Novel plasma biomarkers improve discrimination of metabolic health independent of weight

Abstract

We sought to determine if novel plasma biomarkers improve traditionally defined metabolic health (MH) in predicting risk of cardiovascular disease (CVD) events irrespective of weight. Poor MH was defined in CATHGEN biorepository participants (n > 9300), a follow-up cohort (> 5600 days) comprising participants undergoing evaluation for possible ischemic heart disease. Lipoprotein subparticles, lipoprotein-insulin resistance (LP-IR), and GlycA were measured using NMR spectroscopy (n = 8385), while acylcarnitines and amino acids were measured using flow-injection, tandem mass spectrometry (n = 3592). Multivariable Cox proportional hazards models determined association of poor MH and plasma biomarkers with time-to-all-cause mortality or incident myocardial infarction. Low-density lipoprotein particle size and high-density lipoprotein, small and medium particle size (HMSP), GlycA, LP-IR, short-chain dicarboxylacylcarnitines (SCDA), and branched-chain amino acid plasma biomarkers were independently associated with CVD events after adjustment for traditionally defined MH in the overall cohort (p = 3.3 × 10−4–3.6 × 10−123), as well as within most of the individual BMI categories (p = 8.1 × 10−3–1.4 × 10−49). LP-IR, GlycA, HMSP, and SCDA improved metrics of model fit analyses beyond that of traditionally defined MH. We found that LP-IR, GlycA, HMSP, and SCDA improve traditionally defined MH models in prediction of adverse CVD events irrespective of BMI.

Hypertension promotes microbial translocation and dysbiotic shifts in the fecal microbiome of nonhuman primates

“…However, these biomarkers act as potential predictors for screening and diagnosis of the disease condition and we confirmed barrier dysfunction by detection of higher bacterial genome levels in lymph nodes draining the colon. 34 While providing novel information about microbial signatures of hypertension, possibly more robust work is needed at the species level to understand the alterations in microbial metabolism and inflammation and their contributions to hypertension. Understanding the host-microbiome-metabolic axis will enable us to gain insights into diagnosis and develop a microbiome-related therapeutic intervention to manage blood pressure in hypertensive patients.…”

Transcriptomics for Clinical and Experimental Biology Research: Hang on a Seq

“…High‐throughput profiling technologies are increasingly used to define the molecular repertoire of disease at the (epi)genomic, transcriptomic, proteomic, and metabolomic level. [ 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 ] Such technologies can be used to establish that patients, normally categorized to a single disease, display molecular heterogeneity; [ 15 ] this may be linked to prognosis or be used to select more active drug combinations. [ 16 , 17 , 18 , 19 , 20 ] Transcriptomics has led to various tools for stratified medicine [ 14 , 21 , 22 , 23 , 24 ] by identifying signatures that better match patients to drugs.…”

Revista de Investigaci�n Cl�nica -Clinical and Translational Investigation-: Editors' Choices 6 Years Later

“…However, the results from this study should be taken with caution since the search for these metabolites was empirical, without a clear pathophysiological basis. Furthermore, it should be considered that the levels of the metabolites investigated may vary depending on gender, age, prevalence of diabetes, obesity or hypertension, and drugs administered or timing of their administration 6 . Colorectal cancer is a major health problem worldwide.…”