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Cardiovascular & Hematological Agents in Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 1871-5257
ISSN (Online): 1875-6182

Research Article

Can Rosuvastatin Reduce the Risk of Thrombosis in Patients with Hypercholesterolemia with its Effect on Coagulation Factors and Homocysteine Levels?

Author(s): Mostafa Behnam, Mohammad Reza Deyhim* and Parichehreh Yaghmaei

Volume 22, Issue 4, 2024

Published on: 25 January, 2024

Page: [495 - 502] Pages: 8

DOI: 10.2174/0118715257279903231205110750

Price: $65

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Abstract

Background and Objectives: Hypercholesterolemia is one of the main risk factors for vascular thrombosis in individuals. Therefore, the use of statins is very effective in reducing cholesterol and can reduce the risk of thrombosis in these patients. Rosuvastatin, a member of the statin family which, inhibits cholesterol synthesis. Very few studies have been done in relation to how rosuvastatin can affect thrombosis. So, this research has been tried whether rosuvastatin can have an effect on coagulation factors and homocysteine as risk factors for thrombosis in hypercholesterolemia?

Methods: In this experimental study, 60 patients (30 men and 30 women with a mean age of 40- 70 years) diagnosed with hypercholesterolemia (cholesterol > 250 mg/dl) participated in this research. 30 patients were prescribed rosuvastatin (20 mg/day), and 30 patients were simultaneously taken placebo for three months. All parameters, including FVIII, FV, Fibrinogen, DDimer, plasma homocysteine level and lipid profile, were measured before and after treatment. All the results were statistically compared between the two groups.

Results: In patients who took rosuvastatin, the drug was able to significantly reduce the concentrations of total cholesterol, triglycerides, and low-density lipoprotein (LDL) (P < 0.001). Also, rosuvastatin was able to reduce the concentrations of homocysteine significantly, D-Dimer (P < 0.001), coagulation factor VIII and factor V (P < 0.05). In patients with hypercholesterolemia who took the placebo, did not affect the mentioned variables (P > 0.05).

Conclusion: According to the results, it seems that rosuvastatin may be able to reduce the risk of thrombosis in patients by affecting coagulation factors and homocysteine levels.

Keywords: Hypercholesterolemia, rosuvastatin, homocysteine, lipid profile, thrombosis, coagulation.

Graphical Abstract
[1]
Carvalho, A.C.A.; Colman, R.W.; Lees, R.S. Platelet function in hyperlipoproteinemia. N. Engl. J. Med., 1974, 290(8), 434-438.
[http://dx.doi.org/10.1056/NEJM197402212900805] [PMID: 4359434]
[2]
Aviram, M.; Brook, G.J. The effect of human plasma on platelet function in familial hypercholesterolemia. Thromb. Res., 1982, 26(2), 101-109.
[http://dx.doi.org/10.1016/0049-3848(82)90019-6] [PMID: 7112508]
[3]
Prasad, K.; Mishra, M. Mechanism of hypercholesterolemia-induced atherosclerosis. Rev. Cardiovasc. Med., 2022, 23(6), 212.
[http://dx.doi.org/10.31083/j.rcm2306212]
[4]
Sugrue, D.D.; Trayner, I.; Thompson, G.R.; Vere, V.J.; Dimeson, J.; Stirling, Y.; Meade, T.W. Coronary artery disease and haemostatic variables in heterozygous familial hypercholesterolaemia. Heart, 1985, 53(3), 265-268.
[http://dx.doi.org/10.1136/hrt.53.3.265] [PMID: 3970784]
[5]
Icli, A.; Aksoy, F.; Nar, G.; Kaymaz, H.; Alpay, M.F.; Nar, R.; Guclu, A.; Arslan, A.; Dogan, A. Increased mean platelet volume in familial hypercholesterolemia. Angiology, 2016, 67(2), 146-150.
[http://dx.doi.org/10.1177/0003319715579781] [PMID: 25859052]
[6]
Boos, C.J.; Lip, G.Y.H. Assessment of mean platelet volume in coronary artery disease-what does it mean? Thromb. Res., 2007, 120(1), 11-13.
[http://dx.doi.org/10.1016/j.thromres.2006.09.002] [PMID: 17046049]
[7]
Martinelli, N.; Girelli, D.; Lunghi, B.; Pinotti, M.; Marchetti, G.; Malerba, G.; Pignatti, P.F.; Corrocher, R.; Olivieri, O.; Bernardi, F. Polymorphisms at LDLR locus may be associated with coronary artery disease through modulation of coagulation factor VIII activity and independently from lipid profile. Blood, 2010, 116(25), 5688-5697.
[http://dx.doi.org/10.1182/blood-2010-03-277079] [PMID: 20810930]
[8]
Faeh, D.; Chiolero, A.; Paccaud, F. Homocysteine as a risk factor for cardiovascular disease: Should we (still) worry about? Swiss Med. Wkly., 2006, 136(47-48), 745-756.
[PMID: 17225194]
[9]
Chaturvedula, R.; Rao, K.; Rampure, D.; Rao, D.; Bhaskar, M. Atherogenic activity of hypercholesterolemia and hyperhomocysteinemia in complicated type 2 diabetes mellitus. IJHSR, 2014, 4(4), 61-68.
[10]
Fowler, B. Homocystein--an independent risk factor for cardiovascular and thrombotic diseases. Ther. Umsch., 2005, 62(9), 641-646.
[http://dx.doi.org/10.1024/0040-5930.62.9.641] [PMID: 16218503]
[11]
Deyhim, M.R.; Khoshnaghsh, F. Plasma homocysteine level and risk of thrombosis. J. Appl. Environ. Biol. Sci., 2016, 6(2), 1789-193.
[12]
Wilson, K.M.; McCaw, R.B.; Leo, L.; Arming, E.; Lhotok, S.; Ttglieri, B. Prothrombotic effects of hyperhomocysteinemia and hypercholesterolemia in ApoE-deficient mice. Arterioscler. Thromb. Vasc. Biol., 2007, 27(1), 233-240.
[13]
Zamani, A.; Omrani, G.R.; Lankarani, K.B. Hyperhomocysteinaemia, hyperlipidaemia and risk of venous thromboembolism in Shiraz. East. Mediterr. Health J., 2003, 9(5-6), 935-943.
[http://dx.doi.org/10.26719/2003.9.5-6.935] [PMID: 16450523]
[14]
Kocher, G.; Himmelmann, A. Portal vein thrombosis (PVT): A study of 20 non-cirrhotic cases. Swiss Med. Wkly., 2005, 135(25-26), 372-376.
[http://dx.doi.org/10.4414/smw.2005.11035] [PMID: 16106327]
[15]
Efficacy and safety of statin therapy in older people: A meta-analysis of individual participant data from 28 randomised controlled trials. Lancet, 2019, 393(10170), 407-415.
[http://dx.doi.org/10.1016/S0140-6736(18)31942-1] [PMID: 30712900]
[16]
Soran, H.; Adam, S.; Durrington, P.N. Are recent statin recommendations to employ fixed doses and abandon targets effective for treatment of hypercholesterolaemia? Investigation based on number needed to treat. Eur. J. Prev. Cardiol., 2017, 24(1), 76-83.
[http://dx.doi.org/10.1177/2047487316667785] [PMID: 27609614]
[17]
San Norberto, E.M.; Gastambide, M.V.; Taylor, J.H.; García-Saiz, I.; Vaquero, C. Effects of rosuvastatin as an adjuvant treatment for deep vein thrombosis. Vasa, 2016, 45(2), 133-140.
[http://dx.doi.org/10.1024/0301-1526/a000507] [PMID: 27058799]
[18]
Nguyen, C.D.; Andersson, C.; Jensen, T.B.; Gjesing, A.; Schjerning Olsen, A.M.; Malta Hansen, C.; Büller, H.; Torp-Pedersen, C.; Gislason, G.H. Statin treatment and risk of recurrent venous thromboembolism: A nationwide cohort study. BMJ Open, 2013, 3(11), e003135.
[http://dx.doi.org/10.1136/bmjopen-2013-003135] [PMID: 24202053]
[19]
Biedermann, J.S.; Kruip, M.J.H.A.; van der Meer, F.J.; Rosendaal, F.R.; Leebeek, F.W.G.; Cannegieter, S.C.; Lijfering, W.M. Rosuvastatin use improves measures of coagulation in patients with venous thrombosis. Eur. Heart J., 2018, 39(19), 1740-1747.
[http://dx.doi.org/10.1093/eurheartj/ehy014] [PMID: 29394348]
[20]
Lei, C.; Hau, L.I.; Qiang, X.; Yi, J. The effect of atorvastatin on homocysteine and carotid artery atherosclerosis in patient with H type hypertension. Chinese J. Arteriosclerosis., 2015, 23(8), 817-820.
[21]
Akbari, A.; Islampanah, M.; Arhaminiya, H.; Alvandi Fard, M.M.; Jamialahmadi, T.; Sahebkar, A.H. Impact of statin or fibrate therapy on homocysteine concentration: A systematic review and mata-analysis. Curr. Med. Chem., 2023, 31(14), 1920-1940.
[22]
Zinellu, A.; Mangoni, A.A. Effect of statin treatment on homocysteine concentrations: An updated systematic review and meta-analysis with meta-regression. Expert Rev. Clin. Pharmacol., 2022, 15(4), 443-459.
[http://dx.doi.org/10.1080/17512433.2022.2072293] [PMID: 35482022]
[23]
Geng, J.; Xu, H.; Fu, W.; Yu, X.; Xu, G.; Cao, H.; Lin, G.; Sui, D. Rosuvastatin protects against endothelial cell apoptosis in vitro and alleviates atherosclerosis in ApoE/mice by suppressing endoplasmic reticulum stress. Exp. Ther. Med., 2020, 20(1), 550-560.
[http://dx.doi.org/10.3892/etm.2020.8733] [PMID: 32537013]
[24]
Dennis, W.; Robert, H.; Knopp, M.D. A comparative effect of rosuvastatin and atorvastatin across their dose ranges in patients with hypercholesterolemia and without active arterial disease. Am. J. Cardiol., 2003, 91(1), 33-41.
[http://dx.doi.org/10.1016/S0002-9149(02)02994-6] [PMID: 12505568]
[25]
Guttormsen, A.B.; Schneede, J.; Fiskerstrand, T.; Ueland, P.M.; Refsum, H.M. Plasma concentrations of homocysteine and other aminothiol compounds are related to food intake in healthy human subjects. J. Nutr., 1994, 124(10), 1934-1941.
[http://dx.doi.org/10.1093/jn/124.10.1934] [PMID: 7931702]
[26]
Lüftjohann, D.; Sigit, J.I.; Locatelli, S.; von Bergmann, K.; Schmidt, H.H.A. High-dose simvastatin (80 mg/day) decreases plasma concentrations of total homocyst(e)ine in patients with hypercholesterolemia. Atherosclerosis, 2001, 155(1), 265-266.
[http://dx.doi.org/10.1016/S0021-9150(00)00735-8] [PMID: 11293393]
[27]
Ridker, P.M.; Shih, J.; Cook, T.J.; Clearfield, M.; Downs, J.R.; Pradhan, A.D.; Weis, S.E.; Gotto, A.M. Jr Plasma homocysteine concentration, statin therapy, and the risk of first acute coronary events. Circulation, 2002, 105(15), 1776-1779.
[http://dx.doi.org/10.1161/01.CIR.0000014447.06099.FB] [PMID: 11956118]
[28]
Bao, X.M.; Wu, C.F.; Lu, G.P. Atorvastatin inhibits homocysteine-induced oxidative stress and apoptosis in endothelial progenitor cells involving Nox4 and p38MAPK. Atherosclerosis, 2010, 210(1), 114-121.
[http://dx.doi.org/10.1016/j.atherosclerosis.2009.11.032] [PMID: 20018284]
[29]
Bao, X.; Wu, C.; Lu, G. Atorvastatin attenuates homocysteine-induced apoptosis in human umbilical vein endothelial cells via inhibiting NADPH oxidase-related oxidative stress-triggered p38MAPK signaling. Acta Pharmacol. Sin., 2009, 30(10), 1392-1398.
[http://dx.doi.org/10.1038/aps.2009.135] [PMID: 19767766]
[30]
Ghanima, W.; Abdelnoor, M.; Mowinckel, M.C.; Sandset, P.M. The performance of STA‐Liatest D ‐dimer assay in out‐patients with suspected pulmonary embolism. Br. J. Haematol., 2006, 132(2), 210-215.
[http://dx.doi.org/10.1111/j.1365-2141.2005.05859.x] [PMID: 16398655]
[31]
Ravnskov, U.; de Lorgeril, M.; Kendrick, M.; Diamond, D.M. Importance of coagulation factors as critical components of premature cardiovascular disease in familial hypercholesterolemia. Int. J. Mol. Sci., 2022, 23(16), 9146.
[http://dx.doi.org/10.3390/ijms23169146] [PMID: 36012410]
[32]
Alirezaei, T.; Irilouzadian, R.; Irilouzadian, R. Response: Comment on “Significant decrease in plasma D‐dimer levels and mean platelet volume after a 3‐month treatment with rosuvastatin in patients with venous thromboembolism”. Clin. Cardiol., 2022, 45(10), 976.
[http://dx.doi.org/10.1002/clc.23916] [PMID: 36073528]
[33]
Bordbar, M.; de Mutsert, R.; Cevval, M.; Rosendaal, F.R.; Jukema, J.W.; Lijfering, W.M.; Lijfering, W.M. Differential effect of statin use on coagulation markers: An active comparative analysis in the NEO study. Thromb. J., 2021, 19(1), 45.
[http://dx.doi.org/10.1186/s12959-021-00299-2] [PMID: 34176487]
[34]
Tripodi, A.; Pellegatta, F.; Chantarangkul, V.; Grigore, L.; Garlaschelli, K.; Baragetti, A.; Lemma, L.; Catapano, A. Statins decrease thrombin generation in patients with hypercholesterolemia. Eur. J. Intern. Med., 2014, 25(5), 449-451.
[http://dx.doi.org/10.1016/j.ejim.2014.03.016] [PMID: 24784951]
[35]
Undas, A.; Brummel-Ziedins, K.E.; Mann, K.G. Statins and blood coagulation. Arterioscler. Thromb. Vasc. Biol., 2005, 25(2), 287-294.
[http://dx.doi.org/10.1161/01.ATV.0000151647.14923.ec] [PMID: 15569822]
[36]
Woestijne, A.; Graaf, Y. Low high-density lipoprotein cholesterol is not a risk factor for recurrent vascular events in patients with vascular disease on intensive lipid-lowering medication. J. Am. Coll. Cardiol., 2013, 62(20), 1834-1841.
[37]
Ridker, P.M.; Danielson, E.; Fonseca, F.A.H.; Genest, J.; Gotto, A. Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein. N. Engl. J. Med., 2008, 359(21), 2195-2207.

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