The Study On Relationship Between HbA1C, Postprandial Hyperglycemia, Lipoprotein(a) And The Onset Severity Of Coronary Heart Disease

BackgroundThe prevalence of the coronary heart disease is increasing worldwide owing to the lifestyle changes.Coronary heart disease occurs as the result of a variety of risk factors, such as smoking,family history of premature CVD,obesity,hypertension, hyperlipidaemia and diabetes.Recent studies have shown that some new risk factors are related to the cardiovascular disease,such as HbA1C,Lipoprotein(a),homocysteine, hyperuricemia,hyperfibrinogenemia.Epidemiologic data indicated that hyperglycemia, which was referred to the abnormally increased levels of glucose was an independent predictor of future cardiovascular events,even in nondiabetic subjects.Hyperglycemia is common and associated with markedly increased mortality rates in patients hospitalized with CVD.Results from large studies indicated that individuals with pre-diabetes also had an increased risk of cardiovascular events and mortality,implying that hyperglycemia was a continuous risk factor for CVD.A meta-analysis of several studies concluded that there was a linear relationship between glucose levels and CVD.Early randomized controlled trials indicated that reducing postprandial glycemia appeared to significantly slow atherosclerotic progression and may improve cardiovascular prognosis.The cardiovascular toxicity of postprandial hyperglycemia.is mediated by oxidant stress,which is directly proportional to the increase in glucose after a meal.This transient increase in free radicals acutely triggers inflammation,endothelial dysfunction,hypercoagulability,sympathetic hyperactivity,and a cascade of other atherogenic changes.Many interventional studies have demonstated that blunting the postprandial spikes in glucose could improve inflammation and endothelial function immediately.Lipoprotein(a)[Lp(a)]is a low-density lipoprotein-like particle linked by a disulfide bond to the glycoprotein apolipoprotein(a).Since the discoverry of the Lp(a)by Berg in 1963,this lipoprotein has attracted much attention as a potential risk factor for athrosclerotic cardiovascular disease.Numberous case-control studies and prospective studies have indicated an association between elevated serum concentrations of Lp(a)and the risk of CVD.CVD is the principal cause of mortality globally,particularly in type 2 diabetic subjects,as their CVD mortality risk is equal to that of subjects without diabetes who had a definite cardiovascular disease.The DCCT(Diabetes Control and Complications Trial) and UKPDS(UK Prospective Diabetes Study)demonstrated the importance of HbA1C in the development of long-term diabetes microvascular complications.Further,both studies elegantly demonstrated significant reductions in the risk of developing microvascular complications for every percentage of reduction in HbA1C levels.However,the association of HbA1C with cardiovascular disease(CVD)is less clear.There is uncertainty as to the nature of the relationship.Recent prospective studies have shown that HbA1C is associated with CVD and mortality.This association has also recently been extended to nondiabetic subjects.HbA1c could be considered a good marker for glycated proteins,which play a contributory role in atherosclerosis not only in diabetic but also in nondiabetic subjects.This is supported by the findings that even nondiabetic subjects with CVD have increased levels of HbA1c.James finded that HbA1c had a significant correlation with CVD and MS.Prospective studies have revealed HbA1c to be a predictor of total and all-cause mortality.Research design and methodsThe study subjects were 120 patients who visited the Qilu Hospital with defined coronary heart disease,CVD was defined on clinical grounds supported by at least one objective finding including ischaemic changes or previous documented myocardial infarction in the ECG or coronary angiogram revealing stenosis＞50%of the lumen diameter in any major coronary artery at least.The subjects included acute myocardial infarction 38 cases,unstable angina pectoris 42 cases and chronic stable coronary heart disease.The subjects comprised of 58 females and 62 males,with mean age 62.8±9.6 years.The presence of MS was defined according to the definitions of the Adult Treatment PanelⅢ(ATPⅢ)guideline.Patients with serious renal /hepatic falure or malignant tumor were excluded from the study.Weight,height,and waist measurements were obtained using standardized techniques as detailed elsewhere.Height was measured with a tape to the nearest centimeter.Weight was measured with a traditional balance that was kept on a firm horizontal surface.Waist size was measured using a nonstretchable fiber measure tape. BMI was calculated as the weight in kilograms divided by the square of height in meters. Blood pressure was recorded in the decubitus position using the right arm with a mercury sphygmomanometer.Two readings were taken 5 min apart,and the mean of the two was taken as the blood pressure.After a 12-h fast,blood glucose,serum total cholesterol,serum triglycerides,HDL cholesterol,LDL cholesterol,Apoprotein AⅠ,Apoprotein B and HbA1C were measured.Data management of statistical analyses was done using the SPSS statistical package (Version 13.0).For all analysis,a p value less than 0.05 is considered to reach statistical significance.One-way ANOVA were used as appropriate to compare means among different groups.x~2 test or Fisher's exact test was used to compare proportions among groups.Study subjects with no diabetes mellitus were categorized to four groups by quartiles of HbA1C.Pearson's correlation analysis was carried out to determine the correlation of HbA1C with cardiovascular risk factors.Linear regression analysis was done using HbA1C as the dependent variable and CVD risk factors as independent variables.Logistic regression analysis was done using metabolic syndrome as dependent variables and HbA1C as an independent variable.Receiver operator characteristic(ROC) curves were constructed to identify the cut point of HbA1c with maximum accuracy for determining MS.Sensitivity,specificity and accuracy for predicting MS were calculated for different cut points of HbA1c.Results This study indicated that almost 2 of 3 petients who presented with definited CVD had abnormal glucometabolism.A significant proportion of these at-risk subjects were undetected before admission.In the 120 CVD patients,31.6%of the cases had previously diagnosed diabetes mellitus,24.8%of the cases had IGT,18.2%of the cases had newly diagnosed diabetes(3.4%of the cases were newly diagnosed by fasting blood glucose, 14.8%of the cases were newly diagnosed by postprandial hyperglycemia).The prevalence of the abnormal glucometabolism in the ACS patients was found to be significantly higher than the chronic stable CVD patients.There was a significant difference(P for trend＜0.01)in the level of Lp(a)and HbA1C between the three types of CVD diagnosis.In petients with acute myocardial infarction,the mean Lp(a)was 32.6±20.5mg/dl,and the mean HbA1C was 6.48%±0.4%.In petients with unstable angina pectoris,the mean Lp(a)was 38.7±23.1 mg/dl, and the mean HbA1C was 5.89%±0.5%.In petients with chronic stable CVD,the mean Lp(a)was 32.6±20.5 mg/dl,and the mean HbA1C was 5.46%±0.4%.Age,BMI,waist circumference,sBP and dBR serum total cholesterol,triglycerides, LDL cholesterol increased significantly with increasing quartiles of A1C values(P for trend＜0.01).HbA1C showed a strong association with most CVD risk factors and the metabolic syndrome.Prevalence of metabolic abnormalities and the metabolic syndrome increased corresponded with the increasing of quartiles of A1C(P for trend＜0.01),with the exception of low HDL cholesterol levels.ROC analysis revealed that an HbA1C cut point of 5.6%had maximum accuracy in determining metabolic syndrome(definition of the NCEP-ATPⅢ),with the area under the curve 0.64,sensitivity 57.5%and specificity 64.2%.Conclusions1.Postprandial hyperglycemia is common and usually undignosed in most patients admitted to hospital with CVD.Postprandial hyperglycemia may involve in the genesis of AS and CHD.Postprandial hyperglycemia may be an important proximate cause of adverse cardiovascular events.Improve abnormal postprandial glucometabolism may help improve the prognosis for petients with coronary heart disease. 2.Estimation of HbA1C appears to be a useful measure even among the nondiabetic population in assessing an individual's cardiovascular risk.HbA1c could also be a predictive measure of the detection of MS.3.Lp(a),the serum level of which is under genetic control,is a strong risk factor for cardiovascular events.The CHD risk increases with the increase of the serum Lp(a).