A. Pinto

Effects of ACE-inhibitors and angiotensin receptor blockers on inflammation.

The role of inflammation in cardiovascular disease and in hypertensive disease above all, is complex. Several studies confirm that activation of renin-angiotensin-aldosterone system (RAAS), through increase in the production of angiotensin II (Ang II), is closely related to local vascular inflammation. Over the BP lowering effects of anti-hypertensive treatments, several ancillary effects for every class may be found, distinguishing the various drugs from one another. Given the pro-inflammatory effects of Ang II and aldosterone, agents that interfere with the components of RAAS, such as ACE inhibitors, Angiotensin Receptor Blockers (ARBs), and mineralocorticoid receptor antagonists (spironolactone or the more selective eplerenone), represent logical therapeutic tools to reduce vascular inflammation and cardiovascular risk, as suggested in large clinical trials in patients with hypertension and diabetes. Regarding ACE inhibitors, actually there is no convincing evidence indicating that ACEis reduce plasma levels of major inflammatory markers in hypertension models. Lack of evidence concerns especially these inflammation markers, such as fibrinogen of CRP, which are less closely related to atherosclerotic disease and vascular damage and conversely are affected by several more aspecific factors. Results obtained by trials accomplished using ARBs seem to be more univocal to confirm, although to great extent, these is an anti-inflammatory effect of drugs blocking AT1 receptor. In order to strictly study the effects of blockage of RAAS on inflammation, future studies may explore different strategies by, for example, simultaneously acting on the ACE and the AT1 angiotensin receptors.

Arterial stiffness indexes and serum cytokine levels in seronegative spondyloarthritis: relationships between stiffness markers and metabolic and immunoinflammatory variables

Objective: The aim of this study was to investigate the relationship between immunoinflammatory markers and indexes of arterial stiffness in patients with seronegative spondyloarthritis (SpA). Method: We enrolled consecutive patients with inflammatory seronegative SpA referred to a rheumatology outpatient clinic. Control subjects were patients admitted in the same period for any cause other than chronic inflammatory disease or acute cardiovascular and cerebrovascular events. Carotid-femoral pulse wave velocity (PWV) was measured and the aortic pressure waveform was used to calculate the augmentation index (Aix). We also evaluated plasma levels of C-reactive protein (CRP), interleukin (IL)-1β, tumour necrosis factor (TNF)-α, and interleukin (IL)-6 as markers of immunoinflammatory activation. Results: This study enrolled 53 patients with SpA and 55 control subjects. After adjustment for blood glucose, cholesterol, and triglyceride levels, and systolic (SBP) and diastolic blood pressure (DBP), patients with seronegative SpA showed higher mean PWV and Aix compared to controls. Moreover, in patients with seronegative SpA, we observed higher mean plasma levels of IL-6, IL-1β, and TNF-α in subjects with mean PWV > 8 m/s in comparison with those with PWV < 8 m/s. Multivariate analysis revealed a significant association between PWV > 8 m/s and male gender, age, diabetes, hypertension, low density lipoprotein cholesterol (LDL-C) > 120 mg/dL, total cholesterol (TC) > 200 mg/dL, coronary artery disease (CAD), microalbuminuria, carotid plaque, and plasma levels of IL-6, IL-1β, and TNF-α. Conclusions: These findings emphasize the role of inflammatory variables and metabolic factors in indexes of high arterial stiffness. Thus, an inflammatory-metabolic background may influence the pathogenesis of increased arterial stiffness in seronegative inflammatory arthritis.

Does sympathetic overactivation feature all hypertensives? Differences of sympathovagal balance according to night/day blood pressure ratio in patients with essential hypertension

When evaluating the ‘night/day BP ratio’, both hypertensives and normotensives can be arbitrarily classified into four groups: extreme dippers (ratio ⩽0.8), dippers (0.8<ratio ⩽0.9), mild dippers (0.9<ratio⩽1.0) and reverse dippers (ratio ⩾1.0). Reverse and mild dipper hypertensives have poorer prognoses compared with the physiological dipper profile, but the prognostic relevance of the extreme dipper profile remains uncertain. The evaluation of heart rate variability (HRV), obtained by 24-h Holter ECG monitoring, is the most frequently used noninvasive form of assessment of the activity of the autonomic nervous system. Reverse and mild dipper hypertensives have reduced HRV, indicating an overactivation of the sympathetic nervous system (SNS); however, the HRV behavior in extreme dippers is still controversial. The goal of this study was to compare HRV indexes of extreme vs. reverse dipper essential hypertensives measured on the basis of time domains. We enrolled 125 hypertensive subjects, divided in 4 quartiles according to day/night blood pressure (BP) ratios. The upper and lower quartiles (31 subjects per quartile) were compared; 30 normotensive subjects were enrolled as a control group. Time domain HRV parameters of the three groups revealed a higher degree of sympathetic activation in the lower quartile (reverse dipper) vs. the upper quartile (extreme) and normotensive controls. HRV parameters related to parasympathetic tone did not show any significant variations among the three groups. Contrary to common belief, not all hypertensives have SNS overactivation.

Successful salvage therapy of intravenous cyclophosphamide for refractory polymyositis in an elderly patient: case report.

Dermatomyositis and polymyositis may affect children and adults and are now widely recognized as major causes of disability which, thanks to the introduction of immunosuppressive drugs, is often treatable, at least to some extent. Few data exist regarding polymyositis in elderly patients. We describe a case of refractory life-threatening polymyositis in an elderly patient, successfully treated with intravenous cyclophosphamide.

Diuretic Treatment in Heart Failure.

n engl j med 378;7 nejm.org February 15, 2018 683 3. Kolsum U, Damera G, Pham TH, et al. Pulmonary inflammation in patients with chronic obstructive pulmonary disease with higher blood eosinophil counts. J Allergy Clin Immunol 2017; 140(4): 1181-1184.e7. 4. Pavord ID, Korn S, Howarth P, et al. Mepolizumab for severe eosinophilic asthma (DREAM): a multicentre, double-blind, placebo-controlled trial. Lancet 2012; 380: 651-9. 5. Bafadhel M. Eosinophils in COPD: are we nearly there yet? Lancet Respir Med 2017; 5: 913-4. DOI: 10.1056/NEJMc1715454n engl j med 378;7 nejm.org February 15, 2018 683 3. Kolsum U, Damera G, Pham TH, et al. Pulmonary inflammation in patients with chronic obstructive pulmonary disease with higher blood eosinophil counts. J Allergy Clin Immunol 2017; 140(4): 1181-1184.e7. 4. Pavord ID, Korn S, Howarth P, et al. Mepolizumab for severe eosinophilic asthma (DREAM): a multicentre, double-blind, placebo-controlled trial. Lancet 2012; 380: 651-9. 5. Bafadhel M. Eosinophils in COPD: are we nearly there yet? Lancet Respir Med 2017; 5: 913-4. DOI: 10.1056/NEJMc1715454

39 POLYMORPHISM OF PROINFLAMMATORY AND ANTI-INFLAMMATORY GENES IN PATIENTS WITH ACUTE ISCHEMIC STROKE

Backgrounds: the improvement in heart surgery and anaesthesiology techniques in last decades have improved morbility and mortality ratio also in high surgical risk patients. Enteral ischemia after heart surgery is a rare complication (0.2 2%), but carries significant mortality (70 100%): its incidence has not been changed in these years and cases reported in literature are even increased. Pathogenesis has not been clearly understood, being complex and multifactorial: the principal cause seems to be the reduction in cardiac outflow during operation. Splancnic atherosclerosis could be also implicated in worsening or favouring enteral ischemia. Actually no relevant articles have been yet published concerning splancnic vessels screening before heart surgery. Atherosclerosis extension is only assessed with carotid duplex ultrasound and anamnestic data about previous cardiovascular events. Scope: aims of the study were to evaluate duplex scanning utility and accuracy to identify atherosclerotic lesions in splancnic vessels and to relate them with other arterial districts involvement. Methods: we studied 91 patients previously subjected to coronary angiography before heart surgery (coronary by-pass, valvular prothesis or both) at “Centro Gallucci” of “Azienda Ospedaliera di Padova”. They were all investigated with echocolordoppler of carotid arteries, aorta and its principal branches, and lower limbs arteries: if some haemodinamic stenosis were found a second level (Angio-CT or Angio-NMR) exam was performed to confirm the previous one. Chi-square test was employed in statistical analysis comparing atherosclerotic lesions distribution. Results: prevalence of carotid lesions and peripheral arterial disease was major among patients with at least one coronary artery critical stenosis; this data was not related with the number of vessels involved. Superior mesenteric artery (SMA) plaques were four times more frequent in patients with critical coronaropaty: no patients without critical lesions in coronary arteries had a >70% SMA stenosis. Carotid plaques (>1.5mm thickness), in particular those >50%, were more frequently associated with critical lesions at coronary angiography, even more than intima-medial thickening (95% vs 45%). Among patients with any degree peripheral arterial disease (PAD), 72% had coronary critical stenosis versus 30% in patients without PAD; if haemodinamic stenosis were found in lower limb arteries the prevalence of coronary critical plaques were 95%. Patients with any carotid plaque had a 44% prevalence of SMA stenosis (whatever degree), while in patients without carotid lesions it was 12.5%. No one with unaffected lower limb arterial wall had atherosclerotic SMA involvement, while if PAD was present, there was a 40% prevalence of SMA plaques (any degree). From this study also stand out that in patients with carotid stenosis >50%, and mainly among those with PAD, splancnic vessels were involved more frequently then in people without them. Both carotid plaques and PAD had a 100% sensitivity to predict a critical stenosis at SMA, even if specificity was below 50%. Conclusions: abdominal vessels duplex scanning is indicated before heart surgery only when atherosclerotic plaques are found in carotid and lower limbs arteries. Finding that kind ok lesions in pre-surgery evaluation should suggest the operator to put to use all devices useful for preventing vascular complications in the splancnic district. Echocolordoppler, if performed by an export operator, could be useful to detect the presence of atherosclerotic plaques or abdominal aortic aneurisms in abdominal vessels.