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Available online 19 February 2023
Association of serum uric acid with benefits of intensive blood pressure control
Asociación del nivel de ácido úrico en suero con los beneficios del control intensivo de la presión arterial
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Xiao-Qi Wanga,, Jiang-Shan Tana,, Shu-Yuan Zhangb, Wei-li Zhanga,
Corresponding author
zhangweili1747@yahoo.com

Corresponding authors.
, Jun Caia,
Corresponding author
caijun7879@126.com

Corresponding authors.
a Fu Wai Hospital, State Key Laboratory of Cardiovascular Disease, National Center for Cardiovascular Diseases, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China
b Department of Cardiology, Peking Union Medical College Hospital, Peking, Union Medical College & Chinese Academy of Medical Sciences, Beijing, China
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Abstract
Introduction and objectives

Intensive systolic blood pressure (SBP) control improved outcomes in the Strategy of Blood Pressure Intervention in the Elderly Hypertensive Patients (STEP) trial. Whether the serum uric acid concentration at baseline alters the benefits of intensive SBP control is unknown.

Methods

The STEP trial was a randomized controlled trial that compared the effects of intensive (SBP target of 110 to<130mmHg) and standard (SBP target of 130 to <150mmHg) SBP control in Chinese patients aged 60 to 80 years with hypertension. The primary outcome was a composite of cardiovascular disease events. This post hoc analysis was performed to examine whether the effects of intensive SBP intervention differed by the baseline uric acid concentration using 2 models: restricted cubic spline curves and subgroup analyses, both based on the Fine-Gray subdistribution hazard model in the analysis of the primary outcome and secondary outcomes (excluding all-cause death). In the analysis of all-cause death, the Cox regression model was used. We also examined the change in the follow-up uric acid concentrations.

Results

Overall, the risk of the primary outcome rose as the cumulative uric acid concentration increased in both the intensive and standard treatment groups. Patients with intensive treatment had a lower multivariable-adjusted subdistribution hazard ratio for the primary outcome, but with a wide overlap of 95%CI. Next, we stratified patients according to their baseline uric acid concentration (tertile 1 [T1], <303.0μmol/L; tertile 2 [T2], 303.0 to <375.8μmol/L; and tertile 3 [T3], ≥375.8μmol/L). Subgroup analyses using tertiles provided HRs and 95%CI in T1 (HR, 0.55; 95%CI, 0.36–0.86; P=.008), T2 (HR, 0.80; 95%CI, 0.56–1.14; P=.22) and T3 (HR, 0.86; 95%CI, 0.60–1.21; P=.39), with an interaction P value of .29. The results for most of the secondary outcomes followed the same trends.

Conclusions

There was no evidence that the benefit of the intensive SBP control differed by baseline uric acid concentrations. This trial was registered at ClinicalTrial.gov (Identifier: NCT03015311).

Keywords:
Blood pressure
Hypertension
Intensive blood pressure control
Uric acid
Abbreviations:
SBP
Resumen
Introducción y objetivos

El control intensivo de la presión arterial sistólica (PAS) mejora los resultados de la estrategia de control de la presión arterial en el ensayo STEP con pacientes ancianos hipertensos. Sin embargo, se desconoce si los niveles de ácido úrico pueden afectar los beneficios del control intensivo de la PAS.

Métodos

El ensayo STEP fue un estudio controlado y aleatorizado que comparó el efecto del control intensivo (PAS objetivo de 110 o <130mm Hg) frente al tratamiento estándar (PAS objetivo de 130 o <150mm Hg) de la PAS en pacientes chinos hipertensos de entre 60 y 80 años. El objetivo primario incluyó un conjunto de eventos asociados a la enfermedad cardiovascular. Se utilizaron los modelos de curvas spline cúbicas restringidas y análisis de subgrupos para estudiar si los efectos del control intensivo de la PAS difieren en función las concentraciones basales de ácido úrico. Ambos modelos se basaron en la subdistribución de riesgos de Fine-Gray para el análisis del objetivo primario y los objetivos secundarios. El modelo de regresión de Cox se utilizó para el análisis de muerte por cualquier causa. También se analizaron las concentraciones de ácido úrico durante el seguimiento.

Resultados

El riesgo del objetivo primario se incrementó con el incremento de la concentración de ácido úrico tanto en el grupo de tratamiento intensivo como en el de tratamiento estándar. Los pacientes bajo tratamiento intensivo mostraron menor subdistribución (ajustada de forma multivariable) del cociente de riesgo para el objetivo primario, aunque con un amplio solapamiento del IC 95%. La estratificación de pacientes por terciles de concentración de ácido úrico mostró un CR de 0,55 (IC95%, 0,36-0,86; p=0,008) para el tercil 1 (ácido úrico <303,0μmol/l), de 0,80 (IC95%, 0.56-1.14; p=0,22) para el tercil 2 (AcU 303,0 a <375,8μmol/l) y de 0,86 (IC95%, 0,60–1,21; p=0,39) para el tercil 3 (AcU ≥ 375,8μmol/l); p=0,29 para la interacción. Las tendencias fueron similares para la mayoría de las variables secundarias.

Conclusiones

El beneficio del control intensivo de la PAS no difiere en función de las concentraciones basales de ácido úrico. Número de registro: NCT03015311.X.

Palabras clave:
Presión arterial
Hipertensión
Control intensivo de la presión arterial
Ácido úrico

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