A metabolomic index based on lipoprotein subfractions and branched chain amino acids is associated with incident hypertension

Jose L Flores-Guerrero,Margery A Connelly,Irina Shalaurova,Erwin Garcia,Stephan J.L Bakker,Robin P.F Dullaart

doi:10.1016/j.ejim.2021.07.002

Jose L Flores-Guerrero, Margery A Connelly + Show 4 more

Open Access

https://doi.org/10.1016/j.ejim.2021.07.002

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Abstract

ObjectiveThe present study aims to evaluate the performance of the Diabetes Risk Index (DRI), a metabolomic index based on lipoprotein particles and branched chain amino acids, on the incidence of newly developed hypertension in a large community dwelling cohort. MethodsThe DRI was calculated by combining 6 lipoprotein parameters [sizes of very-low-density lipoprotein (VLDL), low-density lipoprotein (LDL) and high-density lipoprotein (HDL), concentrations of large VLDL, small LDL, and large HDL particles], and the concentrations of valine and leucine. DRI scores were estimated in 4169 participants from the PREVEND prospective cohort. Cox proportional hazards regression was used to evaluate the association of DRI scores with incident hypertension. ResultsDuring a median follow-up of 8.6 years, 924 new hypertension cases were ascertained. In analyses adjusted for age and sex, there was a significant association between DRI and incident hypertension with a hazard ratio (HR) per 1 SD increase of 1.45 (95% CI 1.36,1.54; p < 0.001). After additional adjustment for traditional risk factors, the HR remained significant (HRadj 1.21, 95% CI 1.10, 1.33, p <0.001). Likewise, subjects in the top quartile of DRI presented with a higher risk of hypertension (HRadj 1.64, 95% CI 1.28, 2.10, p <0.001). Furthermore, the net reclassification improvement assessment improved after the addition of DRI to a traditional risk model (p <0.001), allowing proper reclassification of 34% of the participants. ConclusionHigher DRI scores were associated with an increased risk of incident hypertension. Such association was independent of traditional clinical risk factors for hypertension.

Highlights

Hypertension is the leading preventable risk factor for cardiovascu lar disease (CVD) and all-cause mortality worldwide, with a sustained increment in mortality over the last 40 years [1]
Waist circumference showed a sensitivity and specificity of 0.63 and 0.57, respectively (AUC: 0.63), making that the performance of Diabetes Risk Index (DRI) was better than that of the waist circumference (p-value < 0.001). In this large prospective cohort, comprising 4169 participants, we report for the first time that higher scores of DRI, a newly developed risk algorithm based on branched chain amino acids (BCAA) and six lipoprotein particles parameters, are associated with incidence of hypertension
Multivariable adjusted timeto-event analyses showed that the positive association of DRI with hy pertension was present after adjustment for age, sex, glucose, insulin and Body-mass index (BMI)

Summary

Introduction

Hypertension is the leading preventable risk factor for cardiovascu lar disease (CVD) and all-cause mortality worldwide, with a sustained increment in mortality over the last 40 years [1]. Over the same period of time, elevated blood pressure remains the risk factor with the highest disability-adjusted life-years burden [2]. Given the constant rise in hy pertension incidence, improvement in the risk classification for hyper tension development is needed. Improvement in the performance of metabolite measurement plat forms, such as nuclear magnetic resonance (NMR) spectroscopy, has allowed for the quantification of circulating biomarkers and exploration of their associations with incidence of hypertension [3]. The role of branched chain amino acids (BCAA) in the development of hy pertension has gained attention. It has been shown that high concen trations of BCAA, quantified by means of NMR in normotensive subjects are associated with higher risk of hypertension incidence in a period of seven years [4]

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