Evaluation of the Coenzyme Q10 and Some Biochemical Parameters in Patients with Ischemic Heart Disease

1. Introduction

Ischemic heart disease (IHD) is still a significant burden on individuals and healthcare resources worldwide. Despite clinical practice strategies that have evolved to optimize treatment for IHD, the consequences represent a significant burden on human health in terms of mortality and morbidity ( 1 , 2 ). In 2015, IHD affected 110 million people and resulted in 8.9 million deaths. It is the reason for 15.6% of all deaths, making it the most common cause globally. The risk of death from IHD for a given age decreased between 1980 and 2010, especially in developed countries ( 1 ). The IHD has a number of well-determined risk factors, including hypertension, smoking, diabetes mellitus (DM), lack of exercise, obesity, high blood cholesterol, depression, and family history. It should be noted that nearly half of the cases are linked to genetics. Moreover, smoking and obesity are associated with 36% and 20% of cases, respectively ( 1 , 2 ).

Coenzyme Q₁₀ (CoQ₁₀) is an essential human body compound that is synthesized in the mitochondrial inner membrane. The CoQ₁₀ has many important functions in the human body. First, it can be named the key component of the electron transport chain in mitochondria necessary for ATP production as the CoQ₁₀ transfers electrons from complex-1 to complex-3. Furthermore, it plays a role in the transfer of protons in the inner mitochondrial membrane. This process is called protonmotive Q-cycle ( 3 ).

As a result of its important place in the functioning of organisms, there are many diseases and degenerative states associated with the deficiency of CoQ₁₀, such as DM, cardiovascular disease (CVD, including atherosclerosis, hypertension, and dyslipidemia), muscular dystrophy, Alzheimer's disease, and Parkinson's disease ( 4 ). Since CoQ₁₀ is an essential compound of the human body, there is growing evidence that COQ₁₀ is tightly linked to cardiometabolic disorders. Its supplementation can be useful in various chronic and acute disorders ( 5 ).

2. Materials and Methods

This case-control study was conducted at the Intensive Care Unit (ICU) of Ibn-Sina Teaching Hospital and Al-Salam General Hospital in Nineveh Province, Iraq, for two months, from April 1 to June 1, 2022. This study included 90 adult participants divided into two groups:

Case group: Included 60 patients admitted to the ICU and diagnosed with IHDs (myocardial infarction [MI] or angina pectoris).

Control group: Included 30 healthy participants matched in age and gender with the case group.

Diagnosis of IHD was based on symptoms, electrocardiogram, and biochemical markers of myocardial necrosis.

The blood samples were drawn from the vein. After cleaning the venipuncture site with iodine, 5 mm (10 ml) of blood sample was collected from each patient. It should be mentioned that the blood was drawn into a Gel Tube. The specimen for the gel tube was separated by centrifugation at 3,000 rpm for 10 min to get the serum. The separated serum was stored at –20 °C for the subsequent assay of

✓ Lipid profile, CRP, and CPK by COBAS C 111 technique.

✓ Troponin level by COBAS C 411 technique.

✓ Serum CoQ₁₀ by Enzyme-Linked Immunosorbent Assay Kit.

Verbal permission was obtained from each participant before data collection, and the information was anonymous. Names were removed and replaced by identification codes. All information is kept confidential in a password-secured laptop, and data is used exclusively for research purposes.

Official approval was granted from the Scientific Committee in the Department of Clinical Biochemistry, College of Medicine, Tikrit University, Tikrit, Iraq. Letter of facilitation was obtained from Tikrit College of Medicine to Ibn-Sina Teaching Hospital and Al-Salam General Hospital.

2.1. Statistical Analysis

The data were analyzed in the SPSS software (version 26) and presented as mean, standard deviation, and ranges. Frequencies and percentages present categorical data. An independent t-test (two-tailed) was used to compare the continuous variables between study groups. Pearson's correlation test (r) was also used to assess the correlation between the CoQ₁₀ marker level with specific parameters. A P value of less than 0.05 was considered statistically significant.

3. Results

In total, 90 patients participated in this study and were divided into case and control groups. The case group included 60 patients diagnosed with IHD, and the control group included 30 healthy participants.

3.1. Sociodemographic Characteristics

The distribution of study groups by sociodemographic characteristics is shown in figure 1 and table 1. Study participants were within the age ranges of 18-100 years old, with a mean age of 52.37±16.6 years old. The majority of patients in the case group were aged ≥ 60 years (50%), while 50% of the controls were aged < 40 years.

Figure 1. Distribution of study groups by age

In this study, the majority of participants in the case and control groups were male (70% and 80%, respectively) and employees (46.7% and 70%, respectively). Regarding the body mass index (BMI) level, 50% of the case group was overweight, while 66.7% of the control group had normal BMI levels.

3.2. Clinical Information

Table 2 summarizes the distribution of study groups by certain clinical information. It was noticed that 43.4% of the cases and 83.3% of the controls were smokers, and 40% of cases and 53.3% of controls had a positive family history of IHD. Regarding chronic medical diseases, 48.3% of cases had hypertension and DM, while most controls did not have chronic diseases (86.7%).

3.3. Diagnosis of Patients in the Case Group

As shown in figure 2, 81.7% of patients in the case group were diagnosed with MI.

Figure 2. Distribution of case group by diagnosis

3.4. Biochemical parameters

Table 3 tabulates the distribution of study groups by specific biochemical parameters. In the case group, 71.7%, 100%, 63.3%, and 86.7% had high LDH levels, high CRP levels, high CPK levels, and high troponin levels, respectively. In the group of healthy individuals, 36.7% had high LDH levels, all had normal CRP and CPK, and 3.3% had high troponin levels.

3.4.1. Comparison between Study Groups

Table 4. summarizes the comparison of specific biochemical parameters between study groups. it can be noticed that means of serum LDH, CRP, CPK, and troponin were significantly higher in the case group, compared to the control group.

3.5. CoQ10 Marker Level

The comparison in CoQ₁₀ Level between study groups is shown in figure 3 and table 5. In the case group, 65% of patients had low CoQ₁₀ levels, while all controls had normal levels. The mean value of the CoQ₁₀ level was significantly lower in the case group, compared to the control group (6.07 versus 12.41 mg/L, P=0.001).

Figure 3. Mean of CoQ₁₀ in study groups

3.6. Correlation between CoQ10 Marker and Specific Parameters

As shown in table 6 and figures 4, 5, 6, and 7, a statistically significant moderate negative correlation was detected between CoQ₁₀ level and age (r=- 0.409, P=0.001). However, significant weak negative correlations were found between CoQ₁₀ level and all of the serum LDH (r=-0.216, P=0.04), CRP (r=-0.337, P=0.001, and troponin level (r=-0.235, P=0.026). The CoQ₁₀ level had no statistically significant correlations with BMI, serum cholesterol, triglyceride, HDL, and CPK.

Figure 4. Correlation between CoQ₁₀ and age

Figure 5. Correlation between CoQ₁₀ and S. LDH

Figure 6. Correlation between CoQ₁₀ and S. LDH

Figure 7. Correlation between CoQ₁₀ and troponin

4. Discussion

The current study was performed on 90 patients who were divided into two groups. The case group included 60 patients diagnosed with IHD, and the control group included 30 healthy participants.

Based on the findings, 43.4% of cases and 83.3% of controls were current smokers, and 40% of cases and 53.3% of controls had a positive family history of IHD. Regarding chronic medical diseases, 48.3% of cases had hypertension and DM, while most controls did not have chronic diseases (86.7%).

Results of a study conducted by Khandelwal, Kapoor ( 6 ) in 2022 were inconsistent with those of the present study. They studied 284 participants, 135 (47%), 98 (34%), and 82 (29%) of whom had arterial hypertension, DM, and smoking habits, respectively. Another study with different results was published by Bouzidi, Messaoud ( 7 ) in 2020, in which 48.4% of patients had DM, 47.1% of them had hypertension, and smoking was reported in 41.0% of them. In a study performed by Shabana, Shahid ( 8 ) in 2020, DM, hypertension, smoking, and family history were observed in 64.3%, 59.9%, 29.4%, and 36% of the patients, respectively.

Hypertension, DM, and smoking are closely interlinked as the risk factors of IHD due to similar risks, such as endothelial dysfunction, vascular inflammation, arterial remodeling, atherosclerosis, dyslipidemia, and obesity. The CVD complications, namely DM and hypertension, substantially overlap with those of microvascular and macro-vascular diseases. Common mechanisms, such as upregulation of the renin-angiotensin-aldosterone system, oxidative stress, inflammation, and immune system activation, likely contribute to the close relationship between diabetes and hypertension ( 9 ).

4.1. Diagnosis of Patients in the Case Group

In the present research, 81.7% of patients in the case group were diagnosed with MI. This rate is higher than that found in a study performed by Khandelwal, Kapoor ( 6 ) in 2022, in which 70% of patients had MI. Moreover, in the current study, high cholesterol levels, high triglyceride levels, low HDL levels, high LDH levels, high CRP levels, high CPK levels, and high troponin levels were found in 3.3%, 51.7%, 76.7%, 71.7%, 100%, 63.3%, and 86.7% of patients in the case group, respectively. Regarding the healthy individuals in this study, 33.3%, 40%, 53.3%, 6.7%, 100%, and 3.3% had high cholesterol levels, high triglyceride levels, low HDL levels, high LDH levels, normal CRP and CPK, and high troponin levels, respectively. In the present study and by comparison between study groups, mean values of serum LDH, CRP, CPK, and troponin were significantly higher (P<0.05) in the case group, compared to the control group.

4.2. CoQ10 Marker Level

In the case group of the present study, 65% had low CoQ₁₀ levels, while all controls had normal levels. Accordingly, the mean value of the CoQ₁₀ level was significantly lower in the case group (P=0.001). Moreover, a significant moderate negative correlation was detected between CoQ₁₀ level and age (r=-0.409, P=0.001). In addition, CoQ₁₀ had significant weak negative correlations with serum LDH (r=-0.216, P=0.04), CRP (r=-0.337, P=0.001), and troponin level (r=-0.235, P=0.026).

Low serum levels during the acute phase of IHD were associated with long-term mortality in patients, suggesting the utility of low serum CoQ₁₀ levels as a predictor and potential therapeutic target ( 10 ). Accordingly, in their study, Yalcin, Kilinc ( 11 ) explored the relationship between low plasma CoQ₁₀ concentration and coronary artery disease. They observed that plasma CoQ₁₀ concentrations in patients with IHD and controls were 0.77 and 0.41 μmol/l, respectively, with a significant relationship (P<0.01) ( 10 ).

It has been reported that CoQ₁₀ has a wide range of therapeutic effects; however, the mechanism behind these therapeutic benefits is not yet fully understood. In addition to showing potential as an antioxidant and functioning as a cofactor in the mitochondrial respiratory chain, it has been suggested to have gene regulatory properties that might account for its effects on overall tissue metabolism ( 12 ).

Three out of four patients with CVD have low levels of CoQ₁₀. It has been noticed that plasma levels of CoQ₁₀ in those with IHD and dilated cardiomyopathy are much lower than that in healthy individuals. Depending on the severity of the cardiac injury, the circulating level of CoQ₁₀ decreases in direct proportion to disease progression ( 13 ). There are several theories about the mechanism of action of CoQ₁₀ in CVD. First, regarding its antioxidant effect, as mentioned above, ubiquinone should be reduced to ubiquinol to ultimately show its anti-oxidative function. Reactive oxygen species (ROS) can lead to severe cellular damage by means of reacting with cell membranes, DNA, and protein centers ( 14 ).

Besides, the products of oxidative stress and cytokines may cause hypertrophy since they trigger the growth of myocytes. Ubiquinol (a reduced form of COQ₁₀) stops the initial formation of lipid peroxyl radicals. This is why COQ₁₀ is considered a very potent antioxidant against ROS and free radicals in biological membranes ( 15 ).

Secondly, it plays a significant role in the energetic needs of the heart. For example, the contraction of the cardiac, which involves the release of Ca²⁺ from the sarcoplasmic reticulum, and the subsequent activation of the contractile proteins requires energy. There is a theory that reduced energy production may cause myocardial failure in mitochondria. Therefore, as it was mentioned earlier, CoQ₁₀ is the main component in the transport of electrons necessary for ATP production ( 5 ). Furthermore, its anti-inflammatory effect should be considered since CVDs, such as heart failure, are related to a chronic pro-inflammatory state, supposing increased cytokine levels and adhesion molecules ( 16 ). Some new studies have established anti-inflammatory properties of CoQ₁₀, possibly by means of the regulation of nitric oxide, and that mechanism may be effective in heart failure treatment. Therefore, the secretion of cytokines and chemokines would not induce myocardial fibrosis and lead to Heart Failure development ( 17 ).

Moreover, CoQ₁₀ has been reported to have a wide range of therapeutic effects. However, the mechanism behind these therapeutic benefits is not fully understood yet. In addition to showing potential as an antioxidant and functioning as a cofactor in the mitochondrial respiratory chain, CoQ₁₀ has been suggested to have gene regulatory properties that might account for its effects on overall tissue metabolism. Despite reports about its safety, efficacy in different disease states, and deficiency in many conditions, CoQ₁₀ supplementation is not widely prescribed in clinical practices. Potential reasons for this issue include a lack of understanding about the critical role of CoQ₁₀, ignorance of the detrimental effects of CoQ₁₀ deficiency, and the fact that CoQ₁₀ is a nutraceutical rather than a patentable drug ( 12 ).

This was proved in a study performed by Kumar, Kaur ( 13 ), which reported a significant improvement in clinical and hemodynamic parameters and exercise tolerance in patients who received adjunctive CoQ₁₀ in 60-200 mg doses on a daily basis. The above-mentioned study was performed on patients with heart failure, hypertension, IHD, and other cardiac illnesses.

Results of another randomized study that involved diabetic patients with IHD supports those of the present study regarding the anti-inflammatory effect of COQ₁₀. However, no improvement was observed in the cardiometabolic markers in the aforementioned study. They concluded that CoQ₁₀ intake after 8 weeks among diabetic patients with stable IHD had beneficial effects on serum IL-6 levels but did not alter other cardiometabolic markers ( 18 ).

Despite these recommendations, findings of the research on CoQ₁₀ absorption and bioavailability differ and depend on the type of used CoQ₁₀ preparation. Many formulations have been developed to improve CoQ₁₀ solubility in the organism. Recent new formulations for CoQ₁₀ are based on enhancing its water-solubility, as in the cases of Q-Ter or Ubisol-Q₁₀. Ubisoft-Q₁₀ is a nano-micelle formulation that appears to be water-soluble containing CoQ₁₀, where solubilization is achieved due to the amphipathic properties of polyethyleneglycol-derivatized-tocopherol, which allows for the formation of stable and water-soluble nano-miscelle ( 19 ). Q-Ter is a supplement consisting of copovidone that acts as a carrier, CoQ₁₀, and glycine that works as a catalyst. This composition makes Q-Ter 200 times more soluble than pure CoQ₁₀ ( 20 ).

4.3. Sociodemographic Characteristics

The mean age of the participants was 52.37±16.6 years old, ranging from 18 to 100 years. The majority of participants in the case group were aged ≥ 60 years old (50%); while 50% of controls were aged < 40 years old. Regarding gender, the highest proportion of both groups were males (70% in the case and 80% in the control group). In terms of BMI level, 50% of the case group was overweighed, while 66.7% of controls had normal BMI levels.

Regarding the comparison with other studies, Biradar and Rangaswamy ( 21 ) conducted a study in 2022 on 80 patients. In the aforementioned study, the majority of participants were male (n=62, 77.5%) with a male-to-female ratio of 3.4:1. Moreover, the participants were above 18 years old with a mean age of 55.98±13.47 years old ( 21 ). Similar results were observed in a study carried out by Shabana, Shahid ( 8 ) in 2020, which was performed on 1,000 subjects. The mean age of patients with IHD was 59.1±12.7 years old, with a slight male predominance, as they constituted 58.2% of the participants. In the above-mentioned research, the male-to-female ratio was 1.3:1. Moreover, the mean value of the BMI among participants was 22.4±6.7 Kg/m² ( 8 ).

Different results were observed in a study performed by Thabet NI ( 22 ) on 273 patients who were admitted to the coronary care unit with a final diagnosis of IHD. In the aforementioned study, there were 160 (58.6%) males and 113 (41.4%) females with a male to a female ratio of 1.4:1. Moreover, the mean age of participants was 58.9+11.3 years old (range: 27-87 years old). Besides, their mean BMI value was 25.2±5 kg/m² (range: 15-41 kg/m²). In that research, 108 (39.6%), 89 (32.6%), and 86 (31.5%) patients were associated with hypertension, DM, and stroke, respectively ( 22 ).

Different sample sizes in each study as well as socioeconomic, ethnic, environmental, educational, urbanization, physical activity, and drugs, can lead to the observed differences. Another important factor determining the difference was gender, as female participants were more diabetic, hypertensive, obese, hypertriglyceridemic, less or passive smokers, and older, compared to male participants. Meanwhile, the male participants smoked more and were thinner and younger than females, due to cultural habits.

This study confirmed the role of CoQ₁₀ in IHD, where the patients had considerably low serum levels of CoQ₁₀, compared to the control group. The CoQ₁₀ had no significant correlations with BMI and CPK. However, a negative correlation was found between CoQ₁₀ with age, serum LDH, CRP, and troponin.

Authors' Contribution

Study concept and design: O. M. A. A.

Acquisition of data: A. L. H.

Analysis and interpretation of data: M. H. M.

Drafting of the manuscript: Z. D. A.

Critical revision of the manuscript for important intellectual content: O. M. A. A.

Statistical analysis: A. L. H.

Administrative, technical, and material support: M. H. M.

Ethics

Official approval was granted from the Scientific Committee in the Department of Clinical Biochemistry, College of Medicine, Tikrit University, Tikrit, Iraq. Letter of facilitation was obtained from Tikrit College of Medicine to Ibn-Sina Teaching Hospital and Al-Salam General Hospital.

Conflict of Interest

The authors declare that they have no conflict of interest.

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