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MICRONUTRIENTS AND TRACE ELEMENTS IN ACUTE MYOCARDIAL INFARCTION

Sreekanth KS, Geevar Zachariah, Annamalai PT

Departments of Clinical Biochemistry and Cardiology, Amala Cancer Hospital and Research Centre, Amala Nagar, Thrissur - 680 553, Kerala.

SUMMARY

Acute myocardial infarction (AMI) continues to be a major public health problem in the developing world, despite impressive strides made in its diagnosis and management. Among the several causes of the disease alteration in the levels of micronutrients and trace elements are also important. The present study was focused on the alteration of these elements in AMI patients as compared to that of the healthy individuals and their changes depending up on different risk factors. The present study included 300 AMI patients and 100 healthy individuals as controls. We observed a decreased value of vitamin E, vitamin C, zinc and magnesium (p<0.01) in the serum of AMI patients when compared to that of the normal controls. However the values of iron, % transferrin saturation and ferritin were found to be significantly increased in these patients (p<0.01), but the value of total iron binding capacity was found to be significantly decreased (p<0.01) in AMI patients. The distributions of these parameters were significantly differed among various risk factors studied.

INTRODUCTION

Acute myocardial infarction (AMI), an important manifestation of coronary artery disease (CAD) is emerging as one of the major cause of mortality worldwide. Several factors have been attributed for the cause of the disease. But the exact mechanism responsible for the cause and complication is still unknown. Micronutrients and trace elements are very essential for the normal functioning of the body. Even though they are required in very small amounts, an alteration in the level of these elements may lead to serious impairments which in turn lead to diseases like CAD. Prospective studies have demonstrated reduced risk of coronary artery disease in subjects with a greater intake of vitamin E1 or vitamin C2, because these antioxidant vitamins inhibit oxidation of low-density lipoprotein (LDL), a critical event in the coronary artery disease. Further vitamin E and vitamin C, the two essential micronutrients, is capable to remove the oxygen-derived free radicals by virtue of their antioxidant property.

The role of essential micronutrient metals in lipid metabolism is of recent investigation. The metabolism of zinc (Zn) is significantly altered in patients with cardiovascular disease as evidenced by abnormally low plasma or serum concentrations of zinc. Recent studies have shown a relationship between zinc status and the metabolism of cholesterol and lipoproteins3. Magnesium (Mg), another trace element is essential for the activation of a variety of enzymes involved in cellular metabolism, especially in neurochemical transmission and muscular activity. It has been shown that magnesium depletion modifies coronary blood flow, blood clotting and atherogenesis 4. There is a strong relationship between iron levels and cardiovascular disease. It has been observed that the amount of iron has been increased considerably in patients with acute myocardial infarction, which in turn can stimulate the lipid peroxidation5.

The present study evaluate the role of the trace elements such as iron, zinc and magnesium and micronutrients such as vitamin E and vitamin C along with ferritin, total iron binding capacity and % transferrin saturation in patients with acute myocardial infarction and their sequential variation in the complication of acute myocardial infarction associated with different risk factors taken in to account.

MATERIALS AND METHODS

The study period was from November 1999 to September 2003. All patients admitted to the Intensive Coronary Care Unit (ICCU) of Amala Cancer Hospital with a diagnosis of acute myocardial infarction presenting within 24 hours of onset of chest pain during this period were included in the study. Present study included 300 AMI patients and 100 sex and age matched control subjects. Myocardial infarction was diagnosed by at least 0.1-mv ST segment elevation in two or more contiguous limb leads or 0.2-mv ST segment elevation in two or more chest leads associated with typical chest pain. Patients with cardiogenic shock, cerebrovascular accident and significant hepatic or renal disease were excluded. Patients with clear evidence of infection anywhere in the body were also excluded.

In patients included in the study, detailed history was taken and complete physical examination was carried out by the cardiologist. A 12 lead ECG with V3R and V4R is recorded immediately on admission and repeated after 2hrs, 6hrs, 12hrs, 24hrs, 48hrs and pre-discharge. 10ml blood was withdrawn for laboratory analysis. Serial creatine kinase assays were also done to confirm the myocardial infarction and it was done at 2hrs, 6hrs, 12hrs, 24hrs, 48hrs after admission. Chest X- ray was done at the time of discharge from the ICCU. An echocardiographic examination was performed at the time of discharge or at the end of the first week or early second week after admission. All patients were seen in the cardiology out-patient department 4 to 6 weeks after discharge, when a detailed history was taken and complete physical examination was again carried out. A symptom limited treadmill test was done as per the Bruce protocol and maximum heart rate (HR), blood pressure (BP), double product, time to 1 mm ST depression, metabolic equivalences (METs) achieved, duration of exercise, angina, dyspnea and arrhythmias were recorded along with ST segment changes.

The normal volunteers had no past history or evidence of cardiovascular disease, hypertension or diabetes mellitus. The present study does not include control subjects with a history of neoplastic, hepatic, infectious or autoimmune disease or any surgical procedure in the preceding 6 months.

The patients were allowed to relax and on the second day they were subjected to an oral questionnaire as described in our Performa, in order to collect the history of these patients. They were asked about the type of chest pain, the time of onset of the pain, radiation to other parts of the body and any previous history of chest pain. They were also asked about the symptoms associated with the chest pain, history of diabetes, history of hypertension, habits of smoking or alcohol or pan chewing, food habits (vegetarians or non vegetarians) and any positive family history of AMI. Then these patients were categorized according to the following risk factors and based on these risk factors the study has been designed.

1) Age and sex
2) Time of onset of chest pain
3) History of diabetes and hypertension
4) A cholesterol value of <200 mg/dl and >200 mg/dl
5) Habits of smoking and alcohol intake
6) Food habits and a positive and negative family history of AMI.

Plasma tocopherol was assayed using the Emmeric Engel reaction6, Vitamin C was done by the photometric reduction method7, Zinc in the serum was detected by the Nitro-PAPS method8 and magnesium was done by the Xylidyl blue method9. Iron was estimated by the reaction with a, a'-dipyridyl10, Total Iron Binding Capacity (TIBC) was done by the addition of magnesium carbonate, and then following the same reaction for iron 11. Percentage saturation of transferrin was done by using the formula: (iron/TIBC) X 10012 and ferritin was estimated in the serum by a solid phase enzyme linked immunosorbent assay (ELISA)13. The statistical analysis was done by using the 'z- test' and the inter group comparison were done by the analysis of variance (ANOVA)14.

RESULTS

Table 1 represents the values of micronutrients and trace elements in normal and in AMI patients. Here the values of vitamin E, vitamin C, Zn and Mg were found to be decreased significantly (p<0.01) in the serum of the AMI patients when compared to that of the normal controls.

Table 1: Values of micronutrients and trace elements in various groups

Parameters	Groups
	Normal (n=100)	AMI (n=300)
Vitamin E (mg/dl)	5.94± 0.82	2.89± 0.75**
Vitamin C (mg/dl)	1.19± 0.22	0.24± 0.13**
Zn (mg/dl)	48.71± 8.71**	88.82 ± 12.04
Mg (mg/dl)	0.73 ± 0.36**	2.31 ± 0.30

Values are mean ± SD, **p<0.01

Table 2: Micronutrients and trace elements in normal and in AMI patients according to age and sex

Parameters	Age (years)						Sex
	<40		40-60		>60		Male		Female
	Normal n=22	AMI n=27	Normal n=54	AMI n=160	Normal n=24	AMI n=113	Normal n=85	AMI n=261	Normal n=15	AMI n=39
Vitamin E (mg/dl)	5.80±0.86	2.56±0.11*	6.03±0.80	2.98±0.778*	5.86±0.79	2.84±0.55*	5.95±0.82	2.89±0.78*	5.88±0.80	2.84±0.56*
Vitamin C (mg/dl)	1.15±0.24	0.19±0.13*	1.21±0.22	0.23±0.14*	1.19±0.21	0.27±0.12*	1.19±0.23	0.23±0.13*	1.20±0.22	0.29±0.12*
Zn (mg/dl)	89.47±12.08	51.00±8.42*	88.62±11.74	48.08±9.01*	88.69±12.64	49.04±8.31*	89.15±11.95	48.57±8.84	87.00±12.36	49.64±8.01*
Mg (mg/dl)	2.19±0.27	0.72±0.29*	2.36±0.29	0.63±0.31*	2.29±0.30	0.87±0.39*	2.30±0.30	0.71±0.35*	2.36±0.29	0.90±0.37*

Values are mean ±SD; * p<0.01.

Table 2 represents the values of micronutrients and trace elements in normal and in AMI patients according to the age and sex. Irrespective of the age and sex the values of all these parameters were significantly decreased (p<0.01) in all the groups when compared to that of their respective controls. Among the age groups the value of vitamin C was found to be significantly decreased in AMI patients with age

40 years when compared to the other two groups and the value Mg was found to be decreased significantly in AMI patients with age ranges from 40-60 years, when compared to that of the other two groups. Vitamin E and Zn did not show any significant variation among the groups. The values of vitamin C and Mg were found to be significantly decreased in AMI males when compared to that of AMI females. Here also the values of vitamin E and Zn did not show much alteration between the groups.

Table 3: Micronutrients and trace elements according to the time of onset of chest pain

Parameters		Time of onset of chest pain
	Normal	Acute MI
		12am to 6 am (n=50)	6 am to 12 noon (n=94)	12 noon to 6 pm (n-90)	6 pm to 12 am (n=66)
Vitamin E (mg/dl)	5.94±0.82	2.51±088*	2.79±0.67*	3.25±0.75*	2.82±0.55*
Vitamin C (mg/dl)	1.19±0.22	0.21±0.14*	0.24±0.16*	0.22±0.11*	0.29±0.11*
Zn (mg/dl)	88.82±12.04	49.13±7.93*	47.66±8.01*	48.60±10.39*	50.03±7.54*
Mg (mg/dl)	2.31±0.30	0.67±0.26*	0.65±0.35*	0.71±0.35*	0.92±0.38*

Values are mean±SD; * p<0.01

Table 4: Micronutrients and trace elements in patients with diabetes and hypertension

Parameters		Acute MI
	Normal	Diabetes		Hypertension
		Diabetes (n=101)	No diabetes (n=199)	Hypertension (n=62)	No hypertension (n=238)
Vitamin E (mg/dl)	5.94+0.82	2.51+0.74*	3.08+0.69*	2.62+0.56*	2.95+0.78*
Vitamin C (mg/dl)	1.19+0.22	0.21+0.15*	0.25+0.12*	0.22+0.16*	0.24+0.13
Zn (mg/dl)	88.82+12.04	47.65+8.24*	49.24+8.88*	16.55+8.48*	49.27+8.71*
Mg (mg/dl)	2.31+0.30	0.65+0.28*	0.77+0.38*	0.65+0.32*	0.75+0.37*

Values are mean±SD; * p<0.01

Table 3 represents the values of micronutrients and trace elements in normal and in AMI patients according to the time of onset of chest pain. Here the values of vitamin E, vitamin C, Zn and Mg were found to be significantly decreased (p<0.01) in all the AMI patients with different time of onset of chest pain. The values of vitamin E and vitamin C were found to be significantly altered in AMI patients with onset of chest pain from 12 midnight to 6 am when compared to the other three groups. The value of Mg was found to be significantly altered in AMI patients with onset of chest pain from 6 am to 12 noon when compared to the other three groups. However the value of Zn was not differed significantly among the groups with different time of onset of chest pain.

Table 4 represents the values of micronutrients and trace elements in normal and in AMI patients with the history of diabetes and hypertension. Here the values of these micronutrients and trace elements were found to be decreased significantly (p<0.01) in AMI patients with and without the history of diabetics and hypertension when compared to that of the normal healthy individuals. A comparison of AMI patients with and without the history of diabetes have shown the significant values of vitamin E, vitamin C and Mg in AMI patients with the history of diabetes when compared to AMI patients without the history of diabetes. However the values of Zn did not show any significant difference between these two groups. A comparison between the AMI patients with and without the history of hypertension has shown significant values of Zn and Mg in AMI patients with the history of hypertension when compared to that of the AMI patients without the history of hypertension. Vitamin E and vitamin C did not differ between these groups.

Table 5: Micronutrients and trace elements according to blood cholesterol

Parameters		Acute MI
	Normal	Cholesterol
		> 200 mg/dl (n=105	<200 mg/dl (n=195)
Vitamin E (mg/dl)	5.94±0.82	2.51±0.72*	3.09±0.69*
Vitamin C (mg/dl)	1.19±0.22	0.21±0.16*	0.25±0.12*
Zn (mg/dl)	88.82±12.04	47.22±8.36*	49.51±8.77*
Mg (mg/dl)	2.31±0.30	0.64±0.28*	0.78±0.38*

Values are mean±SD; * p<0.01

Table 5 gives the values of micronutrients and trace elements in normal and in AMI patients according to the values of cholesterol. Here the values of vitamin E, vitamin C, Zn and Mg were found to be significantly decreased (p<0.01) in AMI patients with cholesterol value >200 mg/dl and <200 mg/dl. A comparison between the values of these micronutrients and trace elements in AMI patients with cholesterol value>200 mg/dl and <200 mg/dl have shown significant values of vitamin E, Zn and Mg in AMI patients with cholesterol value>200 mg/dl when compared to AMI patients with cholesterol value <200 mg/dl. The value of vitamin C was found to be unaltered between these two groups.

Table 6: Micronutrients and trace elements according to habits of smoking and alcohol intake

Parameters	Smoking				Alcohol intake
	Yes		No		Yes		No
	Normal (n=62)	AMI (n=222)	Normal (n=38)	AMI (n=78)	Normal (n=20)	AMI (n=160)	Normal (n=80)	AMI (n=140)
Vitamin E (mg/dl)	5.90±0.81	2.91±0.82*	6.00±0.81	2.82±0.54*	5.85±0.89	2.99±0.80*	5.96±0.79	2.80±0.69*
Vitamin C (mg/dl)	1.18±0.23	0.22±0.14*	1.20±0.21	0.28±0.12*	1.15±0.25	0.22±0.15*	1.20±0.22	0.25±0.11*
Zn (mg/dl)	89.17±11.40	48.42±9.03*	88.26±13.03	49.52±7.81*	89.24±12.64	48.70±8.66*	88.71±11.91	48.72±8.81*
Mg (mg/dl)	2.28±0.29	0.68±0.33*	2.36±0.30	0.88±0.39*	2.17±0.27	0.66±0.32*	2.35±0.29	0.81±0.39*

Values are mean±SD; * p<0.01

Table 7: Micronutrients and trace elements according to food habits and family history

Parameters	Food habits				Family history
	Vegetarians		Non vegetarians			AMI
	Normal (n=16)	AMI (n=27)	Normal (n=84)	AMI (n=273)	Normal (n=100)	Positive (n=82)	Negative (n=218)
Vitamin E (mg/dl)	5.84±0.78	3.88±0.60*	5.96±0.82	2.79±0.69*	5.94±0.82	3.36±0.73*	2.71±0.69*
Vitamin C (mg/dl)	1.12±0.22	0.21±0.11*	1.19±0.23	0.24±0.14*	1.19±0.22	0.25±0.15*	0.23±0.13*
Zn (mg/dl)	87.34±12.04	46.32±9.43*	89.11±12.06	48.94±8.60*	88.82±12.64	47.85±8.66*	49.03±8.71*
Mg (mg/dl)	2.39±0.31	1.02±0.32*	2.29±0.29	0.70±0.35*	2.31±0.30	0.74±0.35*	0.73±0.36*

Values are mean±SD; * p<0.01

Table 6 represents the values of micronutrients and trace elements in normal and in AMI patients according to the habit of smoking and alcohol intake. Here the values of vitamin E, vitamin C, Zn and Mg were found to be significantly decreased (p<0.01) in AMI patients with and without the habits of smoking and alcohol intake when compared to their respective controls. A comparison of AMI patients with and without the habit of smoking has shown significant values of vitamin C and Mg in AMI patients with the habit of smoking when compared to that of the AMI patients without the habit of smoking. Vitamin E and Zn did not show any significant alteration between the groups. A comparison between the AMI patients with and without the habit of alcohol intake have shown significant value of Mg in AMI patients with the habit of alcohol intake when compared to AMI patients without the habit of alcohol intake. The values of vitamin E, vitamin C and Zn were unaltered between these two groups.

Table 7 represents the values of micronutrients and trace elements in normal and in AMI patients according to the food habits and family history of AMI. The values of all these micronutrients and trace elements were found to be significantly decreased (p<0.01) in AMI patients with the habit of both vegetarian and non vegetarian food intake and with and without the family history of AMI. A comparison between the AMI patients with vegetarian and non vegetarian food intake have shown significant value of vitamin E and Mg in AMI patients with the habit of non vegetarian food intake when compared to that of the AMI patients with the habit of vegetarian food intake. The values of vitamin C and Zn were found to be unaltered between these groups. A comparison between the AMI patients with and without the family history of AMI have shown the significant value of vitamin E in AMI patients without the family history of AMI when compared to AMI patients with the family history of AMI. The values of vitamin C, Zn and Mg were found to be unaltered between these groups.

Table 8 represents the values of iron, TIBC, %transferrin saturation and ferritin in normal and in AMI patients. The values of iron, %transferrin saturation and ferritin were found to be significantly increased (p<0.01) in AMI patients when compared to that of the normal controls. However the value of TIBC was found to be significantly decreased (p<0.01) in AMI patients when compared to that of the normal controls.

Table 8: Values of iron, transferrin saturation (%) and ferritin in normal and AMI patients

Parameters	Groups
	Normal (n=100)	AMI (n=300)
Iron (mg/dl)	99.67±13.51	154.96±23.08*
TIBC (mg/dl)	324.74±15.84	256.21±24.16*
Transferrin saturation %	30.68±4.35	59.87±4.00
Ferritin (ng/ml)	65.78±12.78	131.3±24.76

Values are mean±SD; * p<0.01

Table 9 represents the values of iron, TIBC, %transferrin saturation and ferritin in normal and in AMI patients according to the age and sex. Here the values of iron, %transferrin saturation and ferritin were found to be significantly elevated (p<0.01) in AMI patients with different age groups and sex when compared to that of the normal controls. The value of TIBC was found to be significantly decreased (p<0.01) in AMI patients with different age groups and sex when compared to that of the normal controls.

Table 9: Iron, TIBC, transferrin and ferritin concentrations according to age and sex

Parameters	Age (years)						Sex
	<40		40-60		>60		Male		Female
	Normal n=22	AMI n=27	Normal n=54	AMI n=160	Normal n=24	AMI n=113	Normal n=85	AMI n=261	Normal n=15	AMI n=39
Iron (mg/dl)	99.16±11.34	151.57±24.57*	100.71±13.62	155.83±23.17*	97.80±14.79	154.52±22.45*	100.07±12.93	155.67±23.23*	97.39±16.19	150.20±21.34*
TIBC (mg/dl)	315.72±15.91	251.56±24.57*	329.52±14.96	257.32±24.10*	322.25±13.30	255.74±24.01*	325.19±16.03	256.74±24.22*	322.20±14.42	252.64±23.45*
Transferrin_ saturation %	31.12±3.46	59.85±3.92*	30.58±4.47	60.37±4.16*	30.51±4.76	60.22±3.78*	30.62±4.35	60.35±4.09*	31.05±4.33	59.62±3.30*
Ferritin (ng/ml)	67.55±8.85	128.98±40.17*	69.81±10.44	131.89±22.98*	55.08±14.48	131.09±22.19*	67.88±11.74	131.76±25.37*	53.86±11.87	128.42±20.01*

Values are mean ±SD; * p<0.01.

Table 10: Iron, TIBC, transferrin and ferritin concentrations according to the time of onset of chest pain

Parameters		Time of onset of chest pain
	Normal (n=100)	Acute MI
	Normal (n=100)	12am to 6 am (n=50)	6 am to 12 noon (n=94)	12 noon to 6 pm (n-90)	6 pm to 12 am (n=66)
Iron (mg/dl)	99.67±13.51	154.84±26.36*	156.11±22.52*	154.28±22.11*	154.31±22.40*
TIBC (mg/dl)	324.74±15.84	254.54±26.66*	258.28±24.04*	256.24±23.01*	254.47±23.68*
Transferrin saturation %	30.68±4.35	60.27±4.28*	60.16±4.33*	60.48±3.83*	60.11±3.48*
Ferritin (ng/ml)	65.78±12.78	128.33±35.52*	129.82±221.94*	136.29±22.00*	129.73±20.88*

Values are mean±SD; * p<0.01

Table 11: Iron, TIBC, transferrin and ferritin concentrations in patients with diabetes and hypertension

Parameters		Acute MI
	Normal (n=100)	Diabetes		Hypertension
	Normal (n=100)	Diabetes (n=101)	No diabetes (n=199)	Hypertension (n=62)	No hypertension (n=238)
Iron (mg/dl)	99.67±13.51	154.80±24.47*	155.03±22.33*	155.19±25.07*	154.89±22.51*
TIBC (mg/dl)	324.74±15.84	255.92±23.06*	256.78±26.17*	255.89±24.43*	256.29±24.10*
Transferrin saturation %	30.68±4.35	59.88±4.57*	60.46±3.67*	60.06±3.87*	60.32±4.04*
Ferritin (ng/ml)	65.78±12.78	127.25±29.42*	133.39±21.73*	128.76±23.15	132.00±25.11*

Values are mean±SD; * p<0.01

Table 10 represents the values of iron, TIBC, %transferrin saturation and ferritin in normal and in AMI patients according to the time of onset of chest pain. The values of iron, %transferrin saturation and Ferritin were found to be significantly increased (p<0.01) in AMI patients with different time of onset of chest pain when compared to that of the normal controls. The value of TIBC was found to be significantly decreased (p<0.01) in AMI patients with different time onset of chest pain when compared to that of the normal controls. A comparison between AMI patients with different time of onset of chest pain have shown significant value of ferritin in AMI patients with time of onset of chest pain from 12 midnight to 6 am when compared to the other three groups. The values of iron, TIBC and %transferrin saturation were remained unaltered between the groups.

Table 11 represents the values of iron, TIBC, %transferrin saturation and ferritin in normal and in AMI patients with and without the history of diabetes and hypertension. Here the values of iron, %transferrin saturation and ferritin were found to be significantly increased (p<0.01) in AMI patients with and without the history of diabetes and hypertension when compared to that of the normal controls. The value of TIBC was found to be significantly decreased (p<0.01) in AMI patients with and without the history of diabetes and hypertension when compared to that of the normal controls.

Table 12 represents the values of iron, TIBC, %transferrin saturation and ferritin in normal and in AMI patients according to the values of cholesterol. The values of iron, %transferrin saturation and ferritin were found to be significantly increased (p<0.01) in AMI patients with cholesterol values >200 mg/dl and <200 mg/dl when compared to that of the normal controls. The value of TIBC was found to be significantly decreased (p<0.01) in AMI patients with cholesterol values >200 mg/dl and <200 mg/dl when compared to that of the normal controls.

Table 12: Iron, TIBC, transferrin and ferritin concentrations in patients with diabetes and hypertension

Parameters		Acute MI
	Normal	Cholesterol
		> 200 mg/dl (n=105	<200 mg/dl (n=195)
Iron (mg/dl)	99.67±13.51	155.02±24.89*	154.92±22.02*
TIBC (mg/dl)	324.74±15.84	257.38±25.98*	255.57±23.11*
Transferrin saturation %	30.68±4.35	60.01±4.54*	60.41±3.68*
Ferritin (ng/ml)	65.78±12.78	127.58±29.10*	133.34±21.79*

Values are mean±SD; * p<0.01

Table 13 represents the values of iron, TIBC, %transferrin saturation and ferritin in normal and in AMI patients according to the habit of smoking and alcohol intake. The values of iron, %transferrin saturation and ferritin were found to be significantly increased (p<0.01) in AMI patients with and without the habits of smoking and alcohol intake when compared to that of the normal controls. However the value of TIBC was found to be significantly decreased (p<0.01) in AMI patients with and without the habits of smoking and alcohol intake when compared to that of the normal controls.

Table 13: Iron, TIBC, transferrin and ferritin concentrations according to habits of smoking and alcohol intake

Parameters	Smoking				Alcohol intake
	Yes		No		Yes		No
	Normal (n=62)	AMI (n=222)	Normal (n=38)	AMI (n=78)	Normal (n=20)	AMI (n=160)	Normal (n=80)	AMI (n=140)
Iron (mg/dl)	100.99±11.78	155.58±23.2*	97.51±15.62	153.15±22.53*	98.53±11.53	156.18±23.83*	99.95±13.92	153.56±22.09*
TIBC (mg/dl)	324.95±16.76	256.77±24.26*	324.41±14.17	254.61±23.81*	315.83±16.64	257.22±24.47*	326.97±14.79	255.06±23.76*
Transferrin_saturation %	31.01±3.84	60.39±4.10*	30.14±5.03	59.91±3.69*	30.98±3.51	60.30±4.20*	30.61±4.53	60.22±3.76*
Ferritin (ng/ml)	68.40±10.69	132.13±25.90*	61.50±14.59	129.06±21.00*	66.80±8.81	130.17±26.62*	65.53±13.56	132.65±22.36*

Values are mean ±SD; * p<0.01.

Table 14: Iron, TIBC, transferrin and ferritin concentrations according to food habits and family history

Parameters	Food habits				Family history
	Vegetarians		Non vegetarians			AMI
	Normal (n=16)	AMI (n=27)	Normal (n=84)	AMI (n=273)	Normal (n=100)	Positive (n=82)	Negative (n=218)
Iron (mg/dl)	97.57±15.68	152.68±22.49*	100.07±13.01	155.18±23.11*	99.67±13.51	156.88±20.97*	154.23±20.67*
TIBC (mg/dl)	322.94±14.24	254.36±24.81*	325.09±16.09	256.39±24.08*	324.74±15.84	257.04±23.97*	255.89±24.22*
Transferrin_saturation %	30.38±4.93	59.73±3.32*	30.74±4.22	60.32±4.06*	30.68±4.35	61.12±3.69*	59.94±4.07*
Ferritin (ng/ml)	54.18±11.53	131.46±18.56*	67.99±11.77	131.32±25.27*	65.78±12.78	134.58±21.42*	130.11±25.79*

Values are mean ±SD; * p<0.01.

Table 14 represents the values of iron, TIBC, %transferrin saturation and ferritin in normal and in AMI patients according to the food habits and family history of AMI. The values of iron, %transferrin saturation and ferritin were found to be significantly increased (p<0.01) in AMI patients with the habits of vegetarian and non vegetarian food intake and with and without the family history of AMI when compared to that of the normal controls. The value of TIBC was found to be significantly decreased (p<0.01) in AMI patients with the habits of vegetarian and non vegetarian food intake and with and without the family history of AMI when compared to that of the normal controls. The comparison between the AMI patients with and without the family history of AMI have shown significant value of %transferrin saturation in AMI patients without the family history of AMI when compared to that of the AMI patients with the family history of AMI. However the other parameters did not show significant alteration between the groups.

DISCUSSION

The role of micronutrients and trace elements in the pathogenesis of CAD have been recently reported, hence studies related to this aspect are very rare. However the significant role of antioxidant vitamins such as vitamin E and vitamin C, the two very important micronutrients in the pathogenesis of AMI have been described. Vitamin E which provides protection against endothelial injury have been associated with atherosclerosis by preserving endothelium derived nitric oxide (NO) activity15. Being a chain breaking antioxidant, vitamin E inhibits or delay arterial thrombogenesis16. Vitamin C, a water soluble antioxidant vitamin, have been reported to improve the endothelial function, thus reducing the risk of CAD. The antioxidant activity of vitamin C is not restricted to extra cellular fluids. It is actively transported into cells and may play a role in the regulation of intracellular redox state and antioxidant defenses17, possibly via regulation of intracellular thiol species such as glutathione.

In the present study the values of vitamin E and vitamin C were found to be decreased in AMI patients when compared to that of the normal healthy individuals, indicating the low values of these vitamins in the serum of AMI patients. Irrespective of the risk factors the values of these vitamins were found to be decreased in all the AMI patients either due to a low supplementation or due to an impaired metabolism. Further the value of vitamin C was found to be less in AMI patients with age

40mg/dl when compared to the other age groups. In AMI males the value of vitamin C was found to be less than that in AMI females. According to the time of onset of chest pain the values of vitamin E and vitamin C were found to be less in patients with time of onset of chest pain from 12 midnight to 6 am when compared to that of the other groups. The values of vitamin E and vitamin C were found to be less in AMI patients with the history of diabetes and hypertension, indicating that the values of these vitamins may be less in diabetic and hypertensive patients. Further the value of vitamin E was found to be less in AMI patients the cholesterol value >200 mg/dl, in patients with non vegetarian food intake and in patients without the family history of AMI. Vitamin C was found to be less in patients with the habit of smoking. All these results together indicate the impairment of the endothelial function in these AMI patients due to a reduction in the amount of these antioxidant vitamins in the body.

Zn and Mg, the two essential trace elements require for the normal functioning of the body is thought to impair the oxidative injury by free radicals or ROS18. Zn is an integral component of various metallo-enzymes and along with other metals can activate a wide variety of enzymes. Further Zn functions to stabilize the membranes, perhaps by decreasing the lipid peroxidation of these structures. The salutary effect of Zn in wound healing may be related to the membrane stabilizing effect. Thus cell damage would be decreased19. Hypomagnesaemia has been reported in patients with coronary artery disease20. Magnesium is an obligatory cofactor in the enzyme reactions of GSH synthesis and in all biosynthetic enzyme reactions involving ATP and Mg deficiency has been reported to inhibit biosynthesis of GSH21. Further more, Mg deficiency also leads to reduced levels of endogenous antioxidant defenses (vitamin E and vitamin C), which may limit free radical detoxification21.

In the present study we have observed the decreased value of Zn and Mg in all the AMI patients when compared to that of the normal controls, indicating the deficiency of these trace elements in AMI thus leading to the more complications of the disease. The value of Mg was found to be less in AMI patients with age ranges from 40-60 years and in AMI males when compared to that of the AMI females. The value was found to be even less in patients with the onset of chest pain from 6 am to 12 noon, in patients with the history of diabetes and hypertension, patients with a cholesterol value >200 mg/dl and in patients with the habit of non vegetarian food intake. The value of Zn was found to be less in patients with the history of hypertension and a cholesterol value of >200 mg/dl. These results indicate the impaired values of Zn and Mg in AMI patients and it could potentiate the oxidative injury to myocardium by free radicals.

The presence of iron in cytochromes, catalase, hydroxylase, peroxidases, saturases, lipoxygenases and cyclooxygenases suggest that iron has an important role in various metabolic events related to lipids, such as the oxidative degradation of fatty acids and the synthesis of unsaturated fatty acids, plasminogens and prostaglandins. However, studies in this area are limited. Oxidation of LDL-cholesterol is catalyzed by iron present in atherosclerotic gruel12. Serum deficient in iron has minimal oxidative capacity that increases with iron repletion. Several studies have been conducted in developed countries to assess the association of iron with coronary heart disease or AMI. Iron besides promoting lipid peroxidation could increase the risk of AMI through the elevation of blood haematocrit and blood hemoglobin levels. This in turn increases the viscosity of blood and has a direct thrombogenic effect22. Ferritin is the storage form of iron and high levels of ferritin are always associated with CAD23. The concentration of ferritin in the serum is directly proportional to the levels of body iron stores. The body iron status in turn related to the concentration of the ferritin, its storage form and transferrin, the transport form. The total iron binding capacity (TIBC) is also considered to be an indicator to know the iron status of the body.

The results of the present study have shown increased values of iron, %transferrin saturation and ferritin in AMI patients when compared to that of the normal healthy individuals. The TIBC value was found to be decreased. The value of ferritin was found to be more in patients with time of onset of chest pain from 12 noon to 6 pm and the value of % transferrin saturation was found to be more in AMI patients with a family history of AMI. However all the other parameters did not show much alteration between the groups. So the present study indicates the increased levels of iron, %transferrin saturation and decreased values of TIBC in AMI patients.

The results of the present study indicate the deficiency of the micronutrients such as vitamin E, vitamin C, Zn and Mg in AMI patients and increased values of iron, %transferrin saturation and ferritin and decreased values of TIBC in AMI patients compared to that of the normal controls. These together constitute the further complications and the severity of AMI in these patients.

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