2016年 · 第44卷第11期

In the in-depth development stage of China's medical and health reform, strengthening the medical service capacity of county-level hospitals and keeping common and frequently-occurring diseases and stable diseases at the grass-roots level is of great significance to promote graded medical care and solve the unreasonable medical layout of high monopoly of medical resources in large hospitals in big cities.

Chronic non-communicable diseases (NCDs) have become a topic of increasing concern in the global public health field, and bring global challenges. According to statistics, there were 56 million deaths worldwide in 2012, of which 38 million died from NCD. The main causes of death in NCD were cardiovascular disease, tumor, chronic respiratory diseases and diabetes, accounting for 46.2%, 21.7%, 10.7% and 4%, respectively. Cardiovascular disease is the leading cause of death. Without intervention, the number of people suffering from cardiovascular disease will increase from 17.5 million in 2012 to 23.6 million in 2030, and the number of deaths from NCD per year will increase from 38 million to 52 million in 2030^[1]。 The main cause of the NCD epidemic is an unhealthy lifestyle. Common lifestyle diseases mainly include obesity, hypertension, coronary heart disease, diabetes and cancer. WHO global surveys in the 1990s showed that lifestyle and behavior play a leading role in people's health and longevity, with a weight of 60%; Environmental factors are the next, accounting for 17%; Genetic factors accounted for 15% and conditions of medical services accounted for 8%. Another 30% of lifestyle is determined by diet. For many NCD patients, drugs cannot cure the disease, only control the disease, delay life, and improve quality of life. Therefore, in order to effectively control NCD, the medical model needs to be fundamentally changed, that is, from a simple biomedical model to a new medical model combining physiology-psychology-society-environment.

Warfarin is a coumarin oral anticoagulant, which is suitable for the primary and secondary prevention of venous thromboembolic diseases, the prevention of atrial fibrillation (AF) thromboembolism, valvular disease, prosthetic valve replacement and intracardiac thrombosis, etc. Meta-analysis results of five large clinical trials showed that warfarin anticoagulation therapy reduced the incidence of stroke by 68%, mortality by 33%, and the incidence of composite endpoint events (stroke, systemic embolism, and death) by 48%, and the benefit was more obvious in patients with high risk factors for thromboembolism (such as advanced age, hypertension, history of embolism, and diabetes), thus establishing the importance of warfarin anticoagulation therapy. The survey found that with the increase of warfarin use, the incidence of ischemic stroke decreased correspondingly, while the incidence of hemorrhagic stroke remained basically unchanged^[1]。 Warfarin has saved a lot of lives in long-term clinical application.

Anticoagulation therapy is an important treatment to prevent stroke in patients with atrial fibrillation (AF). In recent years, the new oral anticoagulants (NOAC) have opened a new chapter for clinical anticoagulation therapy. Many large-scale clinical trials have confirmed that NOAC is not inferior or superior to warfarin in the prevention of various embolic events (including stroke). The main adverse reaction of anticoagulant therapy is bleeding. Although the risk of bleeding in NOAC is greatly reduced compared with traditional anticoagulants, the risk of fatal intracranial or gastrointestinal bleeding events in NOAC still exists. In addition, patients receiving NOAC anticoagulant therapy also need antagonists to quickly correct the anticoagulant effect of NOAC in emergencies such as trauma. At the same time, except dabigatran, no other NOAC has specific antagonists that can be used in clinic. At present, there is a lack of clinical treatment methods to correct the anticoagulant effect of NOAC, and most of them are non-specific hemostatic regimens. The lack of NOAC-specific antagonists has become an important factor restricting its clinical application. Therefore, the research and development of NOAC antagonists has become a hot issue in the current cardiovascular field.

CHADS₂And CHA₂DS₂-VASc score is the two most commonly used prediction models for stroke risk in patients with non-valvular atrial fibrillation (AF) in clinic. Clinically, by calculating the score of each item, the risk of patients with AF is stratified, and the intervention treatment for stroke is given to patients with medium and high risk. In recent years, the application of CHADS₂And CHA₂DS₂-The scope of VASc score for predicting stroke has gradually expanded beyond atrial fibrillation. A growing number of studies have found that with or without atrial fibrillation, CHADS₂And CHA₂DS₂-VASc scores can each independently predict stroke occurrence. According to the Frahangmin study, the stroke incidence of non-valvular atrial fibrillation is 4.8 times that of people without atrial fibrillation, and the study also found that coronary heart disease, hypertension, and heart failure can increase the risk of stroke by 2.4, 3.4, and 4.3 times, respectively^[1]。 Atrial fibrillation is a high risk factor for stroke, and non-atrial fibrillation heart disease can also greatly increase the risk of stroke. CHADS₂And CHA₂DS₂-Risk factors in the VASc score include heart failure, hypertension, and vascular disease itself, which also falls into the category of cardiovascular disease. Therefore, in recent years, there have been many studies on CHADS₂And CHA₂DS₂-An exploratory study of the predictive value of VASc score for stroke in patients with non-atrial fibrillation heart disease.

A 63-year-old woman was admitted for "recurrent palpitations for 10 years and one month". When the patient had a palpitation attack, multiple electrocardiograms showed paroxysmal atrial fibrillation (atrial fibrillation), and the effect of drug treatment was not good, and the symptoms of frequent attacks were aggravated 1 month before admission. Past history of "hypertension" and "chronic superficial gastritis", admission physical examination: blood pressure 140/80 mmHg (1 mmHg =0.133 kPa), clear consciousness, no jugular vein distension, clear breathing sounds in both lungs, no rales, heart rate 72 beats/min, uniform rhythm, no murmur, soft abdomen, no tenderness, no swelling in both lower limbs. Admission diagnosis: paroxysmal atrial fibrillation, hypertension grade 2, chronic superficial gastritis. After admission, there were no abnormalities in blood routine, liver and kidney function, coagulation combination, chest radiograph and echocardiography, among which the hemoglobin was 120 g/L. According to the clinical manifestations and auxiliary examination results of the patient, the patient has indications for catheter ablation. Preoperatively, warfarin anticoagulation was given for 3 weeks, and the international standardized ratio (INR) of anticoagulation reached the standard (2~3) every week. Warfarin was discontinued 3 days before admission and switched to low molecular weight heparin 4 100 U subcutaneous injection twice/d. Esophageal ultrasound examination 24 hours before operation showed no abnormalities.

A 56-year-old male was admitted to hospital in July 2015 because of "more than 6 months after gastric cancer surgery, wanting to undergo the sixth chemotherapy". The patient had previously undergone subtotal gastrectomy for gastric cancer, and later undergone hepatic artery interventional chemotherapy many times in the interventional department of our hospital due to the discovery of liver metastasis. The admission diagnosis was postoperative gastric cancer with liver metastasis. In July 2015, he went to the interventional department of our hospital for the 6th routine chemotherapy. On the day of the operation, the interventionist performed routine digital subtraction angiography (DSA), and perfused chemotherapy drugs (5-fluorouracil 750 mg + calcium tetrahydrofolinate 300 mg + oxaliplatin 100 mg + epirubicin 20 mg) through the common hepatic artery and superior mesenteric artery microcatheter. After perfusion of chemotherapeutic drugs, the patient had a sudden retrosternal squeezing sensation accompanied by cold sweat, and blood pressure dropped to 68/40 mmHg (1 mmHg =0.133 kPa). Electrocardiogram was performed immediately at the same time as rapid volume replenishment, which showed "sinus tachycardia with ST segment elevation of anterior and inferior wall 0.1~0.3 mV, accompanied by extensive ST segment depression of anterior and lateral wall 0.2~0.7 mV" (Figure 1), the emergency consultation of cardiology department considers "acute ST-segment elevation myocardial infarction". After communicating with the family and signing the informed consent form, an emergency coronary angiography was performed, but no abnormalities such as thrombosis and stenosis in the coronary arteries were found (Figure 2)。 The patient's symptoms persisted, with dry cough and chills. Continue to give fluid rehydration to expand the volume and dopamine to boost the pressure. Considering the clinical manifestations of the patient and the possibility of allergy, intravenous bolus injection of methylprednisolone 80 mg and intramuscular injection of epinephrine 0.5 mg was performed. After 10 minutes, the patient's chills and dry cough gradually disappeared, the chest tightness symptoms were relieved, the blood pressure recovered to 120/60 mmHg, and the ST segment of the reexamined ECG dropped significantly compared with before. At the end of the intervention, the towel was removed, and a flaky red maculate rash was found on the inner side of the patient's lower limb (Figure 3)。 Follow-up medical history showed that the patient developed flaky rash with pruritus on the lower limbs 3 days ago, thinking that he had eczema, and did not inform the doctor. Preoperative examination was reviewed, blood routine showed that the eosinophils were significantly increased (12%, 0.75×10⁹/L), total blood IgE was increased after surgery, and there was no obvious abnormality in myocardial enzymes. After cetirizine oral anti-allergic treatment, the rash gradually subsided, and he was discharged from hospital 3 days later. After 1 month, there was no chest tightness or chest pain in the follow-up.

Warfarin is an oral anticoagulant with the longest clinical application time, and is widely used in various thromboembolic diseases, especially venous thromboembolic diseases, atrial fibrillation, prosthetic valve replacement, etc. Compared with western countries, the use rate of warfarin in China has been low^[1]The reasons for this are multifaceted. The unique pharmacological properties of warfarin lead to large dose differences in different patients. With the continuous deepening of pharmacogenomics research, the mechanism of warfarin dose differences in different ethnic groups has been revealed. Because the use rate of warfarin in China is low, the accumulated high-quality research evidence is also less. There has been controversy about the efficacy and safety of warfarin in Eastern and Western patients. Although evidence of non-vitamin kanticoagulants (NOAC) shows that they are safe and most patients can use fixed doses^[2]。 However, warfarin still has irreplaceable value, and ensuring the clinical efficacy and safety of warfarin depends on high-quality International Standardized Ratio (INR) under accurate dose adjustment.

international normalized ratio (INR) is a commonly used clinical index to monitor anticoagulation intensity, mainly used to monitor patients with atrial fibrillation (AF) treated with oral warfarin^[1]。 American, Canadian and European guidelines for atrial fibrillation^[2,3,4]It is recommended that the range of INR should be maintained at 2.0 to 3.0. Over 3.0, the risk of bleeding increases, and below 2.0, there will be insufficient anticoagulation^[5]。 However, the human race in East Asian countries is different from that in European and American countries. Among the genetic factors, the distribution of haplotype A and haplotype B in VKORCl gene (vitamin K epoxide reductase complex subunit 1 gene) is different^[6]； Moreover, D-dimer was significantly inhibited when the INR ranged from 1.5 to 2.0 in Asia, while that in Western countries was significantly inhibited at 2.0 to 3.0^[7]； The risk of intracranial hemorrhage was 4.06 times higher in Asian populations than in Caucasians with INR 2.0 to 3.0 for all ethnicities, another Asian study^[8]It has also been confirmed that an INR range>2.3 increases the risk of bleeding in East Asian populations, so there may be differences in the INR range of warfarin for atrial fibrillation. To this end, Japan and other countries have taken the lead in exploring this index and published a number of related articles. Chinese scholars have also explored the INR range suitable for Chinese patients in recent years. However, the range of INR of warfarin therapy in patients with atrial fibrillation in East Asian countries is still a question worth exploring^[9]。

Atherosclerotic cardiovascular disease (ASCVD) is a group of disease syndromes with atherosclerosis as the common pathological basis, mainly involving the heart, brain, kidney and other peripheral arteries, and then causing arterial ischemia as the main clinical manifestation^[1]It has become a group of diseases with the highest morbidity and mortality rate in the world, and it is increasing year by year in China. The pathological basis of ASCVD is atherosclerosis, and low density lipoprotein cholesterol (LDL-C) is the only lipoprotein that can independently cause ASCVD. Its elevation is one of the important pathogenic factors of ASCVD, so reducing LDL-C is the cornerstone of prevention and treatment of ASCVD. Existing cholesterol-lowering drugs are mainly divided into two main categories, namely statins and non-statins. Statins are the most widely used in clinical practice due to their excellent cholesterol-lowering efficacy, good safety profile and abundant evidence support. Despite this, the drug still has many limitations, such as: (1) some people are difficult to tolerate statins; (2) For some people with diseases (especially familial hypercholesterolemia), it is difficult to meet the standard with statin alone, and these problems will limit the application of the drug. Therefore, the research and development of new cholesterol-lowering drugs is on the agenda and in the ascendant. This article will review the latest progress of several types of cholesterol-lowering drugs currently under research.

The alpha-subunit of the "heart" sodium channel encoded since 1992 (Na_VSince the SCN5A gene of 1.5) was cloned, traditional cardiac electrophysiology has long believed that it controls the 0-phase depolarization of the action potential of cardiomyocytes and the rapid conduction performance of myocardial tissue^[1]。 Changes in channel dynamics and protein synthesis and transport caused by SCN5A mutations can lead to peak sodium currents (I_{Na, P}) reduced and/or late sodium current (I_{Na, L}), thereby inducing cardiac sodium channel disease. The diseases associated with SCN5A mutation mainly include progressive cardiac conduction disease (CCD), Brugada syndrome (BrS), early repolarization syndrome (ERS), sinus bradycardia, sinus node dysfunction, atrial fibrillation (AF), long QT syndrome, idiopathic ventricular fibrillation (IVF), dilated cardiomyopathy and electric storm after acute myocardial infarction, etc. These diseases have a very high risk of sudden cardiac death^[2,3]。

According to the data published in the "China Cardiovascular Disease Report 2013 Summary", the total mortality rate of cardiovascular diseases in China increased from 240.03/100,000 in 2004 to 268.92/100,000 in 2010, that is, 1 person dies of cardiovascular diseases every 10 s, among which the increase of deaths from ischemic heart disease is the main reason^[1]。 The fundamental reason for this situation is that although the existing treatment methods of myocardial infarction can relieve the symptoms, they can't inhibit the negative ventricular remodeling after myocardial infarction, and patients will eventually be difficult to escape the fate of developing heart failure. For patients with end-stage heart disease, heart transplantation is the only treatment option, but the number of donors is limited. It is of great significance to find new treatments to inhibit ventricular remodeling after myocardial infarction.

With the development of the global economy, people's lifestyle has undergone profound changes. Although the health level of people has improved significantly worldwide, the epidemic trend of cardiovascular disease risk factors is obvious, which leads to the continuous increase of cardiovascular disease morbidity and mortality. The burden of cardiovascular disease is increasing and has become one of the most important public health problems in the world. According to the World Health Organization's (WHO) 2014 Global Status of NCDs Report, the leading cause of NCDs death worldwide is cardiovascular disease, with approximately 17.5 million people, accounting for 46.2% of all NCDs deaths. According to China Cardiovascular Report 2013^[1]It is estimated that cardiovascular deaths account for the first cause of death in urban and rural residents, with 38.7% in rural areas and 41.1% in urban areas. At present, it is estimated that there are 290 million patients with cardiovascular diseases in China, that is, 1 in every 5 adults suffer from cardiovascular diseases, including 270 million hypertension, at least 7 million stroke, 2.5 million myocardial infarction and 4.5 million heart failure.