Background and Aim. Incidence of coronary restenosis after stent placement is high. Our study was going to investigate whether Lp(a) elevation was potential for predicting coronary restenosis and whether the effects of Lp(a) elevation on coronary restenosis were dependent on LDL-C level. Methods and Results. Totally 832 participants eligible for stent placement were enrolled and followed up for monitoring clinical end points. Baseline characteristics were collected. According to the cut point of Lp(a), participants were divided into low Lp(a) group (Lp(a) < 30？mg/dL) and high Lp(a) group (Lp(a) ≥ 30？mg/dL). Furthermore, based on baseline LDL-C level, participants were divided into LDL-C < 1.8？mmol/L and ≥1.8？mmol/L subgroups. Clinical end points including major adverse cardiovascular events (MACE), cardiovascular death, nonfatal myocardial infarction, ischemic stroke, and coronary revascularization (CR) were compared. Patients in high Lp(a) groups more frequently presented with acute coronary syndrome and three vessel stenoses. In subgroup of LDL-C < 1.8？mmol/L, no significant differences of cardiovascular outcomes were found between low and high Lp(a) groups. While in the subgroup of LDL-C ≥ 1.8？mmol/L, incidences of MACE and CR were significantly higher in high Lp(a) group, and odds ratio for CR was 2.05. Conclusion. With baseline LDL-C and Lp(a) elevations, incidence of CR is significantly increased after stent placement. 1. Introduction Dyslipidemias, especially characterized by high serum level of low density lipoprotein-cholesterol (LDL-C), has been well documented as an important risk factor of atherosclerosis and its manifestation of atherosclerotic cardiovascular diseases (CVD) [1]. In the past decades, accumulating evidence from clinical studies firmly demonstrates that LDL-C decreased by lipid-lowering drug, such as HMG-CoA reductase inhibitor (statins), is crucial for reducing the incidence of coronary heart diseases (CHD), ischemic stroke, and peripheral artery diseases [2–5]. However, some epidemiological studies show that, although target LDL-C level has been achieved by statins therapy, residual cardiovascular risk such as restenosis after stent placement in some population groups is still very high [6–8], suggesting that, besides LDL-C, other risk factors could also play a contributory role in the progression and recurrence of CVD, and identifying those potential risk factors would be useful, helpful, and beneficial for further improving cardiovascular outcome. Lipoprotein(a) (Lp(a)), composed of an LDL-C enriched core with one
References
[1]
Z. Reiner, A. L. Catapano, G. De Backer, et al., “ESC/EAS guidelines for the management of dyslipidaemias: the task force for the management of dyslipidaemias of the European Society of Cardiology (ESC) and the European Atherosclerosis Society (EAS),” European Heart Journal, vol. 32, no. 14, pp. 1769–1818, 2011.
[2]
C. M. Gibson, Y. B. Pride, C. P. Hochberg, S. Sloan, M. S. Sabatine, and C. P. Cannon, “Effect of intensive statin therapy on clinical outcomes among patients undergoing percutaneous coronary intervention for acute coronary syndrome. PCI-PROVE IT: A PROVE IT-TIMI 22 (Pravastatin or Atorvastatin Evaluation and Infection Therapy-Thrombolysis In Myocardial Infarction 22) Substudy,” Journal of the American College of Cardiology, vol. 54, no. 24, pp. 2290–2295, 2009.
[3]
J. Armitage, L. Bowman, K. Wallendszus, et al., “Intensive lowering of LDL cholesterol with 80？mg versus 20？mg simvastatin daily in 12,064 survivors of myocardial infarction: a double-blind randomised trial,” The Lancet, vol. 376, no. 9753, pp. 1658–1669, 2010.
[4]
C. Baigent, L. Blackwell, J. Emberson, et al., “Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170,000 participants in 26 randomised trials,” The Lancet, vol. 376, no. 9753, pp. 1670–1681, 2010.
[5]
T. Ohira, P. J. Schreiner, J. D. Morrisett, L. E. Chambless, W. D. Rosamond, and A. R. Folsom, “Lipoprotein(a) and incident ischemic stroke: The Atherosclerosis Risk in Communities (ARIC) study,” Stroke, vol. 37, no. 6, pp. 1407–1412, 2006.
[6]
C. P. Cannon, E. Braunwald, C. H. McCabe et al., “Intensive versus moderate lipid lowering with statins after acute coronary syndromes,” The New England Journal of Medicine, vol. 350, no. 15, pp. 1495–1504, 2004.
[7]
J. C. LaRosa, S. M. Grundy, D. D. Waters et al., “Intensive lipid lowering with atorvastatin in patients with stable coronary disease,” The New England Journal of Medicine, vol. 352, no. 14, pp. 1425–1435, 2005.
[8]
T. R. Pedersen, O. Faergeman, J. J. P. Kastelein et al., “High-dose atorvastatin vs usual-dose simvastatin for secondary prevention after myocardial infarction: The IDEAL study: a randomized controlled trial,” Journal of the American Medical Association, vol. 294, no. 19, pp. 2437–2445, 2005.
[9]
B. G. Nordestgaard, M. J. Chapman, K. Ray et al., “Lipoprotein(a) as a cardiovascular risk factor: current status,” European Heart Journal, vol. 31, no. 23, pp. 2844–2853, 2010.
[10]
S. Tsimikas and J. L. Hall, “Lipoprotein(a) as a potential causal genetic risk factor of cardiovascular disease: a rationale for increased efforts to understand its pathophysiology and develop targeted therapies,” Journal of the American College of Cardiology, vol. 60, no. 8, pp. 716–721, 2012.
[11]
R. Clarke, J. F. Peden, J. C. Hopewell et al., “Genetic variants associated with Lp(a) lipoprotein level and coronary disease,” The New England Journal of Medicine, vol. 361, no. 26, pp. 2518–2528, 2009.
[12]
A. Cai, W. Li, Y. Zhang, Y. Mo, W. Mai, and Y. Zhou, “Lipoprotein(a): a promising marker for residual cardiovascular risk assessment,” Disease Markers, vol. 35, no. 5, pp. 551–559, 2013.
[13]
L. Berglund and R. Ramakrishnan, “Lipoprotein(a): an elusive cardiovascular risk factor,” Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 24, no. 12, pp. 2219–2226, 2004.
[14]
P. R. Kamstrup, “Lipoprotein(a) and ischemic heart disease-A causal association? A review,” Atherosclerosis, vol. 211, no. 1, pp. 15–23, 2010.
[15]
P. R. Kamstrup, M. Benn, A. Tybj？rg-Hansen, and B. G. Nordestgaard, “Extreme lipoprotein(a) levels and risk of myocardial infarction in the general population: The Copenhagen City Heart Study,” Circulation, vol. 117, no. 2, pp. 176–184, 2008.
[16]
G. Luc, J.-M. Bard, D. Arveiler et al., “Lipoprotein (a) as a predictor of coronary heart disease: The PRIME Study,” Atherosclerosis, vol. 163, no. 2, pp. 377–384, 2002.
[17]
J. S. Danik, N. Rifai, J. E. Buring, and P. M. Ridker, “Lipoprotein(a), measured with an assay independent of apolipoprotein(a) isoform size, and risk of future cardiovascular events among initially healthy women,” Journal of the American Medical Association, vol. 296, no. 11, pp. 1363–1370, 2006.
[18]
B. Cantin, F. Gagnon, S. Moorjani et al., “Is lipoprotein(a) an independent risk factor for ischemic heart disease in men? The Quebec cardiovascular study,” Journal of the American College of Cardiology, vol. 31, no. 3, pp. 519–525, 1998.
[19]
J. Danesh, R. Collins, and R. Peto, “Lipoprotein(a) and coronary heart disease: meta-analysis of prospective studies,” Circulation, vol. 102, no. 10, pp. 1082–1085, 2000.
[20]
Y. Momiyama, R. Ohmori, Z. A. Fayad et al., “Associations between serum lipoprotein(a) levels and the severity of coronary and aortic atherosclerosis,” Atherosclerosis, vol. 222, no. 1, pp. 241–244, 2012.
[21]
S. J. Nicholls, W. H. W. Tang, H. Scoffone et al., “Lipoprotein(a) levels and long-term cardiovascular risk in the contemporary era of statin therapy,” Journal of Lipid Research, vol. 51, no. 10, pp. 3055–3061, 2010.
[22]
S. S. Virani, A. Brautbar, B. C. Davis et al., “Associations between lipoprotein(a) levels and cardiovascular outcomes in black and white subjects: The Atherosclerosis Risk in Communities (ARIC) study,” Circulation, vol. 125, no. 2, pp. 241–249, 2012.
[23]
S. Tsimikas and J. L. Witztum, “The role of oxidized phospholipids in mediating lipoprotein(a) atherogenicity,” Current Opinion in Lipidology, vol. 19, no. 4, pp. 369–377, 2008.
[24]
J. Hoover-Plow and M. Huang, “Lipoprotein(a) metabolism: potential sites for therapeutic targets,” Metabolism, vol. 62, no. 4, pp. 479–491, 2013.
[25]
D. J. Grainger, P. R. Kemp, A. C. Liu, R. M. Lawn, and J. C. Metcalfe, “Activation of transforming growth factor-β is inhibited in transgenic apolipoprotein(a) mice,” Nature, vol. 370, no. 6489, pp. 460–462, 1994.
[26]
F. Kronenberg, M. F. Kronenberg, S. Kiechl et al., “Role of lipoprotein(a) and apolipoprotein(a) phenotype in atherogenesis: Prospective results from the bruneck study,” Circulation, vol. 100, no. 11, pp. 1154–1160, 1999.
[27]
J. D. Spence and M. Koschinsky, “Mechanisms of lipoprotein(a) pathogenicity: prothrombotic, proatherosclerotic, or both,” Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 32, no. 7, pp. 1550–1551, 2012.
