| BackgroundAs increasingly accelerated aging of population in today’s society, cardiovascular morbidity and mortality rates are highest, has become one of the most important public health problem in the 21st century. Calcification of aortic valve disease is becoming a common cardiovascular disease in the elderly. Degenerative aortic valve calcification (DAVC) and calcific aortic stenosis are increasingly affects elderly people.There was confirmed by echocardiography or radiological examination, calcification of aortic valve sclerosis of elderly is about a third in the crowd, this is early stage of degenerative aortic valve calcification and subclinical form. Aortic valve calcification disease is a global disease. After investigation, heart valve disease in the United States over the age of 65 years or older population is 4.4～8.5%, and over the age of 75 years or older population is 11.7%～13.3%. Age, sex, smoking, high cholesterol, high blood pressure, type 2 diabetes increases the risk of the disease. Calcification of aortic valve disease (CAVD) is mainly two types of aortic valve calcification (AVC) and calcification of aortic stenosis (CAS). The most severe form is calcification of aortic stenosis in CAVD development process, about 2% more than 60 people with calcification of aortic stenosis, and has reached the degree to which need operation treatment, and calcification of aortic stenosis in the 75 years of age or older population is 2.8%. In our country, we analyzed the echocardiographic data of 27439 patients, found that 45 years of age or calcification of aortic valve disease in patients with the overall prevalence of 12.8%. The latest research suggests that aortic degeneration can result in higher cardiovascular accident death rate and total mortality, may be is a new independent risk factor for coronary events, many other studies found that aortic degeneration with carotid atherosclerosis, coronary heart disease is closely related to the onset of so degenerative aortic valve calcification becomes more and more attention.Since valvular calcification was known, our understanding of its clinical characteristics and pathological mechanism experienced a series process. In 1904, Monkebery first found that voltinism aortic stenosis (Calcified aortic stenosis, CAS)can appear in the process of natural aging; And 1910 Dewitsky first described the Mitral annulus calcification (Mitral annular calcification, MAC), and argues that the calcification is degeneration. Therefore, degenerative cardiac valvular disease (Senile degenerative heart valvular diseases, SDHVD) is also known as Senile calcified heart valve disease. And with people living standard rise, and gradually into the aging society, proportion of senile degenerative calcified lesions in the aortic valve is rising year by year. For a long time of aortic valve replacement is the only effective treatment option, drugs can only palliative relieve symptoms and curative effect is not exact. But surgical valve replacement also has its limitations, such as valve replacement is costly, and mechanical valve replacement surgery patients need long-term oral anticoagulation drugs, increased in patients with hemorrhagic risk; And the service life of the biological valve is limited, can’t solve the problem. In addition, especially in patients with surgical extracorporeal circulation for elderly patients is high risk. It is very necessary to carry out the degenerative heart valve disease pathogenesis and risk factors of research to look for the early intervention methods. However, the degenerative cardiac valvular disease pathogenesis is still not clear.,which once considered the development of the disease is a process of degeneration associated with aging, but recent research has shown that heart valve calcification is may be ale tissue reaction to start some factor and multiple factors participate in the initiative process.Major clinical features of degenerative aortic valve calcification disease mainly include the following aspects:(1) Degenerative valvular disease progress is slow, asymptomatic period can be decades, even some of life in patients with subclinical process, consciously without any discomfort. However, patients with aortic stenosis once appear the symptom of angina pectoris or syncope, average survival time will be significantly lower, about 2 to 3 years. And about 30% of the degenerative heart valve disease can have left cardiac insufficiency, and if it was reach the progress of heart function failure phase, the average survival time was only about 1.5 years. Through strict and optimizing the medical treatment of the patient’s 5-year survival rate can reach 64%. (2) Simple elderly patients with severe aortic stenosis are common symptoms of angina pectoris, syncope, and heart failure, and often with as the main clinical manifestations of heart failure, severe cases can lead to sudden death. (3) Aortic stenosis murmurs can be widely conduction, the longer the duration of the heavier and narrow noise; when the valve calcification is lighter, and the free vibration, can produce murmur. Valve disloyalty sound severe calcification in the aortic valve components of delay and pulmonary valve components overlap will be more delay, a single mind or disloyalty sound inverse division. Severe aortic stenosis can be the area before the heart touching systolic tremor.Aortic valve calcification is believed to be a degenerative changes, can not be irreparable, but as the pathological and histological observation and understanding of the disease, found that it is not only degeneration, but also with the process of chronic inflammation, participation and lipid infiltration of inflammatory cells. Degenerative heart valve disease in pathological histology mainly exist the following features: valve of collagen and elastic fibers increased, and gradually decompose and fracture, elastic fiber dyeing is irregular. Then visible valve degenerative change since base, pathological changes mainly involving fiber layer, and with the growth of the age, valve collagen fiber hyperplasia, density, edge blur, disorganized and myxoid degeneration. Deep deformation since the fiber gradually extended to the shallow, light colored area is "petals" samples, its edge and interior with collagen fiber and elastic fiber filament connection with lipid accumulation. Valve collagen sponge and fiber layer between the elastic fiber seperation are destroyed, disappear. Tiny calcium salt particles deposit on the first valve base collagen fiber myxoid degeneration and lipid accumulation area, and with the myxoid degeneration and lipid accumulation of extension and expansion. Serious when involving the whole valve leaf fiber layer, the formation of multifocal, amorphous calcium spot. Diseased tissue surrounded by fibrous tissue surrounding the thin-walled blood vessels and bleeding, inflammatory cells infiltration, with occasional sample foreign body giant cells. The nucleus pycnosis, reduce, elastic fiber disintegration. Aortic and mitral valve serious calcified plaque formation is mainly seen in the anterior lobe middle and distal leaves, semilunar nodules may also be affected. There are several pathogenesis theories on degenerative aortic valve disease, but the exact mechanism has not been fully elucidated, and did not reach consensus, the main theories are:(1) Chronic inflammation doctrine:the study found that in the early valve degenerative diseases, the pathological changes have appeared in the chronic inflammatory cell infiltrates, mainly macrophages and T lymphocytes. Some scholars find valvular calcification in patients with elevated levels of inflammatory markers, but how to cause inflammation reaction mechanism is not clear, that could be a long term blood through the heart valve impact, friction and caused by mechanical stress effect. (2) The genetic theory, studies have found that the occurrence of degenerative valvular disease has familial aggregation and genetic predisposition. Now confirmed that the apolipoprotein E gene, vitamin D receptor gene, eNOS G894T polymorphism is associated with the occurrence of degenerative valvular disease. (3) Theory of calcium and phosphorus metabolism disorder:vitamin D deficiency in the elderly, parathyroid hormone secretion to increase, caused two ions migrated from tissue to tissue, increase the intracellular calcium, the occurrence of degenerative valvular disease may be associated with this. Some scholars with trace element determination method to determine the degree of calcification of calcium, phosphorus and magnesium content in different valves, calcified valvular calcium mainly in amorphous form of calcium hydrogen phosphate deposits on the valve, and increased with the severity of calcification. (4) Lipid accumulation theory, some scholars think that hyperlipidemia can cause the process of valvular calcification, in calcified lesions early and sustained progress, plasma lipid in valvular calcification in aggregation, lipid be oxidized into valvular interstitial, role in endothelial cells and valve fibroblasts, activation of inflammatory cells and start the process of calcification. Also has a number of studies mentioned lipid levels were associated with valvular calcification.(5)The extracellular matrix remodeling theory:research has shown that the lesions in the aortic valve, can appear the extracellular matrix remodeling associated with disease progression. Normal the main components of the extracellular Matrix of bone Matrix metalloproteinases, Matrix metalloproteinase (MMPS) can be found in the calcification of the valve, but in the normal valve was not detected. The existing research results show that the MMPS not only cause matrix degradation, and can result in the generation of connective tissue growth factor related, prompting the synthesis of matrix.This study is based on the above theories and cognition,through collecting a large number of clinical data and statistical analysis in order to investigate the aortic degeneration (degenerative aortic valve calcification, DAVC) risk factors, and the differences of risk factors between degenerative aortic valve calcification complicated with hypertension or coronary heart disease.Part I Risk factors of degenerative aortic valve calcification ObjectThere are 2894 cases which were randomly selected NanFang hospital outpatient and hospitalized patients from 2005 to 2012 in the age of 45. there are 1374 cases of aortic valve calcification in the part of this crowd by ultrasound cardiogram explicitly.heart disease with heart valve disease, congenital heart valve malformation, caused by infective endocarditis valve disease, malignant tumor, the combining with other tissues and organs clearly infectious diseases. The group give priority to arterial valve calcification group. The rest is 1520 cases by echocardiography in the diagnosis of without aortic valve calcification, among which 984 were male, female 536 cases. The group is the control group, there aren’t rheumatic heart disease, congenital heart disease, cardiomyopathy, infective endocarditis, etc.MethodRegister the object of study of relevant clinical data:age, gender, aortic sclerosis, white blood cell (WBC), neutrophil, c-reactive protein (CRP), Pro-BNP, creatinine (Cr), urea nitrogen (BUN), uric acid (UA) and urinary inhibition-C (Cys-C), triglycerides (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL C), homocysteine (HCY), height, weight. The chronic kidney disease (CKD) formula of EPI eGFR= a* (serum creatinine/b) c* age calculation of glomerular filtration rate (0.993). Using BMI= weight (kg)/height (m2) to calculate body mass index, according to the above two groups of data for statistical analysis.All cases in the group get completely thoracic echocardiography examination, including M type, two-dimensional and Doppler echocardiography. According to the acoustic cardiogram test results into aortic valve calcification group and non-calcified aortic valve group. Judgement standard of aortic valve calcification lesions are as follows:echogenic valves, valve thickening, leaflets activity is not restricted, valve area>3cm2, transvalvular blood flow rate<2.5m/s is defined as aortic valve calcification; the transvalvular blood flow rate> 2.5 m/s, valve area<3cm2 is defined as aortic stenosis; area method using regurgitation Cambodia, find the largest section image regurgitation area, the percentage of the area accounted for the section left atrium (LV) area of computing,<20% is defined as aortic regurgitation.All datas were analyzed by taking statistical software SPSS 21.0, measurement data with mean+/-standard deviation, count data use cases (%); First of all factors affecting single factor Logistic regression analysis, eliminate some nonsense influencing factors; Then remaining study using multiple Logistic regression analysis, and calculate the Odds ratio (Odds the wire, OR).Result(1) There are 24 (2%)patients suffer from calcific aortic stenosis in degenerative aortic valve calcification group,918 patients (67%) suffer from calcific aortic valve insufficiency,154 patients (11%) with both calcific aortic stenosis and aortic valve insufficiency,278 patients (20%) with no calcific aortic stenosis or aortic valve insufficiency.(2) We found the differences between groups in the description of statistics in front of our preliminary findings included in the study of the indexes in the aortic valve calcification group and control group. More than as a result, we will have differences in the research into the target of univariate factor Logistic regression equation of the evaluation index of all of the effects of degenerative aortic valve calcification. Results showed that gender(P=0.003 OR=0.797)、age(P=0.000 OR=1.196)、aortic atherosclerosis(P=0.000 OR=13.680)、BMI(P=0.000 OR=0.896)、eGFR(P=0.000 OR=0.947)、Cr(P=0.000 OR=1.034)、 Pro-BNP(P=0.000 OR=1.012)、WBC(P=0.000 OR=1.308)、neutrophils (P=0.000 OR=1.586、CRP(P=0.000 OR=1.175)、TG(P=0.000 OR=1.156、TC(P=0.000 OR=0.825)、LDL-C(P=0.000 OR=0.558)、BUN(P=0.000 OR=1.460)、 UA(P=0.005 OR=1.001)、HCY(P=0.000 OR=1.226). The above indicators are meaningful in the univariate factor analysis of Logistic.(3) The factors which are meaningful in the univariate factor Logistic regression analysis research indicators are taken into the multi-factor Logistic regression equation in further analysis (table 1-4), the results showed that female (P=0.045 OR=0.367)、age (P=0.001 OR=1.099)、Pro-BNP (P=0.007 OR=1.005)、 HCY(P=0.014 OR=1.105)、aortic atherosclerosis (P=0.004 OR=15.197)are independent risk factors for the development of degenerative aortic valve calcification.ConclusionBy analyzing the impact factors of the multiple factors Logistic regression analysis,we found that age, female, aortic sclerosis, and homocysteine hematic disease, heart failure and so on are independent risk factors of the development of degenerative aortic valve calcification. And overweight, renal insufficiency and inflammatory cells, CRP, blood lipid, uric acid and urea nitrogen does not increase the risk of aortic valve calcification.Part Ⅱ Differences of risk factors between pure degenerative aortic valve calcification and which complicated with coronary heart disease or hypertensionObjectAll 2894 cases of research object solicitation echocardiography in the diagnosis of aortic valve calcification of the crowd, namely the aortic valve calcification in the first part of study group.MethodAccording to the characteristics of the history of the aortic valve calcification group is divided into three subgroupsrdegenerative aortic valve calcification complicated with hypertension, degenerative aortic valve calcification complicated with coronary heart disease, pure degenerative aortic valve calcification, the group complicated with hypertension or coronary heart disease, respectively, compared with pure degenerative aortic valve calcification group, especially various clinical indicators of differences between groups, further using multivariable Logistic regression method to analyze on the basis of aortic valve calcification, various clinical indicators of abnormal for the risk of high blood pressure, coronary heart disease.Result(1) Taking the impact indicators between hypertension group and pure aortic calcification group all brought into the univariate regression analysis Logistic, the results suggest that BMI (P= 0.003 OR= 1.110), eGFR (P= 0.006 OR= 0.994), WBC (P= 0.016 OR= 1.086), TG (P= 0.000 OR= 1.399),CRP((P= 0.016 OR= 0.973)and other factors are meaningful.(2) Taking the meaningful factors of univariate Logistic regression analysis into the multivariate Logistic regression equation further analysis (Table 2-4), the results show compared with pure degenerative aortic valve calcification BMI (23.82 ± 4.12vs22.18 ± 5.18 P= 0.000 OR= 1.231) of people in degenerative aortic valve calcification complicated with hypertension is higher,; but eGFR of pure degenerative aortic valve calcification in patients (67.28 ±31.34vs74.29 ± 36.24 P= 0.050 OR= 0.992) and CRP (5.50 ± 7.05vs7.41 ± 9.82 P= 0.022 OR= 0.957) is lower.(3) The influence factor between the coronary heart disease group and the pure aortic valve calcification group will be taken into univariate Logistic regression analysis, the results suggest that gender (P=0.020 OR=1.416), BMI (P=0.000 OR=1.101), eGFR (P=0.000 OR=0.990), Cr (P=0.046 OR= 1.002), WBC (P=0.000 OR=1.192), neutrophil (P=0.009 OR=1.096), TG (P=0.008 OR=1.272) and other factors are meaningful.(4) Taking the meaningful factors of univariate Logistic regression analysis into the multivariate Logistic regression equation further analysis (table 2-5), the results indicate that BMI (23.69+3.92vs22.18+5.18 P=0.000 OR=1.138) and WBC (7.63 +2.63vs6.68+2.15 P=0.006 OR= 1.155) of the coronary heart disease group is higher than that of pure degenerative aortic valve calcification group; and eGFR (64.54+28.15vs74.29+36.24P=0.007 OR=0.991) of pure degenerative aortic valve calcification group is higher than that of coronary heart disease group.Conclusion(1)Compare the risk factors of pure degenerative aortic valve calcification with which complicated with hypertension, we find that age, cholesterol, low density lipoprotein cholesterol considered the risk factors of hypertension in the previous study are removed. And BMI of patients suffering from both hypertension and degenerative aortic valve calcification is higher than that of patients suffering from pure degenerative aortic valve calcification, but the former patient’s eGFR, CRP levels are lower than the patients suffering from pure aortic valve calcification.(2) BMI and white blood cell count of patients suffering from both coronary heart disease and degenerative aortic valve calcification is higher than that of patients suffering from pure degenerative aortic valve calcification, while the eGFR level is lower than that of patients who suffering from pure aortic valve calcification. |
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