TY - JOUR
T1 - Impaired HDL metabolism links glyca, a novel inflammatory marker, with incident cardiovascular events
AU - Riggs, Kayla A.
AU - Joshi, Parag H.
AU - Khera, Amit
AU - Singh, Kavisha
AU - Akinmolayemi, Oludamilola
AU - Ayers, Colby R.
AU - Rohatgi, Anand
N1 - Publisher Copyright:
© 2019 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2019/12
Y1 - 2019/12
N2 - High-density lipoproteins (HDL) exert anti-atherosclerotic effects via reverse cholesterol transport, yet this salutary property is impaired in the setting of inflammation. GlycA, a novel integrated glycosylation marker of five acute phase reactants, is linked to cardiovascular (CV) events. We assessed the hypothesis that GlycA is associated with measures of impaired HDL function and that dysfunctional HDL may contribute to the association between GlycA and incident CV events. Baseline measurements of HDL cholesterol (HDL-C), HDL particle concentration (HDLP), apoliprotein A1 (Apo A1), cholesterol efflux capacity, GlycA and high-sensitivity C-reactive protein (hs-CRP) were obtained from the Dallas Heart Study, a multi-ethnic cohort of 2643 adults (median 43 years old; 56% women, 50% black) without cardiovascular disease (CVD). GlycA was derived from nuclear magnetic resonance imaging. Participants were followed for first nonfatal MI, nonfatal stroke, coronary revascularization, or CV death over a median of 12.4 years (n = 197). The correlation between GlycA and hs-CRP was 0.58 (p < 0.0001). In multivariate models with HDL-C, GlycA was directly associated with HDL-P and Apo A1 and inversely associated with cholesterol efflux (standardized beta estimates: 0.08, 0.29,-0.06, respectively; all p ≤ 0.0004) GlycA was directly associated with incident CV events (adjusted hazard ratio (HR) for Q4 vs. Q1: 3.33, 95% confidence interval (CI) 1.99, 5.57). Adjustment for cholesterol efflux mildly attenuated this association (HR for Q4 vs. Q1: 3.00, 95% CI 1.75 to 5.13). In a multi-ethnic cohort, worsening inflammation, as reflected by higher GlycA levels, is associated with higher HDL-P and lower cholesterol efflux. Impaired cholesterol efflux likely explains some of the association between GlycA and incident CV events. Further studies are warranted to investigate the impact of inflammation on HDL function and CV disease.
AB - High-density lipoproteins (HDL) exert anti-atherosclerotic effects via reverse cholesterol transport, yet this salutary property is impaired in the setting of inflammation. GlycA, a novel integrated glycosylation marker of five acute phase reactants, is linked to cardiovascular (CV) events. We assessed the hypothesis that GlycA is associated with measures of impaired HDL function and that dysfunctional HDL may contribute to the association between GlycA and incident CV events. Baseline measurements of HDL cholesterol (HDL-C), HDL particle concentration (HDLP), apoliprotein A1 (Apo A1), cholesterol efflux capacity, GlycA and high-sensitivity C-reactive protein (hs-CRP) were obtained from the Dallas Heart Study, a multi-ethnic cohort of 2643 adults (median 43 years old; 56% women, 50% black) without cardiovascular disease (CVD). GlycA was derived from nuclear magnetic resonance imaging. Participants were followed for first nonfatal MI, nonfatal stroke, coronary revascularization, or CV death over a median of 12.4 years (n = 197). The correlation between GlycA and hs-CRP was 0.58 (p < 0.0001). In multivariate models with HDL-C, GlycA was directly associated with HDL-P and Apo A1 and inversely associated with cholesterol efflux (standardized beta estimates: 0.08, 0.29,-0.06, respectively; all p ≤ 0.0004) GlycA was directly associated with incident CV events (adjusted hazard ratio (HR) for Q4 vs. Q1: 3.33, 95% confidence interval (CI) 1.99, 5.57). Adjustment for cholesterol efflux mildly attenuated this association (HR for Q4 vs. Q1: 3.00, 95% CI 1.75 to 5.13). In a multi-ethnic cohort, worsening inflammation, as reflected by higher GlycA levels, is associated with higher HDL-P and lower cholesterol efflux. Impaired cholesterol efflux likely explains some of the association between GlycA and incident CV events. Further studies are warranted to investigate the impact of inflammation on HDL function and CV disease.
KW - Atherosclerotic cardiovascular disease (ASCVD)
KW - Cardiovascular events
KW - GlycA
KW - HDL
KW - Inflammation
KW - Lipids
UR - http://www.scopus.com/inward/record.url?scp=85090098455&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85090098455&partnerID=8YFLogxK
U2 - 10.3390/jcm8122137
DO - 10.3390/jcm8122137
M3 - Article
C2 - 31817053
AN - SCOPUS:85090098455
SN - 2077-0383
VL - 8
JO - Journal of Clinical Medicine
JF - Journal of Clinical Medicine
IS - 12
M1 - 2137
ER -