Cardiovascular Therapeutics

Objective. We demonstrated that circulating microparticles (MPs) are increased in patients with coronary heart disease (both chronic coronary syndrome (CCS) and acute coronary syndrome). Whether thrombolysis affects MPs in patients with ST-segment elevation myocardial infarction (STEMI) with or without percutaneous coronary intervention (PCI) is unknown. Methods. This study was divided into three groups: STEMI patients with thrombolysis () were group T, patients with chronic coronary syndrome () were group CCS, and healthy volunteers () were the control group. Fasting venous blood was extracted from patients in the CCS and control groups, and venous blood was extracted from patients in the T group before (pre-T) and 2 hours after (post-T) thrombolysis. MPs from each group were obtained by centrifugation. After determining the concentration, the effects of MPs on endothelial nitric oxide synthase (eNOS) and inducible nitric oxide synthase (iNOS) in rat myocardial tissue in vitro were detected by immunohistochemistry and western blotting. Changes in nitric oxide (NO) and oxygen free radicals (O₂^•–) were also detected. The effect of MPs on vasodilation in isolated rat thoracic aortae was detected. Results. Compared with that in the control group ( mg/ml), the concentration of MPs was increased in patients with CCS ( mg/ml) and in STEMI patients before thrombolysis ( mg/ml). However, thrombolysis did not further increase MP levels (post-T,  mg/ml) compared with those in STEMI patients before thrombolysis. Compared with those in the control group, MPs in both CCS and STEMI patients before thrombolysis inhibited the expression of eNOS (both immunohistochemistry and western blot analysis of phosphorylation at Ser1177), NO production in the isolated myocardium and vasodilation in vitro and stimulated the expression of iNOS (immunohistochemistry and western blot analysis of phosphorylation at Thr495), and the generation of O₂^•– in the isolated myocardium. The effects of MPs were further enhanced by MPs from STEMI patients 2 hours after thrombolysis. Conclusion. Changes in MP function after thrombolysis may be one of the mechanisms leading to ischemia–reperfusion after thrombolysis.

Plectranthus barbatus, popularly known as Brazilian boldo, is used in Brazilian folk medicine to treat cardiovascular disorders including hypertension. This study investigated the chemical profile by UFLC-DAD-MS and the relaxant effect by using an isolated organ bath of the hydroethanolic extract of P. barbatus (HEPB) leaves on the aorta of spontaneously hypertensive rats (SHR). A total of nineteen compounds were annotated from HEPB, and the main metabolite classes found were flavonoids, diterpenoids, cinnamic acid derivatives, and organic acids. The HEPB promoted an endothelium-dependent vasodilator effect (~100%; EC50 ~347.10 μg/mL). Incubation of L-NAME (a nonselective nitric oxide synthase inhibitor; EC50 ~417.20 μg/mL), ODQ (a selective inhibitor of the soluble guanylate cyclase enzyme; EC50 ~426.00 μg/mL), propranolol (a nonselective α-adrenergic receptor antagonist; EC50 ~448.90 μg/mL), or indomethacin (a nonselective cyclooxygenase enzyme inhibitor; EC50 ~398.70 μg/mL) could not significantly affect the relaxation evoked by HEPB. However, in the presence of atropine (a nonselective muscarinic receptor antagonist), there was a slight reduction in its vasorelaxant effect (EC50 ~476.40 μg/mL). The addition of tetraethylammonium (a blocker of Ca²⁺-activated K⁺ channels; EC50 ~611.60 μg/mL) or 4-aminopyridine (a voltage-dependent K⁺ channel blocker; EC50 ~380.50 μg/mL) significantly reduced the relaxation effect of the extract without the interference of glibenclamide (an ATP-sensitive K⁺ channel blocker; EC50 ~344.60 μg/mL) or barium chloride (an influx rectifying K⁺ channel blocker; EC50 ~360.80 μg/mL). The extract inhibited the contractile response against phenylephrine, CaCl₂, KCl, or caffeine, similar to the results obtained with nifedipine (voltage-dependent calcium channel blocker). Together, the HEPB showed a vasorelaxant effect on the thoracic aorta of SHR, exclusively dependent on the endothelium with the participation of muscarinic receptors and K⁺ and Ca²⁺ channels.

Background. Cardiovascular diseases (CDs), notably coronary artery disease (CAD) due to atherosclerosis, impose substantial global health and economic burdens. Fatty acid-binding proteins (FABPs), including FABP-4, have been recently linked to CDs. This study conducted a systematic review and meta-analysis to examine FABP-4 levels in CAD and atherosclerosis patients, exploring their potential links to these conditions. Methods. A systematic review and meta-analysis were done based on the PRISMA guideline. The international databases including Medline, Embase, Cochrane Library, Scopus, Web of Science, and UpToDate were searched to find all related studies on the effect of FABP-4 on patients with CAD or atherosclerosis which were published till June 2022 without language restriction. The Cochran’s -test and statistic were applied to assess heterogeneity, a random effect model was used to estimate the pooled standardized mean difference (SMD), a metaregression method was utilized to investigate the factors affecting heterogeneity between studies, and Egger’s test was used to assess the publication bias. Results. Of 1051 studies, 9 studies with a sample size of 2327 were included in the systematic review and meta-analysis. The level of circulating FABP-4 in the patient groups was significantly higher than in the control groups ( (95% CI: 0.30 to 0.91, : 91.47%)). The SMD in female and male patients were 0.26 (95% CI: 0.01 to 0.52, : 0%) and 0.22 (95% CI: 0.08 to 0.35, : 44.7%), respectively. There was considerable heterogeneity between the studies. The countries had a positive relationship with heterogeneity (, ); but BMI, lipid indices, gender, study design, and type of kit had no effect on the heterogeneity. No publication bias was observed (: 0.137). Conclusion. In summary, this meta-analysis revealed elevated circulating FABP-4 levels in CDs, suggesting its potential as a biomarker for these conditions. Further research is warranted to explore its clinical relevance.

Introduction. Although a recent joint society scientific statement (the American Association of Cardiovascular Pulmonary Rehabilitation, the American Heart Association, and the American College of Cardiology) suggests home-based cardiac rehab (CR) is appropriate for low- and moderate-risk patients, there are no paradigms to define such individuals with coronary heart disease. Methods. We reviewed a decade of data from all patients with coronary heart disease enrolled in a single CR center (University of Michigan) to identify the prevalence of low-risk factors, which may inform on consideration for participation in alternative models of CR. Low-risk factors included not having any of the following: metabolic syndrome, presence of implantable cardioverter defibrillator or permanent pacemaker, active smoking, prior stroke, congestive heart failure, obesity, advanced renal disease, poor exercise capacity, peripheral arterial disease, angina, or clinical depression (MI’S SCOREPAD). We report on the proportion of participants with these risk factors and the proportion with all of these low-risk factors. Results. The mean age of CR participants () was 63 years; 25% were women, and 82% were non-Hispanic White. The mean number of low-risk factors was 8.5, which was similar in the 2011-2012 and 2018-2019 cohorts (8.5 vs. 8.3, respectively, ). Additionally, 9.3% of the 2011-2012 cohort and 7.6% of the 2018-2019 cohort had all 11 of the low-risk factors. Conclusion. In this observational study, we provide a first paradigm of identifying factors among coronary heart disease patients that may be considered low-risk and likely high-gain for participation in alternative models of CR. Further work is needed to track clinical outcomes in patients with these factors to determine thresholds for enrolling participants in alternative forms of CR.

Backgrounds. Serum total bilirubin (STB) is recently more regarded as an antioxidant with vascular protective effects. However, we noticed that elevated STB appeared in unstable angina pectoris (UAP) patients with diffused coronary lesions. We aimed to explore STB’s roles in UAP patients, which have not been reported by articles. Methods and Results. 1120 UAP patients were retrospectively screened, and 296 patients were finally enrolled. They were grouped by Canadian Cardiovascular Society (CCS) angina grades. The synergy between PCI with TAXUS stent and cardiac surgery score (SYNTAX score) and corrected thrombolysis in myocardial infarction flow count (CTFC) were adopted to profile coronary features. The results showed that STB, mean platelet volume (MPV), hs-CRP, fasting blood glucose (FBG), red blood cell width (RDW), and CTFC elevated significantly in the CCS high-risk group. STB (, 95% CI: 0.39-0.74, ) and MPV (, 95% CI: 0.42-1.31, ) could indicate SYNTAX score changes for these patients. STB (≥21.7 μmol/L) could even indicate a coronary slow flow condition (AUC: 0.88, 95% CI: 0.84-0.93, ). Moreover, UAP patients with elevated STB had a lower event-free survival rate by the Kaplan-Meier curve. STB ≥21.7 μmol/L could reflect a poor coronary flow status and indicate 1-year poor outcomes for these patients (HR: 2.01, 95% CI: 1.06-3.84, ). Conclusion. Elevated STB in UAP patients has a close relationship with changes in SYNTAX score. STB (over 21.7 μmol/L) could even indicate a coronary slow flow condition and poor outcomes for the UAP patients.

Objective. We aim to conduct a comparison of the safety and effectiveness performance between left bundle branch area pacing (LBBAP) and right ventricular pacing (RVP) regimens for patients with atrioventricular block (AVB). Methods. This observational cohort study included patients who underwent pacemaker implantations with LBBAP or RVP for AVB indications from the 1st of January 2018 to the 18th of November 2021 at West China Hospital. The primary composite outcome included all-cause mortality, lead failure, or heart failure hospitalization (HFH). The secondary outcome included periprocedure complication, cardiac death, or recurrent unexplained syncope. A 1 : 1 propensity score–matched cohort was conducted for left ventricular (LV) function analysis. Results. A total of 903 patients met the inclusion criteria and completed clinical follow-up. After adjusting for the possible confounders, LBBAP was independently associated with a lower risk of the primary outcome (OR 0.48, 95% CI 0.28 to 0.83, ), including a lower risk of all-cause mortality and HFH. No significant difference in the secondary outcome was detected between the groups except that LBBAP was independently associated with a lower risk of recurrent unexplained syncope. In the propensity-score matching cohort of echocardiographic analysis, the LV systolic dyssynchrony index was lower in LBBAP compared with that in RVP ( vs. %, ). Conclusions. Compared to conventional RVP, LBBAP is a feasible novel pacing model associated with a significant reduction in the primary composite outcome. Moreover, LBBAP significantly reduces the risk of recurrent unexplained syncope and improves LV systolic synchrony. This study is registered with ClinicalTrials.gov NCT05722379.