Elevated blood uric acid levels are associated with abnormalities of nucleic acid metabolism in the body and reduced renal excretion, with a normal blood urate saturation level of 6.7 mg/dl, and the international diagnostic criteria for hyperuricemia are defined as blood uric acid levels of >420 umol/l (7 mg/dl) in men and >357umol/l (6 mg/dl) in women, and HUA without episodes of gout is referred to as asymptomatic HUA: HUA is often associated with the traditional metabolic cardiovascular risk factors hypertension, hyperlipidemia, type 2 diabetes mellitus, obesity, and insulin resistance, and thus HUA has long been considered merely a marker of metabolic abnormalities. In the past 20 years more than 10 prospective large-scale clinical studies, about 100,000 cases of more than observation, using multifactorial regression analysis to confirm that HUA is an independent risk factor for cardiovascular disease, there is no evidence-based evidence to show that lowering blood uric acid reduces the risk of cardiovascular events, so the guidelines do not list HUA as an independent risk factor for cardiovascular disease. However, in view of the fact that high uric acid is closely associated with poor vascular, cardiac, and renal prognosis, uric acid-lowering therapy is expected to become a new approach to cardiovascular disease prevention and treatment. In 2002, the Japan Gout Nucleic Acid Metabolism Association was the first in the world to propose that asymptomatic HUA should be given stratified treatment according to cardiovascular risk factors or coexisting cardiovascular diseases. In China, there are a large number of asymptomatic HUA patients with multiple coexisting cardiovascular risk factors or ischemic heart disease, and clinicians have inconsistent views on how to deal with asymptomatic HUA. Whether or not there is a need for treatment of asymptomatic HUA, and how to determine the standard of treatment are problems to be solved at present. For this reason, the Cardiovascular Physicians Branch of the Chinese Medical Doctors’ Association organized experts in related fields to discuss the relationship between HUA and cardiovascular diseases and the necessity of treatment, and finally reached a Chinese expert consensus on the recommendations for the diagnosis and treatment of asymptomatic hyperuricemia combined with cardiovascular diseases. I. Epidemiology of HUA From the epidemiologic data of developed countries in Europe and the United States, the prevalence of HUA increases with the improvement of the country’s economic level, and has a similar epidemic trend with diabetes mellitus and hyperlipidemia, which suggests that HUA is closely related to lifestyle. Epidemiologic data in China support this inference. In the early 1980s, Fang Qi and others showed that the prevalence of HUA in China was 1.4% in men and 1.3% in women, and after the mid-1990s, the prevalence of HUA in men was 8.2%-19.8%, and that of women was 5.1%-7.6%. The prevalence of HUA in China has increased by 10 times during the past 10 years, and the prevalence in the economically developed areas in the south and the coastal regions has increased by 10 times. Moreover, the prevalence of HUA in the south and the economically developed coastal areas is higher than that in the rest of the country during the same period, which should be related to the rapid improvement of the living standard in this area, and the consumption of seafood and high-protein and high-cholesterol food. According to the reports on the prevalence of HUA in recent years, it is conservatively estimated that there are about 120 million HUA patients in China, accounting for about 10% of the total population, and the high incidence of HUA is among middle-aged and old-aged males and postmenopausal females, but the trend of rejuvenation has been aggravated in recent years. Second, the metabolism of uric acid Uric acid is the product of human purine metabolism. There are two sources of purine in the human body, endogenous for its own synthesis or nucleic acid degradation (600mg/d), accounting for about 80% of the total amount of uric acid in the body; exogenous for the intake of purine diet (about 100mg/d), accounting for about 20% of the total amount of uric acid in the body. In the normal state, the body’s uric acid pool is 1,200mg, producing about 750mg of uric acid per day and excreting about 800-1,000mg, with 30% being excreted from the intestinal tract and biliary tract, and 70% being excreted via the kidneys. The kidney is an important organ of uric acid excretion, if the renal creatinine clearance is reduced by 5-25%, it can lead to HUA. under normal circumstances, the body’s daily production and excretion of uric acid basically maintains a dynamic equilibrium, all the factors affecting the blood uric acid production and/or excretion can lead to an increase in the level of blood uric acid. Third, the risk factors of HUA HUA and age, gender, regional distribution, race, genetics, and social status have a certain relationship. HUA is more likely to occur with increasing age, in men, in first-degree relatives with a history of HUA, in people with sedentary lifestyles and high social status, and in patients with cardiovascular risk factors and renal insufficiency. Consumption of high-purine foods, such as meats, seafood, animal offal, and thick broths, as well as consumption of alcohol (beer and liquor) and strenuous physical activity, can all lead to an increase in blood uric acid. Prolonged application of certain drugs can lead to increased blood uric acid, such as thiazide diuretics, compound antihypertensive tablets, pyrazinamide, nifedipine, propranolol and so on prevent uric acid excretion. Fourth, the diagnostic criteria of HUA: 1, the diagnostic criteria of HUA: under the state of normal purine diet, non-same day twice fasting blood uric acid level of male >420umol / l (7mg / dl) or female >357umol / l (6mg / dl). 2, HUA typing diagnosis: typing diagnosis helps to find the cause of HUA, give targeted treatment. HUA patients with low purine diet for 5 days, leave 24 hours urine testing uric acid level. (1) Poor uric acid excretion: uric acid excretion less than 0.48mg/kg/h, uric acid clearance (Cua, uric acid x urine volume per minute/blood uric acid) <6.2ml/min. (2) Excessive production of uric acid: uric acid excretion more than 0.51mg/kg/h, uric acid clearance ≥6.2ml/min. (3) Mixed: uric acid excretion more than 0.51mg/kg/h, uric acid clearance ≥6.2ml/min. (3) Mixed: uric acid excretion more than 0.51mg/kg/h, uric acid clearance ≥6.2ml/min. kg/h, uric acid clearance <6.2 ml/min. Considering the influence of renal function on uric acid excretion, corrected by creatinine clearance (Ccr), HUA is classified according to the Cua/Ccr ratio as follows: >10% for overproduction of uric acid, <5% for poor excretion of uric acid, and between 5-10% for mixed type. Epidemiology of causal relationship between HUA and cardiovascular diseases (a) HUA and cardiovascular risk factors 1, HUA and hypertension In 1879, MOHAMED proposed for the first time that blood uric acid is involved in the development of hypertension, and in 1889, Haig proposed that a low purine diet can be used as a means of preventing high blood pressure. 1990, a number of cardiovascular epidemiology studies consistently confirmed that blood uric acid is an independent risk factor for the development of hypertension, and that blood uric acid is an independent risk factor for the development of high blood pressure. After 1990, several cardiovascular epidemiologic studies have consistently confirmed that blood uric acid is an independent risk factor for the development of hypertension, and that an increase in blood uric acid level of 59.5 umol/l increases the relative risk of hypertension by 25%. Clinical studies have found that 90% of patients with primary hypertension have HUA, while only 30% of patients with secondary hypertension have HUA, suggesting a causal relationship between HUA and primary hypertension. A classic animal test confirms the causal relationship between high uric acid and hypertension, the study through the inducer so that the rat blood uric acid level in 7 weeks rose 1.6mg/dl, systolic blood pressure then increased by an average of 2.2mmHg. However, if at the same time given to lower the blood uric acid drugs, such as allopurinol or benzenesulphonate, the blood uric acid is normal, then the blood pressure is no longer increased, suggesting that high uric acid is associated with elevated blood pressure. 2, HUA and diabetes mellitus Long-term HUA can destroy pancreatic β-cell function and induce diabetes mellitus. Two studies suggest that long-term HUA has a causal relationship with glucose tolerance abnormalities and the development of diabetes. Two prospective clinical studies from Korea and Japan enrolled a total of 2951 middle-aged HUA patients with 6-7 years of follow-up and found that those with baseline blood uric acid levels >398umo/l had a 78% increased risk of long-term glucose intolerance abnormality and the development of type 2 diabetes mellitus compared to those with <280umo/l. 3, HUA and hypertriglyceridemia Epidemiologic data from home and abroad consistently show a correlation between blood uric acid and triglycerides. There is only one prospective cohort study on the relationship between uric acid and triglycerides, which was followed for 8 years and found that basal triglycerides were an independent predictor of future HUA. Animal tests observed that blood triglyceride levels were significantly higher in artificially formed hyperuricemic rats than in blood-uric acid normal rats, suggesting that uric acid has an effect on blood triglyceride metabolism. However, the mechanism of interaction between uric acid and triglycerides and the causal relationship between uric acid and triglycerides are not very clear at present. 4, HUA and metabolic syndrome The pathophysiological basis of metabolic syndrome is hyperinsulinemia and insulin resistance. Insulin resistance increases the production of uric acid during glycolysis and free fatty acid metabolism, while increasing renal reabsorption of uric acid, leading directly to hyperuricemia. Seventy percent of patients with metabolic syndrome also have HUA, which is why Prof. Reaven, the father of the metabolic syndrome, proposed the inclusion of HUA in the metabolic syndrome. HUA is often accompanied by various indicators of metabolic syndrome, such as about 80% of HUA patients with hypertension, 50%-70% with overweight or obesity, and more than 67% with hyperlipidemia. A cross-sectional survey of 1600 people in China showed that the prevalence of HUA in the metabolic risk factor population in China was 20.58% and 30.55% for men and women respectively, and the proportion of HUA combined with three or more metabolic risk factors (obesity, hypertension, hypercholesterolemia, hypertriglyceridemia, and hypoglyceridemia) was as high as 76.92% and 67.64% for men and women respectively. 67.64%. (B) HUA and cardiovascular disease 1, HUA and coronary heart disease (1) uric acid is an independent risk factor for death from coronary heart disease The Chicago Heart Study, the first U.S. National Health and Nutrition Examination Survey (NHANES study), and the MONICA study, which corrected for traditional cardiovascular risk factors and the use of diuretics, found that, regardless of gender, uric acid is an independent risk factor for all-cause mortality and coronary heart disease death in the general population. . For every 59.5umol/l (1mg/dl) rise in blood uric acid, the risk of death increased by 48% in men and 126% in women. Blood uric >357umol/l (6mg/dl) is an independent risk factor for coronary heart disease and blood uric >416.5umol/l (7mg/dl) is an independent risk factor for stroke. For patients with established coronary heart disease, Bickel et al. found that the mortality rate in the blood uric acid >7.5mg/dl (433umol/l) population was five times higher than that in the blood uric acid <5mg/dl (303umol/l) population, and multifactorial analyses confirmed that blood uric acid was an independent risk factor for all-cause mortality and coronary heart disease death in the coronary heart disease population. (2) Uric acid is an independent risk factor for cardiovascular events Four large-scale prospective clinical studies: the MRFIT study, the PIUMA study, the Rotterdam cohort study, and the Worksite study in the United States, have shown that blood uric acid levels are an independent risk factor for acute myocardial infarction, stroke, and all cardiovascular events, and that an elevation of blood uric acid by 86 umol/l is more powerful than an elevation of total cholesterol by 1 umol/l in predicting cardiovascular events. The ability of elevated blood uric acid to predict cardiovascular events was higher than that of elevated total cholesterol of 1.078mmol/l and elevated blood pressure of 21.3mmHg. However, the MONICA study concluded that blood uric acid could not predict the onset of acute myocardial infarction and angina pectoris. Recently, Wen-HarnPan et al. in Taiwan followed 41879 men and 48514 women for 8 years and showed that blood uric acid was also an independent risk factor for all-cause mortality, total cardiovascular events, and ischemic stroke in our general, low-risk and high-risk populations. Whether blood uric acid can be used as an independent risk factor for cardiovascular events and whether there is a gender difference in the effect of blood uric acid on cardiovascular events deserves further investigation. 2, HUA and kidney damage Uric acid is closely related to kidney disease. In addition to uric acid crystal deposition leading to small renal arteries and chronic interstitial inflammation aggravating renal damage, many epidemiological surveys and animal studies show that uric acid can directly make the glomerular entry arteries microangiopathy, leading to chronic kidney disease. Two large-scale prospective studies in Japan confirmed that uric acid is associated with the development of renal lesions. The risk of renal failure was found to be eight times greater in those with blood uric acid >8.5 mg/dl (476 umol/l) than in those with uric acid in the range of 5.0-6.4 mg/dl (298 umol/l-381 umol/l). Blood uric acid = 7.0 mg/dl (420 umol/l) in men and ≥ 6.0 mg/dl (357 umol/l) in women increased the risk of end-stage renal disease by fourfold and ninefold, respectively. Two recent large-scale prospective long-term follow-up studies further confirmed that for every 1 mg/dl increase in blood uric acid, the risk of kidney disease increased by 71% and the risk of deterioration of renal function (3 ml/min/1.73 ml/year decrease in GFR) increased by 14%. Compared to people with normal blood uric acid, those with blood uric acid of 7.0-8.9 mg/dl had a 2-fold increased risk of new kidney disease, and those with ≥9 mg/dl had a 3-fold increased risk of new kidney disease. In a small randomized controlled clinical study investigating the role of uric acid-lowering therapy in delaying renal disease, application of allopurinol 100-300 mg/d for one year resulted in a 50% reduction in the growth rate of blood creatinine compared with the unmedicated group. Indirectly suggests that hyperuricemia is related to the progression of renal impairment. 3, HUA and heart failure There are two prospective studies showing that HUA can be used as an independent predictor of death in acute and chronic heart failure, but whether it can be used as a direct indicator or just an indirect indicator is still unclear. In summary, hyperuricemia is associated with the following cardiovascular risk factors, subclinical damage to target organs, and clinical disease: vi. Clinical studies related to pharmacological treatment of asymptomatic HUA There is no consensus on whether to give uric acid-lowering therapy for asymptomatic HUA in combination with multiple cardiovascular risk factors or cardiovascular disease. There is a lack of high-quality evidence-based evidence on whether uric acid-lowering therapy can be an effective measure to reduce cardiovascular endpoint events, and a limited number of studies are currently available as follows. The LIFE study and the GREACE study indirectly suggest the effect of pharmacologic lowering of blood UA levels on cardiovascular endpoint events. However, neither the LIFE nor the GREACE studies were studies that specifically evaluated the prognostic impact of lowering blood UA levels on cardiovascular disease. An allopurinol intervention randomized controlled study enrolling 169 patients undergoing coronary artery bypass grafting to investigate the effect of preoperative treatment with allopurinol on the prognosis of the procedure showed improved postoperative cardiac function and decreased mortality but increased nonfatal complications in the allopurinol group compared with no allopurinol.Kanby et al. enrolled 48 patients with HUA who had normal renal function and 21 uric acid Normal individuals with HUA were given allopurinol 300 mg/d for 3 months, which showed that blood pressure, blood uric acid, and creatinine clearance improved significantly in the allopurinol group. A randomized, double-blind, placebo-controlled crossover study enrolling 30 adolescent patients with newly diagnosed class I hypertension combined with mild HUA and cross-over administration of allopurinol and placebo 400 mg/d for four weeks showed that allopurinol treatment significantly lowered blood pressure (systolic blood pressure of 6.3 vs. 0.8 mmHg and diastolic blood pressure of 4.6 vs. 0.3 mmHg) compared to placebo, and 2/3 of the patients receiving allopurinol 2/3 of patients treated with allopurinol had normalized blood pressure. Whether uric acid-lowering drugs can be used as a new antihypertensive drug in the clinic needs to be confirmed by large-scale clinical studies, and whether they are suitable for patients with long-term hypertension combined with HUA still needs to be further explored. For long-term HUA, arteriosclerosis has already occurred in the vessel wall and formed hypertension, at this time the hypertension has become non-uric acid dependent, even if the application of uric acid-lowering drugs, it will not produce significant antihypertensive effect. Therefore, HUA should be early detection and early intervention. Seven, asymptomatic hyperuricemia treatment recommendations 1, improve lifestyle. 2006 European League Against Rheumatism (EULAR) on the prevention and treatment of gout recommendations, emphasizing that lifestyle change is the core of the treatment of HUA, including a healthy diet, smoking cessation, adherence to exercise and weight control. For those who have gout, HUA, metabolic cardiovascular risk factors and middle-aged and elderly people, the diet should be based on low purine foods, strictly control the intake of C foods such as meat, seafood and animal offal, and moderately reduce the intake of B foods, and the diet should be based on A foods. 2.Actively treat the metabolic risk factors associated with elevated blood uric acid In 2006, the European League Against Rheumatism (EULAR) recommendations on gout prevention and treatment emphasized that active control of cardiovascular risk factors associated with HUA, such as hyperlipidemia, hypertension, hyperglycemia, obesity, and smoking, should be an important part of the treatment of HUA. 3, HUA patients to avoid the application of drugs that raise blood uric acid: such as diuretics (especially thiazides), glucocorticoids, insulin, cyclosporine, tacrolimus, nicotine, pyrazinamide, niacin and so on. For patients who need to take diuretics and combined with HUA, avoid thiazide diuretics, and at the same time alkalize the urine, drink more water, and keep the daily urine output above 2000ml. For patients with hypertension combined with HUA, antihypertensive drugs other than thiazide diuretics are preferred. 4.Drugs to reduce blood uric acid (1) increase uric acid excretion of drugs to inhibit the active reabsorption of uric acid by the kidneys, including Benzbromarone (Liguixian), probenecid, sulfinpyrazone, etc., probenecid and sulfinpyrazone can only be used in HUA patients with normal renal function, and Benzbromarone can be used in patients with renal insufficiency with Ccr>20ml/min. The representative drug is Benzbromarone (Liguixian). Usage: Adults starting dose 50mg (1 tablet) once a day, after 1-3 weeks according to the blood uric acid level to adjust the dose to 50 or 100mg/d, take after breakfast. In the presence of renal insufficiency (Ccr<60ml/min) the recommended dose is 50mg/day once. Precautions: a. Application must alkalinize the urine, especially with existing renal insufficiency, pay attention to regular monitoring of the first urine PH value in the early morning, and maintain the urine PH between 6.2-6.9. At the same time to ensure that the daily water intake of more than 1500ml. b. Pay attention to monitoring liver and kidney function. c. This class of drugs may cause urate crystals to be deposited in the urinary tract due to the promotion of uric acid excretion, and patients with uric acid stones are relative contraindications. Therapeutic efficacy: Usually take benzbromarone 6-8 days blood uric acid value of 357umol / l (6mg / dl) or so, insist on taking the body can maintain normal blood uric acid level. Benzbromarone does not interfere with the body's nucleic acid metabolism and protein synthesis, long-term use has no effect on blood cells. Alkalizing urine Sodium bicarbonate has the effect of alkalizing urine, increasing uric acid discharge and lowering blood uric acid. Available sodium bicarbonate 3-6g / d, 3 times orally, will maintain the urine PH in the range of 6.2-6.9 is most appropriate, conducive to the dissolution of urate crystals and discharged from the urine, the urinary PH more than 7.0 is easy to form calcium oxalate and other types of stone formation. (2) Inhibition of uric acid synthesis is represented by allopurinol. Usage: Adults, the initial dose of 50mg once a day, 1 ~ 2 times a day, can be increased by 50 ~ 100mg per week, to 200 ~ 300mg a day, divided into 2 ~ 3 times, the maximum amount of a day shall not be greater than 600mg. every 2 weeks to measure the level of blood uric acid, such as has reached the normal level, no longer incremental, such as is still high can be incremental increase in dosage, until the blood uric acid back to 357umol / l (6mg / dl) If still high, the dose can be increased until the blood uric acid returns to below 357umol/l (6mg/dl), then gradually reduce the dose and maintain it for a longer period of time with the minimum effective dose. When renal function decreases, the lowest effective dose that can be tolerated can be reached, such as Ccr<60ml/min, the recommended dose of allopurinol is 50mg-100mg/day, Ccr<15ml/min is prohibited. Commonly used in children for the treatment of secondary hyperuricemia: up to 6 years of age, 50mg each time, 1-3 times a day; 6-10 years of age, 100mg each time, 1-3 times a day. Dosage may be adjusted as appropriate. It is also necessary to drink plenty of water to alkalize the urine. Precautions: allopurinol common adverse reaction is allergy, mild allergy (such as rash) can be treated with desensitization, severe allergy (delayed vasculitis, exfoliative dermatitis) is often fatal, prohibited. Renal insufficiency increases the risk of severe allergy and should be monitored carefully during application. Regularly check liver and kidney function, blood routine during the administration, liver and kidney function and blood cells progressive decline discontinue use. Severe hepatic insufficiency and obvious low blood cells are prohibited. 5. In 2006, the European League Against Rheumatism pointed out in its recommendations on the prevention and treatment of gout that patients with HUA should be actively treated with anti-inflammatory and analgesic drugs if they suffer from gouty attacks, but it is not necessary to stop the use of the original uric acid-lowering drugs. In summary, the Chinese Expert Consensus on Recommendations for the Diagnosis and Treatment of Hyperuricemia in Combination with Cardiovascular Diseases puts forward the following treatment recommendations for asymptomatic patients with HUA: 1. The target value for the treatment of HUA: blood uric acid <357umol/l (6mg/dl). 2.Blood uric acid test should be conducted routinely during physical examination to detect asymptomatic HUA as early as possible. 3.All patients with asymptomatic HUA should undergo therapeutic lifestyle changes; avoiding the application of drugs that increase blood uric acid as much as possible. 4.When asymptomatic HUA is combined with cardiovascular risk factors or cardiovascular diseases (including hypertension, abnormal glucose tolerance or diabetes mellitus, hyperlipidemia, coronary artery disease, stroke, heart failure or renal function abnormality), the blood uric acid value >8mg/dl should be given medication; for HUA without cardiovascular risk factors or cardiovascular diseases, the blood uric acid value >9mg/dl should be given medication. 5.Actively control coexisting cardiovascular risk factors in asymptomatic HUA patients.