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Catecholamines play a major role in atherothrombotic mechanisms in essential hypertension. Alpha 2B -adrenergic receptors (α2B-ARs) are implicated in the pathophysiology of platelet aggregation. In this study, we evaluated platelet α2B-AR gene expression levels in patients with well-controlled essential hypertension compared with normal individuals and investigated their association with increased arterial stiffness. Fifty-nine patients with well-controlled essential hypertension (34 men, mean age 65 ± 9 years) and 26 normotensives (19 men, mean age 64 ± 8 years) were included in the study. For each patient, carotid-femoral pulse wave velocity (PWV) and carotid-radial PWV were evaluated. In addition, blood samples were obtained and platelets were isolated. The α2B-AR gene expression levels in platelets were examined by real-time polymerase chain reaction for each participant. Well-controlled hypertensive patients showed significantly higher gene expression levels of α2B-Rs in platelets compared with normotensives (34.7 ± 29.5 vs 17.6 ± 12.5, respectively, P = .005). Interestingly, we found that carotid-femoral PWV and carotid-radial PWV were positively correlated with platelet α2B-R gene expression levels (r = 0.59, P P = .002, respectively).Platelet α2B-R gene expression levels are increased in patients with well-controlled essential hypertension compared with normotensives and are correlated with increased PWV in those patients. Our data indicate an association of arterial stiffness and platelet α2B-Rs gene expression and indicate the need for further research.

Platelets contain abundant microRNAs (miRs) that regulate gene expression and protein synthesis and may reflect platelet activation. We assessed platelet levels of miR-223, miR-126, and miR-22 in 82 patients with essential hypertension and 28 healthy individuals, using real-time reverse transcription polymerase chain reaction, and evaluated their relation with the patients’ clinical profile. Hypertensives had significantly lower platelet miR-22 and miR-223 levels (97.6 ± 170.3 in hypertensives versus 193.8 ± 228.9 in normotensives, p = 0.011, for miR-22; 91.3 ± 154.1 in hypertensives versus 189.9 ± 266.3 in normotensives, p = 0.022, for miR-223). Significant differences in platelet miR levels were also observed between hypertensives who had cardiovascular disease and those who did not (4.1 ± 3.6 versus 75.1 ± 85.2 for miR-126, 24.3 ± 62.9 versus 122.8 ± 187.9 for miR-22, and 10.1 ± 10.4 versus 119.3 ± 169.0 for miR-223, respectively; p

Catecholamines play a major role in atherothrombotic mechanisms in essential hypertension. Alpha

Peripheral arterial disease (PAD) is associated with high rates of cerebrovascular and cardiovascular events; PAD is a marker of systemic atherosclerosis. As a result, standard therapy for all PAD patients should be directed at both peripheral and systemic atherosclerosis. Modification of established risk factors in the form of smoking cessation, correcting hypertension, optimizing diabetic control and normalizing lipids is essential. Furthermore, novel risk factors have emerged including fibrinogen and other hemostatic factors. Fibrinogen is a coagulation factor and a marker of the acute phase response (inflammation), a platelet activator, a major determinant of plasma viscosity and a component of the atherosclerotic plaque. Fibrinogen appears not only to predict the severity of PAD, but also serves as a marker for future development of PAD. Whether reducing the levels of fibrinogen and other coagulation factors will decrease the incidence and progression of PAD remains to be resolved. This review summarizes the role of fibrinogen in the pathogenesis of PAD and its association with other hemostatic factors. The role of fibrinolysis in patients with PAD is also considered.

Summary Aim: To compare the Framingham and Prospective Cardiovascular Munster (PROCAM) risk calculations. Methods: We calculated the risk in 234 dyslipidaemic patients without overt vascular disease and in different subgroups. For example, the proportion of patients with coronary heart disease (CHD) risk ≥ 20%, the effect of including the family history (FaHist) and of adjusting raised triglyceride (TG) levels. Results: The Framingham risk was significantly (p

Erectile dysfunction (ED) is a common condition with a significant effect on quality of life. The prevalence of ED increases with age and other risk factors (hypertension, diabetes, smoking, coronary heart disease, dyslipidemia and depression). Nitric oxide (NO) activity is adversely affected, in penile and vascular tissue, by these risk factors. Endothelial dysfunction and a reduced generation or bioavailability of NO have emerged as major pathophysiological mechanisms in ED. Hyperlipidemia may impair erectile function by affecting endothelial and smooth muscle cells of the penis. Oxidized low-density lipoprotein is a causative factor for the impaired relaxation response of the corpus cavernosum. Elevated serum cholesterol and reduced high density lipoprotein cholesterol levels are associated with an increased risk of ED. It follows that treating dyslipidemia could have a beneficial effect on ED. Phosphodiesterase type 5 inhibitors are now considered as first line treatment for ED. There is evidence that statins improve responses to these drugs. ED is considered as a warning sign of silent or early vascular disease. The use of statins may be beneficial in these patients.

Pneumocystis jirovecii (former carinii) pneumonia, is a life-threatening opportunistic infection occurring in immunocompromised hosts. The aim of this study was to investigate the predisposing factors, clinical features and outcome of Pneumocystis pneumonia (PCP) in HIV-negative patients. The medical records of 62 adult patients with PCP, hospitalized at the University Hospital of Heraklion, Crete, Greece during a 10-year period (2004-2013) were retrospectively reviewed. All patients were immunosuppressed prior to the development of PCP. Thirty one patients (50%) suffered malignant hematological disease, 16 (26%) solid tumor and 15 (24%) had chronic inflammatory disease. Only 17 (27%) had received long-term systemic corticosteroids. All had symptoms of pneumonia upon admission, while 12 (19%) were suffering respiratory failure. Twenty one (34%) had received trimethoprim/sulfamethoxazole (TMP-SMX) prophylaxis before the PCP onset. Eight patients (13%) were admitted to the ICU. Mortality attributable to PCP reached 29%. Mortality attributable to PCP was higher in patients with solid tumors. TMP-SMX prophylaxis failed in a significant portion of the present cohort. Hence, PCP should be included in the differential diagnosis in immunocompromised patients with symptoms from the respiratory tract even if TMP-SMX has been given as prophylaxis.

Temporal arteritis (TA) is a chronic, systemic vasculitis most often presenting with severe headaches localized in the temporal region, low-grade fever, anorexia, weight loss and generalized malaise. Besides these typical characteristics, a number of vague and non-specific oral and/or ocular symptoms may also be present. A search using Medline (1955-2006) was performed for unusual oral and ocular/orbital presentations of TA. A variety of oral and ocular/orbital manifestations associated with TA have been reported. These can mislead physicians, causing a delay in establishing a diagnosis and initiating treatment. Increased awareness is necessary for the prompt recognition of this potentially devastating disease. Particularly, dentists and ophthalmologists should include TA in their differential diagnosis, as they may be the first to deal with these patients.

The influence of hypertension, and its treatment, on circulating lipid and fibrinogen (Fib) concentrations in patients with essential hypertension was investigated. The lipid profile and Fib levels were measured in 353 patients (131 men) with essential hypertension. Their median age was 60 years (range: 18-85 years). All patients had normal results from liver, renal, and thyroid function tests. There were 162 patients (45.9%) who were not receiving antihypertensive treatment. Of the remaining patients, 117 were taking ‘lipid-hostile’ (β-blockers, thiazide diuretics) antihypertensives and 74 were taking ‘lipid-neutral’ (angiotensin-converting enzyme inhibitors, calcium channel blockers, angiotensin-II receptor blockers) agents. Patients who were taking ‘lipid-hostile’ antihypertensive drugs had significantly higher plasma Fib concentrations when compared with those taking ‘lipid-neutral’ antihypertensives or those not receiving antihypertensive treatment. These differences were not attributable to established factors that influence plasma Fib levels, since when smokers and patients with diabetes mellitus and/or vascular disease were excluded, the difference remained significant. In addition, in these more homogeneous groups, patients receiving ‘lipid-neutral’ treatment had significantly higher serum high-density lipoprotein (HDL) cholesterol levels when compared with both those taking ‘lipid-hostile’ antihypertensives and untreated ones. There were no significant differences in the other lipid variables, independently of the presence/absence or the type of antihypertensives. These results suggest that antihypertensive drugs have additional effects, beyond lowering blood pressure, on other vascular risk factors, like Fib and HDL. These effects may depend on the type of drug used.

To determine the correlation between cardiovascular risk calculated using the Framingham equation and the circulating levels of 4 'emerging'predictors of vascular events: fibrinogen (Fib), lipoprotein (a) (Lp(a)), albumin (Alb) and bilirubin (Bil) (F-L-A-B).A retrospective survey was carried out using patients referred to a specialist university-based clinic. A total of 376 patients with primary dyslipidaemia (209 men), without overt vascular disease, had their cardiovascular risk estimated using the Framingham equation.Among the men, smokers (n=45) were significantly younger (p =0.014) than non-smokers (n=164). Smokers when compared with non-smokers had significantly higher median Fib levels (3.84 (1.15-5.87) vs. 3.08 (1.44-5.47) g/l; p0.0001) and lower median Bil levels (8 (3-17) vs. 10 (1-28) micromol/l; p=0.016). When non-smoker men without clinically evident vascular disease were considered, there was a significant positive Fib and negative Alb correlation with calculated risk, whether the family history was considered or not. Moreover in smokers, the only significant correlation was a negative one between Bil and cardiovascular disease risk. Lp(a) correlated with risk for stroke in women non-smokers whether the family history was considered or not, while Alb correlated with risk for stroke in women non-smokers without family history.Fib, Lp(a), Alb and Bil (F-L-A-B) may be predictors of vascular events in high-risk populations. Prospective studies should evaluate whether the F-L-A-B markers are useful in the assessment of cardiovascular risk load. Such an advantage would make treatment more cost effective by improving patient targeting. The F-L-A-B markers could eventually become targets for new drugs.

High serum levels of total homocysteine (tHcy) are common in dialysis patients with end-stage renal disease (ESRD). We assumed that these patients may have decreased response to conventional folic acid (FOL) and vitamin B12 (B12) administered orally. This study aimed to evaluate the efficacy of an intravenous (i.v.) B12 regimen in ESRD patients and compare it with the conventional regimen.We designed an open label, crossover, non-randomized study of 72 ESRD patients. Our patients were hemodialyzed in two hospitals (HOSP1 and HOSP2). In HOSP1, patients were on 1 mg of FOL and 600 micog of B12 orally for 3 months, and then switching to 1 mg of B12 i.v. for 3 additional months, while the FOL dosage was constant. In HOSP2, patients received the same treatment in reverse.Patients in HOSP1 (n = 37) after i.v. B12 treatment, had significantly lower tHcy (p0.001) and FOL (p0.05) serum levels, compared with those at the end of oral B12 treatment. On the contrary in HOSP2 patients, serum tHcy levels increased significantly (n = 35, p0.0001) when i.v. was switched to oral treatment. There was a significant inverse correlation between tHcy and B12 (p0.0001) at the end of the i.v. treatment period; while treatment there was no correlation between tHcy and FOL serum levels. At the end of the oral treatment period, there was no significant correlation between tHcy and B12 serum levels, while tHcy and FOL serum levels had a significant inverse correlation (p = 0.002).Our results suggest that ESRD patients on dialysis have 'B12 resistance', and that they should have, in addition to their FOL therapeutic regimen, i.v. B12 treatment to reduce their elevated tHcy levels.

There is extensive trial-based evidence showing that antihypertensive drugs reduce the risk of vascular events (e.g. stroke and myocardial infarction) as well as target organ damage (e.g. left ventricular hypertrophy and microalbuminuria). However, some of these benefits appear to be, at least partially, independent of the extent of blood pressure (BP) lowering. It is also evident that in certain clinical situations some antihypertensive drugs are more effective than others. In this review we discuss the effects of antihypertensive drugs on the endothelium, platelets, fibrinolysis and coagulation. These properties may account for the observed BP-independent actions. Antihypertensive drugs exert multiple effects on the vascular endothelium. These include effects on nitric oxide (NO) and angiotensin II-mediated actions. Many BP lowering drugs can inhibit platelet activity, although the relevance of this property is unknown, especially if patients are also taking platelet inhibitors (e.g. aspirin). Antihypertensive drugs also influence fibrinolysis and coagulation. These effects may be mediated by a variety of mechanisms, including altering insulin sensitivity. The haemostatic actions of antihypertensive drugs deserve greater recognition and further investigation.