Cardiovascular Therapeutics

Prediabetes is an intermediate hyperglycaemic state which has been associated with cardiovascular dysfunction. However, cardiovascular dysfunction is not only caused by intermediate hyperglycaemia but also endothelial dysfunction, inflammation, and oxidative stress associated with prediabetes. Bredemolic acid (BA), an isomer of maslinic acid, has been reported to ameliorate the intermediate hyperglycaemia found in prediabetes; however, the effects of this triterpene on cardiovascular function have not yet been determined. Therefore, this study investigated the effects of BA on cardiovascular function in diet-induced prediabetic rats. Thirty-six male rats that weighed 150–180 g were divided into two groups, the non-prediabetic (n = 6) and the prediabetic groups (n = 30), which were fed normal diet (ND) and HFHC diet, respectively. The prediabetic rats were further subdivided into five groups (n = 6) and treated with either BA (80 mg/kg) or metformin (MET, 500 mg/kg) every third day for 12 weeks. After 12 weeks, blood samples and the heart were collected for biochemical analysis. The untreated prediabetic rats showed a significant increase in body mass index (BMI), waist circumference (WC), blood pressure, heart rate, lipid profile, lipid peroxidation, and inflammatory markers with significant decrease in endothelial function and antioxidant biomarkers by comparison with the non-prediabetic animals. The administration of BA significantly improved cardiovascular functions such as blood pressure, heart rate, and endothelial function. There was also a significant decrease in BMI, WC, lipid profile, lipid peroxidation, and inflammation with a concomitant increase in antioxidant capacity. BA administration improved cardiovascular function by attenuation of oxidative stress, inflammatory, and endothelial dysfunction markers.

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Objective. This study aimed to establish a clinical prognostic nomogram for predicting major adverse cardiovascular events (MACEs) after primary percutaneous coronary intervention (PCI) among patients with ST-segment elevation myocardial infarction (STEMI). Methods. Information on 464 patients with STEMI who performed PCI procedures was included. After removing patients with incomplete clinical information, a total of 460 patients followed for 2.5 years were randomly divided into evaluation (n = 324) and validation (n = 136) cohorts. A multivariate Cox proportional hazards regression model was used to identify the significant factors associated with MACEs in the evaluation cohort, and then they were incorporated into the nomogram. The performance of the nomogram was evaluated by the discrimination, calibration, and clinical usefulness. Results. Apelin-12 change rate, apelin-12 level, age, pathological Q wave, myocardial infarction history, anterior wall myocardial infarction, Killip’s classification > I, uric acid, total cholesterol, cTnI, and the left atrial diameter were independently associated with MACEs (all ). After incorporating these 11 factors, the nomogram achieved good concordance indexes of 0.758 (95%CI = 0.707–0.809) and 0.763 (95%CI = 0.689–0.837) in predicting MACEs in the evaluation and validation cohorts, respectively, and had well-fitted calibration curves. The decision curve analysis (DCA) revealed that the nomogram was clinically useful. Conclusions. We established and validated a novel nomogram that can provide individual prediction of MACEs for patients with STEMI after PCI procedures in a Chinese population. This practical prognostic nomogram may help clinicians in decision making and enable a more accurate risk assessment.

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Background. We investigated whether or not the addition of myocardial mass at risk (MMAR) to quantitative coronary angiography was useful for diagnosing functionally significant coronary stenosis in the daily practice. Methods. We retrospectively enrolled 111 consecutive patients with 149 lesions who underwent clinically indicated coronary computed tomography angiography and subsequent elective coronary angiography with fractional flow reserve (FFR) measurement. MMAR was calculated using a workstation-based software program with ordinary thin slice images acquired for the computed tomography, and the minimal lumen diameter (MLD) and the diameter stenosis were measured with quantitative coronary angiography. Results. The MLD and MMAR were significantly correlated with the FFR, and the MMAR-to-MLD ratio (MMAR/MLD) showed a good correlation. The area under the receiver operating characteristic curve (AUC) of MMAR/MLD for FFR ≤ 0.8 was 0.746, and the sensitivity, specificity, positive predictive value, and negative predictive value were 60%, 83%, 68%, and 77%, respectively, at a cut-off value of 29.5 ml/mm. The addition of MMAR/MLD to diameter stenosis thus made it possible to further discriminate lesions with FFR ≤ 0.8 (AUC = 0.750). For the proximal left coronary artery lesions, in particular, MMAR/MLD showed a better correlation with the FFR, and the AUC of MMAR/MLD for FFR ≤ 0.8 was 0.919 at a cut-off value of 31.7 ml/mm. Conclusions. The index of MMAR/MLD correlated well with the physiological severity of coronary stenosis and showed good accuracy for detecting functional significance. The MMAR/MLD might be a useful parameter to consider when deciding the indication for revascularization.

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Aim. The marked variation in bifurcation anatomy has brought about an ongoing search for stents specifically constructed for coronary bifurcations. This study aimed to analyze the angiographic restenosis prevalence and patterns and predictors of different patterns in dedicated bifurcation BiOSS® vs. current generation drug-eluting stents implanted in coronary bifurcation lesions based on data from two clinical trials POLBOS I and II. Methods. Dedicated bifurcation BiOSS® stents were compared with drug-eluting stents (DES) in patients with stable coronary artery disease (CAD) or nonST elevation acute coronary syndrome (NSTE-ACS) (POLBOS I: paclitaxel eluting BiOSS® Expert vs. DES; POLBOS II: sirolimus eluting BiOSS® LIM vs. DES). Provisional T-stenting was the default treatment. Morphological pattern of in-stent restenosis according to the modified Mehran classification adopted for bifurcation lesions was assessed with bifurcation dedicated quantitative coronary angiographic software (CAAS 5.11, Pie Medical Imaging BV, the Netherlands). Results. In total, 445 patients (222 patients in BiOSS group and 223 patients in DES group) were included into the analysis. In BiOSS group 24 cases of angiographic restenosis (10.8%) were recorded, and in DES group—17 cases (7.6%) at 12 months follow-up (angiographic control rate at follow-up—90.3%). In the BiOSS group most frequent medina classification in restenotic cases was 0.0.1 (25%), whereas in DES—0.0.1 and 0.1.1 (23.5% each). In multivariate regression analysis proximal optimization technique was associated with the lowest chance for restenosis (OR 0.15, 95% CI 0.06–0.33), whereas diabetes on insulin was associated with the highest risk of restenosis (OR 4.21, 95% CI 1.48–11.44). Conclusions. The angiographic restenosis pattern and rate was similar between BiOSS stents and DES in coronary bifurcation lesions.

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Objectives. To observe the effect of avβ3 single-stranded (ss) DNA on proliferation and migration of vascular smooth muscle cells (VSMCs) and its potential mechanism. Background. Percutaneous transluminal coronary angioplasty (PTCA) is currently the preferred method for the treatment of coronary heart disease. However, vascular restenosis still occurs after PTCA treatment, severely affecting the clinical efficacy of PTCA. Integrin avβ3, which is widely expressed on various cell surfaces, plays an important role in the proliferation and migration of VSMCs. Methods. In this experiment, we used systematic evolution of ligands by exponential enrichment (SELEX) to screen out avβ3 ssDNA, which has high affinity and specificity to the avβ3 protein. MTT, Transwell, and cell scratch assays were carried out to examine the effect of avβ3 ssDNA on the proliferation and migration of VSMCs. Flow cytometry was performed to detect apoptosis and cell cycle progression. The effect of avβ3 ssDNA on the Ras-phosphatidylinositol-4,5-bisphosphate 3-kinase/mitogen-activated protein kinase (PI3K/MAPK) signaling pathway was evaluated by quantitative reverse transcription polymerase chain reaction and western blot. Results. In the present study, we found that avβ3 ssDNA significantly decreased the expression of osteopontin, focal adhesion kinase, Ras, p-PI3K, and p-MAPK at both mRNA and protein levels (). Avβ3 ssDNA also inhibited VSMC proliferation and migration while promoting apoptosis (), as demonstrated by the upregulation of the proapoptotic proteins Bax and active caspase 3 (). Conclusions. The findings suggest that avβ3 ssDNA inhibited the proliferation and migration of VSMCs by suppressing the activation of Ras-PI3K/MAPK signaling.

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Objective. This study aimed to compare the effectiveness of drug-coated balloons (DCB) with everolimus-eluting stents (EES) in the treatment of in-stent restenosis (ISR) and the differential relative effect of DCB in patients with drug-eluting stents (DES)-ISR and bare metal stents (BMS)-ISR. Background. The efficiency and safety of DCB and EES need to be assessed for the treatment of ISR. Methods. A systematic literature search was conducted using PubMed and EMBASE to identify all relevant studies. Angiographic results and clinical events were separately assessed. Subgroup meta-analyses were performed according to the type of restenosed stent. Results. Six randomized trials with 1134 patients were included. The overall pooled outcomes indicated that DCB was associated with lower minimum lumen diameter (mean difference , 95% CI = −0.29 to −0.05, ) and higher target lesion revascularization (risk ratio , 95% CI = 1.36 to 4.18, ) than EES. However, the subgroup meta-analyses showed that DCB was inferior to EES only in DES-ISR patients, with lower minimum lumen diameter (, 95% CI = −0.37 to −0.14, ), higher percent diameter stenosis (, 95% CI = 1.33 to 9.42, ), more binary restenosis (, 95% CI = 1.20 to 3.58, ), and higher incidence of target vessel revascularization (, 95% CI = 1.22 to 3.50, ) and target lesion revascularization (, 95% CI = 1.28 to 4.22, ). No differences in angiographic results and clinical events were found between DCB and EES in BMS-ISR patients. Conclusions. DCB was inferior to EES in DES-ISR and comparable in BMS-ISR in terms of angiographic results and clinical events.

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