TY - JOUR

T1 - Protein-defined subspecies of HDLs (high-density lipoproteins) and differential risk of coronary heart disease in 4 prospective studies

AU - Sacks, Frank M.

AU - Liang, Liang

AU - Furtado, Jeremy D.

AU - Cai, Tianxi

AU - Sean Davidson, W.

AU - He, Zeling

AU - McClelland, Robyn L.

AU - Rimm, Eric B.

AU - Jensen, Majken K.

PY - 2020

Y1 - 2020

N2 - OBJECTIVE: HDL (high-density lipoprotein) contains functional proteins that define single subspecies, each comprising 1% to 12% of the total HDL. We studied the differential association with coronary heart disease (CHD) of 15 such subspecies. APPROACH AND RESULTS: We measured plasma apoA1 (apolipoprotein A1) concentrations of 15 protein-defined HDL subspecies in 4 US-based prospective studies. Among participants without CVD at baseline, 932 developed CHD during 10 to 25 years. They were matched 1:1 to controls who did not experience CHD. In each cohort, hazard ratios for each subspecies were computed by conditional logistic regression and combined by meta-analysis. Higher levels of HDL subspecies containing alpha-2 macroglobulin, CoC3 (complement C3), HP (haptoglobin), or PLMG (plasminogen) were associated with higher relative risk compared with the HDL counterpart lacking the defining protein (hazard ratio range, 0.96-1.11 per 1 SD increase versus 0.73-0.81, respectively; P for heterogeneity <0.05). In contrast, HDL containing apoC1 or apoE were associated with lower relative risk compared with the counterpart (hazard ratio, 0.74; P=0.002 and 0.77, P=0.001, respectively). CONCLUSIONS: Several subspecies of HDL defined by single proteins that are involved in thrombosis, inflammation, immunity, and lipid metabolism are found in small fractions of total HDL and are associated with higher relative risk of CHD compared with HDL that lacks the defining protein. In contrast, HDL containing apoC1 or apoE are robustly associated with lower risk. The balance between beneficial and harmful subspecies in a person's HDL sample may determine the risk of CHD pertaining to HDL and paths to treatment.

AB - OBJECTIVE: HDL (high-density lipoprotein) contains functional proteins that define single subspecies, each comprising 1% to 12% of the total HDL. We studied the differential association with coronary heart disease (CHD) of 15 such subspecies. APPROACH AND RESULTS: We measured plasma apoA1 (apolipoprotein A1) concentrations of 15 protein-defined HDL subspecies in 4 US-based prospective studies. Among participants without CVD at baseline, 932 developed CHD during 10 to 25 years. They were matched 1:1 to controls who did not experience CHD. In each cohort, hazard ratios for each subspecies were computed by conditional logistic regression and combined by meta-analysis. Higher levels of HDL subspecies containing alpha-2 macroglobulin, CoC3 (complement C3), HP (haptoglobin), or PLMG (plasminogen) were associated with higher relative risk compared with the HDL counterpart lacking the defining protein (hazard ratio range, 0.96-1.11 per 1 SD increase versus 0.73-0.81, respectively; P for heterogeneity <0.05). In contrast, HDL containing apoC1 or apoE were associated with lower relative risk compared with the counterpart (hazard ratio, 0.74; P=0.002 and 0.77, P=0.001, respectively). CONCLUSIONS: Several subspecies of HDL defined by single proteins that are involved in thrombosis, inflammation, immunity, and lipid metabolism are found in small fractions of total HDL and are associated with higher relative risk of CHD compared with HDL that lacks the defining protein. In contrast, HDL containing apoC1 or apoE are robustly associated with lower risk. The balance between beneficial and harmful subspecies in a person's HDL sample may determine the risk of CHD pertaining to HDL and paths to treatment.

KW - ApoC1

KW - Apolipoproteins

KW - Coronary heart disease

KW - Haptoglobins

KW - HDL

KW - Plasminogen

KW - Prospective studies

U2 - 10.1161/ATVBAHA.120.314609

DO - 10.1161/ATVBAHA.120.314609

M3 - Journal article

C2 - 32907368

AN - SCOPUS:85094219762

VL - 40

SP - 2714

EP - 2727

JO - Arteriosclerosis, Thrombosis, and Vascular Biology

JF - Arteriosclerosis, Thrombosis, and Vascular Biology

SN - 1079-5642

IS - 11

ER -