2015年 · 第43卷第11期

There is a persistent risk of new thrombotic events in patients with stable coronary heart disease 1 year after myocardial infarction, but there is no research evidence whether these patients may benefit from dual antiplatelet therapy.

Since 2013, the International Society for Atherosclerosis (IAS), the American College of Cardiology (ACC) /American Heart Association (AHA), the American Lipid Society (NLA), and the China Cholesterol Education Program (CCEP) have successively published blood lipid guidelines and recommendations. The guidelines have commonalities as well as differences and controversies. Importantly, the guidelines have updated their concepts due to advances in lipid metabolism research. Among them, the NLA guide is the most complete, accurate and practical.

Numerous clinical and clinicopathological studies have shown that^[1]The natural process of coronary atheromatous plaque is that the plaque undergoes repeated rupture and healing, which leads to gradual growth, and finally forms obstructive coronary artery disease; During any stage, sudden plaque rupture, massive thrombosis and acute thrombotic events, namely acute coronary syndrome (ACS), may occur. Therefore, the natural course of coronary heart disease is an alternating process of stable and unstable coronary heart disease. For many years, people have worked from different entry points to block and improve the natural course of this coronary heart disease, and achieved significant results. However, there are still many problems to be solved and discussed in how to identify patients who may have obstructive coronary artery disease from patients who complain of chest pain, and what means to find coronary artery disease first.

The patient, a 42-year-old male, came to our hospital on May 9, 2013 because of "cardiac murmur found for 1 month". One month before admission, the patient experienced decreased activity tolerance and occasional edema at the ankle. He was in good health in the past, denied family history of hypertension, coronary heart disease and atrial fibrillation, and had no history of living in epidemic areas. Admission showed mild anemia, heart enlarged to the left, and grade 3 systolic blow-like murmur was heard in the mitral auscultation area. Echocardiography showed that the left atrium and left ventricle were enlarged, no segmental wall motion abnormalities were observed at rest, the left ventricular endocardium was thickened, and a strong echo light mass was detected on the inner wall of the heart chamber, with loose texture, resulting in annular thickening and occlusion of the apex. M-mode ultrasound showed that the apical beat amplitude was normal, and mural thrombosis was considered (Figure 1、Figure 2)； Mitral probe and moderate regurgitation, left ventricular ejection fraction 55%. After that, the patients underwent electrocardiogram and coronary angiography successively, but no obvious abnormalities were found. Serum electrolyte tests showed no abnormalities, creatinine 97 μ mol/L, urea nitrogen 8.2 mmol/L, albumin 39 g/L, alanine aminotransferase 100 U/L, aspartate aminotransferase 80 U/L, cholesterol 2.06 mmol/L, creatine kinase 93 U/L, creatine kinase isoenzyme 27 U/L, myoglobin 82 μ g/L, troponin I 0.15 μ g/L, N-terminal pronatriuretic peptide type B (NT-proBNP) 1 410 ng/L. Coagulation function tests: prothrombin time (PT) 21.8 s, activated partial prothrombin time (APTT) 39.9 s, D-dimer 5.08 mg/L, fibrinogen degradation products 16.44 mg/L. Tumor associated antigen 125 340 700 U/L. No abnormalities were found in the complete set of thyroid function and immune tests. No parasites were found in stool routine. Routine blood test: red blood cells 3.5×10¹²/L, hemoglobin 87 g/L, white blood cells 14.1×10⁹/L, % eosinophils 86.8%, platelets 126×10⁹/L. The diagnoses were: (1) Löffler endocarditis, mitral regurgitation (moderate), New York Heart Association (NYHA) cardiac function class II; (2) Mild anemia. The patient had no evidence of parasites and tumors, and was diagnosed with prednisone 40 mg (once a day, oral) and enoxaparin 5 000 IU (once/12 h, subcutaneous injection). After 5 days of treatment, the total number and proportion of eosinophils in the patient remained high, and fever symptoms gradually appeared. Reexamination ultrasound showed that there was no obvious progression of intracardiac mural thrombosis. Bone marrow cytology and bone marrow biopsy were arranged to confirm the diagnosis of eosinophilic leukemia (Figure 3)。 After the patient was transferred back to the hematology department of the local hospital to receive chemotherapy with hydroxyuria and other drugs, his condition deteriorated further. After many telephone follow-ups, his symptoms of heart failure and anemia gradually worsened. On October 3, 2013, he suffered a sudden cerebral infarction and died after 1 week of treatment due to secondary accumulated pneumonia.

A 60-year-old male was admitted to the hospital on March 17, 2015 due to "intermittent chest pain for more than 9 years, lower limb edema for 3 months, and dyspnea for 20 days". The patient began experiencing post-active retrosternal dullness 9 years ago. Coronary angiography 4 years ago showed 70% eccentric stenosis of the proximal left main trunk; Left anterior descending artery proximal to middle segment stenosis 75%; The left circumflex branch is small, the opening is 90% narrow, and the middle and distal segment is 50% ~60% narrow; The proximal-middle intima of the right coronary artery is not smooth; Stenosis of the middle segment of the posterior descending artery was 30%. After angiography, one drug-eluting stent was placed in the left main trunk and left anterior descending artery respectively. Four months ago, the patient had recurrent chest pain. Coronary angiography was performed in an outside hospital, which showed in-stent restenosis of the left main trunk and left anterior descending artery, with a stenosis degree of 90%, and the stenosis degree of the left circumflex artery and right coronary artery was the same as before. Selective coronary artery bypass grafting was performed, and aspirin was stopped for 5 days before operation. Two great saphenous veins were taken as bypass vessels during operation, one distally anastomosed to the left anterior descending branch and the proximal anastomosed to the ascending aorta, and the other distally anastomosed to the first diagonal branch and the proximal anastomosed to the ascending aorta. The pericardial drainage volume on the day of operation was 700 ml, which was bloody, and the drainage volume on the next day was 200 ml, and the pericardial drainage tube was removed. Postoperatively, aspirin, atorvastatin and isosorbide mononitrate were taken regularly, and there was no episode of chest pain. Three months before admission, depressed edema of both lower limbs gradually appeared, accompanied by cough, cough a small amount of white phlegm, and cough aggravated in the recumbent position. Other hospitals considered "heart failure", and the edema was reduced after diuretic administration of furosemide. The edema worsened 1 month ago and progressed to bilateral lumbosacral region with anorexia, abdominal distension and urine volume of 800 ml/d. 20 d ago, the patient began to have difficulty breathing and could not lie down. Body weight gained 10 kg in 4 months. He had a history of hypertension for more than 9 years, with the highest blood pressure of 160/80 mmHg (1 mmHg =0.133 kPa). After oral administration of amlodipine 2.5 mg/d and irbesartan 150 mg/d, his blood pressure was controlled at about 120/80 mmHg. Diabetic history for more than 10 years, treated with insulin. He has smoked for 40 years, with an average of 20 cigarettes/d, and has not smoked for nearly 4 months. Drinking alcohol for 40 years, averaging 2 taels/d.

A 29-year-old male was admitted to the intensive care unit of our hospital on November 12, 2011 due to "sudden severe chest pain after smoking methamphetamine for more than 1 h". The patient smoked methamphetamine more than 1 h before admission, and a few minutes later, he had sudden chest pain, mainly after the sternum, which was squeezing pain, which was unbearable, accompanied by sweating and pale complexion. About 10 minutes after being admitted to the emergency room of our hospital, the patient had sudden disturbance of consciousness, refused to respond, his limbs twitched, his blood pressure could not be measured, his blood oxygen saturation gradually decreased, and the ECG monitor indicated ventricular fibrillation. Electrical defibrillation, chest cardiac compression, endotracheal intubation, injection of epinephrine, and establishment of venous access were immediately administered. After treatment, the patient recovered spontaneous heart rhythm and respiration, and then was sent to the intensive care unit for further diagnosis and treatment. No previous history of hypertension, diabetes, heart disease, dyslipidemia, denied family history of autoimmune diseases and stroke, and no recent history of upper respiratory tract infection. Drinking for more than 10 years, 2 bottles of beer a day; Smoking for more than 10 years, more than 20 cigarettes a day. At the age of 25, he began to take drugs intermittently, mainly methamphetamine, and the dose was variable, 3 to 4 times/week.

Antiplatelet therapy and revascularization are important measures to save the life of patients with acute coronary syndrome (ACS), reduce the risk of recurrent ischemic events, and improve the long-term outcome of patients. As one of the important revascularization methods in ACS, damage to the blood vessel wall during percutaneous coronary stenting (PCI), collagen exposure, platelet activation, aggregation and adhesion to the injured area, etc. all promote the formation of in-stent thrombosis, which may cause PCI to fail. Therefore, intensive platelet therapy is an important guarantee for the success of PCI. dual oral antiplatelet therapy (DAT) with clopidogrel and aspirin is the cornerstone of prevention of thrombotic events after ACS and/or PCI. However, some patients still develop some serious complications after conventional treatment, such as recurrent myocardial infarction (MI), in-stent thrombosis, stroke, and even death^[1]。 In order to reduce the incidence of major cardiovascular adverse events (MACE), clinicians actively look for solutions, such as increasing the dose of clopidogrel, or combining antiplatelet drugs with different mechanisms of action, or even switching to new antiplatelet drugs to optimize antiplatelet therapy. This article mainly summarizes the treatment progress of oral DAT and triple anti-platelet therapy (TAT) in ACS patients.

Transcribable genes account for 90% of the human genome^[1]However, only 2% of these are protein-encoding genes. The Human Genome Project shows that only about 20,000 to 25,000 protein-encoding genes exist in humans^[2], similar to the number of coding genes of nematodes^[3]。 One can't help but wonder what the remaining 98% of transcribable genes in the genome are and what their functions are. Thanks to the rapid development of sequencing technology and the improvement of transcriptomics bioinformation algorithms, people have gradually realized that except for protein-encoding genes, the vast majority of the genome exist in various tissue cells in the form of non-encoding RNA^[4]。 Among many types of non-coding RNAs, microRNAs (miRNAs) with a length of 21-23 nt have been studied most deeply. MiRNAs were first discovered in nematodes 20 years ago and have been highly conserved over the course of evolution. To date, more than 2 000 miRNAs have been identified in humans. Studies have shown that miRNA can degrade or inhibit the expression of target mRNA mainly by unpaired binding to target mRNA, and plays an important role in gene expression regulation in various biological and pathological processes^[5]。 long non-coding RNA (lncRNA) and its subtype long intergenic non-coding RNA (lincRNA) are another non-coding RNA with biological functions discovered in recent years. lncRNA is a class of RNA molecules that do not encode proteins and have a transcript length of more than 200 nt. lncRNA regulates gene expression levels in the form of RNA at various levels (epigenetic regulation, transcriptional regulation and post-transcriptional regulation, etc.), and is quite conserved in evolution. Studies have shown that lncRNA plays an important role in the formation and development of tumors^[6]。 However, the role of lncRNA in cardiovascular system diseases remains unclear^[7]。 Based on this background, we will review the role of lncRNA in cardiovascular system and related diseases.

The definition of autophagy was proposed by Ashford and Porter in 1962 after discovering the phenomenon of "eating yourself" in cells. It refers to the double membrane detached from the ribosome-free attachment zone of the coarse endoplasmic reticulum to wrap part of the cytoplasm and organelles, proteins and other components that need to be degraded in cells to form autophagosomes, and fuse with lysosomes to form autophagy lysosomes, which degrade the contents wrapped in them to realize the metabolic needs of the cells themselves and the renewal of some organelles. Autophagy can be seen in both physiological and pathological processes of the body. atheroscerosis (AS) is considered to be a chronic inflammatory reaction in the arteries, which progresses slowly and gradually appears clinical symptoms. Its main characteristic is the formation of AS plaques. Risk factors include genetics, sex, hyperlipidemia, diabetes, hypertension, obesity and smoking, etc^[1,2]。 A variety of cells are involved in the occurrence and development of AS, among which vascular endothelial cell (VEC) dysfunction is the initiation step of AS occurrence. Oxidized LDL contacts the damaged VEC and gradually accumulates under the endothelium, and macrophages engulf LDL and gradually form atheromatous plaques^[3]。 When cells are subjected to various stimuli, such as starvation, hormones, chemotherapy, microbial invasion, abnormal protein aggregation, etc., adaptive autophagy in cells will increase, thus maintaining the stability of cell structure and function and the need of metabolism. Intracellularly in coronary plaques, multiple evidences show that autophagy is increased, especially in VEC. Autophagy of VEC can occur very early in the oxidative stress response, degrading damaged organelles, especially polarized mitochondria, before cytochrome C is released^[4]。 This indicates that autophagy of VEC has anti-apoptosis and restores cell function^[5]。 The autophagy activity of cells in vivo decreases with the increase of age, which may also be closely related to the mechanism of age-related diseases^[6]。 However, acute or sustained stress can inhibit the autophagy of VEC, and the cells may die^[4]。 Autophagy inducers may play a self-protective role by increasing cell autophagy and regulating cell function, and may become a new target for preventing and treating coronary heart disease by using autophagy inducers to increase VEC autophagy. At present, the molecular mechanisms and signaling pathways involved in regulating autophagy have not been fully elucidated, and the regulatory factors are complex and numerous^[7]Therefore, this paper summarizes the autophagy inducers of VEC with therapeutic value and their mechanisms of action, in order to provide guidance and help for research.