High-density lipoprotein cholesterol efflux capacity is inversely associated with cardiovascular risk: a systematic review and meta-analysis
Tóm tắt
A low plasma level of high-density lipoprotein (HDL) cholesterol (HDL-C) is associated with cardiovascular risk. A key cardioprotective property of HDL is cholesterol efflux capacity (CEC), the ability of HDL to accept cholesterol from macrophages. In this study, we aimed to identify the predictive value of CEC for cardiovascular risk. The relative risks (RRs) and 95% confidence intervals (CIs) were pooled to analyze the association between CEC and the incidence of cardiovascular events and all-cause mortality. The odds ratios (ORs) and 95% CIs were pooled to estimate the association of CEC and the prevalence of cardiovascular events. A total of 15 studies were included. Results showed that the highest CEC was significantly associated with a reduced risk of cardiovascular events incidents compared to the lowest CEC (RR, 0.56; 95% CI, 0.37 to 0.85; I
2, 89%); the pooled RR of cardiovascular risk for per unit SD increase was 0.87 (95% CI, 0.73 to 1.04; I
2, 67%). Dose-response curve indicated that cardiovascular risk decreased by 39% (RR, 0.61; 95% CI, 0.51 to 0.74) for per unit CEC increase. Similarly, an inverse association was observed between CEC and the prevalence of cardiovascular events (highest vs. lowest, OR, 0.30; 95% CI, 0.17 to 0.5; I
2 = 63%; per unit SD increase, OR, 0.94; 95% CI, 0.90 to 0.98; I
2 = 71%). However, based on the current data, CEC was not significantly associated with all-cause mortality. Findings from this meta-analysis suggest that HDL-mediated CEC is inversely associated with cardiovascular risk, which appears to be independent of HDL concentration. The growing understanding of CEC and its role in cardiovascular risk decrease may improve the accuracy of cardiovascular risk prediction and also open important avenues to develop novel therapeutic targeting HDL metabolism.
Tài liệu tham khảo
Stone NJ, Robinson JG, Lichtenstein AH, Bairey MC, Blum CB, Eckel RH, et al. 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation. 2014;129(25 Suppl 2):S1–45.
Landray MJ, Haynes R, Hopewell JC, Parish S, Aung T, Tomson J, et al. Effects of extended-release niacin with laropiprant in high-risk patients. N Engl J Med. 2014;371(3):203–12.
Schwartz GG, Olsson AG, Abt M, Ballantyne CM, Barter PJ, Brumm J, et al. Effects of dalcetrapib in patients with a recent acute coronary syndrome. N Engl J Med. 2012;367(22):2089–99.
Boden WE, Probstfield JL, Anderson T, Chaitman BR, Desvignes-Nickens P, Koprowicz K, et al. Niacin in patients with low HDL cholesterol levels receiving intensive statin therapy. N Engl J Med. 2011;365(24):2255–67.
Barter PJ, Caulfield M, Eriksson M, Grundy SM, Kastelein JJ, Komajda M, et al. Effects of torcetrapib in patients at high risk for coronary events. N Engl J Med. 2007;357(21):2109–22.
Voight BF, Peloso GM, Orho-Melander M, Frikke-Schmidt R, Barbalic M, Jensen MK, et al. Plasma HDL cholesterol and risk of myocardial infarction: a mendelian randomisation study. Lancet. 2012;380(9841):572–80.
Anastasius M, Kockx M, Jessup W, Sullivan D, Rye KA, Kritharides L. Cholesterol efflux capacity: an introduction for clinicians. Am Heart J. 2016;180:54–63.
Rosenson RS, Brewer HJ, Chapman MJ, Fazio S, Hussain MM, Kontush A, et al. HDL measures, particle heterogeneity, proposed nomenclature, and relation to atherosclerotic cardiovascular events. Clin Chem. 2011;57(3):392–410.
Rosenson RS, Brewer HB, Davidson WS, Fayad ZA, Fuster V, Goldstein J, et al. Cholesterol efflux and atheroprotection: advancing the concept of reverse cholesterol transport. Circulation. 2012;125(15):1905–19.
Moore KJ, Tabas I. Macrophages in the pathogenesis of atherosclerosis. Cell. 2011;145(3):341–55.
Moore KJ, Sheedy FJ, Fisher EA. Macrophages in atherosclerosis: a dynamic balance. Nat Rev Immunol. 2013;13(10):709–21.
Rohatgi A, Khera A, Berry JD, Givens EG, Ayers CR, Wedin KE, et al. HDL cholesterol efflux capacity and incident cardiovascular events. N Engl J Med. 2014;371(25):2383–93.
Greenland S, Longnecker MP. Methods for trend estimation from summarized dose-response data, with applications to meta-analysis. Am J Epidemiol. 1992;135(11):1301–9.
Greenland S. Quantitative methods in the review of epidemiologic literature. Epidemiol Rev. 1987;9:1–30.
Higgins JP, Thompson SG. Quantifying heterogeneity in a meta-analysis. Stat Med. 2002;21(11):1539–58.
Begg CB, Mazumdar M. Operating characteristics of a rank correlation test for publication bias. Biometrics. 1994;50(4):1088–101.
Egger M, Davey SG, Schneider M, Minder C. Bias in meta-analysis detected by a simple, graphical test. BMJ. 1997;315(7109):629–34.
Vaisar T, Pennathur S, Green PS, Gharib SA, Hoofnagle AN, Cheung MC, et al. Shotgun proteomics implicates protease inhibition and complement activation in the antiinflammatory properties of HDL. J Clin Invest. 2007;117(3):746–56.
Davidson WS, Silva RA, Chantepie S, Lagor WR, Chapman MJ, Kontush A. Proteomic analysis of defined HDL subpopulations reveals particle-specific protein clusters: relevance to antioxidative function. Arterioscler Thromb Vasc Biol. 2009;29(6):870–6.
de la Llera-Moya M, Drazul-Schrader D, Asztalos BF, Cuchel M, Rader DJ, Rothblat GH. The ability to promote efflux via ABCA1 determines the capacity of serum specimens with similar high-density lipoprotein cholesterol to remove cholesterol from macrophages. Arterioscler Thromb Vasc Biol. 2010;30(4):796–801.
Hutchins PM, Heinecke JW. Cholesterol efflux capacity, macrophage reverse cholesterol transport and cardioprotective HDL. Curr Opin Lipidol. 2015;26(5):388–93.
Rohatgi A. High-density lipoprotein function measurement in human studies: focus on cholesterol efflux capacity. Prog Cardiovasc Dis. 2015;58(1):32–40.
Blazek A, Rutsky J, Osei K, Maiseyeu A, Rajagopalan S. Exercise-mediated changes in high-density lipoprotein: impact on form and function. Am Heart J. 2013;166(3):392–400.
Rader DJ, Alexander ET, Weibel GL, Billheimer J, Rothblat GH. The role of reverse cholesterol transport in animals and humans and relationship to atherosclerosis. J Lipid Res. 2009;50(Suppl):S189–94.
Mineo C, Shaul PW. Regulation of signal transduction by HDL. J Lipid Res. 2013;54(9):2315–24.
Rader DJ, Hovingh GK. HDL and cardiovascular disease. Lancet. 2014;384(9943):618–25.
Weichhart T, Kopecky C, Kubicek M, Haidinger M, Doller D, Katholnig K, et al. Serum amyloid A in uremic HDL promotes inflammation. J Am Soc Nephrol. 2012;23(5):934–47.
Gansevoort RT, Correa-Rotter R, Hemmelgarn BR, Jafar TH, Heerspink HJ, Mann JF, et al. Chronic kidney disease and cardiovascular risk: epidemiology, mechanisms, and prevention. Lancet. 2013;382(9889):339–52.
Khera AV, Cuchel M, de la Llera-Moya M, Rodrigues A, Burke MF, Jafri K, et al. Cholesterol efflux capacity, high-density lipoprotein function, and atherosclerosis. N Engl J Med. 2011;364(2):127–35.
Bauer L, Kern S, Rogacev KS, Emrich IE, Zawada A, Fliser D, et al. HDL cholesterol efflux capacity and cardiovascular events in patients with chronic kidney disease. J Am Coll Cardiol. 2017;69(2):246–7.
Tejera-Segura B, Macia-Diaz M, Machado JD, de Vera-Gonzalez A, Garcia-Dopico JA, Olmos JM, et al. HDL cholesterol efflux capacity in rheumatoid arthritis patients: contributing factors and relationship with subclinical atherosclerosis. Arthritis Res Ther. 2017;19(1):113.
Kopecky C, Ebtehaj S, Genser B, Drechsler C, Krane V, Antlanger M, et al. HDL cholesterol efflux does not predict cardiovascular risk in hemodialysis patients. J Am Soc Nephrol. 2016;3(28):769–75.
Javaheri A, Molina M, Zamani P, Rodrigues A, Novak E, Chambers S, et al. Cholesterol efflux capacity of high-density lipoprotein correlates with survival and allograft vasculopathy in cardiac transplant recipients. J Heart Lung Transplant. 2016;11(35):1295–302.
Mody P, Joshi PH, Khera A, Ayers CR, Rohatgi A. Beyond coronary calcification, family history, and C-reactive protein: cholesterol efflux capacity and cardiovascular risk prediction. J Am Coll Cardiol. 2016;67(21):2480–7.
Liu C, Zhang Y, Ding D, Li X, Yang Y, Li Q, et al. Cholesterol efflux capacity is an independent predictor of all-cause and cardiovascular mortality in patients with coronary artery disease: a prospective cohort study. Atherosclerosis. 2016;249:116–24.
Zhang J, Xu J, Wang J, Wu C, Xu Y, Wang Y, et al. Prognostic usefulness of serum cholesterol efflux capacity in patients with coronary artery disease. Am J Cardiol. 2016;117(4):508–14.
Ogura M, Hori M, Harada-Shiba M. Association between cholesterol efflux capacity and atherosclerotic cardiovascular disease in patients with familial hypercholesterolemia. Arterioscler Thromb Vasc Biol. 2016;36(1):181–8.
Annema W, Dikkers A, de Boer JF, Dullaart RP, Sanders JS, Bakker SJ, et al. HDL cholesterol efflux predicts graft failure in renal transplant recipients. J Am Soc Nephrol. 2016;27(2):595–603.
Ishikawa T, Ayaori M, Uto-Kondo H, Nakajima T, Mutoh M, Ikewaki K. High-density lipoprotein cholesterol efflux capacity as a relevant predictor of atherosclerotic coronary disease. Atherosclerosis. 2015;242(1):318–22.
Saleheen D, Scott R, Javad S, Zhao W, Rodrigues A, Picataggi A, et al. Association of HDL cholesterol efflux capacity with incident coronary heart disease events: a prospective case-control study. Lancet Diabetes Endocrinol. 2015;3(7):507–13.
Li XM, Tang WHW, Mosior MK, Huang Y, Wu Y, Matter W, et al. Paradoxical association of enhanced cholesterol efflux with increased incident cardiovascular risks. Arterioscler Thromb Vasc Biol. 2013;33(7):1696–705.