The Association Between Arsenic Levels and Oxidative Stress in Myocardial Infarction: A Case-Control Study.

Cardiovascular diseases (CVDs) are known as the first causes of death throughout the world, and mainly myocardial infarction (MI), lead to 7.4 million deaths annually. Atherosclerosis is the major underlying cause of most CVDs. However, exposure to heavy metals, among other factors, deserves further attention as a risk factor for CVDs. This study was designed to evaluate the levels of arsenic (Ars) in myocardial infarction (MI) patients and healthy individuals as well as assess the association between the incidence of MI and Ars, total antioxidant capacity (TAC), and oxidative stress. This case-control study was conducted among patients with MI (n = 164) and normal individuals (n = 61) at Shafa Hospital in Kerman, Iran. Patients were classified into two groups, including coronary artery blocks above 50% (CAB > 50%, n = 83) and coronary artery blocks less than 50% (CAB < 50%, n = 83) based on their angiography findings. The demographic characteristics, clinical history, biochemical parameters, and serum Ars and TAC levels were evaluated. In the present study, both CAB groups had significantly reduced levels of TAC compared with the control. Furthermore, TAC was lower in the CAB > %50 group compared to the CAB < %50 group. Ars levels were significantly higher in both CAB groups compared with the control. There was a significant positive relationship between CAB and Ars, BG, HbA1c, urea, creatinine, TG, TC, and LDL-c, as well as a negative relationship between HDL-c and TAC. Moreover, TAC levels showed a significant inverse correlation with Ars, HbA1c, and creatinine, and a positive correlation with HDL-c. As risk factors, Ars, hs-CRP, TG, TC, and LDL-c enhance the severity of the disease, and HDL-c and TAC decrease the disease severity. Moreover, ROC curve analysis revealed that the highest AUC for the CAB > %50 (AUC = 78.29), and cytotoxic levels for both CAB groups (Ars ≥ 0.105 ppm), and no significant differences were found between the two groups. Our findings suggest that Ars at ≥ 0.105 ppm is able to increase the risk of MI through the increased OS and decreased TAC.

Moderate Endurance Training and MitoQ Improve Cardiovascular Function, Oxidative Stress, and Inflammation in Hypertensive Individuals: The Role of miR-21 and miR-222: A Randomized, Double-Blind, Clinical Trial.

OBJECTIVE: Hypertension (HTN) is among the leading causes of myocardial infarction, stroke, and kidney disease. The MitoQ supplement is a mitochondrial-targeted antioxidant that attenuates the generation of reactive oxygen species (ROS). miRNAs play an essential role in the pathophysiology of HTN. Regular aerobic exercise is recommended to decrease the risk of cardiovascular disease. We aimed to evaluate the effects of MitoQ supplementation and moderate endurance training (ET), alone and in combination, on cardiac function, blood pressure, the circulatory levels of miRNA-21 and miRNA-222, and oxidative status in individuals with HTN. MATERIALS AND METHODS: In a double-blind, randomized clinical trial (except for ET group), 52 male hypertensive subjects (40-55 years old) were randomly divided into four groups (n=13): Placebo, MitoQ (20 mg/day, oral), ET (Cycle ergometer, moderate intensity, 40-60% VO2 peak, three sessions/week for six weeks), and MitoQ+ET. Cardiac echocardiography indices, serum oxidative and inflammation status, and miRNAs 21 and 222 were assessed before and after interventions. RESULTS: Left ventricular mass [effect size (ES): -6.3, 95% confidence interval (CI): -11.2 to -1.4] and end-systolic/ diastolic diameters significantly improved in the intervention groups (ES: -0.05, 95% CI: -0.11 to 0.00 and -0.09, 95% CI: -0.16 to -0.02). Total serum antioxidant capacity (TAC) increased (ES: 36.0, 95% CI: 26.1 to 45.8), and malondialdehyde (MDA) (ES: -0.43, 95% CI: -0.53 to -0.32), IL-6 (ES: -1.6, 95% CI: -1.98 to -1.25), miR-21 (ES: -0.48, 95% CI: -0.61 to -0.35), and miR-222 (ES: -0.31, 95% CI: -0.44 to -0.18) significantly decreased in response to ET, MitoQ, and their combination. CONCLUSION: MitoQ and ET, individually and more pronouncedly in combination, can improve cardiovascular health in people with high blood pressure (BP) by reducing inflammation and increasing antioxidant defense, in association with reduction in circulatory miR-21 and miR-222 levels (registration number: IRCT20190228042870N1).

Effect of Combined Endurance Training and MitoQ on Cardiac Function and Serum Level of Antioxidants, NO, miR-126, and miR-27a in Hypertensive Individuals.

OBJECTIVES: Hypertension (HTN) is one of the most important risk factors for cardiovascular diseases. Despite advances in treatment and control of HTN, the prevalence of HTN is still increasing. MitoQ is a supplement that acts on mitochondria and attenuates reactive oxygen species (ROS), which plays an important role in cardiovascular health. miRNAs play an important role in the pathophysiology of HTN. We evaluated the effects of MitoQ supplementation and endurance training (ET), alone and in combination, on functional indices of the heart and serum levels of miR-126, miR-27a, antioxidants, and NO, in patients with HTN. METHODS: In a double-blind randomized clinical trial, 52 male participants (age 40-55 years) were randomly divided into four groups (n = 13) of placebo, MitoQ (20 mg/day, oral), ET (cycle ergometer, moderate intensity, 40-60% VO2 peak, heart rate 120-140 b/min, 45 min a day, three days/week for six weeks), and MitoQ+ET. Cardiac function indices were assessed by echocardiography before and after interventions. RESULTS: Systolic blood pressure (SBP) significantly decreased in all intervention groups (P < 0.001) while DBP (P < 0.01) and LV hypertrophy (P < 0.05) were significantly decreased only in the MitoQ+ET group. Serum levels of SOD, GPx, and NO and the level of miR-126 significantly increased in all treatment groups, while miR-27a reduced in the ET (P < 0.05) and MitoQ+ET (P < 0.01) groups. CONCLUSIONS: Compared to MitoQ and ET alone, their combination has more prominent improving effects on cardiac health and amelioration of BP in the patients with HTN. These effects are through miR-126 and miR-27a modulation and ameliorating mitochondrial ROS production.

Prevalence and incidence of pre-hypertension and hypertension (awareness/control) in Iran: findings from Kerman coronary artery diseases risk factors study 2 (KERCADRS).

Hypertension (HTN) is an important cause of cardiovascular-related morbidity and mortality. The present study was conducted to investigate the prevalence and incidence rate of pre-HTN, diagnosed and undiagnosed HTN, as well as its control and associated factors in adult population in southeast Iran. In a randomized household survey, 9987 participants aged 15-80 years were recruited into the study. HTN was confirmed through examination or using antihypertensive drug(s). Pre-HTN and HTN were defined as 120-139/80-89 and ≥140/90 mmHg for systolic and diastolic BP, respectively. The prevalence of pre-HTN was 28.5%. The prevalence of HTN was 19.2% (13.9% diagnosed and 5.3% undiagnosed). HTN increased with age (from 4% in 15-24 to 67.8% in 75-80 years). Men had higher pre-HTN (35.6% vs. 23.4%) and undiagnosed HTN (7.5% vs. 3.8%) than women. Of those diagnosed, 46.5% had uncontrolled BP, in which, women had better conditions than men (45.6% vs. 47.4%). Obesity, positive family history of HTN, anxiety, and low physical activity were the most significant predictors of HTN. The prevalence of pre-HTN decreased but there was no change in the prevalence of HTN during the last 5 years. The 5-year incidence rate/100 person-years of pre-HTN and HTN was 6.6 and 3.7, respectively. Although there are some promising signs of reducing pre-HTN and slowing HTN rise, currently, almost one-fifth of the adult population suffers from HTN. Given the poor BP control in patients with diagnosed HTN, especially in men, alarms that more effective interventions and strategies are needed to reduce deleterious consequences of HTN.

The effect of different digoxin concentrations on heart tissue and antioxidant status in iron-overloaded rats.

BACKGROUND: Thalassaemia is a hereditary disorder and has an economic burden on patients and the government. The most prevalent complication in these patients is iron overload which is followed by cardiomyopathy. Digoxin is considered as a treatment against heart failure in thalassaemia. The present study evaluated the effect of two digoxin concentrations on iron content and antioxidative defense in cardiac tissue of iron-overloaded rats. METHODS: The study was conducted on 48 rats which were divided into 6 groups. Group 1 was the control group and did not receive any treatment and group 2 was the iron overload group. In addition groups 3 and 4 were the digoxin control groups which received 1 and 5 mg/kg/day of digoxin, respectively. Groups 5 and 6 received 1 and 5 mg/kg/day of digoxin plus iron-dextran, respectively. After 1 month, malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GPX), and total antioxidant status (TAS) were assessed in cardiac tissues. RESULTS: Co-administration of iron-dextran and digoxin (1 and 5 mg/kg/day) significantly increased SOD and TAS levels (P < 0.0010) and reduced MDA (P < 0.0010) in heart tissue compared to control and iron overload groups. GPX levels significantly reduced in groups 5 and 6 (iron + digoxin 1 (P < 0.0500) and iron + digoxin 5) (P < 0.0010) compared to the iron control group. CONCLUSION: Digoxin remarkably facilitates iron uptake by cardiomyocytes by affecting other channels such as L-type and T-type Ca2+ channels (LTCC and TTCC). Digoxin administration in the iron-overloaded rat model deteriorated antioxidative parameters and increased iron entry into heart tissue at higher doses. Therefore, in patients with beta thalassaemia major, digoxin must be administered with great care and serum iron and ferritin must be regularly monitored.

Effects of digoxin on cardiac iron content in rat model of iron overload.

BACKGROUND: Plasma iron excess can lead to iron accumulation in heart, kidney and liver. Heart failure is a clinical widespread syndrome. In thalassemia, iron overload cardiomyopathy is caused by iron accumulation in the heart that leads to cardiac damage and heart failure. Digoxin increases the intracellular sodium concentration by inhibition of Na+/K+-ATPase that affects Na+/Ca2+ exchanger (NCX), which raises intracellular calcium and thus attenuates heart failure. The mechanism of iron uptake into cardiomyocytes is not exactly understood. METHODS: We assessed the effect of different concentrations of digoxin on cardiac iron content in rat model of iron overload. Digoxin had been administrated intraperitoneally (IP) for one week before main study began to assure increased digoxin levels. Group 1 received four IP injections of iron-dextran (12.5mg/100g body weight) every 5 days evenly distributed over 20 days. Groups 2-4 received 0.5, 1 and 5 mg/kg/day IP digoxin, respectively. Last three groups 5-7 received iron-dextran as group 1 and digoxin concentrations 0.5, 1 and 5 mg/kg/day, respectively. RESULTS: Cardiac iron contents were significantly higher in iron overload groups that received different concentrations (0.5, 1 and 5 mg/kg/day) of digoxin than their counterparts in control groups and this pattern was also observed in pathology assessment. CONCLUSION: It seems that digoxin plays an important role in iron transport into heart in iron overload state but exact mechanism of this phenomenon is not clear. L-type Ca2+ channels are good candidates that probably could be involved in iron accumulation in cardiomyocytes. Thus it would be better to reconsider digoxin administration in thalassemia and iron overload conditions.

Coadministration of Atorvastatin and Amiodarone Increases the Risk of Pulmonary Fibrosis in Rats.

OBJECTIVE: The purpose of this study was to evaluate the effect of atorvastatin administration on amiodarone-induced pulmonary fibrosis in rats. MATERIALS AND METHODS: Thirty-six male Wistar rats were randomly divided into 4 groups. The control group (CTL) received distilled water (0.3 ml intratracheally on days 0 and 2 and 0.5 ml orally from day 0 for 3 weeks). The atorvastatin group (AT), in addition to intratracheal distilled water, received 1 mg/kg of atorvastatin orally from day 0 for 3 weeks. The amiodarone group (AMI) received 2 intratracheal instillations of amiodarone (6.25 mg/kg in 0.3 ml of water) on days 0 and 2 and 0.5 ml of distilled water (like the CTL). The amiodarone plus atorvastatin group (AMI + AT) received both these drugs (same doses and methods as for the AMI and AT). After 28 days, the rate of lung fibrosis was estimated according to pathological criteria of lung sections and measurements of hydroxyproline in pieces of left lung tissue. RESULTS: The lung hydroxyproline content was higher in the treated groups (CTL: 0.35 ± 0.017, AT: 0.38 ± 0.012, AMI: 0.375 ± 0.018 and AMI + AT: 0.38 ± 0.012 unit/mg protein), but did not reach significance when compared with the CTL (p = 0.56). Amiodarone administration significantly increased the score of pulmonary fibrosis (0.5) in comparison with the AT (0.125) and CTL (0) (p < 0.5). The combination of amiodarone and atorvastatin exacerbated the pulmonary fibrosis (1.5; p < 0.01) compared to the AMI (0.5; p < 0.001), AT (0.125) and CTL (0). CONCLUSION: In this study, the concomitant administration of amiodarone and atorvastatin increased pulmonary fibrosis in rats.

The prevalence of low physical activity in an urban population and its relationship with other cardiovascular risk factors: Findings of a community-based study (KERCADRS) in southeast of Iran.

BACKGROUND: The low physical activity (LPA) more or less affects every community. Because of high prevalence of cardiovascular diseases in Iran and their relationship with LPA, this study aimed to measure precisely the epidemic size of LPA and determine its relationship with six other coronary artery disease (CAD) risk factors among an urban population aged 15 to 75 years in Kerman, Iran. METHODS: Using household survey, 5895 adults were randomly recruited through single-stage cluster sampling from 250 postal codes. Demographic characteristics, blood pressure, blood glucose, cholesterol, triglyceride, smoking, opium use, mental status and physical activities at work, rest and recreation were assessed and ranked as low, moderate and intense. Adjusted odds ratio (AOR) was reported as a measure of the relationship between LPA and other CAD risk factors. RESULTS: The prevalence of low, moderate, and intense physical activity were 42.1% (40.3-43.9), 45.0% (43.6-47.4) and 12.4% (11.1-13.9), respectively. LPA showed a sudden rise from 36.8% to 45.4% after the age of 25 years. On average, women had less physical activity than men (45.1% vs. 39.2%, P= 0.01). Participants with low physical activity compared to those without physical activity had significantly higher chance of anxiety [odds ratio 1.39; confidence interval (95% CI) 1.08-1.79; P = 0.01], hypertension (1.59; 1.08-2.35; P = 0.02), hyper-cholesterolemia (1.37; 1.06-1.76; P = 0.02), cigarette smoking (1.52; 1.07-2.11; P = 0.01), opium addiction (1.47; 1.07-2.02; P = 0.02) and overweight/obesity (1.34; 1.05-1.71; P = 0.02). CONCLUSION: LPA was very common in the studied population and almost half of the adults were at risk for CAD because of insufficient level of physical activity. Such risky life-style pattern makes the emerging of CAD epidemic unavoidable, if effective interventions not being in place timely to this community.

Effects of opium consumption on coronary artery disease risk factors and oral health: Results of Kerman Coronary Artery Disease Risk factors Study a population-based survey on 5900 subjects aged 15-75 years.

BACKGROUND: Opium abuse as a relatively common behavior among Iranian population may have an association with the other coronary artery disease (CAD) risk factors. Here, we reported the prevalence of opium abuse and its co-exposures with oral health and other CAD risk factors. METHODS: We recruited 5900 inhabitant aged 15-75 years using a randomized cluster household survey. All were interviewed for level of physical activity (PA), depression, anxiety and opium use and assessed for hypertension, diabetes, hyperlipidemia, and oral health status. Regarding to opium abuse, participants were grouped into: "Non-," "occasional," and "dependent" users. Using logistic regression model for every CAD risk factor, we assessed whether the co-exposure of opium and CAD risk factor is significant. RESULTS: Overall, 10.6% reported ever opium use including 5.6% dependent and 5% occasional users. The prevalence of opium abuse was increased from 2.1% in 15-25 years to 24.5% in 55-64 years group. Opium abuse, in occasional and dependent forms, was associated with depression (adjusted odds ratio [AOR] 1.81 and 2.49) and low PS (AOR 1.43 and 1.71 respectively). Dependents were less obese than nonusers (P < 0.01). Opium abuse had no significant association with hypertension, diabetes, oral health status and lipid profile. CONCLUSIONS: Opium abuse was associated with depression and low PA. No ameliorative effect was observed on hypertension, diabetes, and plasma lipid profile. Therefore, positive association of opium with depression and LPA and the incorrectness of belief on its ameliorative effect on three other important risk factors of CAD should be clearly highlighted in public health messages to the community.

Hypertension: diagnosis, control status and its predictors in general population aged between 15 and 75 years: a community-based study in southeastern Iran.

OBJECTIVES: Hypertension (HTN) is an important cause of cardiovascular related morbidity and mortality. This study aimed at providing the prevalence of pre-HTN, diagnosed and undiagnosed HTN, along with its control and associated factors in an adult population. METHODS: 5,900 participants aged 15-75 years took part in the study. HTN was verified by examination, self-reported history or using anti-hypertensive drug(s). Pre-hypertension and hypertension were defined as 120-139/80-89 mmHg and >140/>90 mmHg for systolic/diastolic BP, respectively. RESULTS: The prevalence of hypertension was 18.4 % from which 10.5 %were diagnosed and 7.9 % were undiagnosed. The prevalence of pre-HTN was 35.5 %. HTN increased by age (2.4 % in 15-24 to 49 % in 55-64 years). The men had higher pre-HTN (42.7 vs. 28.1 %) and undiagnosed HTN (11.3 vs. 4.6 %). Of those diagnosed, 56.3 % had uncontrolled BP levels. Smoking, anxiety, obesity, and positive family history of HTN were the most significant predictors for HTN. CONCLUSIONS: Hypertension affected almost one-fifth of the population. Given the poor control in diagnosed hypertensive patients, it is alarming that the current health system in urban areas in Iran is not effective enough to control the epidemic spread of non-communicable diseases.

The effect of passive opium smoking on cardiovascular indices of rabbits with normal and ischemic hearts.

Some Asian people believe that opium can protect the cardiovascular system. To assess this belief, we investigated the effect of passive opium smoking (POS) on cardiovascular indices in rabbits with ischemic and non-ischemic hearts.Rabbits (n = 43) were divided into control (CTL), short term opium (SO) and long term opium (LO) groups. SO and LO groups were exposed to opium smoking for 3 days and 4 weeks, respectively. ECG, blood pressure (BP), left ventricular pressure and cardiac troponin I levels were recorded. Isoproterenol (ISO) was injected to induce cardiac ischemia and after 4 h the above variables were measured along with cardiac histopathology assessment.All groups showed significant increments in troponin I level (P < 0.05) except the CTL group. This trend was more obvious in ISO-treated groups. Mean arterial pressure (MAP) significantly decreased in all groups (p< 0.05) except the LO group. Opium exposure attenuated ISO-induced myodegeneration but augmented tissue congestion and hemorrhage.In conclusion, higher troponin I serum level and ECG changes were found in passive opium smoking groups. This evidence is against the belief that opium can protect the cardiovascular system.

Passive opium smoking does not have beneficial effect on plasma lipids and cardiovascular indices in hypercholesterolemic rabbits with ischemic and non-ischemic hearts.

BACKGROUND: To scientifically test a traditionally belief of some Asian countries residents that opium may prevent or have ameliorating effects on cardiovascular diseases (CVD) we investigated the effect of passive opium smoking (POS) on plasma lipids and some cardiovascular parameters in hypercholesterolemic rabbits with ischemic and non-ischemic hearts. METHODS: 40 rabbits were fed for 2 weeks with cholesterol-enriched diet and divided to control (CTL), short-term opium (SO) and long-term opium (LO) groups. SO and LO groups were exposed to POS for 3 days and 4 weeks respectively. ECG, blood pressure (BP) and left ventricular pressure recorded and serum lipid and cardiac troponin I levels were measured. Isoproterenol (ISO) injected for induction of cardiac ischemia and after 4h the above variables were measured along with cardiac histopathology assessment. RESULTS: HDL cholesterol decreased significantly in LO compared to CTL group (35+/-5 vs 53+/-5mg/dl). Groups treated with ISO showed significantly higher increments in troponin I level (P<0.05) except for LO group and reduction of BP was higher in ISO and SO+ISO groups compared to CTL and SO groups respectively (-38+/-6 vs -23+/-4 and -37+/-11 vs -11+/-3 percent respectively, P<0.05). Reduction in BP was significantly lower in LO+ISO compared to ISO group. Opium exposure caused a trend of increase in blood pressure, LDL cholesterol and ECG disturbances, attenuated ISO induced myonecrosis but augmented tissue congestion and hemorrhage. CONCLUSION: POS can be considered as a CVD risk factor. Opium does not reduce BP or cholesterol level, as is anticipated by its users.