| As a haematological parameter that is widely used clinically, the red cell distribution width (RDW) reflects heterogeneity in red cell volume (i.e., the so-called nonuniformity in red cell size), and has been previously used for diagnosis and differential diagnosis of different anemia conditions. Some evidences have proved that such nonuniformity is relatively common in human diseases. For example, cardiovascular diseases, phlebothrombosis, cancers, diabetes, community-acquired pneumonia, chronic obstructive pulmonary diseases, hepatorenal diseases and other acute or chronic diseases can all lead to an increase in RDW. Researches made in recent years have revealed that, RDW may be used as a cardiac marker for risk stratification and prognosis evaluation of coronary heart diseases.Various biological phenomena of the human body exhibit a diurnal rhythm, and this applies also to physiological activities and pathological activities of the cardiovascular system. Cardiovascular events (e.g., myocardial infarction and sudden cardiac death), cardiac arrhythmia and variations in ECG parameters exhibit a typical diurnal rhythm as well. Nearly all processes of keeping and regulating the diurnal rhythm of the cardiovascular system are closely correlated with the autonomic nervous system (ANS). The autonomic nervous function may be affected by many pathological conditions such as coronary heart diseases, hypertension, diabetes or the like to cause variations in the diurnal rhythm.ECG parameters commonly used clinically such as the diurnal QTc variation may be used as an effective indicator for myocardial ischemia diagnosis and prognosis determination, and may also be used as a high-risk early-warning indicator for sudden cardiac death. The two indicators, RDW and the diurnal QTc variation, are somewhat similar to each other but also have respective unique features in terms of diagnosis and prognosis evaluation of coronary heart diseases. However, no report on relationship therebetween has been found.The main regulatory factor that affects erythropoiesis under physiological conditions is the erythropoietin (EPO), which also has effects of EPO anti-apoptosis, anti-inflammation, anti-oxidative stress, promoting neovascularization and regulating the nervous system. Researches on animals have revealed that EPO has the effect of regulating the autonomic nervous function, but no specific report on relationships among RDW, ECG parameters and EPO is available yet.Part I Relationship between RDW and diurnal QTc variation in patients with coronary heart diseasesObjective:To analyze relationship between RDW and the Gensini score representing the degree of coronary stenosis and severity of implicated blood vessels in patients who underwent coronary arteriography (CAG), find out relationship between the Gensini score and the diurnal QTc variation in patients with coronary heart diseases, and investigate relationship between RDW and the diurnal QTc variation in patients with coronary heart diseases.Methods:1. Two groups of patients who underwent coronary arteriography (CAG) due to thoracodynia or suspected acute coronary syndrome and was clearly diagnosed to have the coronary heart disease were collected. The coronary disease is defined to be that the diameter of the left main coronary artery, the left anterior descending branch, the left circumflex, the right coronary artery or main branch blood vessels thereof?50%; and variations in clinical indicators were compared between the two groups. Also the following conditions were satisfied:(1) sinus rhythm; (2) effective 24-hour dynamic ECG (HOLTER) records were available. Exclusion criteria:(1) arrhythmia or non-sinus rhythm that has an accompanied effect on the QT interval; (2) medicines that might affect the QT interval having been taken within the last two weeks; (3) diseases that have an accompanied effect on the autonomic nervous function, e.g., diabetes, hyperthyroidism and etc.2. Medical history data and laboratory inspection results (e.g., RDW) of the patients were collected, and diurnal QTc variations of the patients were calculated and analyzed according to the HOLTER results.3. The patients were equally divided into three groups (A, B and C) in an ascending order of their RDW values, and indicators such as the gender percentage, the age structure, the blood pressure, the blood glucose level, the blood lipid level, the nighttime QTc and the average heart rate were compared among the three groups to retrospectively study relationship between RDW and the diurnal QTc variation.Results:The patients were equally divided into three groups (A, B and C) in an ascending order of their RDW values. RDW values, coronary artery scores and diurnal QTc variations were significantly different among these groups (P<0.05). As the RDW values increased, the coronary artery scores gradually rose and the diurnal QTc variation decreased. Pearson's correlation analysis was applied to control confounding factors, and correlation between every two of the coronary artery score, RDW, and the diurnal QTc variation were analyzed. The results showed that the coronary artery score was positively correlated with RDW (r= 0.130, p= 0.020), but was not correlated with the diurnal QTc variation (r=-0.226, p= 0.681); and RDW was correlated with the diurnal QTc variation (r=-0.197, p= 0.035).Conclusions:1. RDW is positively correlated with the Gensini score of patients, and more serious coronary artery stenosis conditions lead to higher RDW levels.2. As RDW values increases, the diurnal QTc variation decreases, so there might be relationship between coronary artery stenosis and autonomic nervous function damages.3. RDW of the patients with coronary heart disease is independently correlated with the diurnal QTc variation.4. The economic RDW value measurement is helpful for diagnosis and prognosis evaluation of coronary heart diseases.Part ? Relationship between EPO and RDW level of patients with coronary heart diseases and regulation effect of EPO on diurnal rhythm of ECG parametersObjective:To investigate relationship between endogenous erythropoietin level and RDW in patients with coronary heart diseases as well as features of the diurnal variation of ECG parameters and relationships with EPO and RDW, and find out the regulation effect of EPO on the diurnal variation of ECG parametersMethods:200 patients who underwent coronary arteriography (CAG) inspection due to thoracodynia or suspected coronary heart diseases were collected and, according to the CAG inspection results, divided into a CHD group and a non-CHD group. Clinical data, parameters of blood routine tests and biochemical indicators (including RDW, EPO and etc.) of all patients were collected to study relationship between RDW and EPO. From these patients,103 patients were randomly selected to undergo a routine HOLTER inspection for collection of clinical data, hemato logical indicators and diurnal heart rate variability time-domain indicator thereof; and 48 patients with coronary heart diseases were randomly selected to undergo the Ewing standard autonomic nervous function test, the electrocardio-scatterplot inspection and the EPO inspection and were divided into an Ewing(+) group and an Ewing(-) group according to the test results of the Ewing standard autonomic nervous function test.Results:(1) RDW values and EPO levels of the CAD group are both higher than those of the non-CAD group; Pearson's correlation analysis showed that RDW was correlated with EPO levels for all patients (r-0.290, p=0.000), and such correlation is more significant for patients with coronary heart diseases (r=0.411, p=0.000); binary logistic multi-factor regression analysis on related factors of coronary heart diseases showed that both EPO and RDW are risk factors and these two factors cannot be put into the equation simultaneously; multiple stepwise regression analysis taking RDW as a dependent variable indicated that EPO is an influencing factor of RDW. (2) SDNN, SDANN, RMSSD, PNN50 of the CAD group were all lower than those of the non-CAD group. For the CAD group, SDNN values were all lower than those of the non-CAD group, and nighttime RMSSD and nighttime PNN50 values were also lower than those of the non-CAD group, but daytime RMSSD and daytime PNN50 values made no significant difference from those of the non-CAD group. For patients in the CAD group, their respective SDNN, RMSSD and PNN50 values made no significant difference between the daytime and the nighttime; and for patients in the non-CAD group, their respective SDNN values made no significant difference between the daytime and the nighttime, but RMSSD and PNN50 values were both higher at the daytime than at the nighttime. (3) 65 patients in the CAD group were equally divided into three groups in an ascending order of their EPO levels, and significant differences were observed among the three groups in terms of diurnal QTc variation, daytime SDNN, daytime RMSSD and nighttime RMSSD, daytime PNN50 and nighttime PNN50. Pearson's correlation analysis showed that the EPO level was negatively correlated with diurnal QTc variation, daytime RMSSD and nighttime RMSSD, daytime PNN50 and nighttime PNN50. (4) 48 patients with coronary heart diseases who had undergone the Ewing standard autonomic nervous function test were divided into the Ewing (+) group and the Ewing (-) group and all underwent the electrocardio-scatterplot inspection and the EPO inspection. A comparison in quantative indices between Lorenz scatterplots of the patients of the two groups showed that of the Ewing (+) group was lower than that of the Ewing (-) group and there was no significant differences between VIA of the two groups. The EPO level of patients in the Ewing (+) group was significantly higher than that of the Ewing (-) group, and the EPO level was negatively correlated with VIL of the Lorenz scatterplot (r=-0.427, p=0.002) (i.e., a higher EPO level corresponds to a lower)but was not correlated with VIA (r=0.091, p=0.539). Binary logistic regression analysis taking whether the autonomic nervous function was damaged (Ewing (+) group=1, Ewing (-) group-0) as a dependent variable showed that EPO (OR=1.394) and diastolic blood pressure (OR=1.091) were risk factors for autonomic nervous function damage; VIL(OR=0.934) was a protective factor for autonomic nervous function, with a lower value corresponding to a poorer autonomic nervous function. ROC curve analysis taking whether the autonomic nervous function was damaged as a state variable and EPO and VIL as inspection variables respectively showed that an area covered by the EPO curve was 0.737 and that covered by the VIL curve was 0.719.Conclusions:1. The RDW level is closely correlated with the endogenous EPO level in patients with coronary heart diseases, both the RDW level and the endogenous EPO level are risk factors for coronary heart diseases, and the endogenous EPO level might be the direct cause of increased RDW in patients with coronary heart diseases.2. As compared with patients without coronary heart diseases, the heart rate variability of patients with coronary heart diseases decreases and the diurnal rhythm of hear rate variability disappears.3. For patients with coronary heart diseases, the EPO level is closely negatively correlated with ECG parameters and is a risk factor for autonomic nervous function, with a higher EPO level corresponding to more serious damage of the autonomic nervous function.4. Relationship between ECG parameters and RDW might be a reflection of the regulation effect of EPO on the autonomic nervous function. |
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