Effectiveness of atorvastatin on the levels of nitric oxide and serum lipids in coronary artery disease patients: Response to clopidogrel resistance

Ali A. R. Aldallal; Bassim I Mohammad; Ahmed N. Rgeeb; Dina A Jamil; Hayder A Al-Aubaidy

doi:10.12688/f1000research.130559.1

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Research Article

Effectiveness of atorvastatin on the levels of nitric oxide and serum lipids in coronary artery disease patients: Response to clopidogrel resistance

[version 1; peer review: awaiting peer review]

Ali A. R. Aldallal¹, Bassim I Mohammad², Ahmed N. Rgeeb³, Dina A Jamil^4,5, Hayder A Al-Aubaidy ⁴

Ali A. R. Aldallal¹, Bassim I Mohammad², [...] Ahmed N. Rgeeb³, Dina A Jamil^4,5, Hayder A Al-Aubaidy ⁴

PUBLISHED 05 Apr 2023

Author details Author details

¹ Department of Pharmacology & Therapeutics, University of Jabbir ibn Hayyan, Al-Najaf, Iraq
² Department of Pharmacology & Therapeutics, University of Al-Qadisiyah, Al-Qadisiyah, Iraq
³ Department of Medicine, University of Kufa, Al-Najaf, Iraq
⁴ Department of Microbiology, Anatomy, Physiology and Pharmacology & Centre for Cardiovascular Biology and Disease Research, La Trobe University, Melbourne, VIC, 3086, Australia
⁵ Oceania University of Medicine, Melbourne, VIC, 3086, Australia

Ali A. R. Aldallal
Roles: Conceptualization, Data Curation, Formal Analysis, Investigation, Methodology, Writing – Original Draft Preparation

Bassim I Mohammad
Roles: Conceptualization, Formal Analysis, Project Administration, Resources, Supervision, Writing – Original Draft Preparation

Ahmed N. Rgeeb
Roles: Conceptualization, Formal Analysis, Investigation, Methodology, Project Administration, Resources, Supervision, Writing – Original Draft Preparation

Dina A Jamil
Roles: Data Curation, Methodology, Resources, Validation, Writing – Review & Editing

Hayder A Al-Aubaidy
Roles: Conceptualization, Project Administration, Validation, Writing – Review & Editing

OPEN PEER REVIEW

REVIEWER STATUS AWAITING PEER REVIEW

Abstract

Introduction and aim: Lipid lower drugs have been widely used to prevent atherosclerosis in patients with heart disease. This study aims to compare the findings between the efficacy of 20 mg/day and 40 mg/day atorvastatin supplementation for 16 weeks, on nitric oxide level and lipid profile in clopidogrel resistant and non-resistant patients with coronary heart disease (CAD).

Methods: This retrospective study included two hundred and eighty-four participants with CAD. Patients were subjected to platelets function to determine the clopidogrel resistance. 88 patients were included into the clopidogrel resistant group, and 196 patients were included into the clopidogrel non-resistant group. Each group was subdivided into two subgroups depending on the daily dose of atorvastatin therapy (daily intake of 20 mg and 40 mg, orally).

Results: Irrelevant to the study group, there was significant increase in serum levels of NO following 40 mg/day clopidogrel supplementation for 16 weeks as compared to 20 mg/day clopidogrel supplementation, P ≤ 0.05. This was associated with a significant reduction in serum lipids (total cholesterol and LDL-C), P ≤ 0.05.

Conclusion: Atorvastatin supplementation improves serum nitric oxide level, and serum lipid profile in patients with CAD with and without clopidogrel resistance.

Keywords

Atorvastatin, Nitric Oxide, Clopedogrel, Serum Lipids, Coronary Artery Disease.

Corresponding author: Hayder A Al-Aubaidy

Competing interests: No competing interests were disclosed.

Grant information: The author(s) declared that no grants were involved in supporting this work.

Copyright: © 2023 Aldallal AAR et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

How to cite: Aldallal AAR, Mohammad BI, Rgeeb AN et al. Effectiveness of atorvastatin on the levels of nitric oxide and serum lipids in coronary artery disease patients: Response to clopidogrel resistance [version 1; peer review: awaiting peer review]. F1000Research 2023, 12:369 (https://doi.org/10.12688/f1000research.130559.1) First published: 05 Apr 2023, 12:369 (https://doi.org/10.12688/f1000research.130559.1) Latest published: 05 Apr 2023, 12:369 (https://doi.org/10.12688/f1000research.130559.1)

Introduction

Statins is a widely known medication which is used to reduce serum lipids. These medications are used to lower the production of endogenous cholesterol via reducing the activation of hydroxymethylglutaryl CoA reductase enzyme. This represents the rate-limiting step in cholesterol synthesis by the liver.¹ This results in decreased low-density lipoprotein (LDL) deposition in the vascular walls by upregulation of hepatic LDL-C receptors, an essential event in the pathogenesis of atherosclerosis.²

Atorvastatin is a widely used statin which augment nitric oxide (NO) activity and production through several ways, which eventually lead to increase expression and activity of endothelial NO synthase enzyme (eNOS). A previous study revealed a significant rise in eNOS levels following atorvastatin therapy in mice model.³ In addition, atorvastatin can reduce NO elimination through its effects on reactive oxygen species (ROS).⁴

The benefits above exert several clinical implications. Especially considering the essential activity of NO as vasodilator, inhibiting platelet aggregation, and it promote endothelial function.⁵ Increased NO production by endothelium could furthermore offer protection against stroke.⁶

Clopidogrel is a known platelet inhibitor, which has been widely used for the prevention of major complications of heart disease following percutaneous coronary intervention (PCI).⁶ Previous studies have shown that there was some inter-individual difference in clopidogrel response⁶^,⁷ and resistance to clopidogrel is related with an augmented risk of major adverse cardiac events (MACE).⁶^,⁷ Among the several risk factors that affect the response of platelet to clopidogrel therapy, smoking is linked with enhanced clopidogrel responsiveness.⁸ Although various processes have been proposed (including those regarding cytochrome P450 enzyme system), the exact mechanism is still unclear.⁸

Antiplatelet therapy is the backbone for the management and prevention of heart disease, including coronary heart disease, transient ischemic attack or minor stroke, and acute coronary syndrome (ACS). Clopidogrel which is P2Y₁₂ inhibitors was the first medication in this category, play an essential role in antiplatelet therapy and consequently in the treatment and prevention of CVD.⁹ However, there are several factors which may alter personal response to clopidogrel therapy. This is in addition to drugs.¹⁰

The main objective of the following project is to measure the efficacy of 2 known doses of atorvastatin (daily intake of 20 mg, and 40 mg oral supplementation for 16 weeks) on serum nitric oxide level and lipid profile in patients with heart disease, with and without clopidogrel resistance.

Methods

Research protocol

This was a comparative retrospective study performed at Al-Najaf Heart Surgery and Catheterization Center, Al-Najaf, Iraq, for the period between January 2019 - Jan 2021. Two hundred forty-eight patients were included in this study (202 males and 82 females), aged between 18-65 years clinically diagnosed with CAD (via angiography). As per the center guidelines, CAD diagnosis was confirmed by two cardiologists based on the clinical findings of 70% or more coronary artery stenosis affected at least one coronary blood vessel.

All CAD patients in this study had platelets reactivity tests to verify the level of clopidogrel resistance, then they were allocated into one of the two study groups: Clopidogrel resistant group (CR) and Clopidogrel non-resistant group (non-CR). All patients had atorvastatin therapy at one of the following two doses (20 mg or 40 mg, oral daily supplement) plus clopidogrel 75 mg/day for 16 weeks.

Subjects

This research was approved by “Human Research Ethics Committee”, College of Medicine, Kufa University (KUM457). Patients provided their oral and written approval to participate in this study. Eighty-eight patients were included in the CR group as compared to 196 participants included in the non-CR group. Data were taken from all the participants in this study including history and physical examinations (Table 1).

Table 1. Basic demographic data of the patients who were included in this study (N=284).

Parameter	Resistant group (n=88)		P-value	Non-Resistant group (n=196)		P-value
Atorvastatin	20 mg (n=37)	40 mg (n=51)	P-value	20 mg (n=94)	40 mg (n=102)	P-value
Age	57.64±1.27	56.09±1.3	0.41	58.13±0.83	57.06±0.77	0.34
BMI (kg/m²)	28.97±0.76	29.26±0.7	0.78	27.92±0.48	28.98±0.47	0.11
Gender (male)	21 (56.8%)	33 (64.7%)	0.44	70 (74.5%)	78 (76.5%)	0.74
Hypertension	24 (64.9%)	35 (62.6%)	0.71	55 (58.5%)	74 (72.5%)	0.33
Diabetes	9 (24.3%)	27 (52.9%)	0.007	50 (53.2%)	63 (61.8%)	0.05
Family history	11 (29.7%)	19 (35.8%)	0.46	38 (40.4%)	37 (36.3%)	0.55
Smoking	9 (24.3%)	18 (35.3%)	0.27	29 (30.9%)	30 (29.4%)	0.82

Participants were excluded if they have been recently diagnosed with acute coronary syndrome; peripheral artery disease; cancer; history of bleeding diathesis; unstable angina class I to III; or if they were aged ≥65 or ≤18; or pregnant or lactating mothers.

Collection and preparation of Blood sample

Eight milliliters of venous blood samples were taken into an EDTA tube from each participant. Blood samples were collected to measure serum levels of nitric oxide, platelet function test, and serum lipids.

Measurement of serum lipid profile

Serum lipid profile (TG, TC, LDL-C, HDL-C) were measured enzymatically using ELIZA kits from BIOLABO, France, kit reference number 95516.

Measurement of nitric oxide levels

Nitric oxide determined colormetrically in sera, based on that fact that both nitrate and nitrite exist in various regions of the cells. These chemical compounds can be produced via nitric oxide pathway without excessive uptake of nitrite and nitrate. Nitrite is able to interact with chromogenic agents to produce light-red azo compound. This can then be calculated by measurement of optical density at 550 nm.¹¹

Platelet aggregation test

Five milliliters of venous blood sample were taken from the participants. Samples were placed in test tubes for 1 hour, then underwent centrifugation at 3000 revolutions per minute for ten minutes at 25 °C. The platelet reactivity test was assisted by means of Multiplate analyzer^® (Verum Diagnostic, GmbH, Munich, Germany). The assay was quantified by the area under the aggregation curve (AUC) in units (U). In this study, the cutoff point for the ADP test that is used to determine the clopidogrel effect is value of UAC is 50 U, so any value ≥50 U is considered as clopidogrel resistance or non-responder, and values <50 U is non-clopidogrel resistance or responder.¹¹

Statistical analysis

All data of the study were examined by using SPSS (version 25, IBM, USA). In this study, descriptive statistics were used as numbers and percentages. To analyze categorical data or variables, we used the “Chi-Square test”. The independent variables student’s test was applied for comparing the results between the clopidogrel resistant group (CR) and clopidogrel non-resistant group (non-CR). Significant P values ≤0.05.

Results

Baseline characteristics and sex comparison

All the demographic data for the participants included in this study are shown in Table 1. No significant differences were noted in the mean levels of age, BMI, gender, hypertension, smoking status, and family history were observed between the study groups except for DM (P=0.054), Table 1.

Atorvastatin efficacy

The effects of atorvastatin on nitric oxide level

No significant relationship was identified between nitric oxide level in the resistant and the non-resistant groups for both the 20 mg and the 40 mg of atorvastatin (Table 2). However, 40 mg/day atorvastatin induced a more significant increase in NO levels across both study groupings, Table 2, P≤0.05.

Table 2. Atorvastatin effect on nitric oxide level among the participants included in this study (N = 248).

Atorvastatin	Resistant group (n=88)	Non-Resistant group (n=196)	P-value
Atorvastatin	Nitric oxide level (uM)	Nitric oxide level (uM)	P-value
Baselines	16.3±2.5	17.98±7.5	0.136*
20 mg	19.82±1.39 (n=37)	24.33±2.1 (n=94)	0.195†
40 mg	27.08±2.32 (n=51)	30.65±1.85 (n=102)	0.251†
P-value	0.016^#	0.24^#

* The Comparison between the baseline measurements for NO between the two study groups.

† The comparison between resistant and non-resistant groups for 20 mg of and the 40 mg of Atorvastatin.

# Within groups comparision for the effect of atorvastatin supplementation.

The correlation between the serum nitric oxide level, and platelet aggregation

A significant negative association between serum nitric oxide level and the percentage of platelet aggregation in all the participants of this study, Figure 1, P<0.05.

Figure 1. Correlation between the serum nitric oxide concentration and platelet aggregation among the participants in this study.

Atorvastatin effect on lipid profile

Irrelevant to the study group, using 40 mg/day atorvastatin significantly reduced serum lipids (total cholesterol and LDL-C), when compared to 20 mg/day atorvastatin dose. However, both triglycerides and HDL-C did not exert similar significance, Table 3.

Table 3. The effects of Atorvastatin on serum lipid profiles and platelet aggregation among the participants of this study.

Parameter	Resistant group		P-value	Non-Resistant group		P-value
Atorvastatin	20 mg (n=37)	40 mg (n=51)	P-value	20 mg (n=94)	40 mg (n=102)	P-value
Total Cholesterol (mg/dl)	210.67±10.75	174.41± 9.64	0.014	225.76± 1.33	170.83±26.86	0.05
Triglycerides (mg/dl)	163.24±18.63	158.51±19.45	0.86	168.63±12.54	159.9±14.36	0.6
LDL (mg/dl)	150.43±13.20	113.74±10.24	0.028	128.59±11.53	114.17±9.51	0.049
HDL (mg/dl)	35.05±8.88	33.99±3.46	0.9	35.14±7.92	33.19±3.12	0.81

Discussion

This is the first clinical study of its type to be conducted in Iraq and Middle East to highlight the therapeutic impacts of atorvastatin on nitric oxide levels and serum lipids and correlate the data with clopidogrel resistance. The study intended to evaluate the dose-response effects of two doses of atorvastatin (20 mg and 40 mg supplementation per a day for 16 weeks) on serum nitric oxide level and serum lipids in CAD patients, with variable clopidogrel resistance. All non-modifiable and modifiable risk factors were considered, including age, gender, obesity, family history of chronic illnesses (hyperglycemia & hypertension) and lifestyle factors. No significant differences between these factors and both doses of atorvastatin in resistant and non-resistant groups were found in exception to diabetes¹²^,¹³ and inconsistent with findings from others.¹⁴ Incidence of diabetes mellitus was significantly associated with both doses of atorvastatin in the clopidogrel resistant and non-resistant groups,¹⁵ but contract with the findings of Pandey et al.¹⁶

We could not find a statistical difference in nitric oxide levels between the clopidogrel resistant and clopidogrel non-resistant groups using 20 mg/day atorvastatin. Similarly, there was no significant difference with 40 mg/day atorvastatin use in both the clopidogrel resistant and non-resistant groups. However, the levels of nitric oxide were significantly elevated by increasing atorvastatin to 40 mg/day in both clopidogrel resistant and non-resistant groups, Table 2. Having said that, we noted a significant adverse correlation between serum levels of nitric oxide and the percentage of platelet aggregation in this cohort. These data are in accordance with the findings from previous studies.¹⁷

Moreover, increasing the dose of atorvastatin to 40 mg/day significantly decreased the level of total cholesterol and HDL-C, but not triglycerides and HDL-C in both study groups (Table 3).¹⁴ There is no clear understanding of the mechanism behind this. One explanation may be related to the link between levels of nitric oxide and its effects on CVD. The elevation in production nitric oxide might be caused by a compensatory mechanism towards CAD, which can produce more nitric oxide from the vascular endothelium.¹⁸^,¹⁹ This contradict the previous knowledge which hypothesized that a) the increased level of nitric oxide is not necessarily reflecting differences in nitric oxide activity, and b) racial differences between our current study participants (Iraqi Nationality) and other nationalities.²⁰ The variation in the outcomes of previous studies may be related to confounding factors which may include inclusion/exclusion criteria, sample size, racial, geographical, and environmental factors.²⁰^–²² Hence, it is worth considering all these factors when assessing the effectiveness of atorvastatin therapy in CAD.

In conclusion, atorvastatin supplementation improves the serum levels of nitric oxide and serum lipids (TC and LDL-C) in patients with CAD with and without clopidogrel resistance.

Limitations

Some of the potential limitations of this study include the fact that this study was taken from one region within Iraq, and it would be more reflective if it includes participants across all regions of Iraq. Second, nitric oxide measurement was assessed colormetrically using enzymatic technique which may possess medium sensitivity. It would be best to use alternative more automated techniques for future assay. Therefore, further, more inclusive, study would be good to have a better insight on the role of atorvastatin on serum nitric oxide level in patients with heart disease with and without clopidogrel resistance.

Authors’ contribution

Conceptualization, A.A., A.R., B.M., and H.A.; methodology, A.A., D.J., B.M., and A.R.; investigation, H.A., A.R., A.A., and B.M.; writing—original draft preparation, A.A., B.M., and A.R.; review and editing, H.A., and D.J.; supervision, B. M., and A.R. Authors have read and agreed to the final version of the manuscript.

Data availability

Figshare. Effectiveness of atorvastatin on the levels of nitric oxide and serum lipids in coronary artery disease patients: Response to clopidogrel resistance. DOI: https://doi.org/10.6084/m9.figshare.21944660.v1.²³

This project contains the following data:

- Correlation between nitric oxide levels and plateet aggregation in the study groups

Data are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).

Acknowledgment

The authors thank members of the Pharmacology and Therapeutic Department of University of Kufa.

References

1. Al-Rasheed NM, Al-Rasheed NM, Hasan IH, et al.: Simvastatin Ameliorates Diabetic Cardiomyopathy by Attenuating Oxidative Stress and Inflammation in Rats. Oxidative Med. Cell. Longev. 2017; 2017: 1092015.
2. Banach M, Aronow WS, Serban C, et al.: Lipids, blood pressure and kidney update 2014. Pharmacol. Res. 2015; 95-96: 111–125. PubMed Abstract | Publisher Full Text
3. Laufs U, Endres M, Custodis F, et al.: Suppression of endothelial nitric oxide production after withdrawal of statin treatment is mediated by negative feedback regulation of rho GTPase gene transcription. Circulation. 2000; 102: 3104–3110. PubMed Abstract | Publisher Full Text
4. Piechota-Polanczyk A, Kopacz A, Kloska D, et al.: Simvastatin Treatment Upregulates HO-1 in Patients with Abdominal Aortic Aneurysm but Independently of Nrf2. Oxidative Med. Cell. Longev. 2018; 2018: 2028936.
5. Amore L, Alghisi F, Pancaldi E, et al.: Study of endothelial function and vascular stiffness in patients affected by dilated cardiomyopathy on treatment with sacubitril/valsartan. Am. J. Cardiovasc. Dis. 2022; 12: 125–135. PubMed Abstract
6. Garry PS, Ezra M, Rowland MJ, et al.: The role of the nitric oxide pathway in brain injury and its treatment--from bench to bedside. Exp. Neurol. 2015; 263: 235–243. PubMed Abstract | Publisher Full Text
7. Kheiri B, Osman M, Abdalla A, et al.: CYP2C19 pharmacogenetics versus standard of care dosing for selecting antiplatelet therapy in patients with coronary artery disease: A meta-analysis of randomized clinical trials. Catheter. Cardiovasc. Interv. 2019; 93: 1246–1252. PubMed Abstract | Publisher Full Text
8. Westphal ES, Aladeen T, Vanini D, et al.: Generic Clopidogrel: Has Substitution for Brand Name Plavix^® Been Effective? J. Pharm. Pract. 2022; 35: 536–540. PubMed Abstract | Publisher Full Text
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11. Kweon OJ, Lim YK, Kim B, et al.: Effectiveness of Platelet Function Analyzer-100 for Laboratory Detection of Anti-Platelet Drug-Induced Platelet Dysfunction. Ann. Lab. Med. 2019; 39: 23–30. PubMed Abstract | Publisher Full Text | Free Full Text
12. Nguyen QD, Peters E, Wassef A, et al.: Evolution of Age and Female Representation in the Most-Cited Randomized Controlled Trials of Cardiology of the Last 20 Years. Circ. Cardiovasc. Qual. Outcomes. 2018; 11: e004713. PubMed Abstract | Publisher Full Text
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Author details Author details

¹ Department of Pharmacology & Therapeutics, University of Jabbir ibn Hayyan, Al-Najaf, Iraq
² Department of Pharmacology & Therapeutics, University of Al-Qadisiyah, Al-Qadisiyah, Iraq
³ Department of Medicine, University of Kufa, Al-Najaf, Iraq
⁴ Department of Microbiology, Anatomy, Physiology and Pharmacology & Centre for Cardiovascular Biology and Disease Research, La Trobe University, Melbourne, VIC, 3086, Australia
⁵ Oceania University of Medicine, Melbourne, VIC, 3086, Australia

Ali A. R. Aldallal
Roles: Conceptualization, Data Curation, Formal Analysis, Investigation, Methodology, Writing – Original Draft Preparation

Bassim I Mohammad
Roles: Conceptualization, Formal Analysis, Project Administration, Resources, Supervision, Writing – Original Draft Preparation

Ahmed N. Rgeeb
Roles: Conceptualization, Formal Analysis, Investigation, Methodology, Project Administration, Resources, Supervision, Writing – Original Draft Preparation

Dina A Jamil
Roles: Data Curation, Methodology, Resources, Validation, Writing – Review & Editing

Hayder A Al-Aubaidy
Roles: Conceptualization, Project Administration, Validation, Writing – Review & Editing

Competing interests

No competing interests were disclosed.

Grant information

The author(s) declared that no grants were involved in supporting this work.

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Published: 05 Apr 2023, 12:369

https://doi.org/10.12688/f1000research.130559.1

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© 2023 Aldallal AAR et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Aldallal AAR, Mohammad BI, Rgeeb AN et al. Effectiveness of atorvastatin on the levels of nitric oxide and serum lipids in coronary artery disease patients: Response to clopidogrel resistance [version 1; peer review: awaiting peer review]. F1000Research 2023, 12:369 (https://doi.org/10.12688/f1000research.130559.1)

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[1] 1. Al-Rasheed NM, Al-Rasheed NM, Hasan IH, et al.: Simvastatin Ameliorates Diabetic Cardiomyopathy by Attenuating Oxidative Stress and Inflammation in Rats. Oxidative Med. Cell. Longev. 2017; 2017: 1092015.

[2] 2. Banach M, Aronow WS, Serban C, et al.: Lipids, blood pressure and kidney update 2014. Pharmacol. Res. 2015; 95-96: 111–125. PubMed Abstract | Publisher Full Text

[3] 3. Laufs U, Endres M, Custodis F, et al.: Suppression of endothelial nitric oxide production after withdrawal of statin treatment is mediated by negative feedback regulation of rho GTPase gene transcription. Circulation. 2000; 102: 3104–3110. PubMed Abstract | Publisher Full Text

[4] 4. Piechota-Polanczyk A, Kopacz A, Kloska D, et al.: Simvastatin Treatment Upregulates HO-1 in Patients with Abdominal Aortic Aneurysm but Independently of Nrf2. Oxidative Med. Cell. Longev. 2018; 2018: 2028936.

[5] 5. Amore L, Alghisi F, Pancaldi E, et al.: Study of endothelial function and vascular stiffness in patients affected by dilated cardiomyopathy on treatment with sacubitril/valsartan. Am. J. Cardiovasc. Dis. 2022; 12: 125–135. PubMed Abstract

[6] 6. Garry PS, Ezra M, Rowland MJ, et al.: The role of the nitric oxide pathway in brain injury and its treatment--from bench to bedside. Exp. Neurol. 2015; 263: 235–243. PubMed Abstract | Publisher Full Text

[7] 7. Kheiri B, Osman M, Abdalla A, et al.: CYP2C19 pharmacogenetics versus standard of care dosing for selecting antiplatelet therapy in patients with coronary artery disease: A meta-analysis of randomized clinical trials. Catheter. Cardiovasc. Interv. 2019; 93: 1246–1252. PubMed Abstract | Publisher Full Text

[8] 8. Westphal ES, Aladeen T, Vanini D, et al.: Generic Clopidogrel: Has Substitution for Brand Name Plavix^® Been Effective? J. Pharm. Pract. 2022; 35: 536–540. PubMed Abstract | Publisher Full Text

[9] 9. Patti G, Micieli G, Cimminiello C, et al.: The Role of Clopidogrel in 2020: A Reappraisal. Cardiovasc. Ther. 2020; 2020: 8703627.

[10] 10. Yigit S, Nursal AF, Uzun S, et al.: Impact of Endothelial NOS VNTR Variant on Susceptibility to Diabetic Neuropathy and Type 2 Diabetes Mellitus. Curr. Neurovasc. Res. 2020; 17: 700–705. PubMed Abstract | Publisher Full Text

[11] 11. Kweon OJ, Lim YK, Kim B, et al.: Effectiveness of Platelet Function Analyzer-100 for Laboratory Detection of Anti-Platelet Drug-Induced Platelet Dysfunction. Ann. Lab. Med. 2019; 39: 23–30. PubMed Abstract | Publisher Full Text | Free Full Text

[12] 12. Nguyen QD, Peters E, Wassef A, et al.: Evolution of Age and Female Representation in the Most-Cited Randomized Controlled Trials of Cardiology of the Last 20 Years. Circ. Cardiovasc. Qual. Outcomes. 2018; 11: e004713. PubMed Abstract | Publisher Full Text

[13] 13. Loch A, Bewersdorf JP, Kofink D, et al.: Generic atorvastatin is as effective as the brand-name drug (LIPITOR^®) in lowering cholesterol levels: a cross-sectional retrospective cohort study. BMC. Res. Notes. 2017; 10: 291. PubMed Abstract | Publisher Full Text | Free Full Text

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Effectiveness of atorvastatin on the levels of nitric oxide and serum lipids in coronary artery disease patients: Response to clopidogrel resistance

Abstract

Keywords

Introduction

Methods

Research protocol

Subjects

Table 1. Basic demographic data of the patients who were included in this study (N=284).

Collection and preparation of Blood sample

Measurement of serum lipid profile

Measurement of nitric oxide levels

Platelet aggregation test

Statistical analysis

Results

Baseline characteristics and sex comparison

Atorvastatin efficacy

Table 2. Atorvastatin effect on nitric oxide level among the participants included in this study (N = 248).

Figure 1. Correlation between the serum nitric oxide concentration and platelet aggregation among the participants in this study.

Table 3. The effects of Atorvastatin on serum lipid profiles and platelet aggregation among the participants of this study.

Discussion

Limitations

Authors’ contribution

Data availability

Acknowledgment

References

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