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Information Technology (IT) could have a prominent role towards the "Active Pharmacovigilance" (AP) paradigm by facilitating the analysis of potential Adverse Drug Reactions (ADRs). PVClinical project aims to build an IT platform enabling the investigation of potential ADRs in the clinical environment and beyond. In this paper, we outline the respective EU regulatory framework and the related Business Processes (BPs), elaborated based on input from clinicians and PV experts as part of the project's "user requirements analysis" phase, highlighting their potential pivotal role in the design of IT tools aiming to support AP.

To briefly present the current situation regarding Geriatric Medicine in Balkan countries and discuss possible perspectives of development by exchange and interaction with countries with more developed Geriatric Medicine. Balkan countries seem to encounter similar difficulties and share common challenges regarding under- and post-graduate education in geriatric medicine, accessibility to comprehensive geriatric assessment and response to special needs of older people in various clinical settings. Proposed solutions need to be pragmatic, effective, applicable in harmony with available services and adjusted to each country’s special context. InterEuropean networking, cooperation among countries under the auspices of EuGMS, and suitable application of experience from countries with developed Geriatrics, could contribute to the development of Geriatric Medicine in Balkan countries as well. To present an insight of the situation of geriatric medicine in Balkan countries, as it was presented in the context of the 2nd pre-congress seminar of the 16th European Geriatric Medicine Society (EuGMS) Congress Athens 2021. Representatives from 8 Balkan countries (Albania, Croatia, Greece, Republic of North Macedonia, Romania, Serbia, Slovenia, Turkey) answered 3 questions to reflect the state of geriatric medicine in their country: education on geriatrics; systems/methods for assessment of functional status and frailty; pre-operative risk assessment. An open discussion followed. Undergraduate education in geriatric medicine seems underestimated in medical faculties of Balkan countries, whereas a high heterogeneity is observed at a post-graduate level. Only a few Balkan countries have geriatric medicine as a recognized medical specialty or subspecialty. Functional status and frailty are only sporadically assessed, and pre-operative risk assessment is very rarely performed with a geriatric focus. Scarcity of expertise and structures relevant to geriatric medicine seems to be common. Developing a training curriculum and geriatrics-related structures are two interconnected aspects. Cooperation among physicians and multidisciplinary teams are essential for the practice of geriatric medicine. A functional geriatric network is eventually necessary and ambulatory geriatric expertise is probably a feasible and clinically relevant starting point. Providing pragmatic solutions to the pressing challenges in variable clinical settings, supplementing and working in harmony with existing components of each health system, is probably the most convincing strategy to gain political support in developing geriatric medicine. Balkan countries share common experiences and challenges in developing geriatrics. Whilst the principles of geriatric medicine are perhaps universal, proposed solutions should be adapted to each country’s specific circumstances. Cooperation of the Balkan countries could promote in each the development of geriatric medicine. EuGMS is willing to foster relevant actions.

BACKGROUND Cardiotrophin 1 (CT-1) is an interleukin 6-related cytokine recently implicated in cardiac hypertrophy and vascular damage in essential hypertension (EH). We aimed first to determine CT-1 levels in naive, untreated patients with grade I EH (UH) as compared with normotensive (NT) individuals and, second, to investigate a possible association of CT-1 levels with indices of arterial stiffness. METHODS We enrolled 45 consecutive untreated patients recently diagnosed with grade I EH by means of office and ambulatory blood pressure (BP) measurements and 25 age- and sex-matched NT subjects. CT-1 levels were measured with a commercially available enzyme-linked immunosorbent assay kit, and indices of arterial stiffness were determined by applanation tonometry. RESULTS CT-1 levels were significantly elevated in UH patients compared with NT subjects (P < 0.001). Furthermore, CT-1 levels correlated positively with office, ambulatory and central BP. A significant bivariable correlation was also found between CT-1 levels and pulse wave velocity (P = 0.02). In the multivariable analysis, central systolic and diastolic BP proved the only significant predictors of CT-1 levels after controlling for other related factors. CONCLUSIONS To our knowledge, this is the first study that correlates CT-1 levels with ambulatory and central BP, as well as with pulse wave velocity in patients with essential hypertension. Thus, studying the effects of CT-1 in the cardiovascular system in patients with EH represents a promising area of investigation in the future.

Resistant hypertension is commonly found in everyday clinical practice. However, the risks of resistant hypertension, as well as the benefits of treatment and control of blood pressure in patients with resistant hypertension remain vaguely clarified. Data from small clinical studies and observational cohorts suggest that patients with resistant hypertension are at increased cardiovascular risk, while control of blood pressure offers substantial benefits. It has to be noted however that data from appropriate large randomized studies are missing, and resistant hypertension remains remarkably understudied. Resistant hypertension has attracted significant scientific interest lately, as new therapeutic modalities become available. The interventional management of resistant hypertension either by carotid baroreceptor stimulation or renal sympathetic denervation is currently under investigation with promising preliminary results. This review presents available evidence regarding the benefits of treatment and control of blood pressure in patients with resistant hypertension and offers a critical evaluation of existing data in this field.

Essential hypertension is associated with increased risk of arterial thrombotic disease. Among other factors, enhanced platelet activity contributes significantly to this phenomenon. An increased level of circulating monocyte-platelet aggregates (MPAs) represents one of the most robust markers of platelet activation; furthermore, these aggregates are also believed to contribute to the pathophysiology of atherothrombotic disease. Putative mechanisms that contribute to platelet activation in essential hypertension include endothelial dysfunction, neurohumoral (sympathetic and renin-angiotensin systems) overactivity, decreased platelet nitric oxide (NO) biosynthesis, and platelet degranulation secondary to increased shear. Current recommendations are that hypertensive patients receive aspirin therapy only if their calculated cardiovascular risk is high and their blood pressure (BP) is adequately controlled. By contrast, the use of antiplatelet treatment in low-risk hypertensive patients is not established and merits further investigation. Moreover, the place of alternative antiplatelet agents other than aspirin, such as clopidogrel, is unclear at present. Some experimental evidence suggests that clopidogrel may confer an additive protective effect over and above aspirin in hypertensive patients, by virtue of effects on the evolution of the atherosclerotic process. This now needs to be investigated in long-term clinical outcome studies.

Aims The aim of this study was to determine the effect of blood pressure (BP) on platelet nitric oxide (NO) signalling and on formation of circulating monocyte-platelet aggregates (MPA), as well as the role of platelet NO in modulating MPA in hypertension. Methods and results We first examined platelet NO signalling in 23 untreated hypertensive (UH) and 23 normotensive (NT) subjects. Platelets from hypertensives exhibited reduced NO synthase activation by albuterol or collagen, as well as suppressed basal and stimulated NO-attributable cyclic guanosine-3′,5′-monophosphate, compared with NT. In a second study, comprising 106 subjects with a wide BP range, circulating MPA showed a strong positive correlation with BP. On multiple regression analysis, using a model incorporating systolic BP (SBP), diastolic BP, age, lipids, gender, and smoking status, the only independent predictor of MPA was SBP. Nitric oxide synthase inhibition with N G-monomethyl-l-arginine increased MPA in NT but not in hypertensives, whereas the NO donor spermine NONOate (SNO) decreased MPA in NT but not in hypertensives. Platelet P-selectin expression was higher in hypertensives than in NT, and its expression was suppressed by SNO in NT only. Conclusion Platelet NO production and responsiveness are suppressed with raised BP, and this may contribute to the increase in platelet P-selectin and hence in circulating MPA in hypertension.

Several epidemiological studies have reported that an elevated heart rate is associated with coronary atherosclerosis independently of other risk factors. In this review we explore the pathophysiologic mechanisms involved in the pro-atherosclerotic effect of elevated heart rate, apart from its association with sympathetic tone. An elevated heart rate enhances the magnitude and frequency of the tensile stress imposed on the arterial wall and prolongs the exposure of coronary endothelium to the systolic low and oscillatory shear stress. Moreover, increased heart rate intensifies the pulsatile motion of the heart and, therefore, the frequency of the periodically changing geometry of the coronary arteries, thereby affecting the local hemodynamic environment. All these processes induce structural and functional changes of the endothelial cells, which are accumulated over the time in atherosclerosis-prone regions promoting atherosclerosis. Heart rate should be considered in every patient with coronary heart disease, especially since it is an easily measurable and reproducible parameter. Slowing the heart rate could potentially decrease the progression of atherosclerosis by reducing the local pro-atherosclerotic vascular environment. This effect may be involved in any beneficial role of heart rate lowering agents in preventing coronary heart disease.

Although conventional linear 3-dimensional (3D) reconstruction of coronary arteries by intravascular ultrasound has been widely used for the assessment of plaque volume and progression; the volumetric error (VE) that is produced has not been adequately studied. Linear and geometrically correct 3D reconstruction was applied in 16 coronary arterial segments from 9 patients. Using geometrically correct reconstruction as reference, VE was assessed in 1-mm-long arterial slices. Although for the entire length of the coronary arteries VEs for lumen, external elastic membrane (EEM), and intima-media volumes were minimal (lumen VE 0.4%, -0.8 to 1.8; EEM VE 0.3%, -0.9 to 1.9; intima-media VE 0.4%, -1.4 to 2.2), the VE in each arterial slice exhibited a large variation from -15.6% to 36.2% for lumen volume, from -12.9% to 33.1% for EEM volume, and from -17.2% to 46.7% for intima-media volume, suggesting that linear reconstruction over- or underestimates the true arterial volumes. Lumen VE, EEM VE, and intima-media VE were also significantly higher in curved arterial subsegments than in relatively straight arterial subsegments (p0.05). In conclusion, in highly curved arterial subsegments, the VE that is produced by linearly stacking the intravascular ultrasound images may be not negligible. Geometrically correct reconstruction of coronary arteries provides more reliable arterial reconstructions and plaque volume measurements. It is anticipated that clinical application of this technique will contribute to more accurate follow-up of the progression of atherosclerosis and assessment of arterial remodeling.

Vascular endothelial growth factor (VEGF) is a specific mitogen for endothelial cells and an inducer of the angiogenic procedure. Endothelial nitric oxide (NO) is a potent vasodilator. Because both are implicated in vascular function, it is possible that they would be significantly affected in arterial hypertension. The aim of the study was the investigation of the levels of the two substances in blood serum and their potential relation in patients with untreated essential arterial hypertension compared to healthy individuals. VEGF levels were found 129.1 +/- 135.9 pg/mL in a group of 28 untreated hypertensive patients vs. 209.0 +/- 133.3 pg/mL in a group of 28 healthy individuals (p = 0.008). Nitrites and nitrates levels (as an indirect index of calculating NO levels) were also lower in hypertensive patients than in healthy individuals (19.8 +/- 9.7 micromol/L vs. 29.6 +/- 15.9 micromol/L, p = 0.014). A positive correlation between NOx (nitrites and nitrates levels) and VEGF was found in healthy individuals (r = 0.55, p = 0.003), but there was no correlation in hypertensive patients. The significant decrease of serum VEGF and NO in arterial hypertension and the existence of a correlation between the two substances in healthy subjects that did not exist in the hypertensive patients are findings that need evaluation.

Numerous factors have been reported to influence the pathogenesis of atherosclerosis. The angiotensin I converting enzyme (ACE) gene is a candidate gene for atherosclerotic-related disease. In the present study, the association between the polymorphism of the ACE gene and peripheral arterial occlusive disease (PAOD) was investigated. Using polymerase chain reaction techniques, 100 patients (age 66.7-7.7 years) with PAOD and 100 age-matched controls were divided into the three ACE genotypes: II, ID and DD (Insertion I and Deletion D). There was no evidence of any association between ACE gene polymorphism and the presence of PAOD (odds ratio 0.759; 95% confidence interval 0.418-1.377). These results indicate an absence of association between DD genotype and PAOD. Further evaluation in a larger population study is required to examine the possibility of an increased risk of PAOD in DD homozygotes.

Background and Purpose: Numerous factors have been reported to influence the pathogenesis of stroke. The angiotensin I-converting enzyme (ACE) gene is a candidate gene for atherosclerotic-related diseases. In the present study, the association between the polymorphism of the ACE gene and ischaemic stroke was investigated. Methods: Using polymerase chain reaction techniques, 100 patients (48 males, age 69.3 ± 9.7 years) with cerebral infarction and 100 age- and sex-matched controls were divided into the following three ACE genotypes [deletion (D) and insertion (I)]: II, ID and DD. Results: There was no evidence of any association between the ACE gene polymorphism and the presence of ischaemic stroke (odds ratio 0.874, 95% confidence interval 0.386–1.973). Conclusions: The DD genotype in the human ACE gene does not appear to be a risk factor for ischaemic stroke. Further evaluation in a larger population study is required to examine the possibility of an increased risk of ischaemic stroke in DD homozygotes.

Primary aldosteronism accompanied by hypokalemia is a cause of secondary hypertension. Diagnosis of primary aldosteronism has increased dramatically in recent years with the wider availability of aldosterone and plasma renin activity measurements. The authors present the case of a patient with resistant hypertension and severe hypokalemia that evaded diagnosis until complications from hypokalemia occurred.

Pheochromocytoma is a tumor of the adrenal medulla that secretes catecholamines (noradrenaline and adrenaline). The clinical presentation is characterized by paroxysmal hypertension, tachycardia, headache, and sweating. Pheochromocytoma is associated with neurofibromatosis type 1. We report the case of a woman with neurofibromatosis type 1 and bilateral adrenal pheochromocytomas who presented with thrombosis of the portal vein, thrombocytosis, hepatic infarct, and stenosis of celiac artery. To our knowledge this is the first report of this constellation of findings as the presenting clinical picture of pheochromocytoma.

Hypertensive patients with retinal arteriolar abnormalities are at increased risk for cardiovascular events. However, the extent of retinal microvascular changes in naïve, never-treated patients with hypertension of short duration has not been established. In addition to this, the lack of relevant data about other phenotypes of hypertension (masked and white-coat hypertension) determined by ambulatory blood-pressure measurement (ABPM) is notable, despite their relationship to increased cardiovascular risk mediated by underlying target-organ and vascular damage.We conducted a study in which nonmydriatic retinal photography was used to assess central retinal artery equivalent (CRAE) and central retinal vein equivalent (CRVE) diameters and the retinal arteriovenus ratio (AVR) in a group of 103 individuals with never-treated hypertension of recent (1 year) appearance, 28 individuals with masked and 20 with white-coat hypertension, and 50 normotensive individuals, as appropriately classified by ABPM.Patients with sustained and masked hypertension had narrower values of CRAE than did normotensive individuals (86.7±10.1 and 87.6±9.2 vs. 94.8±10.6, P0.001 and P = 0.02, respectively). The AVR was lower in patients with sustained hypertension (0.736±0.102), masked hypertension (0.716±0.123), and white-coat hypertension (0.739±0.127) than in normotensive subjects (0.820±0.095), P0.001, P0.001, and P = 0.03, respectively. Both AVR and CRAE were negatively associated with mean systolic and diastolic daytime, nighttime, and 24-hour blood pressures, even after adjustment for other factors.Subtle retinal microvascular signs of pathology are observed in hypertensive patients at early stages of hypertension and in patients with both masked and white coat hypertension. These changes may be indicative or may mediate the differences in cardiovascular mortality in persons with masked and white-coat hypertension, and relevant information about this can be easily accessed with retinal photography.

In a 10-week double-blind randomised placebo-controlled trial, the efficacy, safety and effect on renal function of a single dose of fosinopril 20mg once daily were studied in 23 patients with mild to moderate essential hypertension. After discontinuation of previous antihypertensive treatment and a 4-week washout period, all patients received placebo for the next 2 weeks. Patients were then randomly assigned, in a double-blind fashion, to 1 of 2 groups: the first group (group F) was made up of 12 patients who received fosinopril 20mg once daily; the second group (group PL) was made up of 11 patients who received one matching placebo tablet once daily. The duration of treatment was 4 weeks. At the end of the placebo period and after 4 weeks’ treatment, systolic blood pressure (SBP), diastolic blood pressure (DBP) and heart rate were measured, routine blood and urine investigations performed, and plasma renin activity (PRA), plasma aldosterone and renal haemodynamics determined. A statistically significant reduction in both SBP (p < 0.001) and DBP (p < 0.001) was observed only in group F, 4 weeks after initiation of treatment. Heart rate remained unchanged and there were no adverse events in either group. In group F, PRA increased significantly (p < 0.05) and glomerular filtration rate remained unchanged; renal blood flow was significantly reduced (p < 0.01), although it remained within the normal limits. In conclusion, fosinopril demonstrated an adequate antihypertensive effect and was well tolerated, without any significant changes in renal haemodynamics.

Primary aldosteronism (PA) is a syndrome which includes a group of clinical entities in which aldosterone production is inappropriately high and nonsupressible by sodium loading. The most frequent causes of PA are adrenal adenoma and unilateral or bilateral primary hyperplasia.We report a case of a 55-year-old man with a 10-year history of hypertension in whom functional hormonal studies were indicative of PA. Because adrenal venus sampling was not available at our hospital, the investigation was conducted with a computed tomography (CT) scan and a scan with 131-iodocholesterol (NP-59) which both revealed a left adrenal adenoma.The tumor was excised laparoscopically without any complications and the histological findings confirmed the diagnosis of an aldosterone-producing adenoma. Blood pressure remained normal despite the discontinuation of antihypertensive drugs, further supporting that the adrenal tumor was indeed the cause of high blood pressure. Unfortunately, blood pressure began to rise again 2 months later, and laboratory findings indicated the presence of PA once again. Spironolactone was instituted and blood pressure significantly improved and was finally controlled by the addition of amlodipine.We report this case to underline the difficulties in the discrimination between adenoma and hyperplasia in everyday clinical practice. Although the CT and scintigraphic findings strongly pointed toward an adenoma, the fact that PA re-appeared shortly after the operation, indicated that the underlying cause of the PA was hyperplasia and not adenoma after all.

Interventional activation of the carotid baroreflex has been an appealing idea for the management of resistant hypertension for several decades, yet its clinical application remained elusive and a goal for the future. It is only recently that the profound understanding of the complex anatomy and pathophysiology of the circuit, combined with the accumulation of relevant experimental and clinical data both in animals and in humans, has allowed the development of a more effective and well-promising approach. Indeed, current data support a sustained over a transient reduction of blood pressure through the resetting of baroreceptors, and technical deficits have been minimized with a subsequent recession of adverse events. In addition, clinical outcomes from the application of a new implantable device (Rheos) that induces carotid baroreceptor stimulation point towards a safe and effective blood pressure reduction, but longer experience is needed before its integration in the everyday clinical practice. While accumulating evidence indicates that carotid baroreceptor stimulation exerts its benefits beyond blood pressure reduction, further research is necessary to assess the spectrum of beneficial effects and evaluate potential hazards, before the extraction of secure conclusions.

INTRODUCTION Hypertension is a major public health problem and its prevalence increases with age. Despite an aging population, only a limited number of population-based studies, and fewer Greek studies, have focused exclusively on the elderly. The objective of this study was to investigate the prevalence, awareness, treatment and control of hypertension in the rural residents of Paliouri village in Greece who were aged 65 years and older. METHODS In total there were 171 participants (response rate 89.5%). Six blood pressure (BP) measurements were obtained in two visits and hypertension was defined as a mean systolic BP >or= 140 mmHg and/or mean diastolic BP >or= 90 mmHg, and/or current use of an antihypertensive medication. RESULTS The prevalence of hypertension was 89%. Of the 137 hypertensive patients, 89.8% were aware of their disease, 89.1% were receiving treatment, and the hypertension of 32.8% was controlled. Awareness of hypertension was significantly higher among those with a high frequency of BP measurements, a history of coronary or other chronic disease, lower education, and those living with a spouse. CONCLUSION The findings indicate that hypertension is highly prevalent in this Greek elderly population. Similarly high is the awareness and treatment of hypertension. However, the control rates were relatively low, suggesting that the local health system requires a greater orientation to the prevention and control of hypertension.

We conducted a pH-monitoring study to determine the prevalence of pathologic gastroesophageal reflux (GER+) and laryngopharyngeal reflux (LPR+) in patients with resected benign true vocal fold lesions (TVFLs) and positive reflux finding score (RFS). We compared our findings with those of patients with typical GER disease (GERD) symptoms and normal laryngoscopy. In the group of patients with TVFLs, we compared the pH-monitoring findings of smokers with those of non-smokers. Seventy-two [females 32, mean (SD) age 49.3 (13.1) years] patients with resected TVFLs (polyps: 32, nodules: 20, Reinke’s edema: 12, granulomas: 4, leukoplakia: 4) and 24 [females 14, mean (SD) age 42.2 (13.4) years] patients with typical GERD symptoms, who served as controls for the hypopharyngeal measurements, underwent 24-h double probe, hypopharyngeal and distal esophageal, ambulatory pH monitoring. Thirty-eight (52.8%) patients with TVFLs had GER+ and 52 (72.2%) had LPR+. More laryngopharyngeal reflux episodes (LPREs) were detected in patients with TVFLs compared to those with GERD (P < 0.001). With respect to the specific TVFLs, 12 (37.5%) patients with polyps had GER+ and 24 (75%) had LPR+, 6 (30%) patients with nodules had GER+ and 12 (60%) had LPR+, 6 (50%) patients with Reinke’s edema had GER+ and 8 (66.7%) had LPR+ and all the patients with granuloma or leucoplakia had both GER+ and LPR+. Twenty (55.6%) of the 36 smokers and 32 (88.9%) of the 36 non-smokers with TVFLs had LPR+ (P = 0.003), while GER+ was recorded in 16 (44.4%) smokers and 22 (61.1%) non-smokers (P = 0.238). Smokers had significantly less LPREs (P < 0.001). In conclusion, 24-h double probe pH monitoring may detect GER+ and/or LPR+ in a substantial proportion of patients with resected TVFLs and positive RFS. Our study suggests that LPR+ is more prevalent in patients with TVFLs compared with typical GERD patients and that non-smokers with TVFLs are more likely to have LPR+ than smokers with TVFLs.

Both endothelial and platelet-derived nitric oxide have important vasculoprotective properties. Increasing evidence suggests a dysfunctional platelet nitric oxide synthase type 3 (NOS3) pathway in essential hypertension, whereas for endothelial-derived nitric oxide the picture is more complicated, with many studies suggesting an impairment of endothelial nitric oxide generation, whilst others have suggested that the endothelial nitric oxide pathway is preserved. Controversy also exists as to whether any observed reduction in endothelial or platelet-derived nitric oxide exerts a pathogenetic role or is simply the result of the raised blood pressure. In this review, we examine the evidence that endothelial and/or platelet-derived nitric oxide are disturbed in essential hypertension, and whether such disturbances are cause or effect.

Summary Background Results of several studies published since 1999 suggest that primary hyperaldosteronism (also known as Conn's syndrome) affects more than 10% of people with hypertension; however, such a high prevalence has also been disputed. Experts generally agree that resistant hypertension has the highest prevalence of primary hyperaldosteronism, on the basis of small studies. We aimed to assess the prevalence of primary hyperaldosteronism in a large group of patients with resistant hypertension. Methods Patients with resistant hypertension (blood pressure >140/90 mm Hg despite a three drug regimen, including a diuretic) who attended our outpatient clinic were assessed for primary hyperaldosteronism. Serum aldosterone and plasma renin activity were determined and their ratio was calculated. Patients with a positive test (ratio >65·16 and aldosterone concentrations >416 pmol/L) underwent salt suppression tests with intravenous saline and fludrocortisone. Diagnosis of primary hyperaldosteronism was further confirmed by the response to treatment with spironolactone. Findings Over 20 years, we studied 1616 patients with resistant hypertension. 338 patients (20·9%) had a ratio of more than 65·16 and aldosterone concentrations of more than 416 pmol/L. On the basis of salt suppression tests, 182 (11·3%) patients had primary hyperaldosteronism, and response to spironolactone treatment further confirmed this diagnosis. Hypokalaemia was seen only in 83 patients with primary hyperaldosteronism (45·6%). Interpretation Although the prevalence of primary hyperaldosteronism in patients with resistant hypertension was high, it was substantially lower than previously reported. On the basis of this finding, we could assume that the prevalence of primary hyperaldosteronism in the general unselected hypertensive population is much lower than currently reported. Thus, the notion of an epidemic of primary hyperaldosteronism is not supported. Funding None.

Coronary artery disease (CAD) constitutes the most common cause of morbidity and mortality in developed countries. Statins effectively reduce low-density lipoprotein cholesterol, an important risk factor for CAD and related acute coronary syndromes. They are an extensively studied group of drugs with versatile properties. Overall, they are safe and effective drugs but their myotoxic potential cannot be overlooked. In this review we focus on the pathogenesis of statins' myopathic side effects. Statins can interfere with protein modification at multiple levels. They can affect protein prenylation, an important post-translational modification of membrane bound proteins. They can also adversely affect selenoprotein synthesis, or can interfere with the biosynthesis of dolichols, which are involved in the process of protein glycosylation. Statin-induced myopathy may be also associated with mitochondrial dysfunction. Statins remain the spearhead of our armamentarium in treating atherosclerotic disease. Consistent with their versatile properties it is anticipated to see in the future their indications to expand. Better understanding of the molecular mechanisms involved in statin-induced myopathy may help identify patient groups susceptible to statins' side effects, thereby increasing their safety.

We assessed the effect of the addition of pioglitazone on metabolic control and heart function of patients with type 2 diabetes already receiving sulfonylurea plus metformin. Forty-four patients were given 30 mg of pioglitazone for 3 months. Physical examination, laboratory tests including N-terminal pro-brain natriuretic peptide (NT-proBNP), and echocardiography, were performed at baseline and at study completion. Target HbA(1c) levels were achieved by 44.2% of the patients. Pioglitazone ameliorated lipid profile and lowered liver enzymes and C-reactive protein. Significant increases in NT-proBNP by 39% (P < 0.005) were noticed, but echocardiographic parameters were not altered, even in high-risk subgroups (patients older than 60 years, with diabetes for more than 10 years, with hypertension, with elevated baseline NT-proBNP levels, with left ventricular hypertrophy). In patients with a greater than 60% increase in NT-proBNP levels, a significant increase in left ventricular ejection fraction (P < 0.05) and in fractional shortening (P < 0.05) was found. None of the patients developed edema or signs or symptoms of heart failure. Triple oral combination antidiabetic treatment is an effective therapeutic strategy and weight gain does not abrogate its beneficial actions. Pioglitazone does not affect heart function and even though it increases NT-proBNP, this appears to represent a reaction to volume overload.

Chronic infections, such as hepatitis C, in the setting of rheumatic disorders pose a potential hindrance to optimal management because of possible complications linked to the institution of immune suppression, as well as the high incidence of hepatotoxicity associated with many of the disease-modifying antirheumatic drugs included in the conventional therapeutic regimens. In the setting of hepatitis C, however, the effect of TNFalpha blockade may be potentially beneficial because TNFalpha appears to be involved in the pathogenesis of liver fibrosis through the stimulation of apoptotic pathways. Data related to this subject are, unfortunately, still limited and without detailed information regarding the clinical progression of the rheumatic disorder. We report the cases of two patients, one with ankylosing spondylitis and one with psoriatic arthritis, who were efficiently treated long-term with anti-TNF agents for their rheumatic disease without any evidence of reactivation or flaring of their hepatitis C infection or deterioration of their liver function. Our results indicate that TNFalpha blockade is a highly efficient and uncompromising therapy in hepatitis C-affected individuals with connective tissue disorders. However, systematic, large-scale studies addressing the issue of safety of these new efficient drugs, i.e., monoclonal antibodies targeted against TNFalpha, in patients with chronic hepatitis C will be needed to properly assess the risks and benefits of this treatment in analogous cases.

Several studies have indicated the presence of significant interarm blood pressure (BP) differences; this could result in misclassification of BP status. Nevertheless, the findings of these studies were not consistent. This prospective, observational study investigated the presence and magnitude of interarm BP differences and determined the influence of age, gender, arm circumference, smoking, being hypertensive or diabetic, or having a previous history of cardiovascular disease in these differences. The study included 384 subjects, who were patients, ward visitors, and members of the nursing staff of this Department. BP measurements were recorded simultaneously in both arms by using 2 validated, fully automated oscillometric electronic devices. There were significant differences between the right arm and left arm systolic BP (p10 mm Hg, respectively, and a single patient with both interarm systolic and diastolic BP differences of >10 mm Hg (0.26%). None of the studied demographic or clinical characteristics was a significant predictor of interarm systolic and diastolic BP differences. The authors conclude that significant interarm systolic and diastolic BP differences are frequently present. Therefore, the unilateral measurement of BP may mask the diagnosis or delay the effective treatment of hypertension. It is thus recommended that BP should be simultaneously measured in both arms at the initial consultation and the higher of the 2 readings should be used to guide further management decisions.

Pheochromocytoma is a rare form of secondary hypertension and may be potentially lethal if left untreated. The classical symptoms are paroxysmal hypertension, headaches, palpitations and sweating. They are caused by sudden catecholamine release. Hyperglycemia is reported in some patients with pheochromocytoma but diabetic ketoacidosis is an extremely rare complication of pheochromocytoma with only four cases reported. We report a case of a young woman with pheochromocytoma manifested as diabetic ketoacidosis.

Studies in various ethnic groups have shown contradictory evidence on the association of the angiotensin converting enzyme (ACE) insertion/deletion (I/D) polymorphism with essential hypertension. In addition, mistyping of the insertion allele in heterozygotes has been reported. We analyzed the ACE genotype of 98 hypertensive and 84 normotensive subjects of Greek origin. Genomic DNA was extracted from blood samples and amplified by polymerase chain reaction (PCR). PCR primers were flanking the polymorphic region in intron 16 of the ACE gene. To avoid mistyping of heterozygotes, samples with the DD genotype were also amplified with primers that detect only the insertion allele. The distribution of the DD, ID, and II ACE genotypes was 30, 45, and 23 in hypertensive patients and 29, 40, and 15 in normotensive subjects, respectively. The estimated frequency of the insertion allele was 0.45 in hypertensive and 0.42 in normotensive subjects. The difference was not statistically significant. The results indicate a lack of association between ACE I/D polymorphism and essential hypertension in this Greek population, suggesting that other genes must contribute to the pathogenesis of hypertension. Am J Hypertens 1996; 9:700–702

This study evaluated the long-term effects of percutaneous transluminal renal angioplasty (PTRA) on blood pressure and renal function in patients with renovascular hypertension. Seventy-eight patients with hypertension and unilateral or bilateral stenoses of the renal arteries (16 with fibromuscular dysplasia and 62 with atherosclerosis) were studied. All patients with fibromuscular dysplasia (group A) had normal renal function, while 27 of the 62 patients with atherosclerosis (group B) presented with various degrees of renal failure. PTRA was technically successful in 87.5% patients of group A. The overall technical success rate (complete plus partial) was 72.3% (55/76 renal arteries) in group B. Mean follow-up (range) in months was 42 (12-108) for group A and 39 (13-106) for group B. After successful PTRA, the overall benefit rate (cure plus improved) for hypertension was 100% in group A; 10 of 14 patients were cured and 4 of 14 were improved. In group B, the overall benefit rate was 70.8%; 9 of 48 were cured and 25 of 48 were improved. PTRA was technically successful in 18 of 27 patients with renal failure. Renal function improved in 4 of 18 patients, remained stable in 9 of 18, and deteriorated in 5 of 18 patients. The above results suggest that PTRA is an effective method for the long-term management of patients with renovascular hypertension, although the results were less favorable in the presence of bilateral renal artery stenoses: in addition to improved control of blood pressure, PTRA might improve renal function or delay its progressive deterioration. (Hypertens Res 1995; 18: 27-31)

Dear Editor, We read with great interest the paper by Cowie et al., on clinical applications of B-type natriuretic peptide (BNP) testing.1 Atrial (ANP) and B-type natriuretic peptide are peptide hormones released in response to myocyte stretch. Novel biomarkers have been evaluated for four clinical purposes: prognostic screening in asymptomatic individuals, risk stratification in patients with clinical disease, diagnosis of clinical disease in patients with symptoms of uncertain cause and guidance in the selection or titration of drugs in patients with known disease. A dramatic rise in the number …

Background Acute vigorous exercise, associated with increased release of plasma catecholamines, transiently increases the risk of primary cardiac arrest. We tested the effect of acute submaximal exercise on vasoactive substances and their combined result on platelet function. Methods Healthy volunteers, hypertensive patients and patients with coronary artery disease (CAD) performed a modified treadmill exercise test. We determined plasma catecholamines, thromboxane A2, prostacyclin, endothelin-1 and platelet aggregation induced by adenosine diphosphate (ADP) and collagen at rest and during exercise. Results Our results during exercise showed a) platelet activation (increased thromboxane B2, TXB2), b) increased prostacyclin release from endothelium and c) decreased platelet aggregation in all groups, significantly more in healthy volunteers than in patients with CAD (with hypertensives lying in between these two groups). Conclusion Despite the pronounced activation of Sympathetic Nervous System (SNS) and increased TXB2 levels during acute exercise platelet aggregation decreases, possibly to counterbalance the prothrombotic state. Since this effect seems to be mediated by the normal endothelium (through prostacyclin and nitric oxide), in conditions characterized by endothelial dysfunction (hypertension, CAD) reduced platelet aggregation is attenuated, thus posing such patients in increased risk for thrombotic complications.