although ACS in younger patients are generally associated with a favourable prognosis8-9, the burden of premature coronary disease is substantial. The occurrence of ACS in a young person leads to premature morbidity and mortality in the most productive years of life [3-9].

Besides atherosclerotic coronary artery disease, non-atherosclerotic coronary artery diseases or hyper-coagulability should be considered as factors for young cases of ACS. The predominance of angiographic single vessel disease or infarction with normal coronary arteries in these patients primarily suggest that premature MI probably result from a rapidly progressive event, such as thrombosis or plaque rupture, rather than a gradually evolving process such as atherosclerosis [10].

ACS refers to a spectrum of clinical presentations including Unstable Angina (USA), Non-ST Elevated Myocardial Infarction (NSTEMI) and ST Elevated Myocardial Infarction (STEMI). Patients with ACS generally have symptoms and signs of myocardial ischemia either at rest or with exertion. These symptoms and signs are similar to chronic angina symptoms, consisting of sub-sternal chest pain or discomfort that may radiate to the jaw, left shoulder or arm. Dyspnoea, nausea, diaphoresis or syncope may either accompany the chest discomfort or may be the only symptom of ACS. About one-third of patients with MI have no chest pain per se and they tend to be older, females, diabetics [11,12].

Research is going on look for various risk factors associated for development of coronary artery disease in young patients in various parts of World. The literature regarding clinical profile and risk factor association for ACS in young patients in Himachal Pradesh is not available. Himachal Pradesh is a predominantly rural and Hill State with Altitude of 450-6500 meters above MSL. The life style of people differs in many aspects from people living in plains. ACS in young patients needs more research for exploring the risk factors and outcomes. 

Aims and Objectives 

• To study the various risk factors among of patients of ACS young<45 years

• To study the clinical profile of patients of ACS aged<45 years

This hospital based observational study was carried out in patients of ACS aged<45 years, admitted to Cardiac Care Unit (CCU) of Department of Medicine I.G. Medical College Shimla from 1st June 2013 to 31st May 2014. Total of 50 cases (male= 44, female= 6) of young ACS were included in study. This study was approved by Institution Ethics Committee. The Informed consent was taken from all patients. 

Inclusion Criteria

• Age of patient was 45 years or below

• Patients who fulfilled the criteria of ACUTE CORONARY SYNDROME were included 

Acute, evolving or recent MI defined as the typical rise and/or fall of biochemical markers of myocardial necrosis with at least one of the following: 

• Symptoms of ischemia

• Electrocardiographic changes indicative of ischemia and/or infarction

• Development of pathologic Q waves in the ECG

• Imaging evidence of new loss of viable myocardium or new regional wall motion abnormality

• Occurring at rest (or minimal exertion) and usually lasting >10 minutes

   

Unstable Angina (USA) was defined as angina pectoris (or equivalent type of ischemic discomfort) with at least one of three features: 

• Being severe and of new onset (i.e. within the prior 4-6wks)

• Occurring with a crescendo pattern (i.e., pain that awakens the patient from sleep or that is more severe, prolonged or frequent than previously)

NSTEMI - If a patient with USA develops evidence of myocardial necrosis, as reflected in elevated cardiac biomarkers. 

Exclusion Criteria 

• Patients not giving informed consent

• Patients with advanced co morbid conditions, including malignancies, advanced heart failure or valvular heart diseases

• Patients already on statins

• Patients with secondary causes of cardiovascular diseases like thyroid disorder, renal disorders, liver disorders, Cushing's syndrome, on estrogenic administration which affect lipid metabolism

• Patients with expected transfer to another hospital within 48 hours or if follow up not possible

Method of Study 

All the patients of ACS admitted to CCU, who satisfied the already described inclusion criteria, were provisionally included in the study. At the time of admission, 12 lead ECG was done and blood samples were taken for blood urea, blood sugar, serum sodium, serum potassium and Trop T (in patients suspected with USA and NSTEMI). Sample for serum biochemistry were sent within 24 hours of CCU admission (after overnight fasting of 12 hours). Detailed clinical examination of the patient was done and entered in the predesigned Performa. Patients were treated as per the standard treatment protocol: 

• Oxygen inhalation: 2-4 L/min by nasal cannula, to maintain saturation above 90 %. Bed rest for first 12 hours. In the absence of complications, start ambulation in room by second to third day

• Aspirin: 300 mg tablet (to be chewed) as a loading dose, followed by 150 mg oral tablet once daily

• Clopidogrel: 300 mg loading dose, followed by 75 mg once daily. Coronary reperfusion by thrombolysis with Tenecteplase (intravenous bolus of 0.53 mg/kg over 10 sec) or streptokinase (1.5 million units over 1 hour), in cases with STEMI

• Beta blockers: Metoprolol 12.5mg orally 12hrly to 6 hourly, followed by doses up to 50 mg orally every 6 hourly for 48 hours to achieve target heart rates (unless contraindicated)

• Nitro-glycerine: In patients of persistent chest pain, intravenous infusion started at 5-10 microgram/min, can be increased up to 200 microgram/min if hemodynamic stability is maintained

• Morphine: 2-4 mg intravenous repeated every 5 min, until pain disappears or side effects appear Tab diazepam 5 mg 3-4 times per day

• Low molecular weight heparin (enoxaparin): 1mg/kg subcutaneous BD or unfractionated heparin 800U/hour (maximum of 20000U/ 24 hours)

• ACE inhibitors: ACE inhibitors or Angiotensin Receptor Blockers if ACE inhibitors were not tolerated

• Statins (Atorvastatin), Laxatives and any other drug: Statins (Atorvastatin), Laxatives and any other drug as and when indicated. Serial ECGs of the patients were done 12-hourly for first two days and once daily till discharge and were evaluated for the appearance of any fresh changes of ischaemia or arrhythmias

Following investigations are to be sent on day 1 after admission. Serum Lipid Profile was performed within 24 hours of hospital admission after 12 hours fasting. TROP T/after 6 hrs. (When indicated), Blood Sugar (fasting/post prandial), Liver Function Tests, Renal Function Tests, Complete Hemogram, Urine-Routine and Microscopic Examination, ECG and Chest X-ray PA View.

Clinical Profile of the patients during hospital stay (0-5 days) was studied in detail and patients were observed for any complications of ACS: Cardiogenic Shock, Arrythmias, AV block, Pulmonary oedema, Heart Failure, Cardiac Arrest, Recurrent Myocardial Ischemia, Myocardial Reinfarction, Myocardial Rupture, Cardiac Tamponade, Pericarditis, Pericardial Effusion, Mitral Regurgitation, Embolism and Electromechanical dissociation. 

Statistical Analysis 

Data collected was managed on a Microsoft Excel spreadsheet. All analysis was performed with the Epi Info V7. Data were expressed using mean±standard deviation for continues variables and frequency (percentage) was used to describe distribution of categorical variables. Association of risk factors of disease was carried by using Chi- Square Test.

In our study mean age of patients was 40.3 years with range 25-45 years. Forty-three (86%) were in age group 35-45 years, 7(14%) patients were in age group 25-35 years. Forty (80%) patients were from rural background. 44 (88%) patients were male and 6 (12%) were female. Majority (5) of females were premenopausal (Table 1).

Table 1: Age and Gender distribution of the patients

Out of 50 patients in study 23(46%) were diagnosed as STEMI. Fourteen (28%) were diagnosed as NSTEMI and 13(26%) were diagnosed as USA (Table 2).

Table 2: Distribution of patients according to diagnosis

All 50 (100%) patients had chest pain. Sweating was second most common symptom in 40(80%). Palpitations were present in 18(36%) patients. Syncope or pre syncope was present in 17 (34%) of patients. SOB and vomiting each was present in 7(14%) of patients. Atypical presentations were seen in 7(14%) of patients (Table 3).

Table 3: Distribution of Patients According to Symptoms

Twenty 20(86.96%) patients of STEMI, 12(85.71%) patients of NSTEMI and 10(69.23%) patients of USA had radiating type of pain. Two (8.69%) patients of NSTEMI and2(16.67%) Patients of USA were having localized pain. Ten (43.48%) patients of STEMI and7(50%) patients of NSTEMI were having HTN. One (4.35%) patient of STEMI had past history of CAD and HTN. Five (38.46%) patients of USA had past history of HTN. Fifteen (60.87%) patients of STEMI and 7(50%) NSTEMI patients were having CAD in either of the parents. One (7.14%) patient of NSTEMI and 1 (8.33%) patient of USA had family history of CAD in both parents as well as siblings. Smoking was clearly the most significant risk factor among study group. Forty-three (86%) patients were smokers. Twenty (82.61%) patients of STEMI, 13 (92.86%) patients of NSTEMI and 10 (76.93%) patients of USA were smokers. Twenty-six (52%) patients had history of alcohol abuse. one (62%) out of total 50 patients were having Prediabetes/Diabetes. Fourteen 14(60.87%) of total 23 patients with STEMI had Prediabetes/Diabetes (p>0.05), 9 (64.29%) of total 14 patients of NSTEMI patients had Prediabetes/Diabetes (p>0.05) and 8 (61.54%) of total 13 patients of USA were Prediabetic. Out of 31 patients of ACS with Prediabetes/ Diabetes, 3 (9.6%) were newly diagnosed as Type 2 Diabetes Mellitus and all had STEMI (Table 4).

Table 4: Distribution of Patients According to Risk Factors

Thirty-four (68%) patients had BMI 18.5-25. Eleven patients were Overweight or Obese (BMI>25) and BMI<18.5 was found in 5 patients. These patients were further studied in relation to type of ACS with BMI. Thirty-four patients had BMI in the range of 18.5-25 and out of these, 17 patients had STEMI, 7 had NSTEMI and 10 were having USA. Five patients of STEMI, 5 patients of NTEMI and 1patient of USA had BMI of >25. One patient of STEMI, 2 patients of NSTEMI and 2 patients of USA had BMI of<18.5. Dyslipidaemia was found in 24(48%) of the patients and it was most significant risk factor of CAD in patients with Metabolic Syndrome. Out of 50 patients, 15(30%) patients were having Metabolic Syndrome. Eleven (43.48%) of patients of STEMI, 3(21.43%) of patients of NSTEMI and 2(15.38%) of patients of USA had Metabolic Syndrome.

Among association of risk factors with subtype of ACS of smoking was significantly associated (p<0.05). Alcohol abuse was another risk factor (p<0.05) found to be significant. Dyslipidaemia (p=0.082), HTN (p=0.085), Prediabetes/Diabetes (p=0.032) and Metabolic Syndrome (p=0.402) were not found to be significant (Table 5).

Table 5: Association of risk factors of with type of ACS

Wave inversion in most leads was commonest ECG findingpresentin36(72%) of patients. ST depression was present in 32(64%) patients, ST elevation in 28(56%) patients and waves were seen in 11(22%) patients. TLC was raised in 20 (40%) patients. Leucopoenia i.e. TLC<4000 was detected in 2 (4%) patients and 28 (56%) patients had normal TLC counts. 36 patients had ejection fraction (>60%) and 14 patients had ejection fraction<60%. Out of 14 patients which had ejection fraction (<60%), 10 (43.48%) were STEMI and 3(21.4%) had NSTEMI. One (8.33%) patient of USA is also having E F<60%. ECHO based findings according to territories involved. LAD was involved in 37patients. Out of these 37 patients, LAD alone was involved in 30(81.08%) patients. Twenty (86.96%) patients of STEMI had LAD involvement alone. Six (42.86%) patients of NSTEMI had LAD involvement alone. Four (28.57%) patients of NSTEMI had RC involvement alone. Three (13.04%) patients of STEMI and 3(21.43%) patients of NSTEMI were having combined involvement of RCA and LAD territory. One (7.14%) patient of NSTEMI was having LAD involvement and LV clot on ECHO.

Forty-seven (94%) patients recovered and were discharged on treatment of CAD. Two (4%) patients left against medical advice and 1(2%) patient who presented in Killip class IV, died of cardiogenic shock (Table 6).

Table 6: Distribution of Patients According to Outcome

In our study, patients were in the age group of 25-45 and mean age of presentation was 40.28 years (S D 4.699) of which 84 % were in age group 35-45. In a study by Sricharan KN et al. the mean age of the patients with acute M I was 37.03 years, with a maximum number of patients (70%) in the age group of 35-40 years [13].

Number of males in our study were 44 (88%) and number of females were 6(12%) with ratio of 8:1. A study in Singapore by Sricharan K N et al. showed male preponderance (90%). Male sex has been one of the best documented and the most consistent risk factors for coronary atherosclerosis. This can be explained by the fact that in women there is less prevalence of risk factors like smoking, alcohol abuse and dyslipidaemia and majority of women were premenopausal. The protective effects of oestrogens in preventing atherosclerosis have been clearly demonstrated in epidemiologic studies [13].

In our study, family history of CAD was present in 50% of the patients and these patients have genetic predisposition to CAD. Maximum number of patients had history of CAD in parents than siblings. Parental history of MI is often considered a surrogate for coronary risk factors, having associations with high blood pressure, poor lipid profiles and obesity in children and adults, as well as other biochemical and genetic markers. A study by Zimmerman et al. found higher incidence of CAD in younger men with family history of CAD [9].

In our study 43(86%) patients were smokers (p<0.05), smoking causes spasms in the coronary arteries and also predisposes to coronary artery atherosclerosis. Smoking-induced oxidative stress is considered to favour oxidation of low-density lipoprotein (LDL) and subsequently promotes the atherogenic process.⁸In our study smoking was significantly associated with chest pain and sweating (p<0.05). CAD in young patients is a rapidly progressive form of atheromatous process. Conventional risk factors like smoking, alcoholism, HTN and Diabetes play a larger part in younger patients who had MI. Studies in China and other countries demonstrated that young AMI patients have smoking rates as high as 70–90% and showed association of smoking with chest pain and STEMI in young patients (p<0.05).48 A study by Wang Y et al. showed association of smoking with chest pain and STEMI in young patients (p<0.05).48Most of the previous studies showed smoking as the most significant risk factor in young patients [8,14].

Twenty-six (52%) patients had history of alcohol abuse in our study group. Drinking excessive amount of alcohol causes raised Blood Pressure which predisposes the patients to ACS. Alcohol abuse also predisposes patients to atherosclerosis. A study by Pandey et al. [15] showed that alcoholics tend to develop atherosclerosis earlier in life.

Number of patients in our study with past history of HTN was 23(46%). Mean systolic Blood Pressure was 127.040+20.421 and diastolic BP was 83.6+12.917. In a study of association of hypertension with coronary artery disease onset in the Lebanese population, Milane et al. [16] studied comparison of age of CAD onset between risk factors groups. When comparing CAD age of onset among patients with various risk factors, results showed that there is a significant effect of risk factors on the age of onset of CAD (ANOVA test, p<0.001).

Number of patients in our study with past history of CAD was 4(8%). Thirty-one (62%) patients presented with Prediabetes or Diabetes. Tamita et al. [17] studied the high prevalence of impaired glucose regulation in patients with AMI. Newly diagnosed glucose intolerance predicts long term cardiovascular events in patients with AMI. Its adverse prognostic impact is as large as that of previously diagnosed DM. It was found that only 2% of individuals without previously diagnosed DM were diagnosed as having glucose intolerance. Therefore, the fasting glucose classification is not suitable for screening subsequent high-risk patients with glucose intolerance. Post challenge metabolic status of glucose is a better risk factor for future cardiovascular events than the fasting glucose level and may critically distinguish high risk individuals. Since impaired glucose regulation is an important cardiovascular risk factor.

Out of 50 patients, 24 (48%) patients had dyslipidaemia in our study. Dyslipidaemia was observed in 90% of the young patients of CAD in a study by Sharma et al. [18] of which 72.2% showed increased serum TG and decreased HDL cholesterol and LDL cholesterol were high in 77.8%.

Out of 50 patients of ACS, Metabolic Syndrome was present in 15 (30%) patients. Nineteen (47.5%) patients out of 40 fulfilled > 3/5 criteria for Metabolic Syndrome in a study by Hochman et al. [19]. A study by Pandey et al. [15] showed a high prevalence of multiple life style and metabolic cardiovascular risk factors like physical inactivity, high fat intake, low fruits and vegetables intake, smoking, alcohol, truncal obesity, hypertension, dyslipidaemias and the Metabolic Syndrome.

In our study, chest pain was the most presenting complaint (100%) and association of chest pain in different types of ACS in young patients was found to be significant (p<0.05), followed by sweating (80%) which was significant (p<0.05), palpitations (36%), syncope (34%), atypical symptoms like pain in epigastrium (20%), vomiting (14%) and SOB (14%). A study by Sricharan et al. [13] showed chest pain as the most common presenting complaint.

In our study group of totals 50 patients, 47 patients improved after treatment, 2 patients left against medical advice. One patient, who presented in cardiogenic shock, died. Mortality rate was 2% in our study group. In studies by Hochman et al. [19] and Chun et al. [20] the mean left ventricular function (E F) was 44% (SD 10%) with 3% incidence of heart failure and 4.5% incidence of cardiogenic shock with low in hospital mortality (1.2%).

The present study pointed to the risk factors and clinical profile of young patients with ACS. There was male preponderance; STEMI was most common with LAD most common territory involved. There was statistically significant association of CAD with smoking, total cholesterol levels, dyslipidaemia and Prediabetes. Other risk factors like family history of CAD, HTN, DM, alcohol abuse, cannabis abuse, Met Sand BMI were associated with CAD but not found to be statistically significant. Furthermore, this study also pointed to relevance TROP T, FBS, TLC, urine examination in ACS. Out of 50 patients enrolled in this study, 47 patients improved after treatment, 2 patients left hospital against advice and 1 patient died during hospital stay. This study showed that presentation of ACS in young adults was associated with better outcome and patients with more risk factors tend to develop CAD earlier in life.

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