International Journal of Cardiovascular ResearchISSN: 2324-8602

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Research Article, Int J Cardiovas Res Vol: 5 Issue: 6

Garlic Effects on Coronary Artery Calcium

Madaj Paul M1*, Nelson JR2, Li D1, Ferdinand F1 and Budoff MJ1
1Los Angeles Biomedical Institute at Harbor-UCLA, USA
2University of California- Fresno, USA
Corresponding author : Madaj Paul M
Los Angeles Biomedical Institute at Harbor-UCLA, USA
E-mail: [email protected]
Received: September 27, 2016 Accepted: October 22, 2016 Published:October 28, 2016
Citation: Madaj Paul M, Nelson JR, Li D, Ferdinand F, Budoff MJ (2016) Garlic Effects on Coronary Artery Calcium. Int J Cardiovasc Res 5:6. doi:10.4172/2324-8602.1000285

Abstract

Introduction: Coronary Artery Disease (CAD) is one of the leading causes of morbidity and mortality in the world. Detection as well as modification of risk factors for cardiovascular disease (CVD) has been the topics research over several decades. Garlic has been noted to have a prominent role in the modification of risk factors including hypercholesteerolemia, hypertension and atherosclerosis. Garlic was found to have a role in reduction in SBP in those with elevated blood pressure, both central and peripheral. Previous studies have indicated a role for garlic in prevention of progression of atherosclerosis. Garlic has shown to have an inhibitory role in the progression of non-calcified coronary plaque. We sought to evaluate if the plaque progression properties of aged garlic extract (AGE) were related to remnant lipoproteins. Methods: Study population and randomization- The present study is a placebo-controlled double-blinded study. Seventy two patients were enrolled and underwent CCTA. The Investigational Review Board of Los Angeles Biomedical Research Institute at Harbor- UCLA approved this research project. All the patients signed informed written consent after careful explanation and review of protocol. Eligible participants were 40 to 75 years of age who had at least 2 components of the metabolic syndrome as defined by ATP III Clinical Identification of METs (including impaired fasting glucose >110 mg/dL, treated hypertension or systolic blood pressure >130 mmHg or diastolic blood pressure >85 mmHg, triglycerides >150 mg/dL, HDL cholesterol <35 mg/dL for men or <40 mg/dL for women, abdominal obesity defined by waist circumference >40 in for men or >35 in for women) . Glucose and cholesterol was assayed from serum using an Abbott autoanalyzer. Our participants all have a 10-years Framingham risk of coronary artery disease of 6-20%. Patients were assigned in 1:1 ratio to receive 2400 mg/day of AGE, or placebo. The intended duration of administration for the study group was 52 weeks. Results: Our results demonstrate baseline CAC 488.5 ± 723.2 in placebo group vs 168.4 ± 361.9 in garlic group (p-value 0.04). Follow up CAC results as follows: 577.9 ± 863.1 in placebo group vs 213.6 ± 470.6 in garlic group (p-value 0.05). The lipid profile results were not able to demonstrate statistically significant results. Conclusion: Our study was able to demonstrate a prominent role of garlic on CAC. We show that garlic does contribute and has a prominent role in the prevention and treatment of coronary artery disease. Despite our study not demonstrating a significant reduction in remnant lipoprotein along with triglycerides and inflammatory markers, other studies do demonstrate this link with garlic. Follow up studies are needed to evaluate the role of garlic on the various components of the atherosclerotic process.

Keywords: Coronary artery disease; Hypercholesterolemia; Garlic; Cardiovascular disease

Keywords

Coronary artery disease; Hypercholesterolemia; Garlic; Cardiovascular disease

Abbreviations

CCTA: Cardiac Computed Tomography Angiography; METs: Metabolic syndrome; CAC: Coronary Artery Calcium; SBP: Systolic Blood Pressure; LDL: Low Density Lipoprotein; HDL: High Density Lipoprotein; CRP: C-Reactive Protein

Introduction

Coronary Artery Disease (CAD) is one of the leading causes of morbidity and mortality in the world. Detection as well as modification of risk factors for cardiovascular disease (CVD) have been the topics of research over several decades. Multiple drugs have been studied and used in clinical practice with people seeking “natural” alternatives. In various cultures, garlic has been thought to have therapeutic uses. Thus, recent focus has been on the use of garlic as a validated treatment to reduce CVD risk. Garlic has been noted to have a prominent role in the modification of risk factors including hypercholesterolemia, hypertension and atherosclerosis [1-5]. In a meta-analysis by Reinhart et al. [6] examined the role of garlic on reduction of total cholesterol, driven mostly by reduction in triglycerides (TAG). Garlic was found to have a role in the reduction of SBP in patients with elevated blood pressure, both central and peripheral [7,8]. Garlic has also been demonstrated in studies to have an effect on the lipid profile. Of all the components of the lipid panel, well known are the effects of LDL, triglycerides, total cholesterol and their role in CAD. If fact, the component most potent for creating a proinflamatory state is the remnant lipoprotein cholesterol [9]. Remnant lipoproteins (RLPs) are products of partially catabolized chylomicrons and very-low-density lipoprotein, from which some triglycerides have been removed, that are found to be highly arythmogenic [9]. Remnants are known to cross the endothelial barrier and due to their larger size, they carry 5 to 20 times as much cholesterol per particle as LDL [10]. Remnant (apo A1 remnant ratio) association with short and intermediate term mortality was shown to be a significant predictor, especially in women above 50 years of age [11]. Previous studies have indicated a role for garlic in prevention of progression of atherosclerosis. Garlic has shown to have an inhibitory role in the progression of non-calcified coronary plaque [12]. It has been found in studies to have a prominent role in affecting inflammatory markers demonstrated by decreased levels of CRP and Il-17A [13], thus allowing garlic to have a direct role on the atherosclerotic process [14,15]. We sought to evaluate if the plaque progression properties of aged garlic extract (AGE) were related to remnant lipoproteins.

Materials and Methods

Study population and randomization
The present study is a placebo-controlled double-blinded study. Seventy two patients were enrolled and underwent CCTA. The Investigational Review Board of Los Angeles Biomedical Research Institute at Harbor-UCLA approved this research project. All the patients signed informed written consent after careful explanation and review of protocol. Eligible participants were 40 to 75 years of age who had at least 2 components of the metabolic syndrome as defined by ATP III. Clinical Identification of METs (including impaired fasting glucose >110 mg/dL, treated hypertension or systolic blood pressure >130 mmHg or diastolic blood pressure >85 mmHg, triglycerides >150 mg/dL, HDL cholesterol <35 mg/dL for men or <40 mg/dL for women, abdominal obesity as defined as waist circumference >40 in for men or >35 in for women). Glucose and cholesterol was assayed from serum using an Abbott autoanalyzer. Our participants all have a 10-years Framingham risk of coronary artery disease of 6-20%. Patients were assigned in 1:1 ratio to receive 2400 mg/day of AGE, or placebo. The intended duration of administration the study group was 52 weeks.
Exclusion criteria
We excluded patients with known hypersensitivity to garlic therapy, renal impairment (serum creatinine >1.4 mg/dL), New York Heart Association (NYHA) Functional Classification II-IV heart failure, triglyceride >400 mg/dL at first visit, documented current diabetes or taking any anti-diabetic drug, current tobacco use, or current enrollment in another placebo-controlled trial.
Aged garlic extract
As previously demonstrated, Aged Garlic Extract (AGE, Kyolic®), provided by Wakunaga of America Co., Ltd. (Mission Viejo, California), was formulated by soaking sliced raw garlic in aqueous ethanol for up to 20 month at room temperature. The extract was then filtered and concentrated at low temperature. The AGE used in this trial contained 305 g/L of extracted solids. The finished product used in this clinical study was commercially available.
Clinical analysis
Blood samples were collected after a 12-h fast. Sample were stored at -70oC and analyzed for serum glucose, lipid profile including serum LDL-cholesterol, serum HDL-cholesterol and serum triglyceride using automated diagnostic equipment (DLZ Laboratories).
Statistical analysis
Continuous variables were expressed as mean ± SD. Comparisons of all parameters between the groups of AGE and placebo were made with the Student’s t test. Categorical variables were expressed as counts and percentages and X2 Test was used for comparisons between placebo group and AGE group. To correct for differences in baseline values, we performed multiple linear regression analysis. By multivariable linear regression analysis, we examined if AGE is associated with change in cholesterol values, after adjusting for age, gender, number of risk factors, hyperlipidemia medications, and history of known CAD. A value of P<0.05 was considered statistically significant. All statistical analyses were performed using SAS (Statistical Analysis System) software (version 9.3 SAS institute, Cary, North Carolina).

Results

Our results demonstrate baseline CAC 488.5 ± 723.2 in placebo group vs 168.4 ± 361.9 in garlic group (p-value 0.04). Follow up CAC results as follows: 577.9 ± 863.1 in placebo group vs 213.6 ± 470.6 in garlic group (p-value 0.05). The lipid profile results were not able to demonstrate statistically significant results (Tables 1 and 2).
Table 1: Demographics and Clinical Characteristics of Participants.
Table 2: Lipid results.

Discussion

Through multiple randomized trials, Hom et al. [2] were able to demonstrate a significant reduction in Coronary Artery Calcium (CAC) progression. This is demonstrated through its direct role on the atherosclerotic process [14,15]. In a study by Budoff et al. [14] and Ahmadi et al. [15], aged garlic extract supplemented with B vitamins, folic acid and L-arginine had a positive role in not only reducing atherosclerosis but improvement in oxidative biomarkers and vascular function. Matsumoto et al. [12] was able to establish the role of aged garlic extract and its role in coronary plaque. However, this study did not demonstrate a significant effect of garlic on components of the lipid profile.
In a study by de Vries et al. [16], chylomicrons were shown to be more potent in causing inflammation when compared to hypertriglyceridemia [16,17]. As shown by Matsuo et al. [18], remnant lipoprotein levels have been linked to coronary plaque vulnerability, which is characterized by high necrotic and low fibrotic components. Thus, remnant lipoproteins are well known and becoming more established as risk factors for CAD [17]. Nakamura et al. [19,20] was also able to establish the role of insulin resistance as also contributing to postprandial hyperlipidemia, especially in those with CAD, thus possibly requiring more aggressive treatment of such states. Well known at this time is the role of statins in dyslipidemia treatment. When evaluating for optimal treatment options, multiple risk factors for CAD (e.g. diabetes, hypertension, etc.) need to be accounted for, in which garlic can play a prominent role. In regards to other coronary risk factors, the AGE at Heart trial was able to establish a direct link of garlic on central and peripheral hypertension; as an adjunct or stand-alone treatment [7,8]. In our cohort, the patients SBP was well controlled .Thus, evidence does exist on the role of garlic on modification of coronary artery disease risk factors- especially role in treating hypertension along with altering the lipid profile; more specifically, remnant lipoproteins. Further follow-up on aged garlic and plaque burden; provided through direct imaging; along with inflammatory markers and lipid profile components is needed.

Limitations

Our study is limited by the sample size. We will need a larger sample size in follow up studies to determine the role of garlic on the lipid profile. Our future population may need to include patients with poorly controlled risk factors, including triglycerides, to demonstrate the benefit of garlic.

Conclusion

Our study was able to demonstrate a prominent role of garlic on CAC. We show that garlic does contribute and has a prominent role in the prevention and treatment of coronary artery disease. Despite our study not demonstrating a significant reduction in remnant lipoprotein along with triglycerides and inflammatory markers, other studies do demonstrate this link with garlic. Follow up studies are needed to evaluate the role of garlic on the various components of the atherosclerotic process.

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