In recent years, the prevalence of hyperuricemia and gout in China has increased sharply, the overall prevalence of hyperuricemia in mainland China is 13%, the prevalence of gout is 1.1%, and hyperuricemia shows a trend of rejuvenation.
Uric acid is the final product of purine metabolism in the human body, which is mainly produced by the decomposition of nucleic acids and other purine compounds and food intake of purines through a series of enzymes.
When the body temperature is 37 ° C, the saturated concentration of uric acid in the body is about 420umol / L (7mg / dl), if the body uric acid exceeds this concentration, uric acid will be deposited in a variety of tissues in the form of crystals, including kidneys, joint synovial membranes, soft tissues, etc., clinically can be manifested as gout arthritis, tophi, uric acid kidney stones, gouty nephropathy. Therefore, hematuric uric acid > 420umol/L (7 mg/dl) is defined as hyperuricemia.
According to the pathophysiology of uric acid formation, hyperuricemia is divided into increased uric acid production, decreased uric acid excretion, and sometimes both can be present at the same time.
Increased uric acid production is seen in:
1. Eat foods rich in purines such as seafood, animal offal, old fire soup, and certain vegetables (spinach, cauliflower, asparagus, etc.).
2. Abnormal activity of purine metabolism-related enzymes, such as enhanced activity of phosphate ribophosphate synthase and decreased activity of hypoxanthine phosphate ribose transferase, resulting in excessive purine production and hyperuricemia.
3. Accelerated decomposition of purines, such as leukemia, malignant tumors after chemotherapy, hemolysis, rhabdomyolysis, etc.
Decreased uric acid excretion is seen in:
1. Chronic renal insufficiency, decreased glomerular filtration rate, decreased uric acid excretion.
2. Certain drugs or substances cause increased reabsorption of tubular uric acid, such as aspirin, niacin, lactic acid, alcohol, fructose-rich, glucose drinks, etc.
Most patients with primary hyperuricemia have no clinical symptoms, and the period from elevated uric acid to symptoms can be as long as years to decades, or even lifelong. Therefore, it is easy to be overlooked, most of them wait until after the onset of gout to be diagnosed, and some patients have urinary tract stones, hydronephrosis, and renal insufficiency before they find elevated uric acid.
So does hyperuricemia only damage the joints and kidneys? The answer, of course, is no, as it has been established from previous studies that hyperuricemia increases the risk of cardiovascular disease, affects cardiovascular disease prognosis, and increases mortality.
1. Uric acid and hypertension
Back in 2011, the journal Arthritis Care Res (Hoboken) published a meta-analysis of hyperuricemia associated with the onset of hypertension, which included 18 prospective cohort studies with a total sample size of 55,607 people, including Asia, North America, and Europe, with an average follow-up time of up to 8 years.
Blood uric acid > 6.2 mg/dL (equivalent to 369 umol/L) is defined as hyperuricemia, and hypertension is generally defined as blood pressure ≥ 140/90 mmHg or ≥ 160/95 mmHg or using antihypertensive drugs.
The final results of this meta-analysis show that hyperuricemia is associated with an increased risk of hypertension, and independent of traditional hypertension risk factors, the risk of hypertension > 6.2 mg/dL, and the risk of hypertension is increased by 41%. When analyzed as a continuous variable, for every 1 mg/dL increase in blood uric acid, the risk of hypertension increases by 13%.
In addition, it was found that in the young, female and black populations, the impact of high uric acid on the incidence of hypertension was greater, and the risk of hypertension was higher.
Similarly, another review published in the journal PLoS One in 2014, which included 25 studies with a total sample size of nearly 100,000, showed that hyperuricemia was associated with an increased risk of hypertension, whether treated as a categorical variable or a continuous variable.
Possible mechanisms by which high uric acid causes hypertension:
1. Nitric oxide produced by the vascular endothelium has the effect of regulating vascular tone, preventing platelet adhesion and aggregation, and reducing endometrial hyperplasia, uric acid reacts irreversibly with nitric oxide, leading to nitric oxide depletion, uric acid can block the release of NO mediated by insulin and vascular endothelial growth factor (VEGF), promote the degradation of L-arginine (substrate that produces NO), and ultimately lead to vascular endothelial-dependent diastolic dysfunction, vasoconstriction, and increased blood pressure.
2. The concentration of uric acid is too high, crystals are formed, and uric acid crystals are deposited in the vascular endothelium, resulting in vascular endothelial dysfunction through oxidative stress.
3. Uric acid can increase the expression of angiotensin II in vascular endothelial cells and activate the renin-angiotensin system.
4. Uric acid can promote arterial smooth muscle cell hyperplasia.
2. Uric acid and heart failure
Heart failure is the terminal stage of most cardiovascular diseases, and there have been many studies in the past that have found that serum uric acid may play a crucial role in heart failure, and multiple studies have shown that elevated serum uric acid may be a risk factor for the occurrence and prognosis of heart failure. However, estimates varied widely between studies due to differences in study population, sample size, ethnicity, follow-up time, and study quality.
In 2014, mainland scholars published a meta-analysis in the European Journal of Heart Failure to assess the relationship between blood uric acid and heart failure events and the prognosis of patients with heart failure.
The researchers conducted a systematic literature search of Embase, Medline and the Chinese Biomedical Literature Database to identify studies on the correlation between serum uric acid and heart failure. Five of the studies were on the risk of developing blood uric acid and heart failure, and 28 studies were on the prognosis of blood uric acid and heart failure.
Random-effects model analysis showed that hyperuricemia was associated with an increased risk of heart failure (HR 1.65, 95% CI 1.41-1.94), further analysis showed a dose-effect relationship between serum uric acid levels and the risk of heart failure, and fixed-effect model analysis showed that for every 1 mg/dL increase in blood uric acid, the risk of HF increased by 19% (HR 1.19, 95% CI 1.17 to 1.21).
The results of the prognosis-related analysis of hyperuricemia and heart failure showed that hyperuricemia was associated with an increased risk of all-cause death in patients with heart failure (HR 2.15, 95% CI 1.64-2.83); for every 1 mg/dL increase in serum uric acid, the risk of all-cause death increased by 4% (HR 1.04, 95% CI 1.02-1.06), while the risk of cardiovascular death increased by 45% in patients with heart failure with hyperuricemia.
At present, the role of blood uric acid in the occurrence and development of heart failure is not very clear. Xanthine oxidase is a key enzyme in purine metabolism, and its mediated reactive oxygen species may play a role in pathophysiological processes of chronic heart failure, such as myocardial hypertrophy, myocardial fibrosis, left ventricular remodeling, and impaired contractility.
3. Summary
In addition to his association with hypertension and heart failure, hematuric acid has been found in many studies to increase the risk of coronary heart disease, atrial fibrillation, and stroke.
Hyperuricemia is a chronic pathophysiological process, and many evidences have shown that hyperuricemia is an independent risk factor for hypertension, coronary heart disease, heart failure, stroke and other cardiovascular and cerebrovascular diseases and affects the prognosis of the disease.
Therefore, it is necessary to pay enough attention to hyperuricemia, regularly detect blood uric acid levels, maintain a healthy lifestyle, and detect early, diagnose early, and treat early.
【Reference】
[1]. Qiao T， Wu H， Peng W. The Relationship Between Elevated Serum Uric Acid and Risk of Stroke in Adult: An Updated and Dose-Response Meta-Analysis. Front Neurol. 2021;12:674398.
[2]. Wang J， Qin T， Chen J， et al. Hyperuricemia and risk of incident hypertension: a systematic review and meta-analysis of observational studies. PLoS One. 2014;9(12):e114259.
[3]. Tamariz L， Hernandez F， Bush A， Palacio A， Hare JM. Association between serum uric acid and atrial fibrillation: a systematic review and meta-analysis. Heart Rhythm. Jul 2014;11(7):1102-1108.
[4]. Grayson PC， Kim SY， LaValley M， Choi HK. Hyperuricemia and incident hypertension: a systematic review and meta-analysis. Arthritis Care Res (Hoboken). Jan 2011;63(1):102-110.
[5]. Kim SY， Guevara JP， Kim KM， Choi HK， Heitjan DF， Albert DA. Hyperuricemia and coronary heart disease: a systematic review and meta-analysis. Arthritis Care Res (Hoboken). Feb 2010;62(2):170-180.
[6]. Guidelines for the Diagnosis and Treatment of Hyperuricemia and Gout in China (2019)
Source: Shuangyashan Research Small Black House
Editor: Ren Mileage Reviewer: Xiao Ran