Impaired Fasting Glucose (IFG) Prevalence Among Hypolipidemic Treatment- naïve Patients with Hypertension.

BACKGROUND: Impaired fasting glucose (IFG) predisposes to the future development of type 2 diabetes mellitus (T2DM) and may also be associated with increased cardiovascular disease (CVD) risk. Hypertension is an established CVD risk factor. OBJECTIVE: This study aimed to assess the prevalence of IFG and the associated anthropometric and metabolic disturbances in patients with hypertension. METHODS: Consecutive hypertensive patients not on any hypolipidemic treatment and without a diagnosis of T2DM were included. IFG was defined as serum glucose ≥100 mg/dl according to the American Diabetes Association criteria. RESULTS: The total sample consisted of 1381 participants; between them, 78 patients were diagnosed to have T2DM and they were excluded from the analyses, leaving a final sample of 1303 hypertensive patients [41.0% men; median age 58 (range: 15-90) years] not on any hypolipidemic treatment and without a diagnosis of T2DM. IFG was identified in 469 patients (36%). IFG was more prevalent in males than in females (42.4% vs. 31.8%, p<0.001). Patients with IFG had greater body mass index (BMI), waist-to-hip ratio, systolic blood pressure, pulse pressure, triglycerides, alanine aminotransferase, gamma-glutamyl transferase, and uric acid serum levels compared with patients with normal serum glucose levels. CONCLUSION: This study reveals that in a sample of patients with hypertension, one out of three has IFG. This is more prevalent among men. IFG is associated with the presence of a more aggravated anthropometric and biochemical profile, possibly associated with an increased CVD risk.

Designer Amyloid Cell-Penetrating Peptides for Potential Use as Gene Transfer Vehicles.

Cell-penetrating peptides are used extensively to deliver molecules into cells due to their unique characteristics such as rapid internalization, charge, and non-cytotoxicity. Amyloid fibril biomaterials were reported as gene transfer or retroviral infection enhancers; no cell internalization of the peptides themselves is reported so far. In this study, we focus on two rationally and computationally designed peptides comprised of ß-sheet cores derived from naturally occurring protein sequences and designed positively charged and aromatic residues exposed at key residue positions. The ß-sheet cores bestow the designed peptides with the ability to self-assemble into amyloid fibrils. The introduction of positively charged and aromatic residues additionally promotes DNA condensation and cell internalization by the self-assembled material formed by the designed peptides. Our results demonstrate that these designer peptide fibrils can efficiently enter mammalian cells while carrying packaged luciferase-encoding plasmid DNA, and they can act as a protein expression enhancer. Interestingly, the peptides additionally exhibited strong antimicrobial activity against the enterobacterium Escherichia coli.

Platelet microRNAs in hypertensive patients with and without cardiovascular disease.

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 < 0.001 for all). In addition, we found a significant negative correlation with systolic blood pressure (SBP) (r = -0.43, p < 0.001, for miR-22; r = -0.47, p < 0.001, for miR-223 in hypertensives; and r = -0.54, p < 0.001, for miR-126). Finally, receiver operating characteristic analysis showed that platelet miR levels were also strong prognostic markers for cardiovascular disease in these patients. In conclusion, platelet miR-22 and miR-223 levels are reduced according to the hypertension status and they are negatively correlated with SBP levels. Platelet miR levels are also related to the presence of overt cardiovascular disease in this population. Further studies are needed to elucidate the exact role of platelet miRs in platelet function and their utility as novel biomarkers of atherothrombotic risk in those patients.

Increased platelet alpha2B-adrenergic receptor gene expression in well-controlled hypertensives: the effect of arterial stiffness.

Catecholamines play a major role in atherothrombotic mechanisms in essential hypertension. Alpha2B-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 < .001, and r = 0.39, 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.

Predisposing factors, clinical characteristics and outcome of Pneumonocystis jirovecii pneumonia in HIV-negative 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.

Predisposing factors, clinical characteristics and outcome of Pneumonocystis jirovecii pneumonia in HIV-negative patients.

Pneumocystisjirovecii (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.

Prevalence of metabolic syndrome according to different definitions in a hypertensive population.

AIMS: The metabolic syndrome (MetS) is associated with increased risk of cardiovascular disease (CVD) and diabetes mellitus (DM). Several definitions of MetS have been proposed. The aim of the present study was to estimate and compare the prevalence of MetS according to the National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III), American Heart Association-National Heart Lung and Blood Institute (AHA-NHLBI), International Diabetes Federation (IDF) and the more recent Joint Interim Statement (JIS) definitions in patients attending a hypertension clinic. METHODS: The records of patients referred to the hypertension clinic at the University Hospital (Heraklion, Crete) from January 2001 to June 2009 were screened retrospectively. A total 384 patients (146 men) were included in the study. RESULTS: The prevalence of MetS according to the IDF and JIS definitions was significantly higher compared with that of the NCEP ATP III in both genders (IDF: P = .009 and P = .002, JIS: P = .002 and P = 0.001 for men and women, respectively); this was the case for the AHA-NHLBI definition only among women (P = .03). All MetS components differed significantly (P from < .0001 to .02) between patients with and without MetS for all definitions. CONCLUSIONS: The prevalence of MetS varies considerably depending on the definition used in a hypertensive population in a Mediterranean country. These differences will influence risk assessment.

Measuring the burden of herpes zoster and post herpetic neuralgia within primary care in rural Crete, Greece.

BACKGROUND: Research has indicated that general practitioners (GPs) have good clinical judgment in regards to diagnosing and managing herpes zoster (HZ) within clinical practice in a country with limited resources for primary care and general practice. The objective of the current study was to assess the burden of HZ and post herpetic neuralgia (PHN) within rural general practices in Crete, Greece. METHODS: The current study took place within a rural setting in Crete, Greece during the period of November 2007 to November 2009 within the catchment area in which the Cretan Rural Practice-based Research Network is operating. In total 19 GP's from 14 health care units in rural Crete were invited to participate, covering a total turnover patient population of approximately 25, 000 subjects. For the purpose of this study an electronic record database was constructed and used as the main tool for monitoring HZ and PHN incidence. Stress related data was also collected with the use of the Short Anxiety Screening Test (SAST). RESULTS: The crude incidence rate of HZ was 1.4/1000 patients/year throughout the entire network of health centers and satellite practices, while among satellite practices alone it was calculated at 1.3/1000 patients/year. Additionally, the standardised incidence density within satellite practices was calculated at 1.6/1000 patients/year. In regards to the stress associated with HZ and PHN, the latter were found to have lower levels of anxiety, as assessed through the SAST score (17.4 ± 3.9 vs. 21.1 ± 5.7; p = 0.029). CONCLUSIONS: The implementation of an electronic surveillance system was feasible so as to measure the burden of HZ and PHN within the rural general practice setting in Crete.

Adiponectin promotes endotoxin tolerance in macrophages by inducing IRAK-M expression.

High levels of plasma adiponectin are associated with low levels of inflammatory markers and cardioprotection. The mechanism via which adiponectin exerts its anti-inflammatory effect is yet unknown. In the present study, we demonstrate that globular adiponectin (gAd) induces the expression of the inactive isoform of IL-1R-associated kinases (IRAK), IRAK-M. Homologous deletion of IRAK-M in IRAK-M(-/-) mice abolished the tolerogenic properties of gAd because pretreatment of IRAK-M(-/-) macrophages with gAd did not suppress LPS-induced proinflammatory cytokine production. GAd activated the MAPKs MEK1/2 and ERK1/2 in macrophages via their upstream regulator Tpl2. Activation of ERK1/2 via Tpl2 appeared necessary for the induction of IRAK-M because gAd did not induce IRAK-M in Tpl2(-/-) macrophages or in macrophages pretreated with the MEK1/2 inhibitor UO126. In addition, activation of PI3K and Akt1 also appeared necessary for the induction of IRAK-M by gAd, because treatment of Akt1(-/-) macrophages or pretreatment of macrophages with the PI3K inhibitor wortmannin abolished gAd-induced IRAK-M expression. Analysis of IRAK-M expression in human peripheral blood cells confirmed that serum adiponectin was negatively associated with IRAK-M and responsiveness to LPS. In conclusion, our data demonstrate that IRAK-M is a major mediator of gAd-induced endotoxin tolerance in primary macrophages, expression of which depends on the activation of Tpl2/ERK and PI3K/Akt1 signaling pathways.

The role of fibrinogen and fibrinolysis in peripheral arterial disease.

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.

Fibrinogen, lipoprotein (a), albumin and bilirubin (F-L-A-B) levels and cardiovascular risk calculated using the Framingham equation.

OBJECTIVES: 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). PATIENTS AND METHODS: 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. RESULTS: 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; p<0.0001) 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. CONCLUSION: 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.

Oral and ocular/orbital manifestations of temporal arteritis: a disease with deceptive clinical symptoms and devastating consequences.

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.

A case of eosinophilic gastroenteritis with severe peripheral eosinophilia.

Eosinophilic gastroenteritis is a rare heterogeneous disorder of undetermined etiology that is characterized by eosinophilic infiltration of the gastrointestinal tissues and various clinical manifestations. We report an uncommon case of eosinophilic gastroenteritis involving a patient with a short history of mild upper abdominal pain, severe peripheral eosinophilia (absolute eosinophil count of > 5,000 cells per microL), and ascites. The patient was treated successfully with a course of methylprednisolone.

Effect of antihypertensive treatment on plasma fibrinogen and serum HDL levels in patients with essential hypertension.

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' beta-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.

Overweight and obesity in Greek warship personnel: prevalence and correlations.

OBJECTIVE: To estimate the prevalence of obesity among the personnel of a Greek warship and to highlight the potential relationship of the body-mass index (BMI). METHODS: Data on behavioural and demographic characteristics, among 274 men of a Greek warship, aged between 19 and 38 years, were analysed. RESULTS: 26.5% of participants were overweight and 4.7% obese. BMI was correlated with age, and cigarette pack-years, and inverse correlated with the aerobic exercise. No significant associations were found between BMI and alcohol consumption. CONCLUSION: A relatively high proportion of obesity was found in a Greek military population. Intervention and prevention measures should be targeted at the promotion of physical activity and the reduction of the smoking behaviour of personnel.

Association of serum total homocysteine with the extent of ischemic heart disease in a Mediterranean cohort.

High total homocysteine (tHcy) concentrations increase coronary disease risk. Therefore, the authors examined the relation between tHcy concentrations and the number of stenotic arteries in patients with ischemic heart disease (IHD). They enrolled 155 patients with IHD (135 men) who had undergone selective coronary angiography during the previous 2 years. These patients were divided into 4 groups according to the number of vessels (0, 1, 2, and 3) with > or = 70% stenosis. They also reviewed the major coronary risk factors for each patient (age, gender, hypertension, diabetes mellitus, dyslipidemia, cigarette smoking, obesity), and measured serum concentrations of tHcy, folate, vitamin B12 and lipids. There was a significant positive correlation (rs = 0.19; p = 0.017; n = 155) between tHcy serum concentration and the extent of coronary atherosclerosis, expressed by the number of coronary arteries with significant stenosis. Moreover, the number of affected vessels displayed a significant positive correlation with the presence of diabetes mellitus (rs = 0.30; p < 0.0001; n = 155) and serum concentrations of lipoprotein (a) (rs = 0.25; p < 0.05; n = 67) and a negative correlation with apolipoprotein A-I serum concentration (rs = -0.27; p < 0.01; n = 67). In this study, the serum concentrations of tHcy correlated with the extent of coronary atherosclerosis, independently of other classical risk factors, with the exception of diabetes mellitus.

Diet, serum homocysteine levels and ischaemic heart disease in a Mediterranean population.

Homocysteine (Hcy) is recognised as a risk factor for IHD. Serum Hcy is negatively correlated with serum folate levels, the main sources of which are fruits, vegetables and legumes. The present case-control study was designed to examine the relationship between serum Hcy levels and IHD and to assess the role of dietary factors in the southern Mediterranean population of Crete, Greece. Serum Hcy, folate, vitamin B12, creatinine and glucose levels and a full lipid profile were measured in 152 patients with established IHD, median age 64 (range 33-77) years, and 152 healthy control subjects, age- and sex-matched. Dietary data were assessed using a 3 d food intake record. Compared with controls, patients with IHD had significantly higher daily intakes of vitamin B12 and MUFA and significantly lower intakes of carbohydrate, fibre, folate, cholesterol, n-3 fatty acids and total trans unsaturated fatty acids. Moreover, patients had significantly higher serum Hcy, vitamin B12 and creatinine levels, but significantly lower folate. Serum folate concentrations in both groups had a significant positive correlation with dietary fibre consumption and a significant inverse correlation with vitamin B12 intake. IHD patients should be encouraged to increase their daily dietary intake of fibre, folate and n-3 fatty acids, which are significant components of the traditional Cretan Mediterranean diet. Where dietary folate intake is inadequate, folate supplements are recommended to reduce elevated Hcy levels.

Fatal methotrexate-induced pneumonitis in a psoriatic patient.

Pulmonary toxicity, as an adverse effect of methotrexate (MTX) therapy, is uncommon in psoriatics. This report concerns a patient with psoriatic arthritis who developed fatal pneumonitis with a histopathological pattern of the organizing stage of diffuse alveolar damage and who was receiving MTX at a dose of 15 mg weekly for 1 month. The patient died despite the immediate withdrawal of MTX, the administration of corticosteroids, and adequate supportive care. Since MTX pneumonitis is a potentially fatal complication, new pulmonary symptoms, even in patients on low-dose MTX treatment, should be appropriately investigated.