When we have too much uric acid in our body, it paves the way for disease and shortens our life. It is a well-known culprit for kidney stones and gout, i.e. deposits of uric acid crystals around the joints where it causes severe inflammation. A recent Irish study found that too high a concentration of uric acid reduces life expectancy by up to 11,7 years. The exact data differ according to gender: men with a concentration of uric acid above 535 μmol/l shorten their lives by 11,7 years, and women with a concentration of uric acid above 416 μmol/l by an average of six years. The data refer to a comparison with people of the same sex with lower uric acid levels and are taken from the study Serum uric acid and mortality thresholds among men and women in the Irish health system (European Journal of Internal Medicine), which included data from 26.500 people with elevated levels uric acid.
Today, we are aware that its high levels have a significant impact in the assessment of cardiovascular risk, and these diseases are still the most common in the world. The results of epidemiological studies have shown that hyperuricemia is associated with a higher risk of damage to target organs, cardiovascular morbidity and mortality. Živim.hr.
However, uric acid also has a useful role in our body. Prim. Sonja Frančula-Zaninović, Ph.D. Med., Univ. M.Sc. admin. sanit., spec. internist, subspec. of cardiology, explained everything you need to know about this important biomarker of health.
"For a long time it was considered that uric acid does not play a significant role in our body. Today we know that it has multiple active roles in cell metabolism. Under normal circumstances, it protects our cells from oxidative stress and has a protective effect on the walls of arteries by stabilizing their inner layer (endothelium). However, in the case of its excessive accumulation and ischemia, increased oxidative stress occurs, uric acid then has a pro-oxidative effect, supports systemic inflammation and leads to dysfunction of the endothelium of the vascular system. Those processes encourage atherosclerosis of the arteries, which is the basis of cardiovascular and cerebrovascular diseases," explains prim. Sonja Frančula-Zaninović.
Uric acid is actually the end product of the metabolism of purine, i.e. oxygen bases adenine and guanine, which are an integral part of nucleic acids (RNA, DNA). Most of it is excreted from the body through the kidneys, and a smaller part through the intestines. However, in states of impaired renal function, the intestines may take on a greater role in the excretion of uric acid. Normal values of serum uric acid concentration are 134-337 µmol/l (2,4-6 mg/dl) for women and 182-403 µmol/l (3,4-7,0 mg/dl) for men. An elevated concentration of uric acid in the blood (hyperuricemia) means a level of uric acid in the blood above 356 µmol/l (6 mg/dl) for women, and above 416 µmol/l (7 mg/dl) for men. At elevated concentrations, uric acid in 24-hour urine is also tested (normal limits are considered 600 to 900 mg).
Direction of treatment
"With these tests, we determine whether hyperuricemia in the blood is the result of insufficient excretion by the kidneys (then the level of uric acid in the urine is reduced), increased production of uric acid in the body (then the level of uric acid in the urine is increased) or decreased excretion of uric acid through the intestines (then is also an elevated level of uric acid in the urine). These measurements determine the direction of treatment," says Dr. Frančula-Zaninović. Very often, elevated values of uric acid in the blood are accidentally found during routine laboratory tests. If there are no symptoms, but uric acid levels are elevated, doctors use the term asymptomatic hyperuricemia.
"However, with prolonged hyperuricemia, uric acid is deposited in the form of crystals in the tissues and can lead to various symptoms. The most common clinical picture of symptomatic hyperuricemia is uric arthritis or gout," says the doctor. The disease is most often accompanied by sudden pain, swelling, redness, stiffness of the affected joint (most often the big toe, but any limb joint, one or more of them, can be affected). Gout occurs more often in middle-aged men. It is caused by the deposition of crystals in joint tissue, but they can also be deposited elsewhere, especially in the kidneys. The long-term formation of uric acid crystal deposits leads to the formation of tophi, subcutaneous nodules around the affected joints.
"We have known for years that asymptomatic hyperuricemia is a risk predictor for cardiovascular diseases. Back in the fifties of the last century, the connection between coronary heart disease and hyperuricemia and dyslipidemia was established. Numerous studies have confirmed the connection between the early onset of atherosclerosis and disorders of metabolism, sugar, fat and purine. In addition to being associated with systemic inflammation and oxidative stress, hyperuricemia is often associated with other cardiovascular risk factors such as dyslipidemia, diabetes, and elevated arterial pressure. A linear relationship between the level of uric acid and arterial pressure was observed. In patients with the mentioned cardiovascular risk factors, the level of C-reactive protein and homocysteine increased. The risk of developing cardiovascular diseases is higher in patients with a high cardiovascular risk and hyperuricemia above 356 µmol/l (6 mg/dl) in the blood," points out Dr. Frančula Zaninović.
Atrial fibrillation and heart failure
Also, one of the more common forms of heart rhythm disorders in the elderly is atrial fibrillation, and it occurs more often in people with hyperuricemia. Hyperuricemia is also common in patients with heart failure, explains the cardiologist. The mechanism by which hyperuricemia affects heart failure is not completely clear, but it is certain that oxidative stress, systemic inflammation, activation of the renin angiotensin aldosterone system and endothelial dysfunction form the basis for the development of heart failure. In some studies, it has been proven that heart function improves after the introduction of therapy that reduces the formation of uric acid. The doctor will therefore also ask for the level of uric acid when assessing cardiovascular risk.
"In the assessment of cardiovascular risk, the level of uric acid in the blood is usually determined in addition to the risk factors - arterial pressure, fat and sugar in the blood. In patients with high cardiovascular risk and hyperuricemia, it is recommended to change bad lifestyle habits, adopt a diet with less purine, maintain a body mass index within normal limits and introduce appropriate therapy to reduce the level of uric acid in the blood. Target values should be within physiological limits," says the cardiologist.
It also damages the kidneys
"Kidneys play an important role in maintaining the balance of uric acid in the body. Decreased urinary excretion of uric acid is responsible for most cases of hyperuricemia. Hyperuricemia occurs in diseases of reduced renal function. However, uric acid crystals are also deposited in the kidneys, which leads to a decline in kidney function, reduced secretion of uric acid, and nephropathy develops. Sometimes it is difficult to distinguish whether chronic kidney disease caused hyperuricemia or vice versa. It is recommended that patients with chronic kidney disease regularly monitor the concentration of uric acid in the serum in addition to kidney function, and that patients with gout also measure kidney function in addition to controlling the level of uric acid," explains the doctor. Kidney stones develop in 20 percent of patients with gout, but elevated uric acid also increases the risk of developing chronic kidney disease, and therapy that reduces the formation of uric acid in the body will slow down the progression of chronic kidney disease.
Insulin resistance
Epidemiological studies have also established a close connection between the level of uric acid and the occurrence of metabolic syndrome as well as type 2 diabetes. "Hyperuricemia is actually a biochemical sign of some metabolic, inflammatory-degenerative and hemodynamic disorders: insulin resistance, diabetes, obesity, metabolic syndrome, arterial hypertension, but is also a risk factor for their occurrence. "Hyperuricemia and insulin resistance are part of the same metabolic syndrome," emphasizes dr. Frančula Zaninović. Hyperinsulinemia on the basis of insulin resistance reduces the excretion of uric acid by the kidneys, increases the activity of enzymes involved in purine metabolism. Hyperuricemia and insulin resistance have a pro-oxidative effect and lead to arterial endothelial dysfunction, development of metabolic syndrome and atherosclerosis. Elevated levels of uric acid thus play an active role in metabolic and hemodynamic disorders that lead to sugar intolerance, abdominal obesity, insulin resistance, elevated blood fats and arterial pressure. Together, we call this group of disorders metabolic syndrome.
Simple search
Measuring the concentration of uric acid in the blood is a simple test that is performed during routine laboratory blood tests. However, says dr. Frančula Zaninović, her elevated values are often ignored, especially if the person has no symptoms or any associated diseases. In patients with diabetes, chronic kidney disease or cardiovascular disease, uric acid is more often controlled and patients receive clear instructions on dietary measures, changing lifestyle habits and introducing therapy, says the doctor. Treatment of hyperuricemia is recommended for all patients with frequent attacks of uric arthritis, tophosis, kidney stones, chronic kidney disease, cardiovascular or cerebrovascular disease, diabetes, metabolic syndrome.
"The basis of hyperuricemia treatment is changing bad lifestyle habits, avoiding drugs that can increase the level of uric acid. Physical activity should be increased, arterial hypertension, dyslipidemia and diabetes should be treated. According to today's guidelines, drug treatment of asymptomatic hyperuricemia is not recommended, except in cases of high cardiovascular risk," says Dr. Frančula-Zaninović. In patients who do not have topha, the target level of uric acid in the blood is below 6 mg/dl (356 µmol/l). If the patient has clusters of tophi, the goal of therapy is to dissolve them with therapy, and the target value of uric acid in the blood is less than 5 mg/dl (300 µmol/l), but such values are difficult to maintain. In treatment, the goal is not to lower the level of uric acid below the lower limit of normal values, because its role is still important in protective antioxidant effects.
What causes the increase?
Excessive purine consumption
Purina is found in offal, red meat, blue fish, dried meat products, canned food, legumes, mushrooms, alcoholic beverages, sweetened juices...
Genetics
Some people have a hereditary predisposition for increased production of uric acid or a decrease in its excretion through the kidneys, as well as some diseases in which purines are broken down more: rhabdomyolysis, leukemia, lymphomas, hemolytic anemia, psoriasis, hypothyroidism, glycogenosis, as well as during the treatment of malignant diseases with cytostatics or radiation.
Diabetes
People with diabetes often have increased levels of uric acid.
Gout
People with gout often have increased levels of uric acid.
Dehydration
Insufficient fluid intake can reduce the ability of the kidneys to excrete uric acid, which can result in an increase in its level in the blood.
Kidney disease
The kidneys are responsible for filtering uric acid from the blood. Kidney diseases can reduce their function and cause uric acid to build up.
Some medicines
Diuretics used to treat high blood pressure or acetylsalicylic acid, nicotinic acid and pyrazinamide can increase uric acid.
What to eat and what to avoid
In the treatment of elevated levels of uric acid, it is necessary to adjust lifestyle habits, first and foremost, diet. New research shows that we should be moderate when eating products with a high purine content because they can cost us several years of life. By the way, purines are a group of chemical compounds that are very important for the body, but the problem arises with their absorption because uric acid is created as a breakdown product.
- Preference should be given to foods with a low amount of purine, but you should also limit the intake of saturated fats, pay attention to protein intake, especially if kidney function is impaired.
- Alcoholic drinks are not recommended, especially beer. Carbonated drinks and sweetened juices should be avoided.
- We recommend white fish, white meat, legumes, root vegetables, freshly squeezed vegetable and fruit juices, less sweet fruits, citrus fruits, cereals, nuts, dairy products with less fat.
- Drink enough water.
A lot of purines contain:
- red meat
- entrails
- high fructose corn syrup
- Seafood
- alcohol, especially beer
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