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

Abstract

The 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. Methods: The 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. Results: During 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 (HR adj 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 (HR adj 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. Conclusion: Higher DRI scores were associated with an increased risk of incident hypertension. Such association was independent of traditional clinical risk factors for hypertension.

Branched chain amino acids metabolism in heart failure

“…In the context of insulin resistance, plasma BCAAs levels exhibit a proclivity for elevation, thereby magnifying the nexus between BCAAs and metabolic aberrations (31-33). An intriguing amalgamation known as the diabetes risk index (DRI), which interweaves BCAAs and LP-IR, has duly emerged as a robust biomarker predictive of type 2 diabetes mellitus (T2DM) and newly diagnosed hypertension, irrespective of traditional clinical risk factors (34,35). The tapestry of epidemiological and experimental evidence further bolsters the observed correlation between BCAAs levels and insulin resistance (23).…”

Aberrant branched-chain amino acid catabolism in cardiovascular diseases

“…These processes are also involved in cellular inflammation, aging, obesity and diabetes mellitus, and further contribute to cardiovascular disease. intake, in particular valine intake, is associated with a higher risk of incident hypertension (117)(118)(119)(120). However, due to the diverse pathogenesis of hypertension, the exact mechanism of BCAAs in the development and progression of hypertension has not yet been elucidated, and further investigation is needed to unravel the complexity behind the circulating concentrations of BCAAs.…”

Association between Excessive Dietary Branched-Chain Amino Acids Intake and Hypertension Risk in Chinese Population

“…The clarification of more modifiable risk factors for hypertension has received considerable interest. Despite that associations between BCAAs and hypertension have been estimated in some population-based studies, such relationship still remained inconclusive, and the causality was uncertain due to the lack of relevant prospective studies [17][18][19][20][21][22]. In addition, given that the beneficial roles of BCAAs as essential amino acids could not be neglected, we hypothesized that the dietary BCAAs intake probably did not increase hypertension risk unless the level of dietary intake was beyond a proper range.…”