Current Vascular Pharmacology - Volume 15, Issue 1, 2017

Obstructive sleep apnoea (OSA) is characterized by repetitive interruptions of breathing, causing Chronic Intermittent Hypoxia (CIH) that can be involved in the development and progression of cardiovascular diseases. There is evidence showing a close relationship between OSA and atherosclerosis, even in patients who do not show co-morbidities such as hypertension, diabetes, high levels of lowdensity lipoprotein cholesterol (LDL-C), cigarette smoking and obesity, which can activate the endothelium. This endothelium activation due to CIH and specific to OSA seems to be dependent on a different pathway. The current first line therapy for OSA is the application of the continuous positive airway pressure (CPAP), but it alone is not enough to reduce cardiometabolic risk in patients with OSA. In contrast, statins, via their pleiotropic property, might be able to change inflammation and early atherosclerosis, lipid profile and cardiovascular outcomes in OSA. The role of statins in OSA patients with or without any co-morbidities could potentially prevent coronary vascular risk and stroke and in the future, represent an additional treatment option along with CPAP therapy. Strengthening the prevention strategies against atherosclerosis in OSA should be one of the focal aims for healthcare programs of the future.

Rheumatoid Arthritis (RA) is a chronic inflammatory disease with a potential cardiovascular (CV) risk. Flow-Mediated Vasodilation (FMD) is an ultrasonic method to evaluate endothelial function. RA is a contributor to endothelial dysfunction, a CV risk. Relevant insights on the improvement of the CV outcomes in RA patients may be obtained by a systematic review of trials that investigated the effects of RA treatment on FMD in RA patients. This review found that treatments with antirheumatic drugs and some non-antirheumatic drugs could improve the FMD in RA patients. Treatment with anti-tumour necrosis factor (TNF)-α drugs, including infliximab, etanercept and adalimumab, improved the FMD in RA patients. Treatment with non-anti-TNF-α drugs, including rituximab, anakinra and tocilizumab, also improved the FMD. One trial showed that conventional synthetic Disease-Modifying Antirheumatic Drugs (DMARDs) improved the FMD. Regarding non-antirheumatic drugs, treatment with ramipril, spironolactone and statins/ezetimibe improved the FMD in RA patients. Treatment of advanced glycation endproducts inhibitors improved the FMD in RA patients, while treatment of pioglitazone did not. Overall, treatments for RA improved endothelial dysfunction, as evaluated by FMD, in RA patients. This information may be useful in patient management, although further studies are necessary to establish strategies in relation to endothelial dysfunction among these patients.

Type 2 Diabetes Mellitus (T2DM) and its complications are more prevalent in the elderly. As the general population worldwide is ageing, effective and safe treatment of older T2DM patients is becoming more important in clinical practice. Elderly T2DM patients should be carefully evaluated for functional, mental, geriatric and medical disorders before the initiation of antidiabetic drug therapy and regularly monitored thereafter. Treatment strategy and goals should be individualized based on patient comorbidities and drug pharmacokinetic and pharmacodynamic properties. This narrative review discusses the use of antidiabetic drugs in the elderly T2DM population.

Metabolic syndrome (MetS) is a leading public health and clinical challenge worldwide. MetS represents a group of interrelated risk factors that predict cardiovascular diseases (CVD) and diabetes mellitus (DM). Its prevalence ranges between 10 and 84%, depending on the geographic region, urban or rural environment, individual demographic characteristics of the population studied (sex, age, racial and ethnic origin), as well as the criteria used to define MetS. Persons with MetS have higher mortality rate when compared with people without MetS, primarily caused by progressive atherosclerosis, accelerated by pro-inflammatory and pro-coagulation components of MetS. Considering the high prevalence of metabolic disorders (glucose metabolism disorder, hypertension, dyslipidaemia, obesity etc.), preventive healthcare should focus on changing lifestyle in order to reduce obesity and increase physical activity. This narrative review considers the available evidence from clinical and experimental studies dealing with MetS, and current treatment options for patients with insulin resistance and MetS.

The discovery of small RNAs has shed new light on microRNA (mRNA) regulation and a range of biological processes. The recognition that miRNAs-221 and -222 are sensitive regulators in the endothelium may enable the identification of novel biomarkers and therapeutic targets. Given that endothelial dysfunction precedes the development of atherosclerosis and contributes to the development of cardiovascular damage, circulating miRNAs produced by Endothelial Cells (ECs) are putative biomarkers for a wide range of cardiovascular diseases. Furthermore, EC proliferation and migration have a critical role in the formation of new blood vessels (angiogenesis), an important component of physiological processes and tumour growth. Hence, the use of anti-angiogenic miRNAs might constitute a novel therapeutic strategy. Along with endothelial angiogenesis, several other processes involving ECs (such as neointimal lesion formation, vascular inflammation, lipoprotein metabolism and hypertension) are critical factors in atherogenesis and atherosclerosis. The fact that human blood-derived progenitor cells, endothelial progenitor cells, umbilical vein ECs and quiescent ECs express high levels of miR-221/222 suggests an important role for this miRNA cluster in endothelial (patho) physiology. The present article reviews current knowledge on miRNAs-221/222’s regulation roles in endothelial function and disease in general and angiogenesis in particular.

Background: Few studies assessed gender disparity in lipid goal attainment in the Arabian Gulf. Hence, we estimated gender gaps in lipid target achievements among patients at high and very high atherosclerotic cardiovascular disease (ASCVD) risk in the Centralized Pan-Middle East Survey on the undertreatment of hypercholesterolemia (CEPHEUS). Methods: The study (conducted between November 22, 2009 and July 7, 2010) included 4,384 patients (≥18 years) on lipid lowering drugs at high and very ASCVD risk status from outpatient clinics of 177 specialists and primary care physicians in 6 Arabian Gulf countries. Results: The overall mean age was 57±11 years and 40% (n=1763) were women. Women were more likely to have diabetes mellitus (84 vs 71%; p <0.001) and metabolic syndrome (49 vs 35%; p <0.001) compared with males. Women were less likely to achieve their low-density lipoprotein cholesterol (LDLC) (28 vs 32%; p = 0.002), high-density lipoprotein cholesterol (HDL-C) (42 vs 50%; p <0.001), and apolipoprotein B (Apo B) (38 vs 42%; p = 0.015) targets compared with men. In the very high ASCVD risk cohort, women were significantly less likely to achieve their LDL-C (20 vs 30%; p <0.001), non- HDL-C (34 vs 39%; p = 0.001) and Apo B (34 vs 41%; p <0.001) therapeutic targets compared with men. Conclusion: Women in the Arabian Gulf were less likely to achieve their lipid targets than men. The difference was more significant in the very high ASCVD risk group.

Objective: To evaluate the epidemiological and morphological characteristics of coronary plaque in diabetic patients with symptomatic coronary heart disease (CHD) by dual-source computed tomography (DSCT). Materials and Methods: From June 2013 to December 2014, 267 consecutive patients with type 2 diabetes mellitus were examined by DSCT. Plaque type, distribution, as well as extent and obstructive characteristics were determined for each segment. Results: A total of 225 patients were included in the final study. Among the 225 cases, patients with calcium score >10 accounted for 76.9%. With the increase in calcium score, the number of obstructive stenoses increased from 17 (22.7%) to 150 (66.4%) segments, and non-obstructive stenosis decreased from 58 (77.3%) to 76 (33.6%) segments. A total of 862 (3.8±3.0 per patient) plaques were detected, of which 448 (52%) were calcified plaque, 272 (32%) mixed plaques and 142 (16%) soft plaques. Regarding the stenosis type, there were significantly more mild (54%), followed by moderate (26%) and severe stenosis (20%); 152 (67.6%) patients had ≥2 vascular lesions, while 73 (32.4%) patients with single diseased vessel. 190 (84.40%) patients with atherosclerotic plaque were located in left anterior descending (LAD) coronary artery, 146 (64.9%) patients in right coronary artery (RCA), 114 (50.7%) patients in left circumflex (LCX) coronary artery. The most common site of all detected plaques was the proximal segment of the LAD (18.7%). Conclusion: DSCT showed that coronary arteries of diabetic patients with symptomatic CHD were more prone to calcification. There was more non-obstructive than obstructive lumen narrowing; obstructive stenosis and calcification score was positively correlated; coronary plaques were widely distributed, and mainly located in multiple diseased vessels.

Objective: Historically, a set of 5 Cardiovascular Autonomic Reflex Tests (CARTs) were considered to be the gold standard in the assessment of Cardiovascular Autonomic Neuropathy (CAN). However, measuring diastolic Blood Pressure (BP) response to sustained handgrip is omitted in recent guidelines. We aimed to assess the association between the handgrip and the other 4 tests as well as to identify determinants of the handgrip test results in diabetic patients. Patients and Methods: 353 patients with diabetes (DM) were recruited (age: 60.2±7.4 years; female: 57.2%; BMI: 29.3±2.1 kg/m2; DM duration: 15.6±9.9 years; HbA1c: 7.8±1.4% (66 mmol/mol); with type 1 DM: 18.1%). CAN was assessed by 5 CARTs: the deep breathing test, Valsalva ratio, 30/15 ratio, handgrip and orthostatic hypotension test. Results: Sensitivity and specificity of the handgrip test in the diagnosis of definite CAN were 24.6% (95%CI 17.7-33.1%) and 79.4% (95%CI 73.3-84.4%), respectively. Results of the handgrip test did not show any association with those of the deep-breathing test (γ=0.004, p=0.563), 30/15 ratio (γ=0.282, p=0.357), Valsalva ratio (γ=-0.058, p=0.436) and orthostatic hypotension (γ=-0.026, p=0.833). Handgrip test abnormality showed an independent association with higher initial diastolic BP (OR 1.05, p=0.0009) and an independent inverse association with the presence of hypertension (OR=0.42, p=0.006). Conclusion: Our data confirm that the handgrip test should no longer be part of the cardiovascular autonomic testing being highly dependent on hypertensive status and baseline diastolic BP. Exaggerated exercise pressor response is proposed as putative mechanism for the inverse association between abnormal results of the handgrip test and hypertension. Adequate CARTs are important to allow their use in clinical trials and for the prevention of DM-associated complications by initiating early treatment.

Background: Beta-blockers reduce mortality in chronic heart failure. Objectives: To study intra-hospital mortality and adverse cardiovascular (CV) outcomes in relation to beta-blockade therapy in acute decompensated heart failure. Methods: We retrospectively analyzed a 22-year registry of acute decompensated heart failure (ADHF) in the Middle East. Results: Out of the total 8066 patients admitted for ADHF, 1242(15.4%) were on beta-blockers on admission. Among those, beta-blockers were discontinued in 26.5%. Despite the existence of less CV comorbidities in patients not treated by beta-blockers, in-hospital mortality and stroke/transient ischemic attacks rates were higher in those patients compared with patients on beta-blockers on admission (14.4 vs. 3.6%, p=0.001, 0.6 vs. 0.1%, p=0.02; respectively). Additionally, continuation of beta-blockers during acute decompensation was associated with less mortality risk (p=0.001). The use of beta-blockers on admission and discharge increased significantly with time whereas in-hospital mortality decreased (p=0.001). Nevertheless, admission year was not a predictor of reduced mortality in patients treated with beta-blockers on admission (OR 0.93, 95% CI [0.56-1.54], p=0.77). Conclusion: Previous beta-blockade therapy in patients presenting with ADHF decreases intra-hospital mortality and the incidence of CV events and stroke/transient ischemic attacks. Moreover, nonwithdrawal of beta-blockers during hospitalization has a favorable outcome.

Aims: Specialized nurses estimated the HeartScore in an urban Greek population by recognizing cardiovascular disease (CVD) risk factors in the setting of the Onassis Cardiovascular Prevention Program (OCPP). They also provided nursing consultation and assessed the clinical and biochemical characteristics of the studied population. Methods and Results: Individuals were recruited through TV announcements and via the website of the Onassis Cardiac Surgery Centre. All participants visited the Onassis Cardiac Centre from 20 September to 30 October 2011. Overall, 2,145 individuals were included in the study. CVD risk was calculated by the HeartScore and serum total cholesterol was measured (mean: 193±43 mg/dl). Although 33% of the participants reported dyslipidaemia, only 17% were on hypolipidaemic treatment. Hypertension and dyslipidaemia frequency increased with age. Conclusion: In the present study, specialized nurses estimated the HeartScore in a Greek urban population. The majority of the studied population was undiagnosed and untreated. These results highlight the necessity for both primary and secondary prevention programs that can be carried out by specialized nurses. Such programs may improve the diagnosis and treatment of CVD risk factors; early initiation and optimization of therapy as well as management of drug intolerance (e.g. statins) can contribute to CVD risk reduction.