Cardiovascular Therapeutics

Introduction. In the animal model, preconditioning is a powerful weapon against ischemic damage. The reason why the human heart cannot be protected from ischemic damage by preconditioning remains unclear. There are assumptions that the lack of preconditioning in humans is caused by concomitant diseases such as dyslipoproteinemia and arteriosclerosis. This study investigates whether dyslipoproteinemia and the resulting arteriosclerosis can be a cause of a reduced precondition effect of heart in mice. Methods. LDL receptor-deficient mice were fed a long-term (14-16 weeks) high-fat atherogenic diet to induce arteriosclerosis. Arteriosclerosis was identified by histological examination and vessel contraction tests. LDLR-/- and wild-type mice were randomly assigned to anesthetic-induced, remote ischemic, or no preconditioning. All mice were subjected to 45 minutes of coronary artery occlusion and 180 minutes of reperfusion. The area at risk and infarct size were determined by Evans Blue and triphenyltetrazolium chloride staining. Results. Histopathological examination showed atherosclerosis in high-fat atherogenic fed LDLR-/- mice, and the vessel relaxation capacity was significantly reduced compared to wild-type mice. In the wild type, as expected, infarct size was significantly reduced by preconditioning compared to the control. In LDLR-/- mice, infarct size was significantly reduced by preconditioning compared to the control. Surprisingly, the LDLR-/- control group also had a significantly reduced infarct size compared to the wild-type control group. Conclusion. We were able to demonstrate that a high-fat diet morphologically and functionally triggered atherosclerosis in LDLR-/- mice. Interestingly, LDLR-/- mice with an atherogenic diet had smaller infarct sizes compared to wild-type mice. Moreover, preconditioning additionally reduced myocardial infarct size in LDLR-/- mice. A long-term high-fat atherogenic diet and preconditioning seem to result in additive cardioprotection in LDLR-/- mice.

Background. Atrial fibrillation (AF) is the most common serious cardiac rhythm disturbances and is responsible for substantial morbidity and mortality in general population. Hypertension is the most prevalent and potentially modifiable risk factor for AF. This study is aimed at evaluating the effect of angiotensin receptor blocker (ARB) or calcium channel blocker (CCB) on AF recurrence among patients with hypertension and AF. Methods. The PubMed, EMBASE, Medline, and Cochrane Collaboration of Controlled Clinical Trials registry databases were searched from their inception to September 2020. Results. A total of 7 randomized controlled trials (RCTs) enrolling 1495 patients were included in our study. This finding showed that ARB had a statistically significant superiority in preventing AF recurrence (OR: 0.43, 95% CI: 0.30-0.72, ) and persistent AF (OR: 0.41, 95% CI: 0.24-0.71, ) compared to CCB. Subgroup analysis showed that there was a significant difference in telmisartan subgroup (OR: 0.54, 95% CI: 0.23-1.29, ) and nontelmisartan subgroup (OR: 0.42, 95% CI: 0.23-0.77, ). Subgroup analysis indicated that nifedipine subgroup did not show a statistically significant difference on AF recurrence between ARB and CCB (OR: 0.88, 95% CI: 0.46-1.68, ), but amlodipine subgroup showed that ARB had a significant superiority in prevention of AF recurrence (OR: 0.39, 95% CI: 0.27-0.56, ) compared with CCB. Conclusions. This study suggests that ARB is superior to CCB for preventing the AF recurrence and persistent AF among patients with hypertension and AF.

Background. It has been suggested that the angiotensinogen (AGT) gene rs4762 (p.Thr174Met) polymorphism might be associated with myocardial infarction (MI) risk, but the study results are still debatable. Objective and Methods. In order to explore the relationship between AGT p.Thr174Met polymorphism and MI risk, the current meta-analysis involving 7657 subjects from 11 individual studies was conducted. Results. A significant association between AGT p.Thr174Met polymorphism and MI was found under recessive (OR: 2.26, 95% CI: 1.35-3.77, ), dominant (OR: 1.131, 95% CI: 1.016-1.260, ), codominant (OR: 2.198, 95% CI: 1.334-3.621, ), and additive (OR: 1.363, 95% CI: 1.132-1.641, ) genetic models. In the Asian subgroup, significantly increased MI risk was found under all genetic models (). No significant association between AGT p.Thr174Met polymorphism and MI was found under all genetic models in the Caucasian subgroup (). Conclusions. AGT p.Thr174Met variant might increase MI risk, especially within the Asian population. The Met174 allele of AGT p.Thr174Met might confer the risk for MI.

Background and Aims. A relevant role is emerging for functional foods in cardiovascular prevention. The aim of this study was to assess the effect of a nutraceutical multitargeted approach on lipid profile and inflammatory markers along with vascular remodelling in a cohort of dyslipidemic subjects without history of cardiovascular (CV) disease. Methods and Results. We enrolled 25 subjects (mean age 48.2 years) with low to moderate CV risk profile and total cholesterol (TC) levels between 150 and 250 mg/dl. The patients were assigned to receive for one year a tablet/die of a nutraceutical combination containing red yeast rice (RYR) extract (Monacolin 3 mg/tablet) and coenzyme Q10 (30 mg/tablet). Treatment with the nutraceutical compounds led to a significant reduction of TC (from 227 to 201 mg/dl, ), LDL-c (from 150 to 130 mg/dl, ), triglycerides (from 121 to 109 mg/dl, ), non-HDL-cholesterol (from 168 to 141 mg/dl, ), hs-CRP (from 1.74 to 1.20 mg/l, ), and osteoprotegerin (from 1488 to 1328 pg/ml, ). Levels of HDL-c, Lp(a), glucose, liver enzyme, CPK, or creatinine did not change over time. An ultrasound study was performed to assess changes in mean carotid intima-media thickness (IMT) and maximum IMT (M-MAX) as well as modification in local carotid stiffness by means of determining the carotid compliance coefficient (CC) and distensibility coefficient (DC). At the end of the treatment, we observed small but significant reductions in both mean-IMT (from 0.62 to 0.57 mm, ) and M-MAX (from 0.79 to 0.73 mm, ), and an improvement in carotid elasticity (DC from 22.4 to , and CC from 0.77 to 0.85 mm²/kPa, ). Conclusions. A long-term treatment with a combination of RYR and coenzyme Q10 showed lipid-lowering activity along with a reduction of inflammatory mediators and an improvement of vascular properties in young subjects with a low-to-moderate CV risk profile.

Objectives. Shenfu Injection (SFI) was widely used in the treatment of heart failure (HF) in China. A plethora of systematic reviews/meta-analyses (SRs/MAs) has been conducted in this research area, although with scattered results. The purpose of this overview was to conduct a comprehensive review to summarize and critically evaluate the existing evidence. Methods. Digital databases were searched for SRs/MAs up to January 28, 2021. Two authors independently screened the reviews and assessed the methodological quality of included SRs/MAs using Assessing the Methodological Quality of Systematic Reviews 2 (AMSTAR-2). Quality of evidence for outcomes evaluated within the reviews was appraised with the Grading of Recommendation, Assessment, Development, and Evaluation (GRADE). Results. Thirteen SRs/MAs met the inclusion criteria. Based on AMSTAR-2, the quality of all SRs/MAs was critically low, because all of them have more than one critical domains that were unmet. Based on GRADE, the evidence quality of 24 outcome measures was low or very low, 27 outcome measures was moderate, and none outcome measure was high. Descriptive analysis showed that SFI was an effective and safe method for HF. Conclusions. The use of SFI for the treatment of HF may be clinically effective and safe. However, this conclusion must be interpreted cautiously due to the generally low methodological quality and low evidence quality of the included SRs/MAs. More rigorously designed SRs/MAs and RCTs with high methodological quality are necessary for further proof.

Background. Hydroxychloroquine with or without azithromycin was one of the common therapies at the beginning of the COVID-19 pandemic. They can prolong QT interval, cause torsade de pointes, and lead to sudden cardiac death. We aimed to assess QT interval prolongation and its risk factors in patients who received hydroxychloroquine with or without azithromycin. Methods. This study was a retrospective cohort study. One hundred seventy-two confirmed COVID-19 patients were included in this study, hospitalized at Babol University of Medical Sciences hospitals between March 5, 2020, and April 3, 2020. Patients were divided into two groups: hydroxychloroquine alone and hydroxychloroquine with azithromycin. Electrocardiograms were used for outcome assessment. Results. 83.1% of patients received hydroxychloroquine plus azithromycin vs. 16.9% of patients who received only hydroxychloroquine. The mean age of patients was .The mean of posttreatment QTc interval in the monotherapy group was shorter than the mean of posttreatment QTc interval in the combination therapy group, but it had no significant statistical difference ( milliseconds vs. milliseconds; ). Generally, 22.1% of patients had a prolonged QTc interval after treatment. Male gender, or baseline milliseconds, or high-risk Tisdale score increased the likelihood of prolonged QTc interval. Due to QTc prolongation, fourteen patients did not continue therapy after four days. Conclusions. Hospitalized patients treated by hydroxychloroquine with or without azithromycin had no significant difference in prolongation of QT interval and outcome. The numbers of patients with prolonged QT intervals in this study emphasize careful cardiac monitoring during therapy, especially in high-risk patients.