Key works: metabolic syndrome, homocysteine, myocardial infarction, cardiovascular ..... GRUNDY S.M., BREWER H.B. JR., CLEEMAN J.I. et al., Definition of ...
The Association between Homocysteine Level and Metabolic Syndrome in Patients of Prior Myocardial Infarction LUCIA AGOŞTON-COLDEA¹, TEODORA MOCAN², LĂCRĂMIOARA DOBIE¹, ALINA MĂRGINEAN¹, SILVIA LUPU¹ ¹Department of Medical Sciences, University of Medicine and Pharmacy, Cluj-Napoca ²Department of Normal Morphology and Functions, University of Medicine and Pharmacy, Cluj-Napoca, Romania
Homocysteine is considered to be a risk factor for the development of cardiovascular disease. Several observations suggest that there might be links between hyperhomocysteinemia and insulin resistance, its clinical surrogate of metabolic syndrome. The aim of the present study is to determine whether the presence of the metabolic syndrome is associated with elevated levels of homocysteine in patients with prior myocardial infarction. Methods. We studied 104 consecutive patients with prior myocardial infarction undergoing coronary angiography. Patients were divided into two groups according to the presence or absence of metabolic syndrome, as certified by Adult Treatment Panel III. The dosage of homocysteine was measured by high performance liquid chromatography. The relationship between homocysteine levels and metabolic syndrome was assessed by multivariable regressions after adjustment on the basis of recognized predictive factors: age and sex. Results. Out of a total numbers of patients with myocardial infarction (104; 63.6± 9.2 years of age, 45.1% males) taken in study, 32 (30.1%) had metabolic syndrome. The mean level of homocysteine was significantly higher in the metabolic syndrome group (14.8µmol/L) than in the free metabolic syndrome group (17.9µmol/L) (p≤0.001). We found a positive correlation between plasma homocysteine levels and metabolic syndrome parameters. Conclusion. Elevated homocysteine levels were correlated to the metabolic syndrome in patients with prior myocardial infarction. These data indicate that elevated plasma homocysteine levels are not a risk factor for cardiovascular events in metabolic syndrome patients in contrast to patients without the metabolic syndrome. Key works: metabolic syndrome, homocysteine, myocardial infarction, cardiovascular diseases.
The metabolic syndrome (MetS) has been defined as the simultaneous presence of several risk factors and their joint action leading to pathological consequences. It has been incriminated for a twoto five fold increase of type 2 diabetes development risk as well as for three- to four fold increasing of cardiovascular diseases incidence [1–5]. The synergistic action of different factors induces a higher cardiovascular risk as compared to the effect of a risk factor alone. The prevalence of the MetS has been reported to range between 9% and 24%. Various factors modulate this incidence level. Among them, geographical location and age have been intensely studied [4] [6]. However, levels of MetS can get as high as 46% among symptomatic vascular diseases and it has been demonstrated to be accompanied by vascular injuries [7–9]. Some studies have suggested MetS to be a poor survival inducing factor and to increase the incidence of future cardiovascular ROM. J. INTERN. MED., 2010, 48, 2, 151–158
events [10]. In addition to their atherogenic effects, insulin resistance and its clinical surrogate – MetS – may exert direct myocardial effects. It has not been completely elucidated whether the increased cardiovascular risk associated with the MetS is due to the individual components only, or other risk factors associated with both atherosclerosis and insulin resistance are involved. Homocysteine (Hcy) has been recently suggested to be a risk factor as well as a prognosis factor for the appearance and progression of cardiovascular disease [11] [12]. Hcy levels have been reported to be elevated in up to 30% of patients diagnosed with atherosclerosis, and levels only 12% above the upper limit of normal are associated with a 3-fold increase in the risk of acute myocardial infarction [13]. Toxic properties have been suggested in relationship to vascular endothelium, resulting in endothelial dysfunction. Studies have also demonstrated
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HCy to be a proficient predictor for future cardiovascular disease events in patients with already established coronary artery disease or type 2 diabetes mellitus [14]. Several observations [15] [16] reported significant associations between insulin resistance and hyperhomocysteinemia. Under insulin resistance conditions, hyperinsulinemia may result in elevated Hcy plasma levels, as reported by several in vivo studies [17] [18]. Concurrently, in vitro studies have demonstrated that Hcy may induce insulin resistance by means of insulin-receptor kinase activity down regulation. Therefore, Hcy may constitute both a cause and/or an outcome of insulin resistance [19]. The aim of the present study is to determine whether the presence of the MetS is associated with elevated levels of Hcy in patients with prior myocardial infarction. MATERIAL AND METHODS STUDY PATIENTS
We studied 104 consecutive patients with prior myocardial infarction, between May 2005 and December 2005. The diagnostic of prior myocardial infarction was made in the presence of increased history of the cardiac markers, associated with typical electrocardiography changes and/or typical symptoms, as defined by the Joint Committee of the American College of Cardiology [20]. For each patient included in the study we performed coronary angiography. Those presenting myocardial infarction within the last 3 months or presenting major events during hospitalization (i.e. neoplasia, inflammatory diseases, infections), surgical interventions in the past 2 months or subsequent dyslipidaemia as a result of hypothyroidism, nephrotic syndrome, colestasis were excluded for eliminating major causes of secondary lipid profile alterations. All the patients were evaluated with the same structural quiz, the same clinical and paraclinical protocol, and were divided into two groups according to the presence or absence of MetS. The study protocol was approved by the ethics committee of hospital and all patients gave their informed consent before participation in the study. According to the National Cholesterol Education Program’s Adult Treatment Panel III (NCEP-ATP
2
III) report, the MetS was defined as the presence of 3 or more of the following characteristics: (1) abdominal obesity: waist circumference >102 cm in men and >88 cm in women; (2) hypertriglyceridemia: >150 mg/dL (1.69 mmol/L); (3) low HDL cholesterol: 85 mm Hg diastolic; (5) high fasting glucose: >110 mg/dL (6.1 mmol/L) [2]. BLOOD SAMPLING AND BIOCHEMICAL ANALYSIS
Venous blood samples were obtained after 12 h of fasting, and samples for lipids, glucose, creatinine, insulin and Hcy, were drawn without stasis into evacuated glass tubes containing 1/100 volume of 0.5 mmol of ethylene-diamine-tetra-acetic acid/L. Plasma obtained by centrifugation at 1500 g for 15 minutes was measured in fresh samples. All patients had lipids: cholesterol (TC), HDL-cholesterol (HDL-C), LDL-cholesterol (LDL-C), triglycerides (TG) from the plasma, analyzed by enzymatic tests performed by a Roche-Hitachi 911 analyzer [1] [2]. The fasting plasma glucose was determined with the glucose oxidase–phenol-4aminophenazone peroxidase method, using a BM/Hitachi 717/911 analyzer. Insulin resistance was evaluated by “homeostasis model assessment (HOMA)” formula. This formula was calculated by fasting plasma insulin (µU/mL) × fasting plasma glucose (mmol/L)/22.5 [21]. The creatinine clearance (ml/min) was calculated by Coockroft formula. The fasting Hcy levels were measured in all patients by fluorescence polarization immunoassay on Abbott Imx Analyzer [22]. Normal Hcy levels range between 5 and 15 µmol/L with elevations of 15 to 30 µmol/L, 30 to 100 µmol/L, and >100 µmol/L classified as tertiles mild, moderate, and severe hyperhomocysteinemia, respectively [23]. CLINICAL VARIABLES
We recorded the presence of several risk factors such as: age, sex, family background of coronary heart disease, smoking, hypertension, diabetes mellitus, obesity, dyslipidemia – all defined in accordance to international rules. Family history of coronary heart disease was defined by a history of premature coronary artery disease in first-degree relatives (having occurred in those relatives at age 90 mm Hg or use of hypertension drugs, according to the current definition [24]. The presence of diabetes at baseline was defined as fasting plasma glucose >110 mg/dL (6.1 mmol/L) or use of oral hypoglycemia agents or insulin [25]. A surrogate marker for obesity content is the body mass index (BMI), which is determined by weight (kilograms) divided by height squared (square meters). In clinical terms, a BMI of 25– 29 kg/m² is called overweight; higher BMI (30 kg/m²) are called obesity. The waist circumference was measured on admission, midway between the last rib and iliac crest, and the average of 2 measures was recorded [26]. STATISTICAL ANALYSIS
We used parameters of descriptive statistics as dispersion and centrality indices (mean, median, standard deviation, range). The correlation between metabolic parameters and Hcy was analysed by means of simple linear regression with Pearson coefficient calculus. Hcy was log transformed prior
to regression analysis. The differences in Hcy levels among different groups of patients (formed based on the different number of MetS parameters) were tested by means of independent-samplestudent test or ANOVA-1 way test. All statistical analyses were performed with the Statistical Package for Social Sciences version 6.0 (SPSS) for Windows. The results were considered statistically significant if p
