- Email: [email protected]
Response to Mikhailidis et al
ATHEROSCLEROSIS Atherosclerosis
ELSEVIER
127 (1996)
289-290
Letter to the Editor
Response to Mikhailidis
et al.
Yoshiyasu Tsuda* Second Department
of Internal
Medicine. Received
hypercholestrolemic;
Keywords:
Kagalva
Medical
5 August
1996; accepted
f81
878 98 5111; fax:
0021-9150/96/515.00 Copyright PII SOO21-9150(96)05957-6
17%
I Ikenohe,
7 August
Miki-cho.
Kagulva
761-07.
Japan
1996
Plasma fibrinogen; Pravastatin sodium; Simvastatin
plasma fibrinogen concentration upon simvastatin administration may be related to the initial values’. Two other studies [3,4] also found significant reduction in plasma fibrinogen concentrations after pravastatin sodium administration, although in another study neither pravastatin sodium administration nor simvastatin administration [5] resulted in changed plasma fibrinogen concentrations after treatment. This was in contrast to our results [1] and those obtained in studies [2-41 on pravastatin sodium. In seven other studies on simvastatin cited by Dr. Mikhailidis et al, plasma fibrinogen concentrations were unchanged after simvastatin administration, which further confirmed our observed results. In our preliminary study on pravastatin sodium [6] involving a different group of patients, similar significant reductions in plasma fibrinogen concentrations occurred. However, in the comparative study [2] on pravastatin sodium (n = 16) and simvastatin (n = 16) mentioned above, platelet-thrombus formation was significantly (P < 0.05) inhibited in patients (n = 16) treated with pravastatin sodium, but not in patients (n = 16) treated with simvastatin, for both shear rates of 754 s -- ’ and 2546 s ~ ‘. These results are somewhat inconsistent with the findings [7-91 that pravastatin sodium significantly enhances platelet aggregability [7] and that simvastatin inhibits platelet activity [8,9]. Based on the results obtained in previous studies [lO,l I], it is obvious that decreases in plasma fibrinogen concentration bring about decreases in platelet aggregability. Dr. Mikhailidis et al.‘s other hypothesis, that ‘plasma albumin and fibrinogen concentrations arc inversely
We very much appreciate the interest shown by Dr. Mikhailidis and colleagues regarding our article [ 11, and are pleased to answer their questions and respond to their comments. Kesults of a comparative study [2] similar to ours, on the effects of pravastatin sodium (n = 16) and simvastatin (n = 16) on platelet-thrombus .formation in hypercholestrolemic coronary patients, were reported recently. In that study, the basal mean concentrations ( f S.D.) of total serum cholesterol and LDL cholesterol, as well as triglyceride, before medication showed the inverse situation to our study, being higher in patients treated with simvastatin (6.5 + 0.3 and 4.5 -t 0.3 mmol/l) than in patients treated with pravastatin sodium (6.1 f 0.1 and 4.1 f 0.1 mmol/l) [2]. After 2-3 months of medication, the plasma fibrinogen concentration decreased from 3.6 + 0.2 to 3.2 f 0.9 g/l in patients treated with pravastatin sodium. This decrease occurred in association with significant decreases in total serum cholesterol and LDL cholesterol concentrations (4.6 + 0.2 and 2.8 k 0.1 mmol/l). However, in patients treated with simvastatin, plasma fibrinogen concentration increased from 3.4 + 0.2 to 3.6 + 0.1 g/l, this increase also occurring in association with significant decreases in total serum cholesterol and LDL cholesterol concentrations (4.7 + 0.2 and 2.8 + 0.2 mmol/l). Thus, it is evident that Dr. Mikhailidis et al.‘s hypothesis that ‘any drop in fibrinogen may be related to its initial values’ may not be supported by these results, and may be better rephrased to say that ‘any increase in *Tel.:
Scl~ool,
-t 81 878 984962. 8 1996 Elsrvier
Science
Ireland
Ltd.
All
rights
reserved
290
Y. Tsuda I Atherosclerosis
related in the process of atherogenesis’ [12] is also not supported by the results obtained in our study regarding the patients both before and after treatment with pravastatin sodium. Despite significant reductions in plasma fibrinogen concentrations after pravastatin sodium administration, we found no increases in serum albumin concentrations (from 4.1 f 0.3 to 4.0 f 0.2 g/ dl), and the basal serum albumin concentrations did not show any difference before medication, between patients treated with pravastatin sodium or simvastatin and normal subjects (4.1 f 0.3, 4.1 + 0.3, and 4.1 + 0.3 g/dl, respectively) despite significant differences in basal plasma fibrinogen concentrations between the patients before medication and normal subjects (354 f 85, 313 + 56, vs 259 f 39 mg/dl, P < 0.0003 and P < 0.006, respectively). We also hope that more work will be conducted to clarify these issues.
References [l] Tsuda Y, Satoh K, Kitadai M, Takahashi T, Izumi Y, Hosomi N. Effects of pravastatin sodium and simvastatin on plasma fibrinogen level and blood rheology in type II hyperlipoproteinemia. Atherosclerosis 1996;122:225-233. [2] Lacoste L, Lam JYT. Comparative effect of pravastatin and simvastatin on platelet-thrombus formation in hypercholesterolemic coronary patients. Paper presented at the 45th Annual Meeting of American College of Cardiology, held on March 24428, 1996.
127 (1996)
289-290
[3] Jay RH, Rampling MW, Betteridge DJ. Abnormalities of blood rheology in familial hypercholesterolaemia: effects of treatment. Atherosclerosis 1990;85:249-256. [4] Avellone G, Di Garbo V, Cordova R, Reneli G, De Simone R, Bompiani G. Changes induced by pravastatin treatment on hemostatic and fibrinolytic patterns in patients with type Ilb hyperlipoproteinemia. Curr Therap Res 1994;55: 1335- 1344 [5] Branchi A, Rovellini A, Sommariva D, Guliandolo AG, Fasoli A. Effect of three fibrate derivatives and of two HMG-CoA reductase inhibitors on plasma fibrinogen level in patients with primary hypercholesterolemia. Thromb Haemostas 1993;70:241~ 243. [6] Tsuda Y, Satoh K, Takahashi T et al. Effect of medication with pravastatin sodium on hemorheological parameters in patients with hyperlipoproteinemia. Int Angiol 1993;12:360-364. [7] Broijersen A, Eriksson M, Laesson PT et al. Effects of selective LDL-apheresis and pravastatin therapy on platelet function in familial hypercholesterolaemia. Eur J Clin Invest 1994;24:488498. [8] Coumar A, Gill JK, Barradas MA, O’Donoghue S, Jeremy JY, Mikhailidis DP. The effect of treatment with simvastatin on platelet function indices in hypercholesterolaemia. J Drug Dev 1991;4:79-86. [9] Notarbartolo A, Davi G, Averna M, Barbagallo CM et al. Inhibition of thromboxane biosynthesis and platelet function by simvastatin in type IIa hypercholesterolemia. Arterioscler Thromb Vast Biol 1995;15:247-251. [lo] Niewiarowski S, Kornecki E, Budzynski AZ, Morinelli TA, Tuszynski GP. Fibrinogen interaction with platelet receptors. Ann NY Acad Sci 1983;408:536-555. [ll] Gogstad GO, Brosstad F, Krutnes M-B, Hagen I, Solum NO. Fibrinogen-binding properties of the human platelet glycoprotein IIb-IIIa complex: A study using crossed-radioimmunoelectrophoresis. Blood 1982;60:663-671. [12] Mikhailidis DP, Ganotakis ES. Plasma albumin and platelet function: relevance to atherogenesis and thrombosis. Platelets 1996;in press.
ELSEVIER
127 (1996)
289-290
Letter to the Editor
Response to Mikhailidis
et al.
Yoshiyasu Tsuda* Second Department
of Internal
Medicine. Received
hypercholestrolemic;
Keywords:
Kagalva
Medical
5 August
1996; accepted
f81
878 98 5111; fax:
0021-9150/96/515.00 Copyright PII SOO21-9150(96)05957-6
17%
I Ikenohe,
7 August
Miki-cho.
Kagulva
761-07.
Japan
1996
Plasma fibrinogen; Pravastatin sodium; Simvastatin
plasma fibrinogen concentration upon simvastatin administration may be related to the initial values’. Two other studies [3,4] also found significant reduction in plasma fibrinogen concentrations after pravastatin sodium administration, although in another study neither pravastatin sodium administration nor simvastatin administration [5] resulted in changed plasma fibrinogen concentrations after treatment. This was in contrast to our results [1] and those obtained in studies [2-41 on pravastatin sodium. In seven other studies on simvastatin cited by Dr. Mikhailidis et al, plasma fibrinogen concentrations were unchanged after simvastatin administration, which further confirmed our observed results. In our preliminary study on pravastatin sodium [6] involving a different group of patients, similar significant reductions in plasma fibrinogen concentrations occurred. However, in the comparative study [2] on pravastatin sodium (n = 16) and simvastatin (n = 16) mentioned above, platelet-thrombus formation was significantly (P < 0.05) inhibited in patients (n = 16) treated with pravastatin sodium, but not in patients (n = 16) treated with simvastatin, for both shear rates of 754 s -- ’ and 2546 s ~ ‘. These results are somewhat inconsistent with the findings [7-91 that pravastatin sodium significantly enhances platelet aggregability [7] and that simvastatin inhibits platelet activity [8,9]. Based on the results obtained in previous studies [lO,l I], it is obvious that decreases in plasma fibrinogen concentration bring about decreases in platelet aggregability. Dr. Mikhailidis et al.‘s other hypothesis, that ‘plasma albumin and fibrinogen concentrations arc inversely
We very much appreciate the interest shown by Dr. Mikhailidis and colleagues regarding our article [ 11, and are pleased to answer their questions and respond to their comments. Kesults of a comparative study [2] similar to ours, on the effects of pravastatin sodium (n = 16) and simvastatin (n = 16) on platelet-thrombus .formation in hypercholestrolemic coronary patients, were reported recently. In that study, the basal mean concentrations ( f S.D.) of total serum cholesterol and LDL cholesterol, as well as triglyceride, before medication showed the inverse situation to our study, being higher in patients treated with simvastatin (6.5 + 0.3 and 4.5 -t 0.3 mmol/l) than in patients treated with pravastatin sodium (6.1 f 0.1 and 4.1 f 0.1 mmol/l) [2]. After 2-3 months of medication, the plasma fibrinogen concentration decreased from 3.6 + 0.2 to 3.2 f 0.9 g/l in patients treated with pravastatin sodium. This decrease occurred in association with significant decreases in total serum cholesterol and LDL cholesterol concentrations (4.6 + 0.2 and 2.8 k 0.1 mmol/l). However, in patients treated with simvastatin, plasma fibrinogen concentration increased from 3.4 + 0.2 to 3.6 + 0.1 g/l, this increase also occurring in association with significant decreases in total serum cholesterol and LDL cholesterol concentrations (4.7 + 0.2 and 2.8 + 0.2 mmol/l). Thus, it is evident that Dr. Mikhailidis et al.‘s hypothesis that ‘any drop in fibrinogen may be related to its initial values’ may not be supported by these results, and may be better rephrased to say that ‘any increase in *Tel.:
Scl~ool,
-t 81 878 984962. 8 1996 Elsrvier
Science
Ireland
Ltd.
All
rights
reserved
290
Y. Tsuda I Atherosclerosis
related in the process of atherogenesis’ [12] is also not supported by the results obtained in our study regarding the patients both before and after treatment with pravastatin sodium. Despite significant reductions in plasma fibrinogen concentrations after pravastatin sodium administration, we found no increases in serum albumin concentrations (from 4.1 f 0.3 to 4.0 f 0.2 g/ dl), and the basal serum albumin concentrations did not show any difference before medication, between patients treated with pravastatin sodium or simvastatin and normal subjects (4.1 f 0.3, 4.1 + 0.3, and 4.1 + 0.3 g/dl, respectively) despite significant differences in basal plasma fibrinogen concentrations between the patients before medication and normal subjects (354 f 85, 313 + 56, vs 259 f 39 mg/dl, P < 0.0003 and P < 0.006, respectively). We also hope that more work will be conducted to clarify these issues.
References [l] Tsuda Y, Satoh K, Kitadai M, Takahashi T, Izumi Y, Hosomi N. Effects of pravastatin sodium and simvastatin on plasma fibrinogen level and blood rheology in type II hyperlipoproteinemia. Atherosclerosis 1996;122:225-233. [2] Lacoste L, Lam JYT. Comparative effect of pravastatin and simvastatin on platelet-thrombus formation in hypercholesterolemic coronary patients. Paper presented at the 45th Annual Meeting of American College of Cardiology, held on March 24428, 1996.
127 (1996)
289-290
[3] Jay RH, Rampling MW, Betteridge DJ. Abnormalities of blood rheology in familial hypercholesterolaemia: effects of treatment. Atherosclerosis 1990;85:249-256. [4] Avellone G, Di Garbo V, Cordova R, Reneli G, De Simone R, Bompiani G. Changes induced by pravastatin treatment on hemostatic and fibrinolytic patterns in patients with type Ilb hyperlipoproteinemia. Curr Therap Res 1994;55: 1335- 1344 [5] Branchi A, Rovellini A, Sommariva D, Guliandolo AG, Fasoli A. Effect of three fibrate derivatives and of two HMG-CoA reductase inhibitors on plasma fibrinogen level in patients with primary hypercholesterolemia. Thromb Haemostas 1993;70:241~ 243. [6] Tsuda Y, Satoh K, Takahashi T et al. Effect of medication with pravastatin sodium on hemorheological parameters in patients with hyperlipoproteinemia. Int Angiol 1993;12:360-364. [7] Broijersen A, Eriksson M, Laesson PT et al. Effects of selective LDL-apheresis and pravastatin therapy on platelet function in familial hypercholesterolaemia. Eur J Clin Invest 1994;24:488498. [8] Coumar A, Gill JK, Barradas MA, O’Donoghue S, Jeremy JY, Mikhailidis DP. The effect of treatment with simvastatin on platelet function indices in hypercholesterolaemia. J Drug Dev 1991;4:79-86. [9] Notarbartolo A, Davi G, Averna M, Barbagallo CM et al. Inhibition of thromboxane biosynthesis and platelet function by simvastatin in type IIa hypercholesterolemia. Arterioscler Thromb Vast Biol 1995;15:247-251. [lo] Niewiarowski S, Kornecki E, Budzynski AZ, Morinelli TA, Tuszynski GP. Fibrinogen interaction with platelet receptors. Ann NY Acad Sci 1983;408:536-555. [ll] Gogstad GO, Brosstad F, Krutnes M-B, Hagen I, Solum NO. Fibrinogen-binding properties of the human platelet glycoprotein IIb-IIIa complex: A study using crossed-radioimmunoelectrophoresis. Blood 1982;60:663-671. [12] Mikhailidis DP, Ganotakis ES. Plasma albumin and platelet function: relevance to atherogenesis and thrombosis. Platelets 1996;in press.