Serum Levels of Zn, Cu, Cr and Ni in Iranian Subjects with Atherosclerosis
Issa Nourmohammadi PhD*, Nasser Nazem MD**, Abdulvahab Ehsani-Zenuz MD*, Anahita Moaveni MS*
* Faculty of Medicine, Iran University of Medical Sciences, Tehran ** Rajaee Heart Hospital, Tehran, Iran
Keywords • Zinc • copper • chromium • nickel • atherosclerosis • coronary heart disease
Introduction
In the past years, a number of researchers have shown that classical and extrinsic factors such as smoking, high cholesterol levels and high blood pressure, have a significant role in the pathogenesis of cardiovascular disease. Recently, many other factors have been repeatedly demonstrated to influence this disease which is one of the most prevalent in the developed world.1,2 The search for its etiology has led to some theories that dietary intake of minerals and in particular trace elements may have a role in the progress of atherosclerosis.3,4,5 In this regard, deficiency, lack of homeostatic control, or excessive intake of some of these elements may lead to cardiovascular mortality. Some authors have reported low Zn and high Cu levels in patients with atherosclerosis.6,7 Little has been reported about the changes, if any, in the levels of Cr and Ni of these patients. This research was designed to study the association of zinc, copper, chromium, and nickel in subjects with coronary heart disease.
Materials and Methods
The study consisted of analysis of serum levels of Zn, Cu, Cr and Ni in patients with coronary heart disease (CHD). The experimental group consisted of 60 patients (21 women, 39 men) plus 30 controls (age range: 30-70 years). Patients were selected from cases at Shahid Rajaii Heart Hospital in Tehran and controls were chosen from people with no history of proven CHD. Angiography reports were studied and stenosis percentages of the four major vessels (RCA, LCX, LAD, and LM) were evaluated. The mean percentage of stenosis was then calculated and the patients were divided into groups based on stenosis percent (> 50% and < 50%). All of our patients had lesions with > 50% stenosis. Blood samples were collected in metal-free tubes from patients and controls after an overnight fast.8 Serum was removed by centrifugation and stored in metal-free tubes at -86° C. High density lipoprotein cholesterol (HDL-C), triglyceride (TG) and total cholesterol (TC) were determined by biochemical manual kits (Man and Zist Chemie Co.). Cu, Zn, Cr and Ni were determined by atomic absorption spectro-photometry (UNICAM 929) (Flame atomic absorption spectrophotometry for Zn and Cu and graphite electrothermal furnace for Ni and Cr). Samples were diluted with dionized water, with a dilution factor of 4 for Zn and Cu and a dilution factor of 10 for Ni and Cr.
Results
The mean level of serum Zn was significantly lower in patients than controls (p=0.016). A significant difference of Zn levels in males and females between patients and controls was also seen (p=0.006 and p=0.000 respectively). Total mean Cu levels were higher in the patients with p=0.004, and there was a significant difference between the levels detected in male and female patients and controls (p=0.004 and p=0.001 respectively). Mean level of Cr in the serum of patients was lower than that of controls but this difference was not significant (p > 0.05). The level of Ni in the patients was higher but not significantly different (p>0.05) from controls. These results also differed according to gender. Other biochemical parameters such as TG, TC and LDL-C showed higher levels in patients with the exception of HDL-C which was lower, but not significantly (p>0.05). Table 1 presents the mean levels of all parameters under study for the patient and control groups. These values have been calculated in different sexes and a higher level of Cu in female patients and a lower level of Zn in male patients was evident (p<0.01). The levels of Cr and Ni in both sexes were not significantly different between patient and control group (Table 2).
Discussion
Possible etiological role in the imbalance of homeostasis of certain minerals in the development of coronary artery diseases has been the subject of much discussion. Various experimental models, clinically and statistically, have shown that the nutritional status of elements such as Zn and Cu may have some effect on the pathogenesis of coronary heart disease.9-11 In particular, the status of Zn has been shown to have an important correlation in the metabolism of cholesterol and HDL, two important molecules involved in the disease. The results of this investigation demonstrate that hypozincemia and hypercupremia were consistant with other studies. Animal experimental evidence suggests that the dietary Zn/Cu ratio may be a significant factor in coronary heart disease.7 The exact mechanism of alteration of these trace elements is not known. Some factors such as dietary deficiency, anorexia and possible
use of drugs may be major components. Besides these factors, low serum Zn levels have been related to excess release of steroids due to the release of leucocyte endogenous mediators which redistributes the body Zn from serum and may cause a drop in serum Zn and also due to elevated levels of a-macroglobulin which is a transport protein containing large amounts of Zn.12 A decrease in the levels of Zn and HDL-C strongly suggests the role of Zn in cholesterol and lipid metabolism as observed by Wen Yong.6
Increased levels of Cu may be due to a rise in the copper-binding capacity of ceruloplasmin. In our study, serum Cu was positively related to TC, TG and LDL-C, which suggests that high serum Cu levels may induce the development of CHD. The increase in Cu may also be due to injury and subsequent necrosis of myocardial cells.13,14
Cr deficiency has been shown to increase aortic lesions. Data in relation to this are scarce and even though our findings indicate lower Cr levels in patients, further investigation is needed to clarify this point.15
The role of Ni in CHD has been implicated. Low concentration of exogenous nickel chloride has been shown to induce coronary vasoconstriction in rat hearts.16 This acts as an endogenous vasoactive substance. Hypernickelemia has been reported in patients with acute myocardial infarction and ustable angina pectoris. Even though our patients’ Ni levels were not significantly higher, this is only the preliminary result and further investigation of lipid peroxidation in heart cells, specifically in workers exposed to high levels of Ni in the working environment and its relation to CHD, is needed.
Deficiency or suboptimal intake of micronutriants may play a role in the etiology of CHD. Although there have been some reports that trace elements do not play a role in atherosclerotic changes of arteries, this conflict may be due to differences in the analytical or methodological techniques. We feel that more investigation will clarify the extent of changes in these essential elements, which can become a reliable diagnostic aid in CHD, and the extent of change having prognostic implications.
References