Therapeutic Advances in Cardiovascular Disease

The aim of this study was to investigate the antihypertensive effect of leaves Mangifera indica L. using in vitro and in vivo assays.

The ethanol extract of leaves of M. indica was fractionated to dichloromethanic, n-butyl alcohol and aqueous fractions. The chemical composition of ethanolic extract and dichloromethanic fraction were evaluated by liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). Antioxidant activity was evaluated in the DPPH scavenging activity assay. Angiotensin-converting enzyme (ACE) inhibitory activity was investigated using in vitro and in vivo assays. The chronic antihypertensive assay was performed in spontaneously hypertensive rats (SHRs) and Wistar rats treated with enalapril (10 mg/kg), dichloromethanic fraction (100 mg/kg; twice a day) or vehicle control for 30 days. The baroreflex sensitivity was evaluated through the use of sodium nitroprusside and phenylephrine. Cardiac hypertrophy was evaluated by morphometric analysis.

The dichloromethanic fraction exhibited the highest flavonoid, total phenolic content and high antioxidant activity. Dichloromethanic fraction elicited ACE inhibitory activity in vitro (99 ± 8%) similar to captopril. LC-MS/MS analysis revealed the presence of ferulic acid (48.3 ± 0.04 µg/g) caffeic acid (159.8 ± 0.02 µg/g), gallic acid (142.5 ± 0.03 µg/g), apigenin (11.0 ± 0.01 µg/g) and quercetin (203.3 ± 0.05 µg/g). The chronic antihypertensive effects elicited by dichloromethanic fraction were similar to those of enalapril, and the baroreflex sensitivity was normalized in SHR. Plasma ACE activity and cardiac hypertrophy were comparable with animals treated with enalapril.

Dichloromethanic fraction of M. indica presented an antihypertensive effect, most likely by ACE inhibition, with benefits in baroreflex sensitivity and cardiac hypertrophy. Altogether, the results of the present study suggest that the dichloromethanic fraction of M. indica leaves may have potential as a promoting antihypertensive agent.

The prognostic value of the Global Registry of Acute Coronary Events (GRACE) risk score (GRS) and the Thrombolysis in Myocardial Infarction (TIMI) risk index (TRI) have been reported in patients with coronary artery disease (CAD). In this study, we sought to evaluate the association between TRI and the extent and severity of CAD evaluated by SYNTAX score (SS) and Gensini score in patients with ST elevation myocardial infarction (STEMI).

A total of 290 patients with STEMI were included in the study. GRS and TRI were calculated on admission using specified variables. The extent and severity of CAD were evaluated using the SS and Gensini scores. The patients were divided into low (TRI ⩽19), intermediate (TRI 19–30), and high (TRI ⩾30) risk groups. A Pearson correlation analysis was used for the relationship between TRI, GRS, Gensini score and SS.

There were significant differences in the mean age (p < 0.001), admission heart rate (p < 0.001), admission systolic blood pressure (p = 0.009), SS (p < 0.001), GRS (p < 0.001) and in-hospital major adverse cardiac events (MACE) in all patients between the low, intermediate and high TRI risk groups. There was a positive significant correlation between TRI and SS (r = 0.24, p < 0.001), Gensini score (r = 0.18, p = 0.002), GRS (r = 0.74, p = 0.001) and in-hospital MACE (r = 0.29, p < 0.001).

TRI is significantly related to SS and Gensini score in predicting the extent and severity of CAD in patients with STEMI.

The aim of this retrospective study was to describe demographic and clinical characteristics of patients with diastolic dysfunction heart failure (DHF) in a safety-net institution.

Descriptive statistics were used to summarize characteristics for adults with DHF hospitalized for acute decompensated heart failure (ADHF) between 1 January 2009 and 30 June 2010.

Of 483 patients with an ADHF-related admission, only 83 (17.2%) had pure DHF. Mean age was 59.6 ± 13.1 years old, with nearly equal proportions of male and female patients. Hypertension (89.2%), coronary artery disease (74.7%), and diabetes (63.9%) comorbidities were most common. Diuretics (91.6%), angiotensin converting enzyme inhibitors or angiotensin receptor blockers (69.9%), and β blockers (60.3%) were most frequently prescribed on discharge.

In our population, DHF is more prevalent in younger patients of any ethnicity, especially Hispanic/Latino and black ethnicities, compared with nationwide estimates. Our patients with DHF had higher ejection fractions and were prescribed higher rates of traditional heart failure medications.

Acute coronary syndrome (ACS) continues to be a leading cause of morbidity and mortality worldwide. Galectin-3 and pentraxin-3 are two prognostic biomarkers that have been studied in heart failure (HF). However, there are limited data on these biomarkers in the ACS population. The objective of the study was to determine the variables that are most affected by high concentrations of pentraxin-3 and galectin-3, and the influence they have on outcomes of all-cause mortality in patients with ACS.

We included a total of 160 patients [ST elevation myocardial infarction (STEMI),n = 64; non STEMI/unstable angina (NSTEMI/UA), n = 38; and control subjects with chronic stable angina (CSA)/microvascular angina (MVA) n = 58]. Plasma pentraxin-3 and galectin-3 levels were assessed from these patients at the time of hospital admission. Major adverse cardiovascular events including all-cause mortality, rehospitalizations and coronary artery bypass graft surgery (CABG) were assessed at 6 months.

The median concentration of pentraxin-3 and galectin-3 were significantly higher in STEMI than in NSTEMI patients (p < 0.005) or controls (p < 0.005). Greater numbers of deaths (4 versus 0) were observed in STEMI patients with higher levels of these biomarkers. In addition, ACS patients with high levels of pentraxin-3 and galectin-3 had lower left ventricular ejection fraction (LVEF) (p < 0.005), and a moderate correlation was observed between LVEF and pentraxin-3 levels (r = -0.45, p < 0.005). Patients with higher galectin-3 levels were also observed to have a lower estimated glomerular fraction rate (eGFR), and a moderate correlation was observed between them (r = -0.34, p < 0.005).

Pentraxin-3 and galectin-3 hold much promise in the ACS population as prognostic biomarkers.

The newborn circulating, cardiac and renal renin–angiotensin systems (RASs) are essential for blood pressure control, and for cardiac and renal development. If cardiac and renal RASs are immature this may contribute to cardiovascular compromise in preterm infants. This study measured mRNA expression of cardiac and renal RAS components in preterm, glucocorticoid (GC) exposed preterm, and term piglets.

Renal and cardiac RAS mRNA levels were measured using real-time polymerase chain reaction (PCR). Genes studied were: (pro)renin receptor, renin, angiotensinogen, angiotensin converting enzyme (ACE), ACE2, angiotensin type 1 receptor (AT₁R) and angiotensin type 2 receptor (AT₂R).

All the genes studied were expressed in the kidney; neither renin nor AT₂R mRNA were detected in the heart. There were no gestational changes in (pro)renin receptor, renin, ACE or AT₁R mRNA levels. Right ventricular angiotensinogen mRNA levels in females were lower in preterm animals than at term, and GC exposure increased levels in male piglets. Renal angiotensinogen mRNA levels in female term piglets were lower than females from both preterm groups, and lower than male term piglets. Left ventricular ACE2 mRNA expression was lower in GC treated preterm piglets. Renal AT₂R mRNA abundance was highest in GC treated preterm piglets, and the AT₁R/AT₂R ratio was increased at term.

Preterm cardiac and renal RAS mRNA levels were similar to term piglets, suggesting that immaturity of these RASs does not contribute to preterm cardiovascular compromise. Since preterm expression of both renal and cardiac angiotensin II-AT₁R is similar to term animals, cardiovascular dysfunction in the sick preterm human neonate might be effectively treated by agents acting on their RASs.

The purpose of this study was to determine if a progressive, prescribed home-based aerobic exercise program would alter the natural physiological processes that maintain fluid balance stability in patients with New York Heart Association (NYHA) class III/IV heart failure after medical optimization (titration of oral medical therapy with or without the infusion of an intravenous inotrope).

A total of 56 men and women from a large tertiary trauma I hospital were enrolled with 56 subjects contributing to baseline analysis and 42 subjects at 24 weeks. Subjects were diagnosed with heart failure via NYHA classification IV or III for at least 6 months and were hospitalized for a current acute decompensation exacerbation in which they were being medically optimized. The exercise intervention was a home-based, prescribed, progressive aerobic exercise program lasting for 24 weeks. The exercise participants had weekly phone calls to gather data and progress the exercise program and one 12-week follow up. The usual care participants received random phone calls to collect data and had one 12-week follow up visit to attain physical assessment values.

Subjects were primarily female (59%), nonwhite (54%), and NYHA class IV (52%) versus class III (48%). The mean age was 58 years (±11.8 years). The subjects had a mean ejection fraction of 17.7 % (±7%) and mean maximal oxygen consumption of 12.1 (±3.4). Using a hierarchical multiple regression model, it was demonstrated that an exercise prescription (intensity, frequency, duration) significantly predicted 24 h weight fluctuations within a NYHA class III/IV heart failure population after medical optimization (R² linear = 0.713, F = 3.224, p = 0.015).

This study demonstrated that exercise is a successful adjunctive therapy to managing the daily weight variability or fluid status instability of patients with NYHA class III/IV heart failure that is often a debilitating aspect of the syndrome.

The severity of coronary artery disease (CAD) is directly related to the quality of glucose control in diabetic patients. Additionally, mortality after an acute coronary syndrome is higher in patients with diabetes and it correlates to the level of glucose control. However, the role of higher gluconated hemoglobin in the process of coronary atherosclerosis and clinical outcome of acute myocardial infarction is unknown.

To evaluate the association of HbA1c level and severity of CAD and short-term outcomes of acute ST-elevation myocardial infarction (STEMI) in nondiabetics.

A total of 290 nondiabetic patients with STEMI were prospectively enrolled following their admission. Patients were stratified into 2 groups based on the median percent of HbA1c (⩽5.8% ‘Low’ and >5.8% ‘High’). The severity of CAD based on the Califf scoring system, in-hospital mortality and morbidities of STEMI were compared between groups. Patients were followed for 1 year after discharge to assess readmission and mortality rate.

The severity score for CAD was significantly higher in the ‘High’ versus ‘Low’ HbA1c group (7.7 ± 2.7 and 5.5 ± 2.6, p = 0.001). A total of 15 patients died in both groups during the follow-up period. While in-hospital mortality was similar between the two groups, 12-month mortality was significantly higher in the ‘High’ group (7.7% versus 2.7%, p = 0.043). In addition, the rehospitalization rate within 1 year was 8.8% in the ‘Low’ group, which was significantly lower than 19.0% in the ‘High’ group (p = 0.016).

Among nondiabetic patients presenting with STEMI, the severity of CAD was higher in those with HbA1c level >5.8%; 1-year mortality and hospital readmission rates were also higher in this group of patients.

The blood pressure lowering effect of sesamin has been demonstrated to be associated with the increase in vascular nitric oxide (NO) biological activity by our previous studies and others. The present study was designed to explore the underlying mechanisms involved in the effect of sesamin on aortic NO bioactivity in spontaneously hypertensive rats (SHRs).

Sesamin was orally administered for 8 consecutive weeks in SHRs. Systolic blood pressure (SBP) was measured using the tail-cuff method. The aortas were isolated and in vitro vascular reactivity studies were performed. Superoxide anion production in carotid arteries was assessed by dihydroethidium fluorescence staining. The protein expression of endothelial nitric oxide synthase (eNOS), phosphorylated eNOS (P-eNOS), dihydrofolate reductase (DHFR), nicotinamide adenine dinucleotide phosphate oxidase subunit p47phox, and copper, zinc superoxide dismutase (Cu/Zn-SOD) in aortas was detected by Western blotting. The dimeric form of eNOS in aortas was determined by low-temperature sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). Aortic level of nitrotyrosine and activities of antioxidant enzymes, namely, total SOD (T-SOD), glutathione peroxidase (GPx) and catalase were also detected.

In SHRs, sesamin treatment reduced SBP, improved vascular relaxation induced by acetylcholine and enhanced aortic NO bioactivity. Sesamin treatment enhanced NO biosynthesis in SHR aortas was due to upregulated P-eNOS and suppressed eNOS uncoupling, and the latter effect might be attributed to decreased nitrotyrosine and upregulated DHFR. Sesamin also reduced the NO oxidative inactivation and decreased the superoxide anion production through downregulation of p47^phox and amelioration of eNOS uncoupling. In addition, sesamin treatment did not alter the levels of GPx and catalase activity but obviously reduced the compensatory elevated T-SOD activity and Cu/Zn-SOD protein expression.

Chronic treatment with sesamin could reduce hypertension and improve endothelial dysfunction through enhancement of NO bioactivity in SHR aortas.