Uric acid and adiponectin in cardiovascular disease

Abstract

Uric acid, a product of metabolism, was discovered a quarter of a millennium ago and has been known to be a possible cardiovascular risk factor for well over a century. A much newer discovery, adiponectin, was discovered only a little more than 20 years ago as a protein hormone secreted by adipose tissue and has attracted substantial attention for its association with cardiovascular disease. This thesis will examine the modifying action of overweight on the relationship between uric acid levels and metabolic syndrome, the association between uric acid levels and adverse cardiovascular events and mortality in subjects with or without diastolic dysfunction, and the sex-specific association between adiponectin levels and diastolic dysfunction. In addition, this thesis will determine whether a relevant interaction between uric acid and adiponectin exists with respect to diastolic dysfunction.

Paper 1, a seven-year prospective study with over 6,000 participants, examines whether overweight modifies the association between the uric acid levels and metabolic syndrome. In overweight but not normal-weight subjects, the baseline uric acid levels predicted the development of elevated blood pressure and elevated fasting glucose levels. The baseline uric acid levels and changes in the uric acid levels over seven years predicted metabolic syndrome and most of its components.

A 19-year prospective study of 1,460 women and 1,480 men with endpoints of all-cause mortality, incident myocardial infarction and incident ischaemic stroke is described in Paper 2. Uric acid levels were a predictor of all-cause mortality in subjects with echocardiographic markers of diastolic dysfunction but not in subjects without these markers. Uric acid levels were a stronger predictor of incident ischaemic stroke in subjects with severely enlarged atria than in subjects with normal-sized atria.

Paper 3 describes a cross-sectional study of 1,165 women and 896 men and the sex-specific relationship between adiponectin levels and diastolic dysfunction. Lower adiponectin levels were associated with greater odds of echocardiographic indices of diastolic dysfunction in women but lower odds of diastolic dysfunction in men. Additionally, lower adiponectin levels were associated with a higher left ventricular mass in women only. An interaction between uric acid and adiponectin levels was not observed for any marker of diastolic dysfunction.

These findings support an association between uric acid levels and increased cardiovascular risk, with detrimental effects observed in subjects who already present a state of metabolic derangement and an elevated risk, such as overweight persons and subjects with diastolic dysfunction. Furthermore, adiponectin levels, and thus adipose tissue function, may provide a clue to why heart failure with preserved ejection fraction shows a female preponderance.