Relation Between Serum Uric Acid and Risk of Cardiovascular Disease in Essential Hypertension: The PIUMA Study
Paolo Verdecchia,Giuseppe Schillaci,Gianpaolo Reboldi,Fausto Santeusanio,Carlo Porcellati,Paolo Brunetti +5 more
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TL;DR: In untreated subjects with essential hypertension, raised uric acid is a powerful risk marker for subsequent cardiovascular disease and all-cause mortality.
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Abstract: The question of serum uric acid as an independent risk factor in subjects with essential hypertension remains controversial. For up to 12 years (mean, 4.0) we followed 1720 subjects with essential hypertension. At entry, all subjects were untreated and all were carefully screened for absence of cardiovascular disease, renal disease, cancer, and other important disease. Outcome measures included total cardiovascular events, fatal cardiovascular events, and all-cause mortality. During 6841 person-years of follow-up there were 184 cardiovascular events (42 fatal) and 80 deaths from all causes. In the 4 quartiles of serum uric acid (division points: 0.268, 0.309, and 0.369 mmol/L [4.5, 5.2, and 6.2 mg/dL] in men; 0.190, 0.232, and 0.274 mmol/L [3.2, 3.9, and 4.6 mg/dL] in women), the rate (per 100 person-years) of cardiovascular events was 2.51, 1.48, 2.66, and 4.27, that of fatal cardiovascular events was 0.41, 0.33, 0.38, and 1.23, and that of all-cause deaths was 1.01, 0.55, 0.93, and 2.01, respectively. The relation between uric acid and event rate was J-shaped in both genders. After adjustment for age, gender, diabetes, total cholesterol/HDL cholesterol ratio, serum creatinine, left ventricular hypertrophy, ambulatory blood pressure, and use of diuretics during follow-up, uric acid levels in the highest quartile were associated with increased risk for cardiovascular events (relative risk, 1.73; 95% CI, 1.01 to 3.00), fatal cardiovascular events (relative risk, 1.96; 95% CI, 1.02 to 3.79), and all-cause mortality (relative risk, 1.63; 95% CI, 1.02 to 2.57) in relation to the second quartile. In untreated subjects with essential hypertension, raised uric acid is a powerful risk marker for subsequent cardiovascular disease and all-cause mortality.
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Citations
Is There a Pathogenetic Role for Uric Acid in Hypertension and Cardiovascular and Renal Disease
Richard J. Johnson,Duk Hee Kang,Daniel I. Feig,Salah D. Kivlighn,John Kanellis,Susumu Watanabe,Katherine R. Tuttle,Bernardo Rodriguez-Iturbe,Jaime Herrera-Acosta,Marilda Mazzali +9 more
TL;DR: It is time to reevaluate the role of uric acid as a risk factor for cardiovascular disease and hypertension and to design human studies to address this controversy.
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Uric Acid Stimulates Monocyte Chemoattractant Protein-1 Production in Vascular Smooth Muscle Cells Via Mitogen-Activated Protein Kinase and Cyclooxygenase-2
John Kanellis,Susumu Watanabe,Jinhua Li,Duk Hee Kang,Ping Li,Takahiko Nakagawa,Ann Wamsley,David Sheikh-Hamad,Hui Y. Lan,Lili Feng,Richard J. Johnson +10 more
TL;DR: Uric acid regulates critical proinflammatory pathways in VSMCs, suggesting it may have a role in the vascular changes associated with hypertension and vascular disease.
836
High-dose allopurinol improves endothelial function by profoundly reducing vascular oxidative stress and not by lowering uric acid
TL;DR: The mechanism of improvement in endothelial function with allopurinol lies in its ability to reduce vascular oxidative stress and not in urate reduction, and it is shown that the steep dose–response relationship exists.
609
Uric Acid, Hominoid Evolution, and the Pathogenesis of Salt-Sensitivity
Susumu Watanabe,Duk Hee Kang,Lili Feng,Takahiko Nakagawa,John Kanellis,Hui Lan,Marilda Mazzali,Richard J. Johnson +7 more
TL;DR: It is hypothesized that the mutation provided a survival advantage to early hominoids because of the ability of hyperuricemia to maintain blood pressure under low-salt dietary conditions, such as prevailed during the Miocene.
562
Relations of Serum Uric Acid to Longitudinal Blood Pressure Tracking and Hypertension Incidence
Johan Sundström,Lisa M. Sullivan,Ralph B. D'Agostino,Daniel Levy,William B. Kannel,Ramachandran S. Vasan +5 more
TL;DR: Serum UA level was an independent predictor of hypertension incidence and longitudinal BP progression at short-term follow-up in the Framingham Study, and was positively associated with changes in systolic pressure 4 years later.
540
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