| BackgroundAtrial fibrillation (AF) is the most common sustained cardiac arrhythmia, mortality of which was nearly twice as much as non-AF due to the occurrence of ischemic stroke. Approximately one-fifth of all ischemic strokes have been revealed to be attributable to AF, especially non-valvular atrial fibrillation (NVAF) which is responsible for about 50% of all cardiac emboli causing cardiogenic stroke in older patients. Furthermore, it has been established that more than 90% of thrombi formed in the left atrium originate from the left atrial appendage (LAA) in patients with NVAF. However, it is acknowledged that risk factors for NVAF are hypertension, coronary heart disease, diabetes mellitus and ageing, which are also the main risk factors for atherosclerosis. Accordingly, the patients with NVAF may suffer from aortic and peripheral atherosclerosis simultaneously. In a general population, aortic and carotid atherosclerotic plaques, as source of cerebral emboli, were documented to be strongly independent risk factors for ischemic stroke. Furthermore, the ultrasonic study of SPAFIII indicated that aortic atherosclerotic plaque was an independent risk factor for ischemic stroke in patients with NVAF. However, the contributions of carotid plaque to ischemic stroke in patients with NVAF are not very clear.The pathogenesis of atherosclerosis is multiplicity. Recently, shear stress hypothesis had been raised that non-uniform lamina flow shear stress and low shear stress caused by turbulent blood flow facilitates the initiation and development of atherosclerosis. Irregular stroke volume and a turbulent flow, induced by variations in cardiac cycle length, loss of atrial contraction and irregular ventricular rate during AF, provide a model for the study on the correlation between shear stress and atherosclerosis. Furthermore, several studies showed that low shear stress caused by AF contributed to impairment of endothelium in the brachial artery. Accordingly, it is presumed that abnormal shear stress due to AF may promote the establishment of atherosclerosis.Objectives(1) If carotid atherosclerotic plaque is an independent risk factor for ischemic stroke in patients with NVAF.(2) Screening the risk factors for carotid atherosclerotic plaque in patients with NVAF.(3) Does atrial fibrillation contribute to the occurrence of carotid atherosclerotic plaque, and the possible mechanism between AF and carotid atherosclerotic plaque.Subjects and methodsA total of 185 subjects with persistent non-valvular atrial fibrillation were enrolled with clinical data collected. All patients were diagnosed by history taking and electrocardiogram. Of the 185 patients,144 patients were given written informed consent, who had cranial CT or MRI underwent transesophageal echocardiography, except for 2 patients having esophageal neoplasms by history taking and 2 patients with incomplete data; the remaining 140 participated in our study. Subjects were included 97 males and 43 females, aging 57.89±12.16 years, with duration of AF from one month to 20 years (mean±SD,4.25±4.47 years), who divided into carotid plaque (n= 63) and non-plaque (n= 77) according to carotid ultrasonography. All selected patients were recorded arrhythmia before AF, duration of AF, history of drugs therapy, past medical history, embolic history of systemic circulation, history of living habit; had systemic examination; measured height and weight, calculated BMI; detected blood biochemical indicator; underwent CT or MRI of cranium and routine electrocardiogram. All patients underwent transthoracic, transesophageal echocardiography and carotid ultrasonography, measured the data as followed:atrial septum mobility, aortic diastolic diameter, diameter of LCA, diameter of RCA, aortic systolic diameter, intima medial thickness, IMT of AO, IMT of LCA, IMT of RCA, ejection fraction of LAA, length of LAA, maximum area of LAA, minimum area of LAA, width of opening of LAA, end-diastolic diameter of LA, maximum diameter of LA, minimum diameter of LA, ejection fraction of LA, maximum area of LA, minimum area of LA, end-diastolic diameter of LV, ejection fraction of LV, mass of LV, index of mass of LV, posterior wall thickness of LV, pulsitive index of LCA, pulsitive index of RCA, transverse diameter of RA, longitudinal diameter of RA, resistent index of LCA, resistent index of RCA, end-diastolic diameter of RV, spontaneous echo contras, diastolic blood velocity of LCA, diastolic blood velocity of RCA, mean diastolic blood velocity of CA, ejection velocity of LAA, filling velocity of LAA, peak velocity of AO, peak velocity of E wave, thickness of inter-ventricular septum, mean velocity of E wave, mean velocity of AO, mean blood velocity of LCA, mean blood velocity of LCA, systolic blood velocity of LCA, systolic blood velocity of RCA, peak velocity of A wave.Statistical analysis was performed by SPSS 16.0 software package. Continuous data are given as mean±SD, comparison of which were performed by independent-sample t-test. Discrete variables were expressed as absolute frequencies and percentages when appropriate and analyzed by chi-square test. Binary logistic regression analysis was performed to screen possible independent risk factors for carotid atherosclerotic plaque. the pathogenesis of ischemic stroke was tested by univariate analysis, multivariate non-conditional logistic regression analysis. Partial correlation analysis was performed to determine the correlation between atrial fibrillation and carotid atherosclerotic plaque. A p value of less than 0.05 was considered statistically significant.Results(1) The etiological distribution in patients with NVAF:hypertension and coronary heart disease are the main factors in 140 subjects.(2) General state of health:in the selected subjects,97 males(69.3%) and 43 females(30.7%), males were much more than females, mean age 57.89±12.16 years, duration of AF from 1 month to 20 years. carotid plaque had 63 subjects (45%) and non-plaque had 77 subjects (55%). Compared with non-plaque group, age, systemic blood pressure and diastolic blood pressure of plaque group were increased; heart rate and BMI had no obvious variability.(3) Past history:Compared with non-plaque group, the incidence rate of DM and CHD increased, the incidence rate of hypertension did not have obvious variability.(4) Ischemic stroke:21(15%) were proved to be suffered from symptomatic ischemic stroke by cranial CT or MRI.(5) Construction and function of left ventricle:Compared with non-plaque group, LVDd, LVMI, LVPWT, LVEF, LVW and VST of plaque group did not have significant difference.(6) Construction and function of left atrium:Compared with non-plaque group, LAD-max, ASM, LAEF, LAD-min, LADd, LA-max and LA-min of plaque group did not have significant difference.(7) Blood flow frequency spectrum of bicuspid valve:Compared with non-plaque group, the frequency spectrum of bicuspid valve of plaque group did not have obvious changes, it all showed that A wave disappear. The Vmitral-E, Vmean-E, Vmitral-A of plaque group did not have significant difference compared with non-plaque group.(8) Construction and function of left atrial appendage:compared with non-plaque group, LAA-1, LAA-w, LAA-max, LAA-min and LAAEF did not have significant difference.(9) Blood flow frequency spectrum of left atrial appendage:compared with non-plaque group, VF-LAA and VE-LAA also did not have significant difference.(10) Left atrium thrombus or left atrial appendage thrombus:in the 140 subjects, there were 37 subjects (26.4%) with left atrium thrombus or left atrial appendage thrombus; there were 22 patients (34.9%) in plaque group, and 15 patients (19.5%) in non-plaque group.compared with non-plaque group, the detection rate of left atrium thrombus or left atrial appendage thrombus was higher in plaque group.(11) Left atrium SEC and left atrial appendage SEC:compared with non-plaque group, left atrium SEC and left atrial appendage SEC also did not have significant difference.(12) Measure data of carotid artery:compared with non-plaque group, CAD and IMT were increased in plaque group.(13) Blood flow frequency spectrum of carotid artery:compared with non-plaque group, SR-max and SR-min of plaque group were lower obviously; and Vm, Vs, Vd, PI, RI did not have significant difference.(14) Measure data of aorta:compared with non-plaque group, the data of plaque group all did not have significant difference.(15) Detection rate of aortic plaque; in the 140 subjects, there were 68 subjects(48.6%) with aortic plaque; there were 45 patients (71.4%) in plaque group, and 23 patients (29.9%) in non-plaque group. compared with non-plaque group, the detection rate of aortic plaque was higher in plaque group.(16) Risk factors of ischemic stroke:we used the method of multiple factor analysis of logistic regression and created the best regression model, screened 8 risk factors, there were:LAA thrombus, Aortic arch plaque, Carotid complex plaque, Maximal area of LA>35cm2, Dense SEC of LAA, Ejection fraction of LAA<0.20, LVEF<0.50 and Minimal area of LAA>8 cm2.(17) Clinical risk factors of carotid atherosclerotic plaque:we used the method of multiple factor analysis of binary logistic regression and created the best regression model, results showed that age and diastolic blood pressure were 2 independent risk factors of carotid atherosclerotic plaque.(18) Ultrasonographic risk factors of carotid atherosclerotic plaque: Ultrasonographic data were separated into three groups by carotid, transesophageal and transthoracic echocardiography. Six independent ultrasonic risk factors for carotid atherosclerotic plaque in patients with NVAF were identified by binary logistic regression analysis, including left atrial appendage thrombus, carotid IMT, carotid diameter, maximal SR of carotid artery, carotid minimal flow velocities, and carotid resistant index.(19) Partial correlation analysis showed that after controlling for age, duration of AF and heart rate did not correlate with carotid IMT; that after controlling for diastolic blood pressure, duration of AF and heart rate were not correlated with carotid IMT; and that after controlling for age and diastolic blood pressure simultaneously, duration of AF and heart rate were still uncorrelated with carotid IMT.Conclusion(1) Incidence rate of DM, coronary heart disease and ischemic stroke are increased in carotid plaque group, compared with non-plaque group; meanwhile left atrium thrombus and left atrial appendage thrombus, CAD, IMT-CA, SR-max and SR-min all have significant difference.(2) Atherosclerosis is the independent ultrasonic risk factor for ischemic stroke in patients with persistent NVAF.(3) Age and diastolic blood pressure are acknowledged as the independent clinical risk factors for carotid atherosclerotic plaque and NVAF, which indicates pathophysiological cross-talk between atherosclerosis and NVAF.(4) Left atrial appendage thrombus, carotid IMT, carotid diameter, maximal SR of carotid artery, carotid minimal flow velocities and carotid resistant index are independent risk factors for carotid atherosclerotic plaque. (5) Duration of AF and heart rate are not the risk factors for carotid atherosclerotic plaque in patients with NVAF. We speculated that endothelial dysfunction consequent upon irregular hemodynamics may bridge the gap between thrombosis and atherosclerosis, which warrants further study. |