An increase in the uric acid content of the blood is usually regarded as a sign that you have gout. However, this is not always the case. Researchers from the Albert Einstein College of Medicine, Bronx, New York, have analyzed information from a large collection of US people of different ages and races, looking for a possible relationship between raised serum uric acid and cardiovascular disease.

The first National Health and Nutrition Examinations Survey, known as NHANES-1, enrolled over 20,000 people during the years 1971 to 1975. Serum uric acid levels were measured in over 6,500 of these people, along with information that included their medical history regarding gout, high blood pressure, diabetes, heart disease, smoking status and so on. People with existing illnesses, including gout and heart disease, were excluded from the analysis, leaving roughly 6,000 subjects aged 25 to 74 years.

Medical records and death certificates of the subjects in the analysis were collected over the next 16 years. Attention was focused on the total numbers of deaths, as well as those due to heart and blood vessel disease, especially coronary artery disease (also called ischemic heart disease).

The subjects were grouped into four roughly equal classes, or 'quartiles', on the basis of their uric acid level. Men and women were grouped separately, as the range of uric acid levels is different in each sex. Men had significantly higher levels than women, and black people had higher levels than white people. The levels tended to increase with age in women, but not in men.

Higher levels of uric acid were found in people with higher blood pressure, increased cholesterol, overweight, diabetes (in women), increased alcohol intake, and in those taking a diuretic medication (i.e. 'water pills').

During the 16-year follow-up period, over a quarter of the 6,000 subjects died. Almost half died from cardiovascular causes (predominantly coronary artery disease and stroke). The death rates for coronary artery disease were significantly higher in the quartiles with the highest uric acid levels - over 41.6 mmol/L for men (7.0 mg/dL) and over 33.3 mmol/L (5.6 mg/dL) for women. Men in the highest quartile were 1.77 times as likely to die from coronary artery disease as those in the lowest quartile, while women in the top quartile had a 3-fold chance of dying from coronary artery disease, compared with the lowest quartile women.

The scientists wanted to exclude the possibility that any other factors had influenced this result. Using analyses that eliminated the effects of age, race, body mass index, cholesterol level, smoking, alcohol, high blood pressure, diabetes, and the use of a diuretic medication, they found that for each increase of 6 mmol/L (1 mg/dL) in uric acid in men there was a 9% increase in the risk of overall cardiovascular death, and a 17% increase in fatal heart attacks (i.e. coronary artery disease deaths). For women, the corresponding increased risks for each 1 mg/dL step in uric acid were 26% and 30%, respectively.

This study shows that, for this group of people (whose make-up was the same as the general population of the USA), increased uric acid levels predicted an increased risk of death due to a cardiovascular condition (usually heart attack or stroke). The result is at odds with one from another analysis done on the well-known Framingham Heart Study patients. This may be because the Framingham people were nearly all white, and slightly younger than the selected NHANES people. The cardiovascular mortality rate was twice as high in the NHANES group. The authors of the present study believe that their findings are more representative for the US population.

In addition to gout, increased serum uric acid levels are seen with increased alcohol intake, obesity, diabetes, raised cholesterol, high blood pressure, kidney disease, coronary artery disease, and the use of diuretic medication. If this list sounds familiar, it may be because 5 of these 8 items correspond to those seen in what is known as syndrome X, or the insulin resistance syndrome (see related link below).

There may, indeed, be a close connection between an increase in uric acid and a person's resistance to the actions of insulin. It's not clear which comes first in the relationship - increased uric acid, high blood pressure, insulin resistance, or something else entirely. It has been suggested that uric acid itself can cause cardiovascular disease because it may affect the stickiness and clumping of blood platelets. It's more likely, however, that the increase in serum uric acid seen in people with high blood pressure is due to a change in the kidneys' function that reduces the excretion of uric acid in the urine.

So what can be done with the information from this study? The findings show that the uric acid level can be an additional indicator of possible risk for cardiovascular disease leading to a fatal outcome. It's quite useful to have such an additional warning signal, so that the appropriate steps can be taken. And we all know what these are - exercising (aerobic and anaerobic), sensible eating leading to weight control, and faithfully taking the medications your doctor prescribes.