Abstract and Introduction
Purpose of Review: The metabolic syndrome is defined by the clustering of a number of cardiovascular risk factors and entails an increased risk for cardiovascular disease and mortality from both cardiovascular disease and all causes. In the present paper, we review the most recent evidence on the association between hyperuricemia, metabolic syndrome, and cardiovascular disease.
Recent Findings: Serum urate is frequently elevated in patients with the metabolic syndrome and increases with the number of components of this condition. Hyperuricemia has been related to decreased renal uric acid excretion, which may be mediated by enhanced proximal tubular sodium reabsorption and hyperinsulinemia. Recent epidemiologic studies have shed some light on the prognosis of hyperuricemia. While hyperuricemia appears to show a benign significance in low cardiovascular risk individuals, it clearly increases cardiovascular mortality in patients at high cardiovascular disease risk.
Summary: Clinicians should be aware of the presence of metabolic syndrome in patients with hyperuricemia or gout in order to control its components (high blood pressure, obesity, etc.) and hence reduce the risk for cardiovascular disease. Long-term, randomized interventional clinical trials are needed to test the hypothesis that urate-lowering therapy can reduce cardiovascular risk in these patients.
The metabolic syndrome describes a group of modifiable risk factors occurring in the same individual and associated with an increased risk of developing cardiovascular disease (CVD) and type 2 diabetes mellitus (T2DM). Reports of clustering of metabolic risk factors are not new and date back to the early 1920s. Increased serum urate concentration and gout were already recognized as important features. Interest in the aggregation of these modifiable risk factors was markedly implemented by Reaven, who coined the term ‘syndrome X’ to describe a disorder consisting of insulin resistance, glucose intolerance, increased triglyceride and decreased high-density lipoprotein (HDL) cholesterol levels, and arterial hypertension. He postulated that the common pathophysiological feature was insulin resistance and that all other abnormalities were likely to be secondary to this basic abnormality.
The WHO first described the syndrome in 1998 with the term ‘metabolic syndrome’. The WHO criteria for the metabolic syndrome required the presence of T2DM, impaired fasting glucose, impaired glucose tolerance, or insulin resistance (assessed by the euglycemic insulin clamp technique) plus two additional risk factors. In 1999, the European Group for the Study of Insulin Resistance proposed the term ‘insulin resistance syndrome’ and modified the criteria to require fasting hyperinsulinemia plus two other factors with different cutoff points than those used by the WHO. One of the criteria was an increased waist circumference to reflect abdominal obesity. In 2001, the National Cholesterol Educational Program Adult Treatment Panel III (NCEP ATP III) proposed a simple definition requiring any three of these five risk factors ( Table 1 ): increased waist circumference, high triglyceride level, low HDL cholesterol level, high blood pressure, and high fasting plasma glucose concentration. The NCEP ATP III criteria were updated in 2005 to correspond to the new American Diabetes Association (ADA) standard of a normal fasting glucose level of less than 100 mg/dl. In 2005, the International Diabetes Federation (IDF) proposed a similar definition to that used by the NCEP ATP III with ethnicity-specific waist circumference cutoff points, since Asians (normal waist circumference for men <90 cm; women <80 cm) have a higher incidence of insulin resistance and T2DM at a lower BMI and waist circumference than Europeans (normal waist circumference for men <94 cm; women <80 cm) and US citizens (normal waist circumference for men <102 cm; women <88 cm). For children aged 10-16 years, the metabolic syndrome can be diagnosed with abdominal obesity (using waist circumference percentiles) and the presence of two or more other clinical features (elevated triglycerides, low HDL cholesterol, high blood pressure, increased plasma glucose). Although some of these descriptors (as well as body size and proportions) change with age and development, in the absence of definitive data, the criteria adhere to the absolute values in IDF’s adult definition. The exception is that one (rather than a sex-specific) cutoff is used for HDL. For children older than 16, the IDF adult criteria can be used.