Current Vascular Pharmacology - Volume 14, Issue 4, 2016

The incidence of high blood pressure (BP) along with other cardiovascular (CV) risk factors on human health has been studied for many years. These studies have proven a link between unhealthy dietary habits and sedentary lifestyle with the onset of hypertension, which is a hallmark of CV and cerebrovascular diseases. The Mediterranean diet, declared by the UNESCO as an Intangible Cultural Heritage since 2013, is rich in vegetables, legumes, fruits and virgin olive oil. Thanks to its many beneficial effects, including those with regard to lowering BP, the Mediterranean diet may help people from modern countries to achieve a lower occurrence of CV disease. Data from human and animal studies have shown that the consumption of virgin olive oil shares most of the beneficial effects of the Mediterranean diet. Virgin olive oil is the only edible fat that can be consumed as a natural fruit product with no additives or preservatives, and contains a unique constellation of bioactive entities, namely oleic acid and minor constituents. In this review, we summarize what is known about the effects of virgin olive oil on hypertension.

Introduction: Septic shock is represented by severe hemodynamic changes which are manifested with failure of organ systems and high mortality. Early diagnosis together with timely and appropriate treatment is important to attain better outcome. Objectives: We reviewed the diagnostic approach of septic shock in relation to the microcirculatory abnormalities, novel biomarkers, monitoring, interventions, and therapy. Methods: A narrative literature review was carried out using PubMed, MEDLINE and Google scholar search engines. Results: Septic shock is characterized by extensive microcirculatory alterations. These changes are diverse in nature and lead to inconsistency of response to various interventions. The severity of these abnormalities correlates with the patient prognosis. The pathophysiology of septic shock is highly complex which requires better understanding of disease progression and risk-stratification based on potential sepsis biomarkers such as lactic acid, procalcitonin, C-reactive protein, cytokines, and novel molecular markers. The newly identified candidate biomarkers include soluble Triggering Receptor Expressed on myeloid cells-1, presepsin, soluble urokinase-type Plasminogen Receptor and pro-adrenomedullin, but their clinical utilities still need to be validated by large prospective clinical trials. A number of promising therapies for the management of severe sepsis and septic shock has been proposed with potential implications. Conclusion: It is crucial to improve microvascular perfusion through targeted interventions using patient-centred approach. Moreover, systems biology approach could play a promising role in understanding the immune complexity, characterization of gene expression patterns, and recognition of novel therapeutic targets which could be used as clinical decision making tool in the future.

Cholesterol-lowering effects apart, statins can improve the endothelial function, stabilize the atherosclerotic plaques, decrease the oxidative stress and inflammation and inhibit the thrombogenic response by means of the inhibition of isoprenoids, which serve as lipid attachments for intracellular signaling molecules. We aimed to evaluate whether the effect of statins on RhoA activity mediate extracellular matrix production, particularly affecting collagen type I, in smooth muscle cells (SMCs). Our results showed that lovastatin decreased collagen expression in primary cultured chicken SMCs as determined by incorporation of [H3]-proline, RT-PCR and immunocytochemistry. This fall was parallel to that found in Rho A activity. Similar results were found when GGTI-298, a RhoA inhibitor, was added to the culture medium. Mevalonate or geranylgeranyl pyrophosphate reverted these effects. In order to elucidate the role of Rho A in these events we transfected the cell line A10 (rat SMCs) with constitutively active (G14V) or dominant negative RhoA (T19N) constructs. The last ones showed similar results regarding collagen production that those stated above in lovastatin treated primary SMC cultures. Constitutively active RhoA transfected cells showed the opposite effects. Next we performed a promoter activity assay to exclude post-transcriptional mechanisms implicated in these studies. We found a similar pattern in col1a2 promoter activity to that found in collagen expression. Our results have demonstrated that statins regulate the activation of RhoA through its isoprenylation, which is crucial for the regulation of extracellular matrix synthesis in SMCs.

Objectives: To study the effect of antiplatelet agents on preventing arteriovenous (AV) fistulae thrombosis in hemodialysis (HD) patients after surgical thrombectomy (ST) for acute AV fistulae occlusion. Whether post-operative antiplatelet drugs have similar effects on the patency of AV fistula after surgical thrombectomy in patients with end-stage renal disease who undergo HD has not been investigated. Design, Materials and Methods: We employed the Taiwan National Health Insurance Research Database (NHIRD) from 1999 to 2010 to assess the recurrent occlusion requiring ST and longevity of AV fistula after ST in 1049 patients on regular HD, with or without antiplatelet drugs. Results: From the propensity-score (PS)-matched NHIRD, Multivariate Cox model demonstrated that concomitant antiplatelet medication in the HD patients who received the first ST significantly reduced the duration of recurrent ST (adjusted hazard ratio (HR) 1.69; 95% confidence interval (CI) 1.22-2.35, p=0.002) and the longevity of the fistula (adjusted HR 1.79; 95% CI 1.31-2.46, p<0.001). Conclusion: Treatment with antiplatelet drugs in HD patients did not prevent recurrent thrombosis requiring further ST, but significantly jeopardized the longevity of AV fistula after ST.

Background: Endothelial dysfunction is involved in the pathogenesis of atherosclerosis and cardiovascular complications in chronic kidney disease (CKD). Asymmetric dimethylarginine (ADMA), an endogenous inhibitor of endothelial nitric oxide synthase (eNOS), is considered as a marker of endothelial dysfunction. The aim of this study was to evaluate serum ADMA, eNOS concentration and left ventricular structure and function in CKD patients and to assess the impact of the type of dialyzer on serum ADMA and eNOS concentrations after a haemodialysis (HD) session. Material and Methods: Peripheral blood was collected from 35 predialysis CKD patients, 40 CKD patients on HD and 15 healthy subjects. Patients on HD were divided into two groups according to the dialyzer used based on polynephron or cellulose membranes. Plasma ADMA and eNOS concentrations were assessed. All subjects underwent echocardiography and were evaluated for selected biochemical parameters. Results: We found significantly higher serum ADMA (p<0.05) and significantly lower eNOS (p<0.05) concentration in CKD patients compared with healthy subjects. Both dialyzers significantly reduced serum ADMA concentration (p<0.05) but none of the analysed dialyzers showed superiority when comparing the results. We showed that stage V CKD patients, who had the highest serum ADMA concentration had the lowest left ventricle ejection fraction (LVEF) and the highest left ventricle mass (LVM) and left ventricular end diastolic diameter (LVEDd). Conclusions: Our results supports the presence of endothelial dysfunction in CKD patients. Correlation between elevated serum AMDA concentration and disadvantageous changes in left ventricular structure and function may indicate an important role of endothelial dysfunction in cardiovascular complications in CKD patients.

Objectives: To estimate the prevalence of venous thromboembolism (VTE) risk factors in pregnancy and the proportion of pregnancies at risk of VTE that received the recommended prophylaxis according to the American College of Chest Physicians (ACCP) 2012 published guidelines in antenatal clinics in the Arabian Gulf. Methods: The evaluation of venous thromboembolism (EVE)-Risk project was a non-interventional, cross-sectional, multi-centre, multi-national study of all eligible pregnant women (≥17 years) screened during antenatal clinics from 7 centres in the Arabian Gulf countries (United Arab Emirates, Kuwait, Bahrain, Qatar and Oman). Pregnant women were recruited during a 3-month period between September and December 2012. Results: Of 4,131 screened pregnant women, 32% (n=1,337) had ≥1 risk factors for VTE. Common VTE risk factors included obesity (76%), multiparity (33%), recurrent miscarriages (9.1%), varicose veins (6.9%), thrombophilia (2.6%), immobilization (2.0%), sickle cell disease (2.8%) and previous VTE (1.6%). Only 8.3% (n=111) of the high risk patients were on the recommended VTE prophylaxis. Enoxaparin was used in 80% (n=89) of the cases followed by tinzaparin (4%; n=4). Antiplatelet agents were prescribed in 11% (n=149) of pregnant women. Of those on anticoagulants (n=111), 59% (n=66) were also co-prescribed antiplatelet agents. Side effects (mainly local bruising at the injection site) were reported in 12% (n=13) of the cases. Conclusion: A large proportion of pregnant women in the Arabian Gulf countries have ≥1 VTE risk factor with even a smaller fraction on prophylaxis. VTE risk assessment must be adopted to identify those at risk who would need VTE prophylaxis.

We evaluated the control of cardiovascular disease (CVD) risk factors among patients with atherosclerotic cardiovascular disease (ASCVD) in the Centralized Pan-Middle East Survey on the undertreatment of hypercholesterolaemia (CEPHEUS) in the Arabian Gulf. Of the 4398 enrolled patients, overall mean age was 57 ± 11 years, 60% were males, 13% were smokers, 76% had diabetes, 71% had metabolic syndrome and 78% had very high ASCVD risk status. The proportion of subjects with body mass index <25 kg/m2, HbA1c <7% (in diabetics), low-density lipoprotein cholesterol (LDL-C) <2.6 mmol/L (100 mg/dL) and <1.8 mmol/L (70 mg/dL) for high and very high ASCVD risk cohorts, respectively and controlled blood pressure (<140/90 mmHg) was 14, 26, 31% and 60%, respectively. Only 1.4% of the participants had all of their CVD risk factors controlled with significant differences among the countries (P < .001). CVD risk goal attainment rates were significantly lower in those with very high ASCVD risk compared with those with high ASCVD risk status (P < .001). Females were also, generally, less likely to attain goals when compared with males (P < .001).

Background: Thromboangiitis obliterans (TAO), or Buerger’s disease, is an inflammatory occlusive disorder that affects the limb arteries of young smokers. In the aetiology of TAO the immune system appears to play a critical role; however, information on the aspects involved in the evolution of vascular tissue inflammation and of this disease are still limited. Objective: This study was carried out to investigate HMGB-1 (high mobility group box-1), MMP (matrix metalloproteinase)- 2, MMP-9, MMP-11 and ICAM (intercellular adhesion molecule)-1 circulating levels in subjects with Buerger’s disease. Methods: Between January 2010 and December 2012, eight patients underwent surgical revascularization of the lower limbs and a specimen of the affected arterial wall was obtained for histological confirmation of Buerger’s disease. A blood sample was collected on the same day for measuring HMGB-1, MMP-3, MMP-9 and ICAM-1 by western blot analysis. Controls (n=7) were healthy non-smokers. Results: TAO subjects had a significant increase in HMGB-1, MMP-9 and ICAM-1 compared with controls (P<.0001), while no differences were observed in MMP-2 and MMP-11 levels. Histology confirmed a strong inflammatory infiltrate with signs of necrosis in the arterial wall. Conclusion: These data suggest a role for HMGB -1 in the vascular lesions associated with TAO, unveiling HMGB-1 as a potential target for treating this rare disease.

Background: The primary objective of this study was to evaluate the impact of polypharmacy on primary and secondary adherence to evidence-based medication (EBM) and to measure factors associated with non-adherence among patients who underwent percutaneous coronary intervention (PCI). Methods: We conducted a retrospective analysis for patients who underwent PCI at a tertiary cardiac care hospital in Qatar. Patients who had polypharmacy (defined as ≥6 medications) were compared with those who had no polypharmacy at hospital discharge in terms of primary and secondary adherence to dual antiplatelet therapy (DAPT), beta-blockers (BB), angiotensin converting enzyme inhibitors (ACEIs) and statins. Results: A total of 557 patients (mean age: 53±10 years; 85%; males) who underwent PCI were included. The majority of patients (84.6%) received ≥6 medications (polypharmacy group) while only 15.4% patients received ≤5 medications (nonpolypharmacy group). The two groups were comparable in term of gender, nationality, socioeconomic status and medical insurance. The non-polypharmacy patients had significantly higher adherence to first refill of DAPT compared with patients in the polypharmacy group (100 vs. 76.9%; p=0.001). Similarly, the non-polypharmacy patients were significantly more adherent to secondary preventive medications (BB, ACEI and statins) than the polypharmacy group. Conclusion: In patients who underwent PCI, polypharmacy at discharge could play a negative role in the adherence to the first refill of EBM. Further studies should investigate other parameters that contribute to long term non-adherence.

Background and Objectives: In Qatar, ACS (Acute Coronary Syndrome) has become the leading cause of morbidity and mortality. Guidelines recommend that ACS patients should receive indefinite treatment with antiplatelets, β-blockers, angiotensin converting enzyme inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs) and statins. The study objectives were to assess the use of evidence-based secondary prevention medication at discharge among ACS patients in Qatar and to determine the clinical and demographic characteristics associated with the use of these medications. Setting and Methods: A retrospective medical record review was conducted at the Heart Hospital in Qatar. A random sample of 1068 ACS patients was selected. Patient characteristics were summarized. Prevalence of medications at discharge were computed for each medication as well as for medication combinations. Multiple logistic regression was used to detect patient variables that were associated with the outcomes. A p≤0.05 was considered significant. Main Outcome Measures: -Percentage of ACS patients discharged on each of the following medications: antiplatelets (aspirin, clopidogrel), β-blockers, ACEI or ARBs and statins and on the combination of these medications-Association between the use of these medications and patient characteristics. Results: In total, 1064 records were reviewed. The majority were males (85.3%) and about 1 in 5 (18.7%) were Qatari. At discharge, patients were prescribed the following: aspirin (96.0%), clopidogrel (92.0%), β-blockers (90.6%) and statins (97.7%). ACEI and ARBs were prescribed to 63.5 and 11.3%, respectively. The concurrent 4 medications (aspirin or clopidogrel, statins or other lowering cholesterol medication, β-blockers and ACEI or ARB) were prescribed to 773 patients (77.8%; 95% confidence interval: 75.2-80.4%). Being overweight or obese, and having PCI (percutaneous coronary intervention) or hypertension were associated with higher prescription of the concurrent medications. Those with diabetes had a 52% increase in the odds of prescribing the 4 medications. Those with kidney disease had a 67% reduction in the odds of prescribing. Conclusion: Most ACS patients were prescribed antiplatelets, and statins, but the use of ACEIs or ARBs was suboptimal. Strategies are needed to enhance ACEI or ARB prescribing, especially for high risk patients who would have the greatest therapeutic benefit from these drugs.