IJCA-18472; No of Pages 2 International Journal of Cardiology xxx (2014) xxx–xxx

Contents lists available at ScienceDirect

International Journal of Cardiology journal homepage: www.elsevier.com/locate/ijcard

Letter to the Editor

Elevated concentrations of high-density lipoprotein cholesterol and cardiovascular risk paradox in patients with coronary heart disease and the equivalents Gen-Min Lin a,b,⁎, Yi-Hwei Li b, Chih-Lu Han c a b c

Department of Medicine, Hualien Armed Forces General Hospital, Hualien, Taiwan Department of Public Health, Tzu-Chi University, Hualien, Taiwan Department of Medicine, Taipei Veterans General Hospital, Taoyuan Branch, Taiwan

a r t i c l e

i n f o

Article history: Received 8 June 2014 Accepted 27 July 2014 Available online xxxx Keywords: High-density lipoprotein cholesterol Coronary heart disease Apoprotein A-I

To the Editor, As early as 1951, Barr et al. described that healthy men had higher concentrations of high-density lipoprotein cholesterol (HDL-C) as compared to those with coronary heart disease (CHD) in a cross-sectional study [1]. Subsequently in 1966, Gofman et al. uncovered that the risk of CHD was inversely related to baseline HDL-C concentrations in two prospective community-based studies including Framingham and Livermore studies [2]. Since then, a number of epidemiologic studies found similar results and HDL-C has become a well-known prognostic factor to CHD among general populations. Nowadays, elevation of HDL-C concentrations by lifestyle modifications including diet and exercise is widely encouraged and has been considered a part of the primary prevention of CHD. Many clinical trials were carried out to evaluate the cardiac protective effect of raising HDL-C in addition to lowering low-density lipoprotein cholesterol (LDL-C) among patients with established CHD and the equivalents by medications. These trials mainly included combined drug therapy such as ezetimibe or niacin plus statin, and mono-

⁎ Corresponding author at: Hualien Armed Forces General Hospital, No. 163, Jiali Rd., Xincheng Township, Hualien County 97144, Hualien, Taiwan. Tel.: +886 3 826 0601. E-mail address: [email protected] (G.-M. Lin).

therapy with new cholesteryl ester transfer protein (CETP)-inhibiting drugs [3–6]. Although atherosclerotic plaque regression was observed in dual lipid-lowering therapy, the benefits to reduce vascular events by raising HDL-C concentration were still lacking [5]. As is known, some negative results in clinical trials were caused by direct adverse effects of drugs to the cardiovascular system [4]. In addition, CETP inhibitors were known to have an effect on the component and function of HDL particles that increase HDL-C by modulation of the catabolism of HDL-C. Therefore, a concern has been focused on the effectiveness of the secondary prevention by increasing “dysfunctional HDL-C” among patients with CHD and the risk equivalents. Recently, Angeloni et al. assessed the protective effect of HDL-C in a large prospective cohort of patients with CHD undergoing coronary artery bypass grafting (CABG) [6]. Since HDL particles from patients with CHD have been found with endothelial dysfunction and less effect of anti-inflammation, their findings confirmed that the protective effect of HDL-C is lost in the secondary prevention of CHD [7]. In fact, Sbrana et al. has demonstrated a U-shaped relationship between HDL-C and acute cardiac events in a chronic CHD cohort [8]. In addition, we also found that higher HDL-C could predict higher survival rate in normal and underweight patients but did not alter the risk of mortality in overweight and obese patients in an Asian CHD cohort [9]. Aside from those with CHD, HDL-C is not associated with cardiovascular events in the population with the CHD equivalents including insulin dependent diabetes mellitus, end-stage renal disease, heavy coronary artery calcification, inflammation, and on potent statin therapy [10–14]. In some populations, a sex difference was present that the HDL-C paradox is predominantly seen in men rather than women [13,14]. To our best knowledge, the athero-protective effect of HDL-C is related to the activity of reverse cholesterol transport by which peripheral cholesterol is returned to the liver. Notably, the cholesterol-poor HDL particles that are produced by the overexpression of apoprotein A-I in animal models, or that have been infused into subjects as reconstituted HDL particles, are better cholesterol acceptors compared with the cholesterol-enriched HDL particles produced after niacin or CETP inhibitor treatment [15]. In addition, Huang et al. found that the oxidation of either apoprotein A-I or HDL particles by myeloperoxidase may impair their cholesterol acceptor function and elevated oxidized Trp72 apoprotein A-I concentrations in subjects were associated with increased CHD risk [16]. Therefore, as was described in our study [8],

http://dx.doi.org/10.1016/j.ijcard.2014.07.153 0167-5273/© 2014 Elsevier Ireland Ltd. All rights reserved.

Please cite this article as: Lin G-M, et al, Elevated concentrations of high-density lipoprotein cholesterol and cardiovascular risk paradox in patients with coronary heart di..., Int J Cardiol (2014), http://dx.doi.org/10.1016/j.ijcard.2014.07.153

2

G.-M. Lin et al. / International Journal of Cardiology xxx (2014) xxx–xxx

HDL particles may be dysfunctional and HDL-C was not associated with the risk of mortality in obese CHD patients. In contrast, lower HDL-C may reflect malnutrition in normal or underweight patients, probably leading to higher mortality risk. Of interest, Corsetti et al. identified a subgroup of men at high-risk for incident CHD with high HDL-C and high C-reactive protein in the prevention of renal and vascular end-stage disease (PREVEND) study [13]. The study concluded that high HDL-C associated risk likely relates to impaired HDL particle remodeling in the setting of inflammation. However, the result seems contrary to the Justification for the Use of Statins in Primary Prevention: An Intervention Trial Evaluating Rosuvastatin (JUPITER) trial that HDL-C concentrations were strongly predictive of vascular events in the placebo cohort with C-reactive protein greater than 2 mg/L [14]. The conflicting results between PREVEND and JUPITER may be caused by different risk stratifications of C-reactive protein. In the future, the relationship between HDL-C and CHD can be explored in some ways. First, HDL-C particle numbers measured by nuclear magnetic resonance spectroscopy are found to be more related to incident CHD than HDL-C in the general population and those on potent statin treatment [17,18]. Second, further studies should clarify the mediators of higher HDL-C paradox in specific conditions such as a sex difference, and the status of obesity and inflammation along with the development of new drugs in order to elevate functional HDL-C among patients with CHD and the risk equivalents. Conflict of interest The authors declare no conflict of interests and no financial support from any institutes. References [1] Barr DP, Russ EM, Eder HA. Protein–lipid relationship in human plasma. II. In atherosclerosis and related conditions. Am J Med 1951;11:480. [2] Gofman JW, Young W, Tandy R. Ischemic heart disease, atherosclerosis and longevity. Circulation 1966;34:679–97.

[3] Lüscher TF, Taddei S, Kaski JC, et al. Vascular effects and safety of dalcetrapib in patients with or at risk of coronary heart disease: the dal-VESSEL randomized clinical trial. Eur Heart J 2012;33:857–65. [4] Nicholls SJ, Brewer HB, Kastelein JJ, et al. Effects of the CETP inhibitor evacetrapib administered as monotherapy or in combination with statins on HDL and LDL cholesterol: a randomized controlled trial. JAMA 2011;306:2099–109. [5] Duivenvoorden R, Fayad ZA. Safety of CETP inhibition. Curr Opin Lipidol 2012;23: 518–24. [6] Gadi R, Amanullah A, Figueredo VM. HDL-C: does it matter? An update on novel HDL-directed pharmaco-therapeutic strategies. Int J Cardiol 2013;167:646–55. [7] Angeloni E, Paneni F, Landmesser U, et al. Lack of protective role of HDL-C in patients with coronary artery disease undergoing elective coronary artery bypass grafting. Eur Heart J 2013;34:3557–62. [8] Sbrana F, Puntoni M, Bigazzi F, et al. High density lipoprotein cholesterol in coronary artery disease: when higher means later. J Atheroscler Thromb 2013;20:23–31. [9] Lin GM, Li YH, Lin CL, Wang JH, Han CL. Low high-density lipoprotein cholesterol and low/normal body mass index are associated with increased mortality in coronary artery disease patients in Taiwan. Circ J 2013;77:2079–87. [10] Reckless JP, Betteridge DJ, Wu P, Payne B, Galton DJ. High-density and low-density lipoproteins and prevalence of vascular disease in diabetes mellitus. Br Med J 1978;1:883–6. [11] Kessler M, Zannad F, Lehert P, et al. Predictors of cardiovascular events in patients with end-stage renal disease: an analysis from the Fosinopril in dialysis study. Nephrol Dial Transplant 2007;22:3573–9. [12] Orakzai SH, Nasir K, Blaha M, Blumenthal RS, Raggi P. Non-HDL cholesterol is strongly associated with coronary artery calcification in asymptomatic individuals. Atherosclerosis 2009;202:289–95. [13] Corsetti JP, Gansevoort RT, Sparks CE, Dullaart RP. Inflammation reduces HDL protection against primary cardiac risk. Eur J Clin Invest 2010;40:483–9. [14] Ridker PM, Genest J, Boekholdt SM, et al. HDL cholesterol and residual risk of first cardiovascular events after treatment with potent statin therapy: an analysis from the JUPITER trial. Lancet 2010;376:333–9. [15] Rader DJ, Tall AR. The not-so-simple HDL story: Is it time to revise the HDL cholesterol hypothesis? Nat Med 2012;18:1344–6. [16] Huang Y, DiDonato JA, Levison BS, et al. An abundant dysfunctional apolipoprotein A1 in human atheroma. Nat Med 2014;20:193–203. [17] Mackey RH, Greenland P, Goff Jr DC, Lloyd-Jones D, Sibley CT, Mora S. High-density lipoprotein cholesterol and particle concentrations, carotid atherosclerosis, and coronary events: MESA (multi-ethnic study of atherosclerosis). J Am Coll Cardiol 2012; 60:508–16. [18] Mora S, Glynn RJ, Ridker PM. High-density lipoprotein cholesterol, size, particle number, and residual vascular risk after potent statin therapy. High-density lipoprotein cholesterol, size, particle number, and residual vascular risk after potent statin therapy. Circulation 2013;128:1189–97.

Please cite this article as: Lin G-M, et al, Elevated concentrations of high-density lipoprotein cholesterol and cardiovascular risk paradox in patients with coronary heart di..., Int J Cardiol (2014), http://dx.doi.org/10.1016/j.ijcard.2014.07.153

Elevated concentrations of high-density lipoprotein cholesterol and cardiovascular risk paradox in patients with coronary heart disease and the equivalents.

Elevated concentrations of high-density lipoprotein cholesterol and cardiovascular risk paradox in patients with coronary heart disease and the equivalents. - PDF Download Free
171KB Sizes 0 Downloads 4 Views