Hyperuricemia and Incidence of Hypertension Among Men Without Metabolic Syndrome

Abstract

Abstract-The aim of this project was to study the risk of developing hypertension over a 6-year follow-up in normotensive men with baseline hyperuricemia (serum uric acid Ͼ7.0 mg/dL) but without diabetes/glucose intolerance or metabolic syndrome. We analyzed the data on men without metabolic syndrome or hypertension at baseline from the Multiple Risk Factor Intervention Trial. These men (nϭ3073; age: 35 to 57 years) were followed for an average of 6 years by annual examinations. Follow-up blood pressure among those with baseline was consistently higher than among those with normal serum uric acid concentration. We used Cox regression models for adjustment for the effects of serum creatinine, body mass index, age, blood pressure, proteinuria, serum cholesterol and triglycerides, alcohol and tobacco use, risk factor interventions, and use of diuretics. In these models, normotensive men with baseline hyperuricemia had an 80% excess risk for incident hypertension (hazard ratio: 1.81; 95% CI: 1.59 to 2.07) compared with those who did not. Each unit increase in serum uric acid was associated with a 9% increase in the risk for incident hypertension (hazard ratio: 1.09; 95% CI: 1.02 to 1.17). We conclude that the hyperuricemia-hypertension risk relationship is present among normotensive middle-aged men without diabetes/glucose intolerance or metabolic syndrome. in Ϸ3.9 million ambulatory care visits annually. 1,2 Many more have asymptomatic hyperuricemia, a risk factor for gout and for higher cardiovascular risk. 3 Hypertension is also very common, affecting Ϸ1 in every 4 adults. 4 Among those with prehypertension, those in the highest uric acid quartile were at Ͼ2 times greater risk for microalbuminuria than those in the lowest quartile, but this relationship was not found among normotensive subjects. 5 Animal and human studies have repeatedly shown a statistically independent association between serum uric acid and risk for hypertension. 6 -13 In a recent review, Johnson et al 8 have marshaled evidence that fulfills all of the Bradford Hill criteria for causality. 14 However, the issue of causality has been challenged. Skeptics cite studies that point to the strong coincidence of other cardiovascular risk factors, such as metabolic syndrome as a whole and its individual components as potential confounders. [15][16][17] Furthermore, many studies have linked a single baseline measurement of serum uric acid to onset of hypertension many years later: a limitation considering the fact that hyperuricemia, not necessarily a "trait," like serum cholesterol, can fluctuate up and down over time in response to common environmental changes such as diet, medications, and so forth.One way to overcome the above limitations would be to assemble a cohort of subjects who are at risk for hypertension but not hypertensive (thereby affording statistical power to detect small risk differences) and free of renal disease, diabetes, and metabolic syndrome. These individuals should then be followed over time with several repeated measures of ...

Associations between serum uric acid levels and the incidence of hypertension and metabolic syndrome: a 4-year follow-up study of a large screened cohort in Okinawa, Japan

“…In this 4-year follow-up study, we observed that elevated SUA levels were significantly and independently associated with the incidences of 10 In that study, subjects with hyperuricemia were at an 80% higher risk of developing hypertension, compared with those without hyperuricemia. The MRFIT study was a randomized, controlled trial in a cohort of men who were at high risk for adverse coronary events.…”

“…MetS is characterized by the presence of multiple common cardiovascular risk factors, such as central obesity, atherogenic dyslipidemia (hypertriglyceridemia and low high-density lipoprotein cholesterol (HDL-C)) levels, hyperglycemia and elevated blood pressure (BP). Elevated SUA levels are prevalent in patients with hypertension 1,2 and MetS, [3][4][5][6][7] and these levels can be a significant predictor of the development of hypertension 3,[8][9][10] and MetS. [11][12][13][14] Although evidence has suggested that elevated SUA levels might have a role in hypertension, 15 a causal relationship has not been established.…”

Interaction between serum uric acid and triglycerides in relation to blood pressure

“…12 A study found that men with hyperuricemia had more risk for incident hypertension. 13 Each unit increase in SUA was associated with a 9% increase in the risk for incident hypertension. Although the mechanism by which uric acid has a pathogenetic role in hypertension was unclear; hyperuricemia was associated with deleterious effects on endothelial function, platelet adhesion and aggregation, or oxidative metabolism.…”

Prediction models for the risk of new-onset hypertension in ethnic Chinese in Taiwan

“…4 Therefore, we constructed the prediction models for hypertension risk using a community-based cohort of middle-aged and elderly ethnic Chinese in Taiwan as the following strategies. First, we incorporated gender, age, body mass index (BMI), systolic (SBP) and diastolic blood pressures (DBP) as the clinical model and included white blood cell count, fasting glucose and uric acid [12][13] as the biochemical models. Second, we proposed two different scoring systems: regression coefficient-based scores 14 and point-based scores.…”