Current Vascular Pharmacology - Volume 21, Issue 4, 2023

Objective: Cardiac rehabilitation (CR) has progressed over the years from a basic monitoring procedure for a safe return to physical activity to a multidisciplinary strategy that emphasizes patient education, specifically for designed exercise training, risk factor management, and the general health of cardiac patients. Methods: Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) reporting was used for this systematic review. The studies included were retrieved via an electronic search of Google Scholar and PubMed using the following terms: cardiac rehabilitation (CR), cardiac diseases, coronary artery bypass graft, heart failure, cardiac rehabilitation guidelines, rehabilitation, recovery of function, cardiac rehabilitation importance, cardiac rehabilitation outcomes, physical therapy modalities, secondary prevention, physical medicine, and cardiac rehabilitation phases. Results: Publications (n=24) that included worldwide standards demonstrating the implementation of CR programs in a variety of scenarios were reviewed. These publications are based on well-defined guidelines that represent best practices from several cardiology societies, which use varying valid programs by comparing those guidelines with CR/secondary prevention programs. Conclusion: Several indications have been used in the development of the CR program, with the goal of regaining autonomy and increasing physical, psychological, and social activities. With the Saudi Vision 2030 initiatives for health national transformation programs, there are targets set to ensure the reduction and prevention of noncommunicable diseases and to reduce cardiovascular disease risks by initiating an accredited CR program and guidelines for Saudi Arabia.

Background: Offspring exposed in foetal life to gestational diabetes mellitus (GDM) are at increased risk for future metabolic diseases. Objective: To explore the prognostic role of abdominal aorta intima-media thickness (aIMT) in neonates exposed to GDM as a possible biomarker for later atherogenesis and its possible correlation with thioredoxin- interacting protein (TXNIP), a protein involved in oxidative stress. Methods: In this prospective, observational study, mother-infant pairs were studied in 2 groups (57 patients with GDM and 51 controls without GDM). TXNIP levels were measured in the placenta, as well as in the umbilical and neonatal blood. The data were correlated with aIMT in neonates. Results: aIMT was increased in GDM offspring (patients: median [range]=0.39 mm [0.31-0.46] vs controls: median=0.28 mm [0.23-0.33]; p=0.001) and remained significant after adjusting for possible confounders (e.g., triglycerides, blood pressure, vitamin D, birth weight and gender; β coefficient=0.131 p=0.049). TXNIP levels were increased in trophoblasts (p=0.001) and syncytiotrophoblasts (p=0.001) and were decreased in endothelial cells (p=0.022) in GDM offspring vs controls. Moreover, TXNIP levels in trophoblasts positively correlated with aIMT (r=0.369; p=0.001). TXNIP levels in umbilical/ neonatal blood were not associated with GDM. Conclusion: Increased aIMT was demonstrated in the offspring of mothers with GDM. Non-invasive measurement of aIMT could be used as a biomarker to identify children at increased risk for atherogenesis later in life. This information may encourage early preventive measures. TXNIP may be associated with GDM and/or aIMT.

Background: We previously reported that endothelins (ETs) regulate tyrosine hydroxylase (TH) activity and expression in the olfactory bulb (OB) of normotensive and hypertensive animals. Applying an ET receptor type A (ETA) antagonist to the brain suggested that endogenous ETs bind to ET receptor type B (ETB) to elicit effects. Objective: The aim of the present work was to evaluate the role of central ETB stimulation on the regulation of blood pressure (BP) and the catecholaminergic system in the OB of deoxycorticosterone acetate (DOCA)-salt hypertensive rats. Methods: DOCA-salt hypertensive rats were infused for 7 days with cerebrospinal fluid or IRL-1620 (ETB receptor agonist) through a cannula placed in the lateral brain ventricle. Systolic BP (SBP) and heart rate were recorded by plethysmography. The expression of TH and its phosphorylated forms in the OB were determined by immunoblotting, TH activity by a radioenzymatic assay, and TH mRNA by quantitative real-time polymerase chain reaction. Results: Chronic administration of IRL-1620 decreased SBP in hypertensive rats but not in normotensive animals. Furthermore, the blockade of ETB receptors also decreased TH-mRNA in DOCA-salt rats, but it did not modify TH activity or protein expression. Conclusion: These findings suggest that brain ETs through the activation of ETB receptors contribute to SBP regulation in DOCA-salt hypertension. However, the catecholaminergic system in the OB does not appear to be conclusively involved although mRNA TH was reduced. Present and previous findings suggest that in this salt-sensitive animal model of hypertension, the OB contributes to chronic BP elevation.

Introduction: PEACE MENA (Program for the Evaluation and Management of Cardiac Events in the Middle East and North Africa) is a prospective registry in Arab countries for in-patients with acute myocardial infarction (AMI) or acute heart failure (AHF). Here, we report the baseline characteristics and outcomes of in-patients with AHF who were enrolled during the first 14 months of the recruitment phase. Methods: A prospective, multi-centre, multi-country study including patients hospitalized with AHF was conducted. Clinical characteristics, echocardiogram, BNP (B-type natriuretic peptide), socioeconomic status, management, 1-month, and 1-year outcomes are reported. Results: Between April 2019 and June 2020, a total of 1258 adults with AHF from 16 Arab countries were recruited. Their mean age was 63.3 (±15) years, 56.8% were men, 65% had monthly income ≤US$ 500, and 56% had limited education. Furthermore, 55% had diabetes mellitus, 67% had hypertension; 55% had HFrEF (heart failure with reduced ejection fraction), and 19% had HFpEF (heart failure with preserved ejection fraction). At 1 year, 3.6% had a heart failure-related device (0-22%) and 7.3% used an angiotensin receptor neprilysin inhibitor (0-43%). Mortality was 4.4% per 1 month and 11.77% per 1-year post-discharge. Compared with higher-income patients, lower-income patients had a higher 1-year total heart failure hospitalization rate (45.6 vs 29.9%, p=0.001), and the 1-year mortality difference was not statistically significant (13.2 vs 8.8%, p=0.059). Conclusion: Most of the patients with AHF in Arab countries had a high burden of cardiac risk factors, low income, and low education status with great heterogeneity in key performance indicators of AHF management among Arab countries.

Objectives: This study aims to determine the protective effect of cilostazol on myocardium in obese Wistar rats with induced ischemia-reperfusion injury (IRI). Methods: Four groups with 10 Wistar rats were included: 1] Sham Group: IRI was not established in normal weight-Wistar rats. 2] Control Group: IRI but no cilostazol in normal weight-Wistar rats. 3] Cilostazol in normal weight-Wistar rats: IRI and cilostazol was administered. 4] Cilostazol in obese- Wistar rats: IRI and cilostazol was administered. Results: Tissue adenosine triphosphate (ATP) levels were significantly higher and superoxide dismutase (SOD) levels significantly lower in the control group than in the sham group and normal weight cilostazol group (p=0.024 and p=0.003). Fibrinogen levels were 198 mg/dL in the sham group, 204 mg/dL in the control group, and 187 mg/dL in the normal-weight cilostazol group (p=0.046). Additionally, plasminogen activator inhibitor-1 (PAI-1) levels were significantly higher in the control group (p=0.047). The level of ATP was significantly lower in the normal-weight cilostazol group than in the obese group (104 vs 131.2 nmol/g protein, p=0.043). PAI-1 level was 2.4 ng/mL in the normal weight cilostazol group and 3.7 ng/mL in the obese cilostazol group (p=0.029). Normal-weight Wistar rats with cilostazol had significantly better histologic outcomes than the control group and obese Wistar rats (p=0.001 and p=0.001). Conclusion: Cilostazol has a protective effect on myocardial cells in IRI models by decreasing inflammation. The protective role of cilostazol was reduced in obese Wistar rats compared with normal-weight Wistar rats.

Background: Hypertension treatment with renin-angiotensin system inhibitors (RASi) presents contradictions about the recovery of damage in cardiovascular autonomic modulation characterized by reduced heart rate variability (HRV) and increased blood pressure variability (BPV). Conversely, the association of RASi with physical training can influence achievements in cardiovascular autonomic modulation. Objective: To investigate the effects of aerobic physical training on hemodynamics and cardiovascular autonomic modulation in hypertensive volunteers untreated and treated with RASi. Methods: A non-randomized controlled trial in which 54 men (≅ 40-60 years old) with a history of hypertension for >2 years were allocated in accordance with their characteristics into three groups: untreated (Control; n=16), treated with type 1 angiotensin II (AT1) receptor blocker (losartan; n=21), and treated with angiotensin-converting enzyme inhibitor (enalapril; n=17). All participants underwent hemodynamic, metabolic, and cardiovascular autonomic evaluation using baroreflex sensitivity (BRS) and spectral analysis of HRV and BPV, before and after 16 weeks of supervised aerobic physical training. Results: The volunteers treated with RASi had lower BPV and HRV, both in the supine position and in the tilt test, with the losartan group having the lowest values. Aerobic physical training increased HRV and BRS in all groups. However, the association of enalapril with physical training appears to be more prominent. Conclusion: Long-term treatment with enalapril and losartan may harm the autonomic modulation of HRV and BRS. Aerobic physical training is essential to promote positive adjustments in the autonomic modulation of HRV and BRS in hypertensive patients treated with RASi, especially with enalapril.

Aim: To assess the current dyslipidemia management in the Arabian Gulf region by describing the demographics, study design, and preliminary results of out-patients who achieved low-density lipoprotein cholesterol (LDL-C) goals at the time of the survey. Background: The Arabian Gulf population is at high risk for atherosclerotic cardiovascular disease at younger ages. There is no up-to-date study regarding dyslipidemia management in this region, especially given the recent guideline-recommended LDL-C targets. Objective: Up-to-date comprehensive assessment of the current dyslipidemia management in the Arabian Gulf region, particularly in view of the recent evidence of the additive beneficial effects of ezetimibe and proprotein convertase subtilisin/kexin-9 (PCSK-9) inhibitors on LDL-C levels and cardiovascular outcomes. Methods: The Gulf Achievement of Cholesterol Targets in Out-Patients (GULF ACTION) is an ongoing national observational longitudinal registry of 3000 patients. In this study, adults ≥18 years on lipidlowering drugs for over three months from out-patients of five Gulf countries were enrolled between January 2020 and May 2022 with planned six-month and one-year follow-ups. Results: Of the 1015 patients enrolled, 71% were male, aged 57.9±12 years. In addition, 68% had atherosclerotic cardiovascular disease (ASCVD), 25% of these patients achieved the LDL-C target, and 26% of the cohort were treated using combined lipid-lowering drugs, including statins. Conclusion: The preliminary results of this cohort revealed that only one-fourth of ASCVD patients achieved LDL-C targets. Therefore, GULF ACTION shall improve our understanding of current dyslipidemia management and “guideline gaps” in the Arabian Gulf region.