Gouty arthritis is a common form of inflammatory arthritis, occurring more frequently in men than in women. The condition has a male–female ratio of 3 or 4 to 1, although that ratio narrows as adults age; because the uricosuric effects of estrogen decline with menopause, the risk for gout increases in postmenopausal women.1,2 Mean age at disease onset is 40 to 60 in men,3,4 with onset in women averaging seven years later.5
Apart from the pain and loss of function associated with this disorder of purine metabolism6 and the risk for a chronic form of the disease, gout is almost universally linked with serious comorbidities that require timely intervention. These include hypertension, dyslipidemia, hyperglycemia and diabetes, obesity, metabolic syndrome, cardiovascular disease (CVD), renal insufficiency, and coronary heart disease (CHD).2,3,7 The presence of gout is independently associated with a risk for acute myocardial infarction (AMI) and increased rates of all-cause mortality.3,8-10
EPIDEMIOLOGY
In 2007, the National Arthritis Data Workgroup11,12 estimated that about three million US adults had had “self-reported gout” in the previous year. An estimated six million US adults have been diagnosed with gout,2,11 and its incidence and prevalence are increasing. The incidence of primary gout more than doubled between 1977-1978 and 1995-1996,13 especially affecting the aging population. The prevalence of gout among 1,000 managed care patients ages 65 to 74 increased by at least 30% between 1990 and 1999, while prevalence among those older than 75 almost doubled during this same period.14
Numerous factors appear to contribute to these trends, including aging of the population, dietary trends (ie, increased consumption of red meat, organ food, game, and shellfish and reduced consumption of low-fat dairy products), presence of certain comorbid conditions (ie, hypertension, dyslipidemia, diabetes, metabolic syndrome, end-stage renal disease), the increasing prevalence of obesity in younger adults, use of specific prescription medications, and increased incidence of organ transplantation.1,7,8,15-19
The body’s underexcretion or overproduction of uric acid (a byproduct of purine metabolism12) can lead to hyperuricemia. This condition, defined as a serum urate level exceeding 7.0 mg/dL in men or 6.0 mg/dL in women20,21 (levels above 9.0 mg/dL are considered very high22), is the primary risk factor for gout.8,23,24 As with gout, the incidence of hyperuricemia has increased in recent years,20 with researchers attributing the trend to worldwide popularization of the Westernized diet (particularly use of high-fructose corn syrup20,25) and increased use of certain medications, including thiazide diuretics, cyclosporine, and low-dose aspirin.2,20,25,26
As serum urate levels rise, the patient with hyperuricemia may experience urate supersaturation, often followed by crystallization of the excess urate into monosodium urate (MSU) crystals. Subsequently, circulating MSU crystals may deposit in body tissues, especially in the joint spaces. The body’s ensuing inflammatory response to the MSU deposits is gout.20
In addition to hyperuricemia, risk factors for gout include a high-purine diet, habitual alcohol consumption (especially beer and fortified wines27), diuretic therapy (particularly in patients with heart failure or renal insufficiency), obesity, hypertension, and high levels of fructose consumption.7,28 Additionally, cyclosporine use in an organ transplant recipient, poorly controlled uric acid levels, and a long history of gout increase the patient’s risk for chronic tophaceous gout.24,29 Tophi may be more common in a patient with a history of organ transplantation.16
Genetic variants are currently being investigated to possibly identify a predisposition to gout. The most significant genetic factors appear to involve mechanisms that regulate serum uric acid levels—particularly urate underexcretion.23 Other factors that contribute to underexcretion or overproduction of uric acid are shown in Table 1.1,15,26,30-33
A dynamic relationship exists between gout and a number of pathologic processes. According to researchers investigating nearly 178,000 patients with gout in a managed care database, 36% had hypertension, 27% had dyslipidemia, and 15% had diabetes.8 In a smaller cohort study conducted in Spain and Mexico, it was demonstrated that 93% of patients with gout had one or more associated diseases, in order of decreasing frequency: hypertriglyceridemia, obesity, hypertension, metabolic syndrome, hyperglycemia, chronic renal failure, diabetes, and ischemic heart disease.3
Of particular clinical importance in this study was a finding that the first gout attack generally preceded the diagnosis of the associated diseases.3 Thus, a diagnosis of gout should lead the primary care provider to discuss modifiable risk factors with the patient—but also to investigate for comorbid illnesses that may require timely management.2
In a 12-year-long prospective study of more than 50,000 men participating in the Health Professionals Follow-Up Study,9 it was found that men with gout had a 28% increased risk for all-cause mortality, a 38% increased risk for CVD-related death, and a 55% increased risk for CHD-related death, compared with men who did not have gout (excluding other risk factors).9 Similarly, researchers for the Multiple Risk Factor Intervention Trial10 demonstrated a clinically significant association between gout and an increased risk for AMI: 10.5% of men with gout, compared with 8.43% of men without gout, had an AMI during mean follow-up of 6.5 years.10