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Biomedical Research

The prevalence of hyperhomocysteinemia and its correlation with conventional risk factors in young patients with myocardial infarction in a tertiary care centre of India

Author(s): Kumar A, Khan S A, Parvez A, Zaheer M S, Rabbani M U, Zafar L

Vol. 22, No. 2 (2011-04 - 2011-06)

Kumar A, Khan S A, Parvez A, Zaheer M S, Rabbani M U, Zafar L

Department of Medicine, Jawaharlal Nehru Medical College, Aligarh Muslim University, Aligarh, India.

Abstract

Coronary artery disease (CAD) has become the most common cause of mortality in the en-tire world. Indians are more prone to premature coronary artery disease. About 20% pa-tients with CAD have no identifiable risk factors. Thus the importance of homocysteine as a risk factor for CAD in Indian patients needs to be recognized. The aim of this study was to assess the homocysteine levels in young patients with myocardial infarction (MI) and to compare them with conventional risk factors. The study was conducted in 30 male pa-tients of acute myocardial infarction admitted in Coronary Care Unit. All were younger than 45 yrs with no history of previous CAD. Plasma homocysteine was assayed using photometry. Fasting lipid profile and other risk factors were compared. In the present study the mean age of the patients was 39.5 ± 2.8 years. The prevalence of hyperhomocys-teinemia was 83.3%. The mean homocysteine was more in smokers than in nonsmokers (32.1 ± 3.5 vs 24.3 ± 5.7, p< 0.001). Homocysteine level had significant negative correlation with serum HDL level (Pearson’s coefficient -0.437; p value =0.016). No association of hy-perhomocysteinemia with other conventional risk factors was found. Plasma homocysteine has emerged as a significant independent risk factor for young MI patients. Therefore, plasma homocysteine should be evaluated in all young patients with myocardial infarction especially in the absence of traditional risk factors.

Key words: Myocardial infarction, young patients, plasma homocysteine, conventional risk factors, serum lipid profile
Accepted December 07 2010

Introduction

Coronary artery disease (CAD) has become a major health problem all over the world. It is the most common cause of mortality in the entire world [1]. Coronary artery disease (CAD) is the leading causes of death each year in the United States and Europe, accounting for nearly 40% of all deaths [2]. India is in epidemiological transition. In addition to the burden of endemic infections, the emerg-ing threat of non-communicable diseases is a matter of concern. Previously, CAD was considered to be a result of an urban lifestyle, however, recently published studies have indicated that CAD is also on the rise in rural areas [3, 4]. The prevalence of CAD is four-fold higher in ur-ban India and two-fold higher in rural India than in the United States [4]. The incidence of CAD in the young has been reported to be 12%–16% in Indians [5, 6]. About 50% of the CAD-related deaths in India occur below the age of 50 years, and about 25% of acute myocardial in-farction in India occurs under the age of 40 years [7, 8].

Although traditional risk factors such as hyperlipidemia, smoking, hypertension, and diabetes mellitus are thought to explain most CAD, 15% to 20% of those with CAD have no identifiable risk factors and therefore miss the opportunity for primary prevention [9]. For this reason, epidemiologists and biologists have tried to identify other risk factors that predict a portion of CAD events that might improve primary prevention efforts. Elevated plas-ma homocysteine level is a suggested and biologically plausible candidate. Interest in homocysteine as a causal factor was spurred by the observation that more than 50% of children with the genetic disorder homocystienuria die of premature vascular disease [10] and strategies that re-duce homocysteine levels in these children have been shown to decrease vascular event rates [11]. In humans, moderate increase of homocysteine levels can occur be-cause of less severe genetic mutations associated with enzyme abnormalities in the metabolic pathway involving folate and homocysteine. However, inadequate intake of vitamin B12, which play an important role in homocys-teine metabolism, may be an important cause of elevation of homocysteine level.

This study was carried out to assess the homocysteine levels in CAD patients and to compare these with conven-tional risk factors such as hypertension, smoking, diabe-tes, obesity, family history and abnormal lipid profile. Present study was conducted in CAD patients less than 45 years of age in Indian population [12]) who had acute myocardial infarction.

Material and Methods

The present study was conducted in the Department of Medicine, J.N. Medical College Hospital, AMU, Aligarh. A total of 30 male patients of acute myocardial infarction admitted in Coronary Care Unit were studied. A diagnosis of CAD was strictly based on WHO criteria i.e. ischemic type chest pain, evolutionary changes on serially obtained EKG tracings, rise of serum cardiac markers and echocar-diograms. The local institutional review committee ap-proved the protocol, and informed consent was obtained from each subject involved in the study. The name, age, sex, occupation and clinical history were noted. Previous history of diabetes, smoking, hypertension, positive fam-ily history, and hospitalization for ischemic heart disease, were noted. Negative history of jaundice, alcoholism, burning micturition, haematuria, tremors and pregnancy were ascertained. Patients with no definite acute myocar-dial infarction, age more than 45 years, impaired renal function, hypo/ hyperthyroidism were excluded from the study. It was made sure that patients were not on drugs (e.g. theophylline, oral contraceptives, methotrexate, anti-convulsants, penicillamine, acetylcysteine and vitamins) known to affect the homocysteine levels. A thorough clin-ical examination was done. Fasting blood samples were taken for biochemical tests. Estimation of plasma homo-cysteine was done by photometry using the diaenzyme homocysteine 2-reagent enzymatic assay kit. Statis-tical analysis was performed using SPSS version 16.0 statistical package for windows (SPSS, Chicago, IL). Un-paired t test for independent samples was used in compar-ing data between two groups. Linear relationship among continuous variables was analysed using Pearson’s corre-lation coefficient. All p values were two tailed and values of <0.05 were considered to indicate statistical signifi-cance. All confidence intervals were calculated at 95% level.

Results

All the patients included in this study were below the age of 45 years. The mean age of patients was 39.5 ± 2.8 years. Out of 30 patients, 11(36.7%) were hypertensive, 10(33.3%) were smoker, and diabetes was present in 9(30%) patients. Obesity (BMI ≥30 kg/m2) was present in 7(23.3%) patients while 14(46.7%) patients had sedentary lifestyle. None of the patients had family history of pre-mature CAD. Twenty patients (66.7%) had LDL >100 mg/dl while TG >150mg/dl was present in 10 (33.3%) of patients and low HDL (<40mg/dl) was present in 8 (26.7%) patients (Table1).

Normal levels of plasma homocysteine usually range from 5 to15 mmol/L [13]. Higher fasting values are arbi-trarily classified as moderate (16 to 30 mmol/l), interme-diate (31 to 100 mmol/L) and severe (>100 mmol/L) hy-perhomocysteinemia. In our study, the prevalence of moderate and intermediate hyperhomocysteinemia was 43.3% and 40.0% respectively. The mean homocysteine level was 26.9 ± 6.2 μmol/L. Smokers had significantly higher level of plasma homocysteine than non smokers (32.1±3.5 vs 24.3±5.7, p< 0.001). We found higher mean homocysteine level in patients without diabetes than in patients with diabetes but the difference was not signifi-cant (Table 1).

Table 1. Mean homocysteine level with respect to conventional risk factors and outcome

Table 1

Table 2. Correlation of homocysteine level with age and serum lipid profile

Variables Pearson’s coefficient p value
Age 169 373
LDL 075 693
HDL 437 016
TG 185 328
Total cholesterol 000 999

Table 3. Salient features of the coronary artery disease (CAD) epidemic in India [5, 6, 14, 15]

  • India topped the world with 1,531,534 cardiovascular disease-related deaths in 2002
  • Median age of first heart attack in Indians is 53 years
  • Incidence of CAD in young Indians is about 12%–16%, which is higher than any other ethnic group
  • About 5%–10% of heart attacks occur in Indian men and women younger than 40 years
  • Age-standardized estimates for disability-adjusted life-years lost due to CAD per 1000 popu-lation in India are three times higher than in developed countries

Table 4. Prevalence of hyperhomocysteinemia in India

Study Age of participants Prevalence
Chacko K A [21] 1998, Cochin >40 yrs 41.1%
Yashwant K et al. [22], 2009,Chandigarh <40 yrs 58.0%
Nair et al. [23], 2002, Mumbai >40 yrs 19%
Deepa et al. [24], 2000, Chennai >40 yrs 19%
Puri A et al. [25], 2003, Kanpur <45 yrs 72.5%
Khare et al. [26], 2004, Mumbai <40 yrs 25.1%
Our study <45 yrs 83.3%

Table 5. Mean homocysteine (μmol/l) in different Indian studies

STUDY CASES CONTOLS
Puri A et al25, 2003,Kanpur 27.8 ± 13.11(n=51) 13.22± 7.4 (n=15)
T.Angeline et al. [28], 2005, Madurai 24.59 ± 6.14( n=60) 13.73± 3.54 (n=35)
R Abraham et al. [29], 2006, Pondicherry 22.81 ± 13.9, n=70 (7.77 ± 7.3, n=70).
Harish Rao B et al. [30], 2007, Bangalore 18.59 ± 2.63(n=156) 11.69 ± 2.8 (n=117)
Mili Gupta et al. [31], 2005, Chandigarh 16.57 ± 6.86(n=100) 11.47 ± 5.19 (n=50)
Col DS Jaswal et al. [32], 2008 34.14 (n=100) 24.85 (n=100)
Bhagwat V R et al. [33],2009, Maharashtra 32.48 ± 18.99(n=50) 18.49 ± 8.41 (n=50)

Homocysteine level had significant negative correlation with HDL level (Pearson’s coefficient -0.437; p value =0.016) (Table 2). In our study we did not find significant association of homocysteine with increasing age, hyper-tension, diabetes, obesity, sedentary lifestyle, high LDL and hypertriglyceridemia. There was no significant differ-ence in mean homocysteine level in patients with STEMI and NSTEMI.

Discussion

Young patients in most populations are characterized by less extensive coronary artery disease and relatively fa-vorable prognosis as compared to older patients. In con-trast, young Asian Indians with CAD usually have a poorer prognosis because of extensive atherosclerosis and multi-vessel disease. Studies in the past have shown that high rates of CAD in Asian Indians are accompanied by paradoxically low prevalence of conventional risk factors such as hypertension, hypercholesterolemia and smoking. (Table 3)

In the present study the mean age of the patients was 39.5 ± 2.8 years. In the Indian subcontinent CAD occurs about a decade earlier, as compared to the western world. The incidence of CAD in men below 45 years of age was as high as 18% as given by health information India in 1988.

Boushey et al [16] reported a meta-analysis of 27 obser-vational studies in which it was estimated that about 10% of coronary heart disease in the general population might be attributed to homocysteine. Graham et al.[17] in the large European collaborated study (ECAP) concluded that homocysteine was an independent risk factor for athero-sclerotic disease. A study by Chambers et al.[18] sug-gested plasma homocysteine as an independent risk factor in Indian migrants to UK. Population studies have shown that plasma homocysteine concentrations are higher in immigrant ethnic Indians compared to North Americans and European Whites [18, 19]. Reduced intake of vitamin B12 has been reported in Indians and cooking may further destroy folate content [20]. This may account for higher homocysteine levels in Indians. The prevalence of hyper-homocysteinemia was 83.3% in our study. In CAD pa-tients this was 72.5% in the study done by Puri et al [25]. The prevalence rate in other Indian studies is shown in Table 4.

In our study the mean level of homocysteine in patients was 26.9 ± 6.2 μmol/L. In a study of plasma homocyste-ine in young MI patients Puri et al [25] found mean level of homocysteine as 27.8 ± 13.11 μmol/L. In the hyperlipi-demic patients homocysteine was 28.7 ± 4.6 while in the normolipidemic patients it was 19.9 ± 7.34 μmol/L (p=0.001). Thus there was a significant difference in the homocysteine levels in relation to the lipid profile. In our study no significant difference in mean homocysteine level between patients having ST elevation myocardial infarction as compared to patients with non-ST elevation myocardial infarction. There is significant variation in mean homocysteine level among patients of CAD in dif-ferent parts of India. Deepa et al [24] described that there was no difference in plasma homocysteine levels in sub-jects with and without CAD. Chacko [21] and Sastry [27] found similar conclusions in their study. A review of oth-er Indian studies is given in Table 5.

Conclusion

Our study concludes that intermediate grade of hyperho-mocysteinemia is present in most of the patients of acute myocardial infarction. Significantly higher level of homo-cysteine is found in smokers. However, there is no sig-nificant association between hyperhomocysteinemia and other conventional risk factors (age, hypertension, obe-sity, diabetes and sedentary lifestyle). Thus, plasma ho-mocysteine should be evaluated in all young patients of myocardial infarction especially in the absence of tradi-tional risk factors.

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Correspondence to:
Abhishek Kumar

C/O- Professor R. Dayal
HIG 56, Awantika Phase 1
Ramghat Road
Aligarh 202001, India

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