Original Research|Articles in Press

The association between triglyceride-rich lipoproteins, circulating leukocytes, and low-grade inflammation: The Brazilian Longitudinal Study of Adult Health (ELSA-Brasil)

Published:February 07, 2023DOI:


      • Triglyceride-rich lipoproteins (TRLs) were independently associated with GlycA.
      • Medium and large TRLs were the main TRL subclasses related to GlycA.
      • Medium, large, and very large TRLs were associated with circulating leukocytes.
      • TRLs were more strongly related to neutrophils and lymphocytes than monocytes.
      • The total number of TRLs was not associated with C-reactive protein.


      Experimental studies have linked triglyceride-rich lipoproteins (TRLs) to inflammation, but the extent of this phenomenon in vivo has not been completely elucidated.


      We investigated the association between TRL subparticles and inflammatory markers (circulating leukocytes, plasma high-sensitivity C-reactive protein [hs-CRP], and GlycA) in the general population.


      This was a cross-sectional analysis of the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil). TRLs (number of particles per unit volume) and GlycA were measured by nuclear magnetic resonance spectroscopy. The association between TRLs and inflammatory markers was determined by multiple linear regression models adjusted for demographic data, metabolic conditions, and lifestyle factors. Standardized regression coefficients (beta) with 95% confidence intervals are reported.


      The study population comprised 4,001 individuals (54% females, age 50 ± 9 years). TRLs, especially medium and large subparticles, were associated with GlycA (beta 0.202 [0.168, 0.235], p<0.001 for total TRLs). There was no association between TRLs and hs-CRP (beta 0.022 [-0.011, 0.056], p = 0.190). Medium, large, and very large TRLs were associated with leukocytes, with stronger connections with neutrophils and lymphocytes than monocytes. When TRL subclasses were analyzed as the proportion of the total pool of TRL particles, medium and large TRLs were positively related to leukocytes and GlycA, whereas smaller particles were inversely associated.


      There are different patterns of association between TRL subparticles and inflammatory markers. The findings support the hypothesis that TRLs (especially medium and larger subparticles) may induce a low-grade inflammatory environment that involves leukocyte activation and is captured by GlycA, but not hs-CRP.

      Graphical abstract



      ASCVD (Atherosclerotic cardiovascular disease), BMI (Body mass index), CAC (Coronary artery calcification), ELSA-Brasil (Brazilian Longitudinal Study of Adult Health), HDL (High-density lipoprotein), hs-CRP (High-sensitivity C-reactive protein), LDL (Low-density lipoprotein), NMR (Nuclear magnetic resonance), TRL (Triglyceride-rich lipoprotein)
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        • Ginsberg H.N.
        • Packard C.J.
        • Chapman M.J.
        • et al.
        Triglyceride-rich lipoproteins and their remnants: metabolic insights, role in atherosclerotic cardiovascular disease, and emerging therapeutic strategies-a consensus statement from the European Atherosclerosis Society.
        Eur Heart J. 2021; 42: 4791-4806
        • Generoso G.
        • Janovsky C.C.P.S.
        • Bittencourt M.S.
        Triglycerides and triglyceride-rich lipoproteins in the development and progression of atherosclerosis.
        Curr Opin Endocrinol Diabetes Obes. 2019; 26: 109-116
        • Varbo A.
        • Benn M.
        • Tybjærg-Hansen A.
        • Nordestgaard B.G.
        Elevated remnant cholesterol causes both low-grade inflammation and ischemic heart disease, whereas elevated low-density lipoprotein cholesterol causes ischemic heart disease without inflammation.
        Circulation. 2013; 128: 1298-1309
        • Higgins L.J.
        • Rutledge J.C.
        Inflammation associated with the postprandial lipolysis of triglyceride-rich lipoproteins by lipoprotein lipase.
        Curr Atheroscler Rep. 2009; 11: 199-205
        • Schwartz E.A.
        • Reaven P.D.
        Lipolysis of triglyceride-rich lipoproteins, vascular inflammation, and atherosclerosis.
        Biochim Biophys Acta. 2012; 1821: 858-866
        • Zewinger S.
        • Reiser J.
        • Jankowski V.
        • et al.
        Apolipoprotein C3 induces inflammation and organ damage by alternative inflammasome activation.
        Nat Immunol. 2020; 21: 30-41
        • Alipour A.
        • van Oostrom A.J.
        • Izraeljan A.
        • et al.
        Leukocyte activation by triglyceride-rich lipoproteins.
        Arterioscler Thromb Vasc Biol. 2008; 28: 792-797
        • She Y.
        • Mangat R.
        • Tsai S.
        • Proctor S.D.
        • Richard C.
        The interplay of obesity, dyslipidemia and immune dysfunction: a brief overview on pathophysiology, animal models, and nutritional modulation.
        Front Nutr. 2022; 9840209
        • Peng X.
        • Wu H.
        Inflammatory links between hypertriglyceridemia and atherogenesis.
        Curr Atheroscler Rep. 2022; 24: 297-306
        • Pirillo A.
        • Bonacina F.
        • Norata G.D.
        • Catapano A.L.
        The interplay of lipids, lipoproteins, and immunity in atherosclerosis.
        Curr Atheroscler Rep. 2018; 20: 12
        • Otvos J.D.
        • Shalaurova I.
        • Wolak-Dinsmore J.
        • et al.
        GlycA: a composite nuclear magnetic resonance biomarker of systemic inflammation.
        Clin Chem. 2015; 61: 714-723
        • Ballout R.A.
        • Remaley A.T.
        GlycA: a new biomarker for systemic inflammation and cardiovascular disease (CVD) risk assessment.
        J Lab Precis Med. 2020; 5: 17
        • Aquino E.M.
        • Barreto S.M.
        • Bensenor I.M.
        • et al.
        Brazilian longitudinal study of adult health (ELSA-Brasil): objectives and design.
        Am J Epidemiol. 2012; 175: 315-324
        • Schmidt M.I.
        • Duncan B.B.
        • Mill J.G.
        • et al.
        Cohort profile: longitudinal study of adult health (ELSA-Brasil).
        Int J Epidemiol. 2015; 44: 68-75
        • Friedewald W.T.
        • Levy R.I.
        • Fredrickson D.S.
        Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge.
        Clin. Chem. 1972; 18: 499-502
        • Jeyarajah E.J.
        • Cromwell W.C.
        • Otvos J.D.
        Lipoprotein particle analysis by nuclear magnetic resonance spectroscopy.
        Clin Lab Med. 2006; 26: 847-870
        • Aru V.
        • Lam C.
        • Khakimov B.
        • et al.
        Quantification of lipoprotein profiles by nuclear magnetic resonance spectroscopy and multivariate data analysis.
        TrAC. 2017; 94: 210-219
        • Emeasoba E.
        • Ibeson E.
        • Nwosu I.
        • Montemarano N.
        • Shani J.
        • Shetty V.
        Clinical relevance of nuclear magnetic resonance LipoProfile.
        Front Nucl Med. 2022;
      1. WHO Guidelines on Physical Activity and Sedentary Behaviour.
        World Health Organization, Geneva2020
        • Matthews D.R.
        • Hosker J.P.
        • Rudenski A.S.
        • Naylor B.A.
        • Treacher D.F.
        • Turner R.C.
        Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man.
        Diabetologia. 1985; 28: 412-419
      2. The jamovi project (2021). jamovi (Version 2.2) [Computer Software]. Retrieved from

        • Patil I.
        Visualizations with statistical details: the 'ggstatsplot' approach.
        J. Open Source Softw. 2021; 6: 3167
        • den Engelsen C.
        • Koekkoek P.S.
        • Gorter K.J.
        • van den Donk M.
        • Salomé P.L.
        • Rutten G.E.
        High-sensitivity C-reactive protein to detect metabolic syndrome in a centrally obese population: a cross-sectional analysis.
        Cardiovasc Diabetol. 2012; 11: 25
        • Carvalho L.S.F.
        • Benseñor I.M.
        • Nogueira A.C.C.
        • et al.
        Increased particle size of triacylglycerol-enriched remnant lipoproteins, but not their plasma concentration or lipid content, augments risk prediction of incident type 2 diabetes.
        Diabetologia. 2021; 64: 385-396
        • Chung C.P.
        • Ormseth M.J.
        • Connelly M.A.
        • et al.
        GlycA, a novel marker of inflammation, is elevated in systemic lupus erythematosus.
        Lupus. 2016; 25: 296-300
        • Amigó N.
        • Fuertes-Martín R.
        • Malo A.I.
        • et al.
        Glycoprotein profile measured by a 1 H-nuclear magnetic resonance based on approach in patients with diabetes: a new robust method to assess inflammation.
        Life. 2021; 11: 1407
        • Malo A.I.
        • Girona J.
        • Ibarretxe D.
        • et al.
        Serum glycoproteins A and B assessed by 1 H-NMR in familial hypercholesterolemia.
        Atherosclerosis. 2021; 330: 1-7
        • Moreno-Vedia J.
        • Rosales R.
        • Ozcariz E.
        • et al.
        Triglyceride-rich lipoproteins and glycoprotein A and B assessed by 1H-NMR in metabolic-associated fatty liver disease.
        Front Endocrinol (Lausanne). 2021; 12775677
        • Duprez D.A.
        • Otvos J.
        • Sanchez O.A.
        • Mackey R.H.
        • Tracy R.
        • Jacobs D.R.
        Comparison of the predictive value of GlycA and other biomarkers of inflammation for total death, incident cardiovascular events, noncardiovascular and noncancer inflammatory-related events, and total cancer events.
        Clin Chem. 2016; 62: 1020-1031
        • Gruppen E.G.
        • Kunutsor S.K.
        • Kieneker L.M.
        • et al.
        GlycA, a novel pro-inflammatory glycoprotein biomarker is associated with mortality: results from the PREVEND study and meta-analysis.
        J Intern Med. 2019; 286: 596-609
        • Akinkuolie A.O.
        • Glynn R.J.
        • Padmanabhan L.
        • Ridker P.M.
        • Mora S.
        Circulating N-linked glycoprotein side-chain biomarker, rosuvastatin therapy, and incident cardiovascular disease: an analysis from the JUPITER trial.
        J Am Heart Assoc. 2016; 5e003822
        • Otvos J.D.
        • Guyton J.R.
        • Connelly M.A.
        • et al.
        Relations of GlycA and lipoprotein particle subspecies with cardiovascular events and mortality: a post hoc analysis of the AIM-HIGH trial.
        J Clin Lipidol. 2018; 12 (e2): 348-355
        • Olson M.L.
        • Rentería-Mexía A.
        • Connelly M.A.
        • et al.
        Decreased GlycA after lifestyle intervention among obese, prediabetic adolescent Latinos.
        J Clin Lipidol. 2019; 13: 186-193
        • Demidowich A.P.
        • Wolska A.
        • Wilson S.R.
        • et al.
        Colchicine's effects on lipoprotein particle concentrations in adults with metabolic syndrome: a secondary analysis of a randomized controlled trial.
        J Clin Lipidol. 2019; 13 (e2): 1016-1022
        • Levine J.A.
        • Han J.M.
        • Wolska A.
        • et al.
        Associations of GlycA and high-sensitivity C-reactive protein with measures of lipolysis in adults with obesity.
        J Clin Lipidol. 2020; 14: 667-674
        • Ritchie S.C.
        • Würtz P.
        • Nath A.P.
        • et al.
        The biomarker GlycA is associated with chronic inflammation and predicts long-term risk of severe infection.
        Cell Syst. 2015; 1: 293-301
        • Joshi P.H.
        • Khokhar A.A.
        • Massaro J.M.
        • et al.
        Remnant lipoprotein cholesterol and incident coronary heart disease: the Jackson heart and framingham offspring cohort studies.
        J Am Heart Assoc. 2016; 5e002765
        • Bittencourt M.S.
        • Santos R.D.
        • Staniak H.
        • et al.
        Relation of fasting triglyceride-rich lipoprotein cholesterol to coronary artery calcium score (from the ELSA-Brasil Study).
        Am J Cardiol. 2017; 119: 1352-1358
        • Cardoso R.
        • Generoso G.
        • Staniak H.L.
        • et al.
        Predictors of coronary artery calcium incidence and progression: the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil).
        Atherosclerosis. 2020; 309: 8-15
        • Harada P.H.
        • Benseñor I.M.
        • Bittencourt M.S.
        • et al.
        Composite acute phase glycoproteins with coronary artery calcification depends on metabolic syndrome presence - the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil).
        J Cardiol. 2019; 73: 408-415