Vitamin D Deficiency in Patients with Diabetes in French Guiana: Epidemiology and Relation with Microvascular and Macrovascular Complications.

Vitamin D (VD) insufficiency is common among patients with diabetes in French Guiana. The study aimed to evaluate the prevalence of VD deficiency in the different type of diabetes encountered and to analyze the relationship between VD deficiency and diabetes complications. METHODS: An observational study was conducted between May 2019 and May 2020 in French Guiana, based on data from the CODIAM study (Diabetes Cohort in French Amazonia), describing the characteristics of patients with diabetes mellitus. Among 600 patients enrolled with diabetes, 361 had an available VD assay. RESULTS: The mean 25(OH)VD (hydroxycalciferol) level was 27.9 ng/mL. The level of VD was inversely proportional to the HbA1c (glycated hemoglobin) level. Patients with angina pectoris had a greater proportion of deficiencies VD < 20 ng/mL than those without angina. By contrast, patients with retinopathy had higher vitamin D concentrations than those without retinopathy. There was no association between vitamin D and arteriopathy, stroke, nephropathy and polyneuropathy. VD deficiency was more frequent in women, and in patients with a high school education. CONCLUSION: The prevalence of VD deficiency was high in patients with diabetes in French Guiana, emphasizing the importance of VD supplementation.

Corn silk decoction for blood lipid in patients with angina pectoris: A systematic review and meta-analysis.

The aims of this study were to evaluate the efficacy of corn silk decoction on lipid profile in patients with angina pectoris. PubMed, Cochrane, Embase, Google Scholar, Chongqing VIP Chinese Science and Technology Periodical Database, China National Knowledge Infrastructure, and Wanfang database were searched up to January 2019 for randomized controlled trials that assessed the impact of corn silk decoction on total cholesterol, triglycerides, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol in patients with angina pectoris. Study evaluation and synthesis methods were in accordance with the Cochrane Handbook, and data were analyzed using Review Manager (version 5.3) software. Random effects model was applied in this systematic review and meta-analysis to compensate for potential heterogeneity among the included studies. A total of four randomized controlled trials were eligible for meta-analysis. Pooled results of these studies indicated that corn silk decoction might improve high-density lipoprotein cholesterol and reduce total cholesterol, triglycerides, and low-density lipoprotein cholesterol in patients with angina pectoris. Subgroup analyses showed that corn silk decoction or modified corn silk decoction plus conventional pharmaceutical treatment could have favorable effects on blood lipids. However, the lack of blinding in most studies may have led to overestimation of these effects. Further studies with better design are needed to confirm these findings.

There is No Association Between the Omega-3 Index and Depressive Symptoms in Patients With Heart Disease Who Are Low Fish Consumers.

BACKGROUND: Long chain Omega-3 polyunsaturated fatty acids (LCn3PUFAs) may improve cardiovascular health and depression. This study investigated the relationships between erythrocyte membrane LCn3PUFA status, depression and angina symptoms in patients with heart disease. METHODS: We recruited 91 patients (65 males and 26 females, mean age 59.2±10.3 years) with heart disease and depressive symptoms (Center for Epidemiological Studies Depression Scale, CES-D ≥ 16) and low fish/fish oil intakes. The Omega-3 Index (EPA+DHA) of erythrocyte membranes (as a percentage of total fatty acids) was assessed by gas chromatography. Depression status was measured by both self-report and clinician-report scales; CES-D and the Hamilton depression scale (HAM-D). Angina symptoms were measured using the Seattle Angina Questionnaire and the Canadian Cardiovascular Society Classification for Angina Pectoris. RESULTS: The mean Omega-3 Index was 4.8±1.0% (±SD). Depression scores measured by CES-D and HAM-D were 29.2±8.8 (moderate to severe) and 11.0±5.7 (mild) (arbitrary units) respectively reflecting a different perception of depressive symptoms between patients and clinicians. Angina status was inversely associated with depression scores (r>-0.26, P<0.03). There were no significant relationships between individual LCn3PUFA or the Omega-3 Index and either the depression scores or the angina symptoms. CONCLUSION: Worse angina status was associated with worse depression, but the Omega-3 Index was not associated with symptoms of depression or angina in patients with heart disease.

Clinical Therapeutic Effects of Aspirin in Combination with Fufang Danshen Diwan, a Traditional Chinese Medicine Formula, on Coronary Heart Disease: A Systematic Review and Meta-Analysis.

BACKGROUND/AIMS: Coronary heart disease is characterized by vascular stenosis or occlusion resulting in myocardial ischemia, hypoxia and necrosis. In China, the combination of aspirin and Fufang Danshen Diwan (FDD), a traditional Chinese medicine formula, has been suggested in the treatment of coronary heart disease. There have been several studies comparing the effectiveness of aspirin alone and in combination with FDD to treat coronary artery disease; however, it remains unclear whether combined aspirin therapy is superior. This study was thus designed to clarify this issue through a systematic review and meta-analysis. METHODS: Databases including PubMed, EMBASE, China National Knowledge Infrastructure (CNKI) database, Wanfang Data and VIP Information were searched. Papers were reviewed systematically by two researchers and analyzed using Cochrane software Revman 5.1. RESULTS: Fourteen randomized controlled trials enrolling 1367 subjects were included. Meta-analyses revealed that aspirin in combination with FDD was significantly more effective at alleviating angina pectoris and improving electrocardiogram (ECG) results relative to aspirin therapy alone, reflected by the summary effects for the clinical markedly effective (OR = 2.45; 95% CI 1.95-3.08) and the total effective (OR = 3.92; 95% CI 2.87-5.36) rates. In addition, combined aspirin and FDD was significantly more efficacious than aspirin monotherapy at improving blood lipid levels, as indicated by the following outcomes: 1) reduction of TC level (SMD -1.12; 95% CI -1.49 to -0.76); 2) reduction of TG level (SMD -0.94; 95% CI -1.15 to -0.74); 3) reduction of LDL level (SMD -0.68; 95% CI -0.88 to -0.48); and 4) improvement of HDL level (SMD 0.52; 95% CI 0.04 to 0.99 ). No serious adverse events were reported in any of the included trials. CONCLUSION: The present meta-analysis demonstrated that aspirin in combination with FDD was more effective than aspirin alone for treating coronary heart disease. More full-scale randomized clinical trials with reliable designs are recommended to further evaluate the clinical benefits and long-term effectiveness of FDD for the treatment of coronary heart disease.

Identification of more objective biomarkers for Blood-Stasis syndrome diagnosis.

BACKGROUND: Blood-stasis syndrome (BSS) is one of the Traditional Chinese medicine (TCM) syndrome differentiations that are commonly seen in stroke and ischemic heart diseases; however, the BSS differentiation criterion is not standardized. More objective biomarkers for BSS diagnosis are needed. METHODS: Acute ischemic stroke (AIS) or unstable angina (UA) patients with BSS and healthy controls were enrolled. The miRNA and mRNA expression profiles of UA patients and AIS patients were compared to those of healthy controls to identify the differentially expressed miRNA and mRNA of BSS. Bioinformatics analysis was used to identify significantly deregulated miRNAs and mRNAs correlated to BSS. QRT-PCR was performed to validate the bioinformatics analysis results. RESULTS: Approximately 401 mRNAs and 11 miRNAs were differentially expressed in both UA and AIS patients compared to healthy controls. Gene ontology (GO) functional analysis was performed, and multiple GO terms were enriched. Among the overlapping DE miRNAs and mRNAs, miR-146b-5p, -199a-5p and 23 targeted mRNAs were pivotal genes in the BSS genomic characteristics. These 2 miRNAs and 23 mRNAs formed network-type biomarkers for BSS. CONCLUSIONS: The genomic characteristics of BSS were shown in this study. miR-146b-5p, -199a-5p and the 23 targeted mRNAs formed a diagnostic network for BSS. Further improvement and validation of this diagnostic network might lead to more objective diagnostic criteria for BSS.

Development of protocatechualdehyde proliposomes-based sustained-release pellets with improved bioavailability and desired pharmacokinetic behavior for angina chronotherapy.

The present study was aimed to develope a proliposomal formulation to decrease the hepatic first-pass metabolism of protocatechualdehyde (PD), followed by pellet coating to modify the drug release for angina chronotherapy. PD proliposomes were prepared by depositing PD-phospholipid complex on mannitol powders to improve the drug encapsulation. Afterwards, the PD proliposomes were prepared into pellet cores via extrusion-spheronization using 10% κ-carrageenan as pelletization aid prior to the development of PD sustained-release pellets (PD-SRPs). Eudragit® NE 30D was chosen as coating material and the desired drug release profile of PD-SRPs was calculated for formulation optimization by deconvolution based on the circadian rhythm of variant angina. A high similarity factor (f2=85.72) was achieved when the coating weight was 30% and the sustained release behavior also prevented the destruction of liposomes by gastric fluids. Pharmacokinetic studies revealed a basically consistent trend between the actual and the predicted plasma concentration-time curve with absolute percent errors (%PE) of concentrations <10% in 2-12h. Meanwhile, a relative bioavailability of 200% was achieved compared with pure PD. Therefore, the development of proliposomes-based PD-SRPs was an effective strategy to provide both improved oral bioavailability and desired drug plasma concentration-time course for angina chronotherapy.

[Application of ″Fu Yang and activating blood circulation″ in treatment of unstable angina pectoris patients].

Coronary heart disease(CHD) has become a major public health problem in the world, while the unstable angina (UA) is one of an important type. Hypofunction of yang qi in chest and cardiac blood stasis has been considered as the basic pathogenesis of UA.According to the deficiency of yang and blood stasis run through the process of CHD, fu yang and activating blood circulation could be main treatment. Wenxin decoction which has the function of fu yang and activating blood circulation, not only can effectively improve the symptoms of angina pectoris, the ischemic ECG, but also can significantly improve blood rheology, blood lipids and so on. So deepening the theory of ″fu yang and activating blood circulation″ and the application of ″Wenxin decoction″ in the treatment of UA would have an important clinical value for improving the therapeutic efficacy of CHD.

Tanshinone IIA - loaded pellets developed for angina chronotherapy: Deconvolution-based formulation design and optimization, pharmacokinetic and pharmacodynamic evaluation.

This paper put forward a deconvolution-based method for designing and optimizing tanshinone IIA sustained-release pellets (TA-SRPs) with improved efficacy in the treatment of variant angina. TA-SRPs were prepared by coating TA ternary solid dispersion immediate-release pellets (TA-tSD-IRPs) with the blends of polyvinyl acetate (PVAc) and polyvinyl alcohol-polyethylene glycol (PVA-PEG) using fluidized bed technology. The plasma concentration-time curve of TA-tSD-IRPs following oral administration as a weight function was investigated in New Zealand white rabbits. The predicted/expected plasma concentration-time curve of TA-SRPs as a response function was simulated according to the circadian rhythm of variant angina during 24h based on chronotherapy theory. The desired drug release profile of TA-SRPs was obtained via the point-area deconvolution procedure using the weight function and response function, and used for formulation optimization of TA-SRPs. The coating formulation of TA-SRPs was optimized as 70:30 (w/w) PVAc/PVA-PEG with 5% (w/w) coating weight due to in vitro drug release profile of these TA-SRPs was similar to the desired release profile (similarity factor f2=64.90). Pharmacokinetic studies of these optimized TA-SRPs validated that their actual plasma concentration-time curve possessed a basically consistent trend with the predicted plasma concentration-time curve and the absolute percent errors (%PE) of concentrations in 8-12h were less than 10%. Pharmacodynamic studies further demonstrated that these TA-SRPs had stable and improved efficacy with almost simultaneous drug concentration-efficacy. In conclusion, deconvolution could be employed in the development of TA-SRPs for angina chronotherapy with simultaneous drug efficacy and reduced design blindness and complexity.

Clinical research on shengjie tongyu granules in the treatment of meteorological cardiovascular disease.

This paper aims to study the effect of Shengjie Tongyu granules on the treatment of meteorological cardiovascular disease in clinical treatment. Tongxinluo capsule that is clinically recognized as the effective drug in treating coronary heart disease and angina and was adopted as positive control. The results showed that, angina score and TCM score of two groups were all significantly improved after the treatment (P<0.01), but there was no statistical significance in comparison between groups (P>0.05); total effective rate of angina in the treatment group (77.78%) was superior than the control group (62.52%) after the treatment; but the difference had no statistical significance (P>0.05); total effective rate of TCM syndrome in the treatment group (75%) was superior than the control group (58.62%), and the difference had statistical significance (P<0.05). All these findings suggested that, Shengjie Tongyu granules can effectively improve the clinical symptoms of patients with coronary heart disease and angina, with the curative effect similar to Tongxinluo capsule; meanwhile, it can increase HDL-C and improve abnormal lipid metabolism of angina patient. In the treatment process, there is no significant untoward effect, blood, routine urine test and hepatorenal function have no abnormality, which proves that this drug is safe.

Innovative Strategy in Treating Angina Pectoris with Chinese Patent Medicines by Promoting Blood Circulation and Removing Blood Stasis: Experience from Combination Therapy in Chinese Medicine.

Coronary heart disease (CHD) is one of the leading causes of death worldwide. Moreover, angina pectoris is one of the most important types of CHD. Therefore, prevention and effective treatment of angina pectoris is of utmost importance in both China and western countries. However, undesirable effects of antianginal therapy do influence treatment adherence to a certain extent. Therefore, it's not surprising that, complementary and alternative medicine (CAM), including Chinese medicine (CM), are widely welcomed among patients with CHD, hoping that it might complement western medicine. In our previous studies, blood stasis syndrome (BSS) (Xueyu Zheng) was the main syndrome (Zheng-hou) of angina pectoris. Currently, China Food and Drug Administration authoritatively recommended more than 200 Chinese patent medicines (CPMs) as complementary or adjunctive therapies for symptom management and enhancing quality of life along with mainstream care on angina pectoris management in mainland China. This paper reviewed 4 kinds of most frequently-used CPMs by promoting blood circulation and removing blood stasis in the treatment of angina pectoris. It aims to evaluate the current evidence of CPMs in combination therapy for angina pectoris. This review indicated that CPMs as adjunctive treatment to routine antianginal therapy play an active role in reducing the incidence of primary endpoint events, decreasing anginal attack rate, and improving electrocardiogram. Additionally, CPMs have been proven relatively safe. Further rigorously designed clinical trials should be conducted to confirm the results.

The association between blood lipid and phlegm turbidity syndrome of angina pectoris: a systematic review and meta-analysis.

BACKGROUND: A series of case-control studies have been conducted to investigate the association between blood lipid and phlegm turbidity syndrome of angina pectoris, but produced inconsistent results. OBJECTIVE: We performed a meta-analysis to determine the association between blood lipid and phlegm turbidity syndrome of angina pectoris more precisely. METHODS: Manual screening as well as screening of the China National Knowledge Infrastructure (CNKI), Chinese Journal full-text database (VIP), Wanfang database (WF), ScienceDirect, Pubmed, the Cochrane Library, and Embase were carried out for relevant literature. The formula was translated to calculate the pooled mean value and standard deviation value. The "Newcastle-Ottawa Quality Assessment Scale: Case-Control Studies" (NOS) was taken to assess the quality of the included studies. The Revman 5.2.6 software provided by "The Cochrane Collaboration" was used to analyze the collected data. The subgroup analysis was established according to the sample size proportion between the test group and the control group. Sensitivity analysis was constructed by using two different effect models. Besides, a funnel plot was created to analyze potential publication bias. RESULTS: No statistically meaningful difference existed between the test group and control group of total cholesterol (TC) and low-density lipoprotein-cholesterol (LDL-C) in non-Qi and yin deficiency syndrome (QYDS) and non-Yang deficiency syndrome (YDS) subgroup, whereas the two biotic indicators in the test group were higher than the non-phlegm syndrome group in other subgroups. Triglyceride (TG) in phlegm syndrome group showed superior to non-phlegm syndrome group in the rest subgroups except for the non-CCS (Cold coagulating syndrome)-non-YDS subgroup. High-density lipoprotein-cholesterol (HDL-C) levels of the phlegm group were lower than that of the non-phlegm group in all subgroups. CONCLUSION: When comparing with Traditional Chinese Medicine (TCM) syndromes of asthenia nature, such as YDS, QYDS, and heart qi deficiency syndrome), the levels of TG, TC, and LDL-C were higher in phlegm turbidity syndrome. However, for sthenia syndromes such as Qi stagnation syndrome (QSS), heart blood stasis syndrome (HBSS), and CCS, there was no obvious difference. Furthermore, HDL-C levels in the phlegm turbidity group were lower than those of the non-phlegm group. Nevertheless, these results should be confirmed with further studies.

Impact of intensive statin use on the level of inflammation and platelet activation in stable angina after percutaneous coronary intervention: a clinical study.

BACKGROUND AND OBJECTIVE: This study was designed to investigate whether high-dose atorvastatin before percutaneous coronary intervention (PCI) can reduce inflammation, platelet activation, and major adverse cardiac events (MACE) in patients with stable angina who are undergoing long-term statin therapy. METHODS: In total, 215 patients with chronic stable angina were randomized to pretreatment with 80 mg of atorvastatin (12 h before PCI; n = 106) or with 20 mg of atorvastatin (12 h before PCI; n = 109). All patients underwent PCI. Serum levels of interleukin-6, high-sensitivity C-reactive protein, tumor necrosis factor-α, GMP-140, and p-selectin were measured 24 h before and after PCI. The 30-day incidence of MACE was determined. RESULTS: No differences in baseline characteristics were observed between the groups. The levels of inflammation and platelet activation were significantly lower after 24 h in the group that received intensive statin therapy (P < 0.05). The levels of inflammation and platelet activation increased sharply 24 h after PCI in the group that received the lower dose of atorvastatin (P > 0.05). In other words, pretreatment with a high dose of atorvastatin decreased the incidence of MACE sharply within 30 days (P < 0.05). CONCLUSIONS: Pretreatment with a high dose of atorvastatin significantly reduced inflammation, platelet activation, and the incidence of MACE in patients with stable angina.

Serum low-density lipoprotein and heart rate related to the effectiveness in the treatment of angina pectoris with two similar Chinese medicine herbal formulae.

OBJECTIVE: To explore the effectiveness related indicators which might help identify the indications of Tongxinluo Capsule () and Kangxin Capsule () targeting on qi deficiency and blood stasis pattern in Chinese medicine (CM) in the treatment of angina pectoris. METHODS: The data from a multicenter, randomized and double-blinded study conducted at 5 centers in China were obtained for the analysis. A total of 239 patients with angina pectoris and CM syndrome of qi deficiency and blood stasis were randomly assigned in a 1:1 ratio to Tongxinluo Capsule group (119 cases) and Kangxin Capsule group (120 cases). Angina effectiveness and electrocardiogram (ECG) improvement were selected as the therapeutic outcomes. RESULTS: After a 4-week treatment, the effective rates of Tongxinluo Capsule and Kangxin Capsule were 43.70% and 25.00%, respectively (P <0.05). Serum low-density lipoprotein (LDL) level was found to influence the effectiveness of Tongxinluo Capsule which had higher effective rate in the patients with lower level of LDL. Heart rate was found to influence the effectiveness in the patients treated with Kangxin Capsule which had higher effective rate in the patients with heart rate [Symbol: see text]80 beats/min. CONCLUSION: LDL level and heart rate were the indicators which help indentify the indications of Tongxinluo Capsule and Kangxin Capsule, respectively, in the treatment of angina pectoris with CM syndrome of qi deficiency and blood stasis.

Puerarin inhibits C-reactive protein expression via suppression of nuclear factor kappaB activation in lipopolysaccharide-induced peripheral blood mononuclear cells of patients with stable angina pectoris.

Puerarin (4'-7-dihydroxy-8-beta-D-glucosylisoflavone), the most abundant isoflavone-C-glucoside extracted from the root of the plant Pueraria lobata, has demonstrated anti-inflammatory activity in cellular models of inflammation. In this report, we examined the ability of puerarin to modulate C-reactive protein (CRP) expression and key molecules in the nuclear factor kappa B (NF-kappaB) pathway to determine its molecular target. The protein and mRNA levels of CRP were determined in lipopolysaccharide (LPS)-induced peripheral blood mononuclear cells of patients with unstable angina pectoris. Also, we detected the I-kappaBalpha phosphorylation and the p65NF-kappaB expression in peripheral blood mononuclear cells under our experimental condition. The results indicated that puerarin inhibited the expression of the protein and mRNA levels of CRP in LPS-induced peripheral blood mononuclear cells. Subsequently, we determined that the inhibition of CRP expression was because of a dose-dependent inhibition of phosphorylation and degradation of inhibitor kappaB(I-kappaB), which resulted in a reduction of p65NF-kappaB nuclear translocation. We conclude that puerarin acts as an anti-inflammatory agent by blocking NF-kappaB signalling, and may possibly be developed as a useful agent for the chemoprevention of atherosclerosis.

Serum selenium and prognosis in cardiovascular disease: results from the AtheroGene study.

OBJECTIVE: Experimental data suggest a protective role of the essential trace element selenium against cardiovascular disease (CVD), whereas epidemiological data remains controversial. We aimed to investigate the impact of serum selenium concentration in patients presenting with stable angina pectoris (SAP) or acute coronary syndrome (ACS) on long term prognosis. METHODS: Baseline selenium concentration was measured in 1731 individuals (852 with SAP, and 879 with ACS). During a median follow-up of 6.1 years, 190 individuals died from cardiovascular causes. RESULTS: In those ACS patients who subsequently died of cardiac causes, selenium levels were lower compared to survivors (61.0microg/L versus 71.5microg/L; P<0.0001). In a fully adjusted model, patients in the highest tertile of selenium concentration had a hazard ratio of 0.38 (95% CI: 0.16-0.91; P=0.03) as compared with those in the lowest. No association between selenium levels and cardiovascular outcome was observed in SAP. CONCLUSIONS: Low selenium concentration was associated with future cardiovascular death in patients with ACS.

Long-acting diltiazem HCl for the chronotherapeutic treatment of hypertension and chronic stable angina pectoris.

Hypertension is associated with increased cardio- and cerebrovascular morbidity and mortality; antihypertensive drugs have been shown to reduce the risk of adverse cardio- and cerebrovascular events. These events tend to be more common during the morning hours, a time when both normo- and hypertensives show a circadian peak in blood pressure (BP). Although clinicians have a number of safe and well-tolerated antihypertensive agents in various classes and formulations at their disposal, few are designed to specifically attenuate the morning BP surge while maintaining 24-h efficacy. A novel, once-daily, long-acting formulation of diltiazem HCl (DTZ-LA) has been developed with chronodynamics in harmony with diurnal BP variation. DTZ-LA effectively reduces BP in a dose-dependent fashion over a 24-h dosing interval in patients with moderate-to-severe essential hypertension. When compared with a morning dose, the evening dose is associated with significant and clinically meaningful greater reductions in BP during the morning hours, when adverse cardiovascular events tend to cluster. Evening-dosed DTZ-LA was more effective than morning-dosed amlodipine in reducing morning diastolic BP in African-Americans. Evening-dosed DTZ-LA was also more effective than evening-dosed ramipril in reducing morning BP. Evening dosing of DTZ-LA significantly increased exercise tolerance in patients with angina pectoris over the 24-h interval. DTZ-LA is associated with adverse effects consistent with other diltiazem formulations, and overall is safe and well tolerated, even when titrated to doses of 540 mg/day.