International Journal of Cardiology 186 (2015) 5–6
Contents lists available at ScienceDirect
International Journal of Cardiology journal homepage: www.elsevier.com/locate/ijcard
Letter to the Editor
Variation of lipoprotein(a) plasma levels after premature myocardial infarction Georg Goliasch a,⁎, Franz Wiesbauer a, Hermann Blessberger a,b, Gerald Maurer a, Kurt Derfler c, Walter S. Speidl a,⁎ a b c
Department of Internal Medicine II, Medical University of Vienna, Austria Linz General Hospital, Johannes Kepler University School of Medicine, Department of Internal Medicine I — Cardiology, Linz, Austria Department of Internal Medicine III, Division of Nephrology, Medical University of Vienna, Austria
a r t i c l e
i n f o
Article history: Received 18 February 2015 Accepted 17 March 2015 Available online 18 March 2015 Keywords: Lipoprotein a Lipids Secondary prevention Premature myocardial infarction Acute coronary syndrome
Myocardial infarction (MI) in very young individuals (≤ 40 years) represents a rare disease with an unfavorable prognosis. Therefore, aggressive treatment of all modifiable risk factors should be advised. Elevated levels of lipoprotein(a) [Lp(a)] are an independent risk factor for coronary artery disease and the development of acute coronary events [1,2]. Increased plasma concentrations of Lp(a) have been associated with increased risk for premature myocardial infarction [3,4] and current guidelines recommend screening for elevated Lp(a) in selected patient groups like premature coronary heart disease [5]. Until now, treatment of elevated levels of Lp(a) has been challenging. Medical treatment with niacin shows only moderate effects with major side effects and lipid apheresis as the most effective therapeutic option is costly and time consuming. Recent studies have shown that Lp(a) can be substantially lowered by treatment with inhibitors of proprotein convertase subtilisin/kexin type 9 (PCSK9) [6–8]. Plasma levels of Lp(a) are to a large extent genetically
⁎ Corresponding authors at: Department of Internal Medicine II, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Wien, Austria. E-mail addresses: [email protected] (G. Goliasch), [email protected] (W.S. Speidl).
http://dx.doi.org/10.1016/j.ijcard.2015.03.211 0167-5273/© 2015 Elsevier Ireland Ltd. All rights reserved.
determined via variation in the apolipoprotein(a) gene and remain stable with little variation over time. However, it is not known whether Lp(a) levels in the post-MI period are representative for the stable phase of the disease in these young patients. This could lead to an over- or underestimation of Lp(a) plasma levels during the index hospitalization leading to a possible overtreatment or restraint of a potentially beneficial treatment. We enrolled MI survivors (≤ 40 years) and measured plasma levels of Lp(a) (Roche Diagnostics, Basel, Switzerland; upper normal limit 75 nmol/L) in 40 patients during the postinfarction period (3.2 ± 2.1 days post-MI) and after one year follow-up in a stable phase of the disease. The study is in line with the Declaration of Helsinki and was approved by the Ethics Committee of the Medical University of Vienna. The exact study protocol has been previously described in detail [9]. Mean age of our patients was 36 ± 4 years, 93% were male, 83% were active smokers and 35% had a positive family history of MI. All patients were treated with statins but no patients received niacin or underwent lipid apheresis. Lp(a) significantly increased from 34.0 ± 46.3 nmol/L in the post-MI period to 48.4 ± 67.8 nmol/L (p = 0.013; Wilcoxon signed-rank test) at follow-up (Fig. 1A). Interestingly, this change of Lp(a) correlated significantly with baseline levels (r = 0.61; p b 0.0001; Spearman correlation; Fig. 1B). The increase was only present in patients with Lp(a) levels above the median of 15 nmol/L [delta Lp(a) + 29.3 ± 35.1 nmol/L (− 12.5 to + 128.4 nmol/L); p = 0.002]. Plasma levels of Lp(a) ≤ 15 nmol/L remained stable over time [delta Lp(a) − 0.3 ± 4.3 nmol/L (− 12.2 to + 7.6 nmol/L); p = 0.76]. Low levels of Lp(a) directly after premature MI could possibly be used to rule out a significant involvement of Lp(a) in the early onset of the disease and no further testing of these patients seems to be necessary. However, Lp(a)-testing should be repeated in the stable phase of the disease in patients with Lp(a) N 15 nmol/L and, if elevated, additional screening of first-degree relatives may be advised. As the increase of Lp(a) after the post-MI period significantly correlates with baseline values, the role of Lp(a) in young patients with mildly elevated plasma levels during the early post-MI period could be significantly underestimated.
6
G. Goliasch et al. / International Journal of Cardiology 186 (2015) 5–6
Fig. 1. a. Time trend of Lp(a) plasma levels between infarction and follow-up; b. Correlation between baseline Lp(a) levels and the change of Lp(a) between baseline and follow-up.
Conflict of interest The authors report no relationships that could be construed as a conflict of interest. References [1] A. Bennet, E. Di Angelantonio, S. Erqou, G. Eiriksdottir, G. Sigurdsson, M. Woodward, et al., Lipoprotein(a) levels and risk of future coronary heart disease: large-scale prospective data, Arch. Intern. Med. 168 (2008) 598–608. [2] S.W. Kwon, B.K. Lee, B.K. Hong, J.Y. Kim, E.Y. Choi, J.M. Sung, et al., Prognostic significance of elevated lipoprotein(a) in coronary artery revascularization patients, Int. J. Cardiol. 167 (2013) 1990–1994. [3] A.G. Bostom, L.A. Cupples, J.L. Jenner, J.M. Ordovas, L.J. Seman, P.W. Wilson, et al., Elevated plasma lipoprotein(a) and coronary heart disease in men aged 55 years and younger. A prospective study, JAMA 276 (1996) 544–548. [4] J. Pineda, F. Marin, P. Marco, V. Roldan, J. Valencia, J.M. Ruiz-Nodar, et al., Premature coronary artery disease in young (age b 45) subjects: interactions of lipid profile, thrombophilic and haemostatic markers, Int. J. Cardiol. 136 (2009) 222–225. [5] European Association for Cardiovascular P, Rehabilitation, Z. Reiner, A.L. Catapano, G. De Backer, I. Graham, et al., ESC/EAS guidelines for the management of dyslipidaemias: the
[6]
[7]
[8]
[9]
Task Force for the management of dyslipidaemias of the European Society of Cardiology (ESC) and the European Atherosclerosis Society (EAS), Eur. Heart J. 32 (2011) 1769–1818. F.J. Raal, R.P. Giugliano, M.S. Sabatine, M.J. Koren, G. Langslet, H. Bays, et al., Reduction in lipoprotein(a) with PCSK9 monoclonal antibody evolocumab (AMG 145): a pooled analysis of more than 1,300 patients in 4 phase II trials, J. Am. Coll. Cardiol. 63 (2014) 1278–1288. N.R. Desai, P. Kohli, R.P. Giugliano, M.L. O'Donoghue, R. Somaratne, J. Zhou, et al., AMG145, a monoclonal antibody against proprotein convertase subtilisin kexin type 9, significantly reduces lipoprotein(a) in hypercholesterolemic patients receiving statin therapy: an analysis from the LDL-C Assessment with Proprotein Convertase Subtilisin Kexin Type 9 Monoclonal Antibody Inhibition Combined with Statin Therapy (LAPLACE)-Thrombolysis in Myocardial Infarction (TIMI) 57 trial, Circulation 128 (2013) 962–969. E.M. Roth, M.R. Taskinen, H.N. Ginsberg, J.J. Kastelein, H.M. Colhoun, J.G. Robinson, et al., Monotherapy with the PCSK9 inhibitor alirocumab versus ezetimibe in patients with hypercholesterolemia: results of a 24 week, double-blind, randomized Phase 3 trial, Int. J. Cardiol. 176 (2014) 55–61. F. Wiesbauer, H. Blessberger, D. Azar, G. Goliasch, O. Wagner, L. Gerhold, et al., Familial-combined hyperlipidaemia in very young myocardial infarction survivors (b or =40 years of age), Eur. Heart J. 30 (2009) 1073–1079.
Contents lists available at ScienceDirect
International Journal of Cardiology journal homepage: www.elsevier.com/locate/ijcard
Letter to the Editor
Variation of lipoprotein(a) plasma levels after premature myocardial infarction Georg Goliasch a,⁎, Franz Wiesbauer a, Hermann Blessberger a,b, Gerald Maurer a, Kurt Derfler c, Walter S. Speidl a,⁎ a b c
Department of Internal Medicine II, Medical University of Vienna, Austria Linz General Hospital, Johannes Kepler University School of Medicine, Department of Internal Medicine I — Cardiology, Linz, Austria Department of Internal Medicine III, Division of Nephrology, Medical University of Vienna, Austria
a r t i c l e
i n f o
Article history: Received 18 February 2015 Accepted 17 March 2015 Available online 18 March 2015 Keywords: Lipoprotein a Lipids Secondary prevention Premature myocardial infarction Acute coronary syndrome
Myocardial infarction (MI) in very young individuals (≤ 40 years) represents a rare disease with an unfavorable prognosis. Therefore, aggressive treatment of all modifiable risk factors should be advised. Elevated levels of lipoprotein(a) [Lp(a)] are an independent risk factor for coronary artery disease and the development of acute coronary events [1,2]. Increased plasma concentrations of Lp(a) have been associated with increased risk for premature myocardial infarction [3,4] and current guidelines recommend screening for elevated Lp(a) in selected patient groups like premature coronary heart disease [5]. Until now, treatment of elevated levels of Lp(a) has been challenging. Medical treatment with niacin shows only moderate effects with major side effects and lipid apheresis as the most effective therapeutic option is costly and time consuming. Recent studies have shown that Lp(a) can be substantially lowered by treatment with inhibitors of proprotein convertase subtilisin/kexin type 9 (PCSK9) [6–8]. Plasma levels of Lp(a) are to a large extent genetically
⁎ Corresponding authors at: Department of Internal Medicine II, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Wien, Austria. E-mail addresses: [email protected] (G. Goliasch), [email protected] (W.S. Speidl).
http://dx.doi.org/10.1016/j.ijcard.2015.03.211 0167-5273/© 2015 Elsevier Ireland Ltd. All rights reserved.
determined via variation in the apolipoprotein(a) gene and remain stable with little variation over time. However, it is not known whether Lp(a) levels in the post-MI period are representative for the stable phase of the disease in these young patients. This could lead to an over- or underestimation of Lp(a) plasma levels during the index hospitalization leading to a possible overtreatment or restraint of a potentially beneficial treatment. We enrolled MI survivors (≤ 40 years) and measured plasma levels of Lp(a) (Roche Diagnostics, Basel, Switzerland; upper normal limit 75 nmol/L) in 40 patients during the postinfarction period (3.2 ± 2.1 days post-MI) and after one year follow-up in a stable phase of the disease. The study is in line with the Declaration of Helsinki and was approved by the Ethics Committee of the Medical University of Vienna. The exact study protocol has been previously described in detail [9]. Mean age of our patients was 36 ± 4 years, 93% were male, 83% were active smokers and 35% had a positive family history of MI. All patients were treated with statins but no patients received niacin or underwent lipid apheresis. Lp(a) significantly increased from 34.0 ± 46.3 nmol/L in the post-MI period to 48.4 ± 67.8 nmol/L (p = 0.013; Wilcoxon signed-rank test) at follow-up (Fig. 1A). Interestingly, this change of Lp(a) correlated significantly with baseline levels (r = 0.61; p b 0.0001; Spearman correlation; Fig. 1B). The increase was only present in patients with Lp(a) levels above the median of 15 nmol/L [delta Lp(a) + 29.3 ± 35.1 nmol/L (− 12.5 to + 128.4 nmol/L); p = 0.002]. Plasma levels of Lp(a) ≤ 15 nmol/L remained stable over time [delta Lp(a) − 0.3 ± 4.3 nmol/L (− 12.2 to + 7.6 nmol/L); p = 0.76]. Low levels of Lp(a) directly after premature MI could possibly be used to rule out a significant involvement of Lp(a) in the early onset of the disease and no further testing of these patients seems to be necessary. However, Lp(a)-testing should be repeated in the stable phase of the disease in patients with Lp(a) N 15 nmol/L and, if elevated, additional screening of first-degree relatives may be advised. As the increase of Lp(a) after the post-MI period significantly correlates with baseline values, the role of Lp(a) in young patients with mildly elevated plasma levels during the early post-MI period could be significantly underestimated.
6
G. Goliasch et al. / International Journal of Cardiology 186 (2015) 5–6
Fig. 1. a. Time trend of Lp(a) plasma levels between infarction and follow-up; b. Correlation between baseline Lp(a) levels and the change of Lp(a) between baseline and follow-up.
Conflict of interest The authors report no relationships that could be construed as a conflict of interest. References [1] A. Bennet, E. Di Angelantonio, S. Erqou, G. Eiriksdottir, G. Sigurdsson, M. Woodward, et al., Lipoprotein(a) levels and risk of future coronary heart disease: large-scale prospective data, Arch. Intern. Med. 168 (2008) 598–608. [2] S.W. Kwon, B.K. Lee, B.K. Hong, J.Y. Kim, E.Y. Choi, J.M. Sung, et al., Prognostic significance of elevated lipoprotein(a) in coronary artery revascularization patients, Int. J. Cardiol. 167 (2013) 1990–1994. [3] A.G. Bostom, L.A. Cupples, J.L. Jenner, J.M. Ordovas, L.J. Seman, P.W. Wilson, et al., Elevated plasma lipoprotein(a) and coronary heart disease in men aged 55 years and younger. A prospective study, JAMA 276 (1996) 544–548. [4] J. Pineda, F. Marin, P. Marco, V. Roldan, J. Valencia, J.M. Ruiz-Nodar, et al., Premature coronary artery disease in young (age b 45) subjects: interactions of lipid profile, thrombophilic and haemostatic markers, Int. J. Cardiol. 136 (2009) 222–225. [5] European Association for Cardiovascular P, Rehabilitation, Z. Reiner, A.L. Catapano, G. De Backer, I. Graham, et al., ESC/EAS guidelines for the management of dyslipidaemias: the
[6]
[7]
[8]
[9]
Task Force for the management of dyslipidaemias of the European Society of Cardiology (ESC) and the European Atherosclerosis Society (EAS), Eur. Heart J. 32 (2011) 1769–1818. F.J. Raal, R.P. Giugliano, M.S. Sabatine, M.J. Koren, G. Langslet, H. Bays, et al., Reduction in lipoprotein(a) with PCSK9 monoclonal antibody evolocumab (AMG 145): a pooled analysis of more than 1,300 patients in 4 phase II trials, J. Am. Coll. Cardiol. 63 (2014) 1278–1288. N.R. Desai, P. Kohli, R.P. Giugliano, M.L. O'Donoghue, R. Somaratne, J. Zhou, et al., AMG145, a monoclonal antibody against proprotein convertase subtilisin kexin type 9, significantly reduces lipoprotein(a) in hypercholesterolemic patients receiving statin therapy: an analysis from the LDL-C Assessment with Proprotein Convertase Subtilisin Kexin Type 9 Monoclonal Antibody Inhibition Combined with Statin Therapy (LAPLACE)-Thrombolysis in Myocardial Infarction (TIMI) 57 trial, Circulation 128 (2013) 962–969. E.M. Roth, M.R. Taskinen, H.N. Ginsberg, J.J. Kastelein, H.M. Colhoun, J.G. Robinson, et al., Monotherapy with the PCSK9 inhibitor alirocumab versus ezetimibe in patients with hypercholesterolemia: results of a 24 week, double-blind, randomized Phase 3 trial, Int. J. Cardiol. 176 (2014) 55–61. F. Wiesbauer, H. Blessberger, D. Azar, G. Goliasch, O. Wagner, L. Gerhold, et al., Familial-combined hyperlipidaemia in very young myocardial infarction survivors (b or =40 years of age), Eur. Heart J. 30 (2009) 1073–1079.
