G Model
JJCC-885; No. of Pages 2 Journal of Cardiology xxx (2014) xxx–xxx
Contents lists available at ScienceDirect
Journal of Cardiology journal homepage: www.elsevier.com/locate/jjcc
Editorial
Can lipid profiles predict clinical outcomes in hemodialysis patients with ischemic heart disease?
Keywords: Hemodialysis Percutaneous coronary intervention Lipid profiles Malnutrition
Needless to say, drug-eluting stents (DESs) significantly reduce the risk of restenosis after percutaneous coronary intervention (PCI). However, effects of DES implantation have been limited in patients on maintenance hemodialysis (HD) [1,2]. Basically, patients with renal impairment, particularly endstage renal disease, frequently have systemic atherosclerosis [3]. One possibility is that higher rates of prevalence of traditional risk factors, such as advanced age, diabetes, and hypertension in the HD population may affect such high cardiovascular events [3]. In this issue of the Journal of Cardiology, Nagata et al. [4] report that low-density lipoprotein (LDL) cholesterol levels could not predict major adverse cardiac events in HD patients undergoing PCI. It is well known that lipid profiles greatly affect clinical outcome in non-HD populations [5]. Moreover, many studies have shown beneficial effects of statins on the improvement of clinical outcome data in non-HD patients undergoing coronary revascularization. However, in HD patients, there are limited studies to show the beneficial effects of statins on the improvement of the clinical outcome. For instance, 4D (Die Deutsche Diabetes Dialyze) study did not prove that statins do not affect clinical outcome in HD patients [6]. Therefore, whether statin use has a beneficial effect on clinical outcomes in the HD population has been controversial and the debate is ongoing regarding the ideal LDL cholesterol level. From these points, the findings of the article by Nagata et al. [4] are concurring with the previous reports. A recent post hoc analysis of the 4D study revealed that treatment with atorvastatin significantly reduces cardiac events in HD patients with type 2 diabetes, if they have pretreatment LDL levels >145 mg/dl [7]. Because of the limited number of enrolled patients in the study by Nagata et al. [4], further studies should be warranted. Also, the importance of HDL levels should also be investigated. Protein-energy wasting (PEW), commonly observed in patients with end-stage renal disease, is associated with increasing risk of cardiovascular morbidity and mortality [8]. The PEW is also considered to be due to inflammatory processes rather than inadequate nutritional intake. These associations are malnutrition, inflammation, and atherosclerosis syndrome [9]. Inflammatory
processes are related to atherosclerosis progression, resulting in worse clinical outcomes in the HD population [10]. From this point of view, a simple method to clarify the risk stratification for cardiovascular mortality is attractive. Recently, the geriatric nutritional risk index (GNRI) has been reported as a new screening tool for PEW [11]. In assessing GNRI, serum albumin levels and body mass index are important factors [12]. Nagata et al. [4] also suggested that body mass index independently predicted the incidence of major adverse cardiac events. Epicardial coronary artery stenosis has a clinical impact on HD patients. In addition, coronary microcirculatory impairment has been an important issue in HD patients [13]. In such situations, specific medical treatment such as nicorandil may have beneficial effects on improving coronary microcirculatory flow, resulting in better clinical prognosis in the HD population [14]. As described above, the manifestation and etiology of cardiovascular disease between non-HD and HD subjects are quite different. Also, unfortunately, evidence-based medical therapies to improve clinical outcomes in HD patients have been limited. Taken together, we should provide optimal strategies for cardiovascular prevention, diagnosis, and decision-making in patients on HD to improve their clinical outcomes. However, before that, we have to know the characteristics precisely. References [1] Nakazawa G, Tanabe K, Aoki J, Yamamoto H, Higashikuni Y, Onuma Y, Yachi S, Nakajima H, Hara K. Impact of renal insufficiency on clinical and angiographic outcomes following percutaneous coronary intervention with sirolimuseluting stents. Catheter Cardiovasc Interv 2007;69:808–14. [2] Aoyama Y, Hirayama H, Ishii H, Kobayashi K, Ishikawa K, Takigawa M, Nanasato M, Yoshida Y, Aoyama T, Yoshikawa D, Matsubara T, Murohara T. Impact of chronic kidney disease on a re-percutaneous coronary intervention for sirolimus-eluting stent restenosis. Coron Artery Dis 2012;23:528–32. [3] Herzog CA, Asinger RW, Berger AK, Charytan DM, Dı´ez J, Hart RG, Eckardt KU, Kasiske BL, McCullough PA, Passman RS, DeLoach SS, Pun PH, Ritz E. Cardiovascular disease in chronic kidney disease. A clinical update from kidney disease: improving global outcomes (KDIGO). Kidney Int 2011;80:572–86. [4] Nagata I, Ike A, Nishikawa H, Zhang B, Sugihara M, Mori K, Iwata A, Kawamura A, Shirai K, Uehara Y, Ogawa M, Miura S, Saku K. Associations between lipid profiles and MACE in hemodialysis patients with percutaneous coronary intervention: from the FU-Registry. J Cardiol 2014. http://dx.doi.org/10.1016/ j.jjcc.2014.03.016 (in press). [5] Turner RC, Millns H, Neil HA, Stratton IM, Manley SE, Matthews DR, Holman RR. Risk factors for coronary artery disease in non-insulin dependent diabetes mellitus: United Kingdom Prospective Diabetes Study (UKPDS: 23). BMJ 1998;316:823–8. [6] Wanner C, Krane V, Ma¨rz W, Olschewski M, Mann JF, Ruf G, Ritz E, German Diabetes and Dialysis Study Investigators. Atorvastatin in patients with type 2 diabetes mellitus undergoing hemodialysis. N Engl J Med 2005;353:238–48.
http://dx.doi.org/10.1016/j.jjcc.2014.04.001 0914-5087/ß 2014 Published by Elsevier Ltd on behalf of Japanese College of Cardiology.
Please cite this article in press as: Ishii H, Murohara T. Can lipid profiles predict clinical outcomes in hemodialysis patients with ischemic heart disease? J Cardiol (2014), http://dx.doi.org/10.1016/j.jjcc.2014.04.001
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JJCC-885; No. of Pages 2 2
Editorial / Journal of Cardiology xxx (2014) xxx–xxx
[7] Ma¨rz W, Genser B, Drechsler C, Krane V, Grammer TB, Ritz E, Stojakovic T, Scharnagl H, Winkler K, Holme I, Holdaas H, Wanner C, German Diabetes and Dialysis Study Investigators. Atorvastatin and low-density lipoprotein cholesterol in type 2 diabetes mellitus patients on hemodialysis. Clin J Am Soc Nephrol 2011;6:1316–25. [8] Fouque D, Kalantar-Zadeh K, Kopple J, Cano N, Chauveau P, Cuppari L, Franch H, Guarnieri G, Ikizler TA, Kaysen G, Lindholm B, Massy Z, Mitch W, Pineda E, Stenvinkel P, et al. A proposed nomenclature and diagnostic criteria for proteinenergy wasting in acute and chronic kidney disease. Kidney Int 2008;73:391–8. [9] Stenvinkel P, Heimbu¨rger O, Lindholm B, Kaysen GA, Bergstro¨m J. Are there two types of malnutrition in chronic renal failure? Evidence for relationships between malnutrition, inflammation and atherosclerosis (MIA syndrome). Nephrol Dial Transplant 2000;15:953–60. [10] Takahashi R, Ito Y, Takahashi H, Ishii H, Kasuga H, Mizuno M, Suzuki Y, Yuzawa Y, Maruyama S, Murohara T, Imai E, Matsuo S. Combined values of serum albumin, C-reactive protein and body mass index at dialysis initiation accurately predicts long-term mortality. Am J Nephrol 2012;36:136–43. [11] Takahashi H, Ito Y, Ishii H, Aoyama T, Kamoi D, Kasuga H, Yasuda K, Maruyama S, Matsuo S, Murohara T, Yuzawa Y. Geriatric nutritional risk index accurately predicts cardiovascular mortality in incident hemodialysis patients. J Cardiol 2013;(December). http://dx.doi.org/10.1016/j.jjcc.2013.10.018 [Epub ahead of print]. [12] Yamada K, Furuya R, Takita T, Maruyama Y, Yamaguchi Y, Ohkawa S, Kumagai H. Simplified nutritional screening tools for patients on maintenance hemodialysis. Am J Clin Nutr 2008;87:106–13.
[13] McIntyre CW. Haemodialysis-induced myocardial stunning in chronic kidney disease– a new aspect of cardiovascular disease. Blood Purif 2010;29: 105–10. [14] Nishimura M, Tokoro T, Nishida M, Hashimoto T, Kobayashi H, Imai R, Yamazaki S, Okino K, Iwamoto N, Takahashi H, Ono T. Oral nicorandil to reduce cardiac death after coronary revascularization in hemodialysis patients: a randomized trial. Am J Kidney Dis 2009;54:307–17.
Hideki Ishii (MD, PhD)* Toyoaki Murohara (MD, PhD) Department of Cardiology, Nagoya University Graduate School of Medicine, Nagoya, Japan *Corresponding author at: Department of Cardiology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan. Tel.: +81 52 744 2147; fax: +81 52 744 2210 E-mail address: [email protected] (H. Ishii). 7 April 2014
Please cite this article in press as: Ishii H, Murohara T. Can lipid profiles predict clinical outcomes in hemodialysis patients with ischemic heart disease? J Cardiol (2014), http://dx.doi.org/10.1016/j.jjcc.2014.04.001
JJCC-885; No. of Pages 2 Journal of Cardiology xxx (2014) xxx–xxx
Contents lists available at ScienceDirect
Journal of Cardiology journal homepage: www.elsevier.com/locate/jjcc
Editorial
Can lipid profiles predict clinical outcomes in hemodialysis patients with ischemic heart disease?
Keywords: Hemodialysis Percutaneous coronary intervention Lipid profiles Malnutrition
Needless to say, drug-eluting stents (DESs) significantly reduce the risk of restenosis after percutaneous coronary intervention (PCI). However, effects of DES implantation have been limited in patients on maintenance hemodialysis (HD) [1,2]. Basically, patients with renal impairment, particularly endstage renal disease, frequently have systemic atherosclerosis [3]. One possibility is that higher rates of prevalence of traditional risk factors, such as advanced age, diabetes, and hypertension in the HD population may affect such high cardiovascular events [3]. In this issue of the Journal of Cardiology, Nagata et al. [4] report that low-density lipoprotein (LDL) cholesterol levels could not predict major adverse cardiac events in HD patients undergoing PCI. It is well known that lipid profiles greatly affect clinical outcome in non-HD populations [5]. Moreover, many studies have shown beneficial effects of statins on the improvement of clinical outcome data in non-HD patients undergoing coronary revascularization. However, in HD patients, there are limited studies to show the beneficial effects of statins on the improvement of the clinical outcome. For instance, 4D (Die Deutsche Diabetes Dialyze) study did not prove that statins do not affect clinical outcome in HD patients [6]. Therefore, whether statin use has a beneficial effect on clinical outcomes in the HD population has been controversial and the debate is ongoing regarding the ideal LDL cholesterol level. From these points, the findings of the article by Nagata et al. [4] are concurring with the previous reports. A recent post hoc analysis of the 4D study revealed that treatment with atorvastatin significantly reduces cardiac events in HD patients with type 2 diabetes, if they have pretreatment LDL levels >145 mg/dl [7]. Because of the limited number of enrolled patients in the study by Nagata et al. [4], further studies should be warranted. Also, the importance of HDL levels should also be investigated. Protein-energy wasting (PEW), commonly observed in patients with end-stage renal disease, is associated with increasing risk of cardiovascular morbidity and mortality [8]. The PEW is also considered to be due to inflammatory processes rather than inadequate nutritional intake. These associations are malnutrition, inflammation, and atherosclerosis syndrome [9]. Inflammatory
processes are related to atherosclerosis progression, resulting in worse clinical outcomes in the HD population [10]. From this point of view, a simple method to clarify the risk stratification for cardiovascular mortality is attractive. Recently, the geriatric nutritional risk index (GNRI) has been reported as a new screening tool for PEW [11]. In assessing GNRI, serum albumin levels and body mass index are important factors [12]. Nagata et al. [4] also suggested that body mass index independently predicted the incidence of major adverse cardiac events. Epicardial coronary artery stenosis has a clinical impact on HD patients. In addition, coronary microcirculatory impairment has been an important issue in HD patients [13]. In such situations, specific medical treatment such as nicorandil may have beneficial effects on improving coronary microcirculatory flow, resulting in better clinical prognosis in the HD population [14]. As described above, the manifestation and etiology of cardiovascular disease between non-HD and HD subjects are quite different. Also, unfortunately, evidence-based medical therapies to improve clinical outcomes in HD patients have been limited. Taken together, we should provide optimal strategies for cardiovascular prevention, diagnosis, and decision-making in patients on HD to improve their clinical outcomes. However, before that, we have to know the characteristics precisely. References [1] Nakazawa G, Tanabe K, Aoki J, Yamamoto H, Higashikuni Y, Onuma Y, Yachi S, Nakajima H, Hara K. Impact of renal insufficiency on clinical and angiographic outcomes following percutaneous coronary intervention with sirolimuseluting stents. Catheter Cardiovasc Interv 2007;69:808–14. [2] Aoyama Y, Hirayama H, Ishii H, Kobayashi K, Ishikawa K, Takigawa M, Nanasato M, Yoshida Y, Aoyama T, Yoshikawa D, Matsubara T, Murohara T. Impact of chronic kidney disease on a re-percutaneous coronary intervention for sirolimus-eluting stent restenosis. Coron Artery Dis 2012;23:528–32. [3] Herzog CA, Asinger RW, Berger AK, Charytan DM, Dı´ez J, Hart RG, Eckardt KU, Kasiske BL, McCullough PA, Passman RS, DeLoach SS, Pun PH, Ritz E. Cardiovascular disease in chronic kidney disease. A clinical update from kidney disease: improving global outcomes (KDIGO). Kidney Int 2011;80:572–86. [4] Nagata I, Ike A, Nishikawa H, Zhang B, Sugihara M, Mori K, Iwata A, Kawamura A, Shirai K, Uehara Y, Ogawa M, Miura S, Saku K. Associations between lipid profiles and MACE in hemodialysis patients with percutaneous coronary intervention: from the FU-Registry. J Cardiol 2014. http://dx.doi.org/10.1016/ j.jjcc.2014.03.016 (in press). [5] Turner RC, Millns H, Neil HA, Stratton IM, Manley SE, Matthews DR, Holman RR. Risk factors for coronary artery disease in non-insulin dependent diabetes mellitus: United Kingdom Prospective Diabetes Study (UKPDS: 23). BMJ 1998;316:823–8. [6] Wanner C, Krane V, Ma¨rz W, Olschewski M, Mann JF, Ruf G, Ritz E, German Diabetes and Dialysis Study Investigators. Atorvastatin in patients with type 2 diabetes mellitus undergoing hemodialysis. N Engl J Med 2005;353:238–48.
http://dx.doi.org/10.1016/j.jjcc.2014.04.001 0914-5087/ß 2014 Published by Elsevier Ltd on behalf of Japanese College of Cardiology.
Please cite this article in press as: Ishii H, Murohara T. Can lipid profiles predict clinical outcomes in hemodialysis patients with ischemic heart disease? J Cardiol (2014), http://dx.doi.org/10.1016/j.jjcc.2014.04.001
G Model
JJCC-885; No. of Pages 2 2
Editorial / Journal of Cardiology xxx (2014) xxx–xxx
[7] Ma¨rz W, Genser B, Drechsler C, Krane V, Grammer TB, Ritz E, Stojakovic T, Scharnagl H, Winkler K, Holme I, Holdaas H, Wanner C, German Diabetes and Dialysis Study Investigators. Atorvastatin and low-density lipoprotein cholesterol in type 2 diabetes mellitus patients on hemodialysis. Clin J Am Soc Nephrol 2011;6:1316–25. [8] Fouque D, Kalantar-Zadeh K, Kopple J, Cano N, Chauveau P, Cuppari L, Franch H, Guarnieri G, Ikizler TA, Kaysen G, Lindholm B, Massy Z, Mitch W, Pineda E, Stenvinkel P, et al. A proposed nomenclature and diagnostic criteria for proteinenergy wasting in acute and chronic kidney disease. Kidney Int 2008;73:391–8. [9] Stenvinkel P, Heimbu¨rger O, Lindholm B, Kaysen GA, Bergstro¨m J. Are there two types of malnutrition in chronic renal failure? Evidence for relationships between malnutrition, inflammation and atherosclerosis (MIA syndrome). Nephrol Dial Transplant 2000;15:953–60. [10] Takahashi R, Ito Y, Takahashi H, Ishii H, Kasuga H, Mizuno M, Suzuki Y, Yuzawa Y, Maruyama S, Murohara T, Imai E, Matsuo S. Combined values of serum albumin, C-reactive protein and body mass index at dialysis initiation accurately predicts long-term mortality. Am J Nephrol 2012;36:136–43. [11] Takahashi H, Ito Y, Ishii H, Aoyama T, Kamoi D, Kasuga H, Yasuda K, Maruyama S, Matsuo S, Murohara T, Yuzawa Y. Geriatric nutritional risk index accurately predicts cardiovascular mortality in incident hemodialysis patients. J Cardiol 2013;(December). http://dx.doi.org/10.1016/j.jjcc.2013.10.018 [Epub ahead of print]. [12] Yamada K, Furuya R, Takita T, Maruyama Y, Yamaguchi Y, Ohkawa S, Kumagai H. Simplified nutritional screening tools for patients on maintenance hemodialysis. Am J Clin Nutr 2008;87:106–13.
[13] McIntyre CW. Haemodialysis-induced myocardial stunning in chronic kidney disease– a new aspect of cardiovascular disease. Blood Purif 2010;29: 105–10. [14] Nishimura M, Tokoro T, Nishida M, Hashimoto T, Kobayashi H, Imai R, Yamazaki S, Okino K, Iwamoto N, Takahashi H, Ono T. Oral nicorandil to reduce cardiac death after coronary revascularization in hemodialysis patients: a randomized trial. Am J Kidney Dis 2009;54:307–17.
Hideki Ishii (MD, PhD)* Toyoaki Murohara (MD, PhD) Department of Cardiology, Nagoya University Graduate School of Medicine, Nagoya, Japan *Corresponding author at: Department of Cardiology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan. Tel.: +81 52 744 2147; fax: +81 52 744 2210 E-mail address: [email protected] (H. Ishii). 7 April 2014
Please cite this article in press as: Ishii H, Murohara T. Can lipid profiles predict clinical outcomes in hemodialysis patients with ischemic heart disease? J Cardiol (2014), http://dx.doi.org/10.1016/j.jjcc.2014.04.001
