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A prop to explain LDL particles
Journal of Clinical Lipidology (2013) 7, 88–89
Letters to the Editor Dimitri P. Mikhailidis, MD, FRCP, FRCPath London, UK Moses S. Elisaf, MD, PhD Ioannina, Greece
Evaluation of the incidence and risk factors for development of fenofibrate-associated nephrotoxicitys In the Journal, Attridge et al1 report that 27% of fenofibrate-treated patients experienced an increase in serum creatinine (SCr) levels $0.3 mg/dL during the first 6 months of treatment. Chronic kidney disease (CKD), diabetes mellitus (DM), high-dose fenofibrate ($145 mg/day), and the use of concomitant drugs (eg, angiotensin-converting enzyme inhibitors, furosemide) were more prevalent in these patients. We assessed the effect of various fibrates on SCr levels in 130 patients with dyslipidemia.2 The use of fenofibrate and ciprofibrate, but not gemfibrozil, significantly increased SCr by 12% and 17%, respectively, during an 8-month follow-up. Metabolic syndrome (MetS) increases the risk for both DM and CKD.3 We reported significant increases in SCr levels in patients with MetS receiving micronized fenofibrate 200 mg/day for 3 to 12 months.4,5 The coadministration of atorvastatin 20 mg/day alleviated this potentially adverse effect of fenofibrate.4 This could be attributed to the beneficial effects of atorvastatin on kidney function in patients with MetS.6 These benefits of atorvastatin are more evident in patients with CKD.6 Fenofibrate and atorvastatin can synergistically reduce levels of serum uric acid,4 a change associated with better renal outcomes in patients with MetS.6 Therefore, it would be useful to know how fenofibrate affected levels of serum uric acid in the study by Attridge et al,1 especially in patients with CKD, DM and those on diuretics. It is uncertain whether an increase in SCr by fenofibrate represents a nephrotoxic effect. The Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study included 9795 patients with type 2 DM.7 Despite greater levels of SCr in the fenofibrate group, a slower rate of decline in the estimated glomerular filtration rate was noted compared with the placebo group.7 Fenofibrate also decreased albuminuria more than placebo.7 Michael S. Kostapanos, MD London, UK Ioannina, Greece Vasilios G. Athyros, MD, PhD Thessaloniki, Greece
http://dx.doi.org/10.1016/j.jacl.2012.02.008
References 1. Attridge RL, Linn WD, Ryan L, et al. Evaluation of the incidence and risk factors for development of fenofibrate-associated nephrotoxicity. J Clin Lipidol. 2012;6:19–26. 2. Tsimihodimos V, Kakafika A, Elisaf M. Fibrate treatment can increase serum creatinine levels. Nephrol Dial Transplant. 2001;16:1301. 3. Kostapanos MS, Liamis GL, Elisaf M. Features of the metabolic syndrome relating to cardiorenal outcomes. Arch Med Sci. 2008;4:424–426. 4. Athyros VG, Mikhailidis DP, Papageorgiou AA, et al. Targeting vascular risk in patients with metabolic syndrome but without diabetes. Metabolism. 2005;54:1065–1074. 5. Filippatos TD, Kiortsis DN, Liberopoulos EN, et al. Effect of orlistat, micronised fenofibrate and their combination on metabolic parameters in overweight and obese patients with the metabolic syndrome: the FenOrli study. Curr Med Res Opin. 2005;21:1997–2006. 6. Athyros VG, Mikhailidis DP, Liberopoulos EN, et al. Effect of statin treatment on renal function and serum uric acid levels and their relation to vascular events in patients with coronary heart disease and metabolic syndrome: a subgroup analysis of the GREek Atorvastatin and Coronary heart disease Evaluation (GREACE) Study. Nephrol Dial Transplant. 2007;22:118–127. 7. Davis TM, Ting R, Best JD, et al, Fenofibrate Intervention and Event Lowering in Diabetes Study Investigators. Effects of fenofibrate on renal function in patients with type 2 diabetes mellitus: the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) Study. Diabetologia. 2011;54:280–290.
A prop to explain LDL particles In my practice, I often order analyses of my patients’ lipids and lipoproteins by using nuclear magnetic resonance, which provides me with the number of lipoprotein particles as well as the cholesterol content of each major lipoprotein group, ie, very low-density lipoprotein, lowdensity lipoprotein (LDL), and high-density lipoprotein. Explaining these new measures to patients needs more than a few words and a written laboratory report. So, I came up with a simple model to help illustrate the concept of the LDL particle to patients. I hope the readership of the Journal will find this useful as well.
1933-2874/$ - see front matter Ó 2013 National Lipid Association. All rights reserved.
Letters to the Editor
89 representing the plasma LDL cholesterol content (in mg/ dL). On the bag of larger eggs, I represented the LDL particle number as 900 (nmoles/L). The bag containing the smaller eggs was labeled 1800 (nmoles/L) because it contained twice the number of eggs. I tell the patients, ‘‘You’ve heard about good cholesterol (also known as HDL cholesterol) and bad cholesterol (the cholesterol in the LDL). However, the LDL level may not tell the whole story. The LDL exists as tiny particles made up of several different fats, including cholesterol and a large protein. It is these particles that go into artery walls and form blockages that we call atherosclerosis, which can lead to heart attacks and strokes.’’ (I then point to a wall poster showing plaque progression). I then hold up the bags representing the same volume of blood. ‘‘This represents blood samples from two different patients that have the same LDL level, and you can see both bags are the same size. However, the patient with the small LDL has twice as many individual particles as the one with large LDL. So the patient with many small LDL has greater risk than the patient with fewer particles, even though their LDL cholesterol is exactly the same. An advanced cholesterol test, like you had, shows us this difference in risk, which may be missed by a standard test.’’ Almost all my patients seem to understand the concept of particle number after such an explanation.
I purchased bags of plastic eggs that contained 6 large eggs in a bag, and another bag of equal size that held 12 smaller eggs. I labeled both bags with a value of 90,
Daniel C. Ginsberg, MD, FACP Tacoma, WA http://dx.doi.org/10.1016/j.jacl.2012.02.009
Letters to the Editor Dimitri P. Mikhailidis, MD, FRCP, FRCPath London, UK Moses S. Elisaf, MD, PhD Ioannina, Greece
Evaluation of the incidence and risk factors for development of fenofibrate-associated nephrotoxicitys In the Journal, Attridge et al1 report that 27% of fenofibrate-treated patients experienced an increase in serum creatinine (SCr) levels $0.3 mg/dL during the first 6 months of treatment. Chronic kidney disease (CKD), diabetes mellitus (DM), high-dose fenofibrate ($145 mg/day), and the use of concomitant drugs (eg, angiotensin-converting enzyme inhibitors, furosemide) were more prevalent in these patients. We assessed the effect of various fibrates on SCr levels in 130 patients with dyslipidemia.2 The use of fenofibrate and ciprofibrate, but not gemfibrozil, significantly increased SCr by 12% and 17%, respectively, during an 8-month follow-up. Metabolic syndrome (MetS) increases the risk for both DM and CKD.3 We reported significant increases in SCr levels in patients with MetS receiving micronized fenofibrate 200 mg/day for 3 to 12 months.4,5 The coadministration of atorvastatin 20 mg/day alleviated this potentially adverse effect of fenofibrate.4 This could be attributed to the beneficial effects of atorvastatin on kidney function in patients with MetS.6 These benefits of atorvastatin are more evident in patients with CKD.6 Fenofibrate and atorvastatin can synergistically reduce levels of serum uric acid,4 a change associated with better renal outcomes in patients with MetS.6 Therefore, it would be useful to know how fenofibrate affected levels of serum uric acid in the study by Attridge et al,1 especially in patients with CKD, DM and those on diuretics. It is uncertain whether an increase in SCr by fenofibrate represents a nephrotoxic effect. The Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study included 9795 patients with type 2 DM.7 Despite greater levels of SCr in the fenofibrate group, a slower rate of decline in the estimated glomerular filtration rate was noted compared with the placebo group.7 Fenofibrate also decreased albuminuria more than placebo.7 Michael S. Kostapanos, MD London, UK Ioannina, Greece Vasilios G. Athyros, MD, PhD Thessaloniki, Greece
http://dx.doi.org/10.1016/j.jacl.2012.02.008
References 1. Attridge RL, Linn WD, Ryan L, et al. Evaluation of the incidence and risk factors for development of fenofibrate-associated nephrotoxicity. J Clin Lipidol. 2012;6:19–26. 2. Tsimihodimos V, Kakafika A, Elisaf M. Fibrate treatment can increase serum creatinine levels. Nephrol Dial Transplant. 2001;16:1301. 3. Kostapanos MS, Liamis GL, Elisaf M. Features of the metabolic syndrome relating to cardiorenal outcomes. Arch Med Sci. 2008;4:424–426. 4. Athyros VG, Mikhailidis DP, Papageorgiou AA, et al. Targeting vascular risk in patients with metabolic syndrome but without diabetes. Metabolism. 2005;54:1065–1074. 5. Filippatos TD, Kiortsis DN, Liberopoulos EN, et al. Effect of orlistat, micronised fenofibrate and their combination on metabolic parameters in overweight and obese patients with the metabolic syndrome: the FenOrli study. Curr Med Res Opin. 2005;21:1997–2006. 6. Athyros VG, Mikhailidis DP, Liberopoulos EN, et al. Effect of statin treatment on renal function and serum uric acid levels and their relation to vascular events in patients with coronary heart disease and metabolic syndrome: a subgroup analysis of the GREek Atorvastatin and Coronary heart disease Evaluation (GREACE) Study. Nephrol Dial Transplant. 2007;22:118–127. 7. Davis TM, Ting R, Best JD, et al, Fenofibrate Intervention and Event Lowering in Diabetes Study Investigators. Effects of fenofibrate on renal function in patients with type 2 diabetes mellitus: the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) Study. Diabetologia. 2011;54:280–290.
A prop to explain LDL particles In my practice, I often order analyses of my patients’ lipids and lipoproteins by using nuclear magnetic resonance, which provides me with the number of lipoprotein particles as well as the cholesterol content of each major lipoprotein group, ie, very low-density lipoprotein, lowdensity lipoprotein (LDL), and high-density lipoprotein. Explaining these new measures to patients needs more than a few words and a written laboratory report. So, I came up with a simple model to help illustrate the concept of the LDL particle to patients. I hope the readership of the Journal will find this useful as well.
1933-2874/$ - see front matter Ó 2013 National Lipid Association. All rights reserved.
Letters to the Editor
89 representing the plasma LDL cholesterol content (in mg/ dL). On the bag of larger eggs, I represented the LDL particle number as 900 (nmoles/L). The bag containing the smaller eggs was labeled 1800 (nmoles/L) because it contained twice the number of eggs. I tell the patients, ‘‘You’ve heard about good cholesterol (also known as HDL cholesterol) and bad cholesterol (the cholesterol in the LDL). However, the LDL level may not tell the whole story. The LDL exists as tiny particles made up of several different fats, including cholesterol and a large protein. It is these particles that go into artery walls and form blockages that we call atherosclerosis, which can lead to heart attacks and strokes.’’ (I then point to a wall poster showing plaque progression). I then hold up the bags representing the same volume of blood. ‘‘This represents blood samples from two different patients that have the same LDL level, and you can see both bags are the same size. However, the patient with the small LDL has twice as many individual particles as the one with large LDL. So the patient with many small LDL has greater risk than the patient with fewer particles, even though their LDL cholesterol is exactly the same. An advanced cholesterol test, like you had, shows us this difference in risk, which may be missed by a standard test.’’ Almost all my patients seem to understand the concept of particle number after such an explanation.
I purchased bags of plastic eggs that contained 6 large eggs in a bag, and another bag of equal size that held 12 smaller eggs. I labeled both bags with a value of 90,
Daniel C. Ginsberg, MD, FACP Tacoma, WA http://dx.doi.org/10.1016/j.jacl.2012.02.009