European Journal of Cardiovascular Medicine

Acute myocardial infarction (AMI) is one of the most common clinical manifestation of coronary atherosclerosis representing a spectrum of conditions ranging from silent ischemia at one end to unstable angina, Non ST-segment Elevation Myocardial Infarction (NSTEMI) and ST-segment elevation myocardial infarction (STEMI) at the other end^.(1) Acute myocardial infarction (AMI) is the significant cause of death worldwide, with India having a huge burden of associated morbidity and mortality.⁽²⁾

The assessment of an individual patient’s risk factors determines the likelihood that a cardiovascular event will occur in a particular time period.⁽³⁾ MI presenting in young age has a different pathophysiology, risk factor and clinical profile compared  with older people.

Diabetes and hypertension is significantly higher among the elder group. Mean systolic BP and fasting plasma glucose levels were also higher in the elderly group.

There is a clear male preponderance in ACS (Acute Coronary Syndrome) patients, especially in younger MI cases. It may be due to presence of risk factors like smoking, hypertension and a poor lipid profile compared with females. However, this ratio changes after menopause, when the risk increases rapidly in women to equal that of men. This may be due to loss of the cardio-protective properties of estrogen. With increasing prevalence of smoking in females, this protection by estrogen has lost its effect, so an increasing number of young women with MI can also be expected.

There is a strong relation between serum total cholesterol and cardiovascular risk. Moreover, LDL cholesterol levels in young adulthood predict development of CVD (Cardiovascular Disease) later in life, supporting the idea that the relationship between LDL-C and development of CVD should be viewed as a continuous process beginning early in life. The efficacy of LDL-C lowering drug therapies to reduce CHD event rate and mortality has been shown in various clinical trials.

The aim of this study was to compare the epidemiological and risk factor profiles, including age, sex, family history of premature coronary heart disease (CHD), diabetes mellitus (DM), hypertension (HTN), smoking, dyslipidemia, obesity, and metabolic syndrome, in patients with acute coronary syndrome (ACS) across different age groups admitted to a tertiary care hospital in Kolkata, and to evaluate and compare novel atherogenic risk factors such as Apo-A, Apo-B, homocysteine, and lipoproteins among these patients.

It was a hospital based comparative Study conducted on 200 ACS patients admitted in a tertiary care hospital after taking approval from institution’s ethical and scientific committee and informed consent from the patient. Patients were divided into two groups. Group A: 100 patients less than 45years of age & Group B: 100 patients above age of 45 years. All patients fulfilling the criteria for ACS were eligible for participation in this study. Patients with Rheumatic heart disease, dilated cardiomyopathy, Stable angina, Acute or chronic liver disease, known case of nephropathy were excluded in this study.

All patients were subjected to full history taking, full general examination, and cardiac examination, ECG, echocardiography and laboratory investigation in the form of complete blood picture, renal function tests, liver function tests, and lipid profile (Serum cholesterol and  triglycerides(TGs),serum HDL and serum LDl, Lipoprotein(a), Apo(a1) ,apo(b), homocysteine were measured.

AMI is defined when there is acute myocardial injury with clinical evidence of acute myocardial ischemia and typical rise and/or fall of cardiac markers of myocardial necrosis with at least one of the following:

• Ischaemic symptoms
• Electrocardiogram (ECG) changes indicative of ischaemia (ST elevation or depression)
• Development of Pathological Qwaves in ECG
• Echocardiographic evidence of new regional wall motion abnormality
• Identification of coronary thrombus by angiography.

Important definitions:

Diabetes was defined as having a history of diabetes diagnosed and/or treated with medication and/or diet or fasting blood glucose 126 mg/dl or greater.

Hypertension was defined as having a history of hypertension diagnosed and/or treated with medication, diet, and/or exercise, blood pressure greater than140 mmHg systolic or 90 mmHg diastolic on at least two occasions.

Current smoker was defined as a person smoking cigarettes within 1 month of index admission.

A positive family history for Coronary artery disease (CAD) was defined as evidence of CAD in a parent, sibling, or children before 55 years of age.

Total cholesterol, TGs were estimated by enzymatic spectrophotometric method (Roche Diagnostics GmbH), LDL-C and HDL-C were estimated using direct method using auto analyser and Lp(a), ApoA, ApoB, and hsCRP were estimated by using turbidimetric immunoassay (Erbamanheim). Homocysteine (Roche Diagnostics GmbH) were determined by enzyme-linked immunosorbent assay on Cobas c501 autoanalyzer (Roche Diagnostics GmbH).

STATISTICAL ANALYSIS

Descriptive statistics was done for all data and were reported in terms of mean and percentages. Appropriated statistical tests of comparison were applied. Continuous variables were analyzed with t test and Mann Whitney U test where applicable. Categorical variables were analyzed with the help of chi square test. Statistical Significance was taken as p<0.05. The data was analyzed using SPSS version 22.

Table 1 – Comparison of biochemical parameters in both the groups

In our study mean age for group A was 37.04±4.57 years and for group B was 58.01±6.84 years. Our Study shows 94% male patients in group A and 84%male patients in group B. In our study there is statistically significant difference (p value 0.024) in number of females in both the groups with more females affected in group B. 58% patients were smokers in group A and 48% in group B. In our study the difference of smoking in both groups was statistically non-significant (p value 0.157). In this study 10% patients of group A were found hypertensive while 39% patients in group B were found hypertensive. The difference in prevalence of hypertension in both groups was found to be statistically significant (p value <0.001). In our study prevalence of diabetes was found to be 10% in group A and 28% in group B. The prevalence of diabetes was more in group B and the difference was statistically significant (p-value 0.001).

In our study obesity was prevalent in 8% patients in group A and 13% patients of group B. The difference was not statistically different (p value 0.249).

In our study a positive family history was present in 34% of patients of group A and only 16% patients of group B. The difference in prevalence among both groups was statistically significant (p value 0.003).

 In our study HDL-C value was 31.74± 4.04 vs 34.09± 6.57 (mg/dl) in group A and B respectively. The values were lower for group A and the difference was found to be statistically significant (p 0.003). In our study mean value of LDL-C in group A was 99.83 ±25.86 and 96.56±33.09 (mg/dl) in group B. The difference in value of LDL-C in both these groups was found to be statistically non-significant (p value 0.438).

In our study mean triglyceride value were found to be 151.70±22.40 mg/dl in group A and 149.97±17.61 mg/dl in group B. The difference of value in both the group was found to be not statistically significant (p value 0.546).

In our study mean homocysteine values were 24.21±8.61 µmol/l in group A and22.11±6.52 µmol/l in group B. The difference of levels was not statistically different in both the groups. (p value 0.053).

In our study the mean values of lipoprotein were found to be 32.02±9.68mg/dl in group A and 32.11±9.21mg/dl in groupB. The difference of levels was found to be non- significant (p value 0.632).

In our study the mean values of cholesterol were 177.08±29.45 mg/dl in group A and 182.06±26.04 mg/dl in group B. The difference of the values was found to be statistically non-significant (p value 0.632).

In our study mean values of Apo-A1 were 114±10.45 mg/dl in group A and 122.02±15.87 mg/dl in group B. The difference of values was found to be statistically significant (p value <0.001).

In our study mean values of Apo-B were 95.43±24.62 mg/dl in group A and 92.65±16.10 mg/dl in group B. The difference was found to be statistically non-significant (p value 0.346).

Age in our study is comparable to many of the previous studies such as those carried out by SN Uddin et al(2003), Prajapati J et al (2015), Das PK et al (2015).(4-6) In our study mean age of presentation was found to be 37.04±4.57years in younger age group and 58.01±6.84 years in older age group. The youngest patient in our study presenting with ACS was 24-year-old, suggesting a very early onset of ACS .This requires increased attention in younger age group and need of preventive measures from very early period of life.

In our study, there is a statistically significant difference in prevalence of females in both age group (p 0.024). Similar results were seen in studies by RumboldtZ et al (1995) (7),Badran, H. M et al (2009)(8), Das P K et al (2015)(6), Prajapati J et al (2015)(5), Gupta MD et al (2018)(9).The most obvious finding in our study was a very high prevalence of ACS among men as compared to women in both the age groups. It may be due to presence of risk factors like smoking, hypertension and a poor lipid profile compared with females. However, this ratio changes after menopause. This may be due to loss of the cardio-protective properties of estrogen and so a statistically significant difference in number of females in both age groups. However, with increasing prevalence of smoking in females, this protection by estrogen has lost its effect, so an increasing number of young women with MI can also be expected.

Smoking and tobacco chewing have also been traditionally recognized as the most common risk factors for heart disease in both age group patients more particularly in males. In our study, nearly half of the patients in both the age groups were either tobacco chewer or cigarette smoker. While the number is large, it should be emphasized that cigarette smoking is a reversible risk factors for ACS.

In our study no statistically significant difference was noticed between prevalence of smoking between both the age groups (p 0.157). This result is in concordance with earlier studies by Prajapati J et al (2015) (5) and Dzubur et al (2019)(10).in our study 58% of younger population and 48% of older population was found to be smoker. But many earlier studies have shown contrary patterns with statistically higher smoking prevalence among younger population Kaul Uet al (1986)(11), Garoufalis, S et al (1998)(12),Badran, H. M et al (2009)(8),Siddique MA et al (2010)(13), DasPKetal(2015)(6).

There was a statistically significant difference in prevalence of diabetes among both age groups according to our study (p 0.001). These results are in concordance with earlier studies Kaul U et al (1986)(11),Garoufalis S et al (1998)(12), Badran HMet al (2009)(8), Siddique MA et al (2010)(13), Gupta MD et al(2018)(9), DzuburA et al (2019)(10). In our study diabetes was prevalent in 28% of older age group and only 10% of study population in younger group.

In our study hypertension was found to be more in older age group (39%) as compared to the younger age group (10%) and the difference was statistically significant (p0.001).Similar results were shown by previous studies by Garoufalis,S et al (1998)(12), Badran, H. M et al (2009)(8),Siddique MA et al (2010)(13), Das P K et al (2015)(6), Prajapati J et al (2015)(5), Gupta MD et al (2018)(9).

In our study obesity in younger and older age groups was found only in 8% and 13% of study population and the difference of obesity between both the groups was not statistically significant (p 0.249). Similar results was shown by studies conducted by Garoufalis S et al (1998) 10% vs 10.7% ; Das P K et al ( 2015) 8.1% vs 7.8% ; Gupta MD et al ( 2018) 16% vs 8%.The difference amongst the two groups was found to be non-significant in these studies as well.

In our study positive family history of CAD was found in much more of younger age group patients as compared to older age group (34% vs 15%). The difference is highly significant (p 0.003). Our results are in concordance with earlier studies Kaul U et al (1986),Garoufalis S et al (1998), Badran HM et al (2009), Siddique MA et al (2010), Das P K et al (2015), Prajapati J et al (2015), Gupta MD et al (2018).

Our study showed a statistically significant difference in HDL levels between both the groups (p 0.003) .similar results to our study were shown by Badran HM et al (2009), Gupta MD et al (2018).

In our study we did not find any statistically significant difference in LDL levels between both the groups (p 0.438). Similar results were obtained by earlier studies by Siddique MA et al (2010) (p 0.670) and Gupta MD et al (2018) (p 0.651).

In our study we did not find any statistically significant difference in levels of triglycerides in between both the study groups .Similar results were shown by earlier studies conducted by Siddique MA et al (2010), Prajapati J et al (2015), Gupta MD et al (2018).

In our study the difference in levels of homocysteine were statistically non- significant between the two study groups (24.21±8.61 vs 22.11±6.52 µmol/l) with P value 0.053.Similar results were shown by earlier study conducted by Prajapati J et al (2015), Gupta MD et al (2018).Elevated homocysteine levels (>15 μmol/L) were found in 80% and 82% of patients in the young and the older groups. The reason behind the high prevalence of hyper homocysteinaemia in our patients could be their poor diet because of poverty , prevalent smoking . However because of prevalent non-vegetarian diet in region severe hyper homocysteinemia in uncommon in both age groups.

In our study the difference in values of lipoprotein (a) was found to be statistically non-significant between the younger and older age group (p 0.207). The mean lipoprotein (a) values were 32.02±9.68 vs 32.11±9.21(mg/dl) in group A and group B respectively. Our results were in concordance with earlier studies by Prajapati J et al (2015), Gupta MD et al (2018). High Lp(a) levels are highly correlated with the severity of ACS, and the effect of Lp(a) on the atherogenicity is reported to be multiplicative and not additive . In the present study, 55% and 53% patients in the young and the older groups respectively had elevated Lp(a) levels (>30 mg/dL).

In our study the difference in levels of cholesterol was statistically non- significant between both study groups (0 0.632).Similar findings were reported earlier by a study conducted by Gupta MD et al (2018).

In our study the difference between levels of Apo-A was statistically significant. With relatively lower values found in younger age group.114.93±10.45 vs 122.02±15.87 mg/dl in group A and group B respectively (p <0.001).similar results were shown by earlier study conducted by Sniderman AD et al in 2016(14) with lower values of Apo-A in younger age group than in older age group and the difference was found to be statistically significant. The difference of value increased with an increasing age of patient. Gupta MD et al (2018) showed a similar trend of lower Apo- A in younger age group as compared to older age group, however this difference was not found to be statistically significant. ApoA is the main protein moiety in HDL and a stronger prognostic marker than HDL. Similar to HDL, lowest levels of ApoA1 was observed in younger MI patients indicating it as a potent risk factor in addition to HDL-C.

In our study the difference between levels of Apo-B between both groups was statistically non-significant (p 0.346). Similar results were shown with a study conducted by Gupta MD et al (2018) (9).

Based on the study findings we investigated role of conventional and non- conventional biochemical risk factors and the age-related differences in atherosclerotic risk factors in patient presenting with ACS. Dyslipidaemia and smoking were the most common ACS risk factors in patients of both the groups. Hypertension and diabetes mellitus were more common among older patients, while family history of CAD was more common among younger patients. Among novel atherogenic risk factors, low HDL-C and Apo A1 levels are possible risk factors for MI at young age. However, a comprehensive, multi centre study is required to offer a better picture of the novel risk-factor profile in young and older patients with ACS.

LIMITATIONS OF STUDY

1. Study population was small, and was conducted in a single centre so the results of the study did not corroborate with many other epidemiological Studies conducted
2. Since this is an observation from a tertiary care hospital certain biasness may come. Most of ACS cases were referred from different hospitals. So, the results may not be proper reflection of the disease incidence and prevalence in the community.
3. Diagnostic modalities-this study was based on estimation  of a number of biochemical parameters, so the results of this study would be influenced by the laboratory values which demand immense technical skill of the technician involved.
4. It is difficult to compare the result with other studies; all have applied different methods for analysis.

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