Plasma total homocysteine (THCY) level and other

　　　　 作者：Akande AA1， Salisu OT1， Omotoso ABO2， Kolo PM2

【摘要】 Objective: The aim of this study is to assess the correlation between traditional cardiovascular risk factors and elevated plasma tHcy level in Nigerian hypertensive. Methods: Thirtysix hypertensive patients were recruited with 36 age and sexmatched controls. The age， sex and anthropometric measurements including height， weight and body mass index (BMI) were taken. Plasma total cholesterol， low density lipoprotein cholesterol (LDLC)， high density lipoprotein cholesterol (HDLC)， triglycerides and tHcy were analyzed. The results of the two groups were compared.Results: The mean total cholesterol and LDLC were significantly higher in the subjects than in the controls (P=0.01 and 0.03 respectively). On the other hand， means of HDLC and triglycerides were not significantly different between the two groups (P=0.06 and 0.68 respectively). Mean total plasma tHcy was (12.95±4.9)μmol/L in hypertensive patients when compared with (11.29±3.6) μmol/L in the controls (P=0.09)， however the mean tHcy was significantly higher in hypertensive patients who had stroke or myocardial infarction than those without these complications (one way Anova F=3.63， P=0.04). Significant positive correlation was seen between tHcy and systolic blood pressure， diastolic blood pressure， BMI and LDLC. Conclusion: The study suggests that elevated plasma tHcy may predict occurrence of cardiovascular complications in hypertensive inpiduals..

【关键词】 Plasma homocysteine; Lipid profile; Hypertension

　　 INTRODUCTION

　　Elevated plasma tHcy has been implicated especially among Caucasians as a risk factor for coronary artery disease， stroke and venous thromboembolism[1，2]. Several crosssectional studies， some population based， have reported a positive association of plasma tHcy with systolic and diastolic blood pressure， and hypertension[3，4]. The vascular risk associated with hyperhomocysteinemia has been observed to be stronger in hypertensive inpiduals[5]. In the third National Health and Nutrition Examination Survey (NHANES III)， persons in the highest quartiles of plasma tHcy had a 2 to 3 fold increase in the prevalence of hypertension compared to those in the lowest quartiles[6]. Although， there is a considerable body of evidence to implicate tHcy in the pathogenesis of hypertension， its role as a cause or effect of hypertension has been controversial. While some authors consider raised tHcy level to be a marker of atherosclerosis or acute inflammation， others suggest that it may be the consequences of reduced renal function in patients with hypertension[7，8]. However， tHcy lowering therapies with folic acidbased regimens have been followed by decreases in blood pressure[9]. In Nigeria， tHcy levels have been assessed in apparently healthy populations[10，11]but has not been well studied in hypertensive patients， hence this study.

　　MATERIAL AND METHODS

　　Thirtysix hypertensive Nigerians seen at the cardiology clinic and medical wards of the University of Ilorin Teaching Hospital were recruited as hypertension group， and 36 healthy normotensive inpidual as controls. The hypertension group had a thorough clinical examination to establish diagnosis of hypertension， identify other cardiovascular risk factors and to determine target organ damage associated with hypertension. Both the hypertension group and the controls were educated on the aims and objectives of the study. The controls were aged 18 years or above with no history of hypertension (systolic blood pressure &< 140 mmHg and diastolic blood pressure of &< 90 mmHg). The hypertension group were above 18 years old with systolic blood pressure ≥140 mmHg and/or diastolic of ≥90 mmHg. Exclusion criteria for the patients and the controls included history of sickle cell disease， folic acid supplementation， malnutrition， renal disease and pregnancy. The hypertension group underwent detailed medical history interrogatoire， physical examination and anthropometric measurements. The blood pressure was measured twice from the left arm in the sitting position after interval of at least 5 minutes rest. The mean of the two readings was used to define hypertension according to the JNC VII criteria[12]. When systolic and diastolic blood pressure reading belonged to different categories， the higher of the two categories was used. The participants' weight and the height were measured， body mass index were calculated using the formula: Wt/Ht2 (Kg/m2). Blood specimens for fasting glucose， lipid profile and tHcy were obtained after an overnight fast without tourniquet application and were refrigerated immediately after separation at -20 ℃. Plasma tHcy level was determined as a free plus protein bound tHcy using the fluorescent polarization immunoassay (FPIA) procedure Abbort IMx Analyzer. The stability of plasma tHcy in samples stored at temperatures below -20 ℃ has been reported previously[13]. Fasting plasma glucose was estimated by the Glucose Oxidase method using 4aminophenazone as an oxygen acceptor[14]. The batch assay was controlled by the Randox commercial control sera as well as intra and interbatch runs. Total cholesterol and triglyceride levels were determined using standard enzyme colorimetric method using QCA kit. HDLC and LDLC were determined as above after precipitation with dextrasulphateMg and polyvinyl sulphate respectively[15]. All the subjects had ECG and Left ventricular hypertrophy (LVH) determined using Araoye's criteria for LVH in the Black race[16].

　　The data were analyzed using the SPSS version 14 and the numerical values were presented as mean±standard deviation. Student ttest was used to compare means of continuous variables while chisquare test was used for proportions. One way Anova modeling was used to compare tHcy in hypertensive patients without complications， those with myocardial infarction and stroke. Test of correlation was done using the Pearson correlation method. A statistically significant association was taken at P&< 0.05.

　　RESULTS

　　Thirtysix subjects， comprising of 16 males and 20 females were compared with 36 normotensive healthy controls made up of 18 males and 18 females. Table 1 shows the characteristics of the study group. The mean age of the patients was (53.3±8.5) years which was not significantly (P=0.29) different from (49±12.7) years of the controls. The mean body weight and the body mass index (BMI) of the patients were similar to that of the controls (P=0.34 and 0.26 respectively). Mean systolic blood pressure (SBP) of the patient group was (158.3±21) mmHg which was higher than (126±15) mmHg of the controls (P=0.01). The diastolic blood pressure of the patients was (105.3±13.8) mmHg， also significantly higher (P=0.01) than (84±7.6) mmHg of the controls . Although the serum levels of Urea and Creatinine of the patients were within the reference interval， it was significantly higher than that of the controls (P=0.01 and 0.04 respectively).

　　Table 1 Characteristics of study group (Mean±SD)

　　VariablePatientsControlPvalueNumber3636-Age (years)53.3±8.549 ±12.70.29Weight (kg)72±8.969.2±7.20.34Height (m)1.61±3.81.63±4.30.52BMI (kg/m2)25.6±6.524.1±3.50.26SBP (mmHg)158.3±21126±150.01DBP (mmHg)105.3±13.884±7.60.01Urea (mmol/L)5.4±2.74.3±2.40.01Creatinine (μmol/L)96±2387±19.20.04

　　BMIbody mass index， SBPsystolic blood pressure， DBPdiastolic blood pressure.

　　Table 2 shows lipid profile， tHcy and electrocardiographic parameters of the patients and the control. While the mean total cholesterol and low density lipoprotein cholesterol of the hypertension group were significantly higher in the patients than in the controls (P=0.01 and 0.03 respectively)， the means of high density lipoprotein cholesterol and triglycerides were not significantly different between the two groups (P=0.06 and 0.68 respectively). Mean total plasma tHcy was (12.95±4.9) μmol/L which was higher than (11.29±3.6) μmol/L in the controls. However， the difference was not statistically significant (P=0.09). Mean tHcy was (15.94±6.0) μmol/L in the hypertensive males as compared with (10.55±1.9) μmol/L in the hypertensive females (P=0.04). Majority of our male patients had stroke (62.5%) and myocardial infarction (83%) were males. The incidence of left atrial enlargement and left ventricular hypertrophy were higher in the hypertensive patients than the normotensive controls (P=0.01 and 0.01 respectively).

　　Table 2 Comparison of lipid profile， homocysteine and electrocardiographic features of patients and controls

　　VariablePatientsControlPNumber3636-FBS(mmol/L)4.50±1.004.20±1.200.24Total cholesterol(mmol/L)5.30±1.004.40±1.300.01HDLC(mmol/L)1.14±0.281.32±0.40.06LDLC(mmol/L)3.60±0.902.90±0.700.03Homocysteine (μmol/L)12.95±4.911.29±3.600.09Number with LAE(%)26(68.4%)3(7.9%)0.01Number with LVH(%)30(78.9%)5(13.2%)0.01

　　FBSfasting blood sugar， HDLChigh density lipoprotein cholesterol， LDLCLow density lipoprotein cholesterol，LAE left atrial enlargement， LVHleft ventricular hypertrophy.

　　Of the 36 hypertension patients， 22(61.1%) had no complications， while 6(16.7%) and 8(22.2%) had myocardial infartion and stroke. The mean tHcy level of the simple hypertension patints was 11.3 μmol/L， significant higher than 14.24 μ mol/L and 18.3 μ mol/L of the patients with hypertension complications of myocardial infarction and stoke (F=3.63， P=0.04).Our study showed significant positive correlation between tHcy and BMI， SBP， DBP， LDLC and duration of hypertension. However， there was no correlation between tHcy and age， total cholesterol， HDLC and triglycerides.

　　Table 3 Shows correlation of serum homocysteine with other risk cardiovascular factors.

　　ParametersCorrelation

　　coefficientPHomocysteine and age0.1830.47Homocysteine and BMI0.6300.01Homocysteine and SBP0.7340.01Homocysteine and DBP0.5490.02Homocysteine and total Cholesterol0.4210.08Homocysteine and LDLC0.530.02Homocysteine and HDLC0.30.22Homocysteine and Triglycerides0.4320.07Homocysteine and

　　duration of hypertension0.6420.01

　　Key: BMI: body mass index; SBP: systolic blood pressure; DBP: diastolic blood pressure; LDLC: low density lipoprotein cholesterol; HDLC: high density lipoprotein cholesterol.

　　It is well established that systemic hypertension is one the commonest noncommunicable diseases in Nigeria and it is associated with a lot of cardiovascular morbidity and mortality[17]. It is the commonest cause of heart failure， stroke and chronic kidney failure in Nigerian populations[18]. The mean total cholesterol and LDLC were significantly higher in the patients than in the control subjects. However， the means of HDLC and triglycerides were not different between the two groups. This largely concurs with the results of previous studies in hypertensive patients in Nigeria and Bangladesh[19，20]. High levels of total cholesterol， LDLC， and triglycerides， and reduced HDLC are known risk factors for stroke and coronary artery disease.

　　The low incidence of ischemic heart disease in our patients may explain why plasma tHcy was not significantly different (P=0.09) between the patients and controls. Previous studies which attempt to define the relationship between tHcy and blood pressure have yielded different results[6，21]. In the Framingham Heart Study[21]， no major relation of baseline plasma tHcy levels to hypertension incidence or longitudinal blood pressure progression was found. However， data from the Third National Health and Nutritional Examination Survey (1988～1994) showed that tHcy has an independent positive association with the blood pressure after adjusting for cardiovascular risk factors[6].

　　Our study also showed that， although the plasma tHcy of the patients and controls did not differ significantly， comparison of hypertensive patients who were free of stroke or myocardial infarction with those who had these complications， showed higher tHcy level in the latter than the former. In the same vein， the level of this biomarker was higher in the male than female hypertensive subjects (P=0.04). It may be a reflection of incidence of cardiovascular complications in the subjects studied as more of our male patients suffered stroke and myocardial infarction than females. These suggest that elevated tHcy level in patients with high blood pressure may predict occurrence of cardiovascular complications. In a study by Glew et al[22] on serum lipid profiles and tHcy levels in adults with stroke or myocardial infarction in Gombe， North Eastern Nigeria， 85% of the stroke patients have tHcy level above 10 μmol/L.

　　Plasma tHcy in our study exhibited positive correlation with SBP， DBP， BMI and LDLC. An elevated plasma tHcy level may have interaction with these positive correlates to increase risk of cardiovascular complications. In the European Concerted Action Project[23]on tHcy and risk of vascular disease， tHcy powerfully increases the risk associated with hypertension and cigarette smoking. Increased arterial stiffness， endothelial dysfunction， reduced nitric oxide generation and insulin resistance are possible mechanisms by which tHcy increases blood pressure and risk of cardiovascular complications[24]. On the other hand， subclinical renal dysfunction in hypertensive patients may also account for increases in the plasma tHcy level. Whichever is the case， the clustering of hyperhomocysteinaemia with hypertension， dyslipidaemia and other cardiovascular risks increases cardiovascular morbidity and mortality. Some clinical trials have shown that folic acidbased tHcy lowering therapy is associated with reduction of blood pressure and cardiovascular events[25，26]. This may provide opportunity for communitybased intervention through folic acid and vitamin supplementation to reduce cardiovascular mortality and complications of systemic hypertension.

　　In conclusion， the results of our study have suggested that elevated plasma tHcy level may be associated with cardiovascular complications in hypertensive inpiduals. We however， recommend largescale longitudinal casecontrol studies to validate the influence of plasma tHcy on cardiovascular mortality in Nigerian hypertensive patients.

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