Hyperuricemia as a Risk Factor of Coronary Heart Disease: The Framingham Study

Abstract

Uric acid values were obtained on subjects of the original Framingham cohort at their fourth and 13th biennial examinations. The mean uric acid value for men was 5.0 mg/dl at the fourth examination and 5.7 mg/dl at examination 13 and was 3.9 mg/dl and 4.7 mg/dl, respectively, for women. This secular trend was due to both "laboratory drift" and increasing use of diuretics. Serum uric acid values were consistently higher in subjects of both sexes who were taking antihypertensive drugs at both examinations. Serum uric acid values correlated with systolic and diastolic blood pressure in both sexes; the relationship was stronger in women than in men and for systolic than for diastolic pressure. Correlations were stronger at examination 4 than at examination 13 when more antihypertensive treatment was used. Examination 4 serum uric acid predicted the subsequent development of coronary heart disease, in general, and myocardial infarction, in particular, but not angina pectoris. The uric acid relationship with myocardial infarction was equally strong in both sexes, even correcting for antihypertensive treatment. However, in multivariate analysis, including age, systolic blood pressure, relative weight, cigarette smoking, and serum cholesterol, serum uric acid did not add independently to the prediction of coronary heart disease.

Is serum uric acid a risk factor for coronary heart disease?

“…[2][3][4][5][6][8][9][10][11][12]17 The question as to whether high disease which could confound the observed association. This review assesses the role of elevated serum uric acid as an independent role for coronary heart disease.…”

“…6 By contrast the Framingham Study found the relation to be independent of antihypertensive treatment but the relationship was attenuated upon adjustment for other cardiovascular risk factors including blood pressure and cholesterol. 4 The NHANES study 12 and the Chicago Heart Association Detection Project in Industry 8 both found the relation between uric acid and risk of CHD in men to be attenuated after adjustment for a range of other cardiovascular risk factors, but neither of these studies ascertained which factors were responsible for the attenuation. The Social Insurance Institution of Finland Study observed the relationship to be confounded by pre-existing CHD.…”

“…[1][2][3][4] However, hyperuricaemia has also been shown to be associated with many cardiovascular risk factors, in particular hypertension, pre-existing CHD, hyperlipidaemia and the use of antihypertensive treatment. [4][5][6][7][8][9][10][11] Thus the role of serum uric acid as an independent risk factor for CHD remains uncertain. Although earlier studies suggested uric acid to be an independent risk factor for CHD 1,2 there is now increasing evidence that the association of hyperuricaemia with CHD events is dependent on the association between uric acid and other cardiovascular risk factors.…”

“…Although earlier studies suggested uric acid to be an independent risk factor for CHD 1,2 there is now increasing evidence that the association of hyperuricaemia with CHD events is dependent on the association between uric acid and other cardiovascular risk factors. [3][4][5][6][8][9][10][11][12] Several investigators conclude that the association is explained by secondary associations of uric acid with hypertension, diuretic agents and elevated levels of tryglyceride. [3][4][5][6][8][9][10][11][12] It has also been postulated that hyperuricaemia may be part of the insulin resistance syndrome.…”

“…[3][4][5][6][8][9][10][11][12] Several investigators conclude that the association is explained by secondary associations of uric acid with hypertension, diuretic agents and elevated levels of tryglyceride. [3][4][5][6][8][9][10][11][12] It has also been postulated that hyperuricaemia may be part of the insulin resistance syndrome. [13][14][15][16] A number of investigators have suggested an independent role of uric acid on the risk of CHD in women but not in men.…”