Luca Zanoli

Increased arterial stiffness in inflammatory bowel diseases is dependent upon inflammation and reduced by immunomodulatory drugs

BACKGROUND Inflammatory bowel diseases (IBD) are associated with an increased cardiovascular risk that is not fully explained by traditional cardiovascular risk factors but may be due to inflammation and mediated by an increased arterial stiffness. AIMS Study 1, to investigate the relationship between inflammation and arterial stiffening; Study 2, to look whether aortic stiffening is reduced by immunomodulatory therapy in IBD. METHODS Study 1 (Cross-sectional study): pulse wave velocity (PWV) was measured in 74 IBD subjects (40 ulcerative colitis and 34 Crohns disease) and 80 matched controls. Study 2 (Longitudinal study): the effect of therapy on PWV was measured at baseline and 3.4 ± 0.5 years later in 14 IBD subjects treated only with salicylates, 11 subjects treated with steroids and azathioprine, 7 subjects treated with anti TNF-alpha and 30 matched controls. RESULTS Study 1: All parameters were comparable between subjects with ulcerative colitis and Crohns disease. Compared to controls, subjects with ulcerative colitis and those with Crohns disease have both higher carotid-femoral PWV (7.0 ± 1.1, 7.8 ± 1.7 and 8.0 ± 1.6 m/s, respectively; P < 0.001) and carotid-radial PWV (7.2 ± 0.9, 8.8 ± 1.4 and 8.8 ± 1.3 m/s, respectively; P < 0.001). In fully adjusted models carotid-femoral PWV was positively associated with disease duration whereas carotid-radial PWV was associated with C-reactive protein and history of relapse. Study 2: in fully adjusted model carotid-femoral PWV increased significantly at follow-up in IBD subjects treated with salicylates but not in those treated with steroids and azathioprine or anti TNF-alpha. CONCLUSION Increased arterial stiffness in IBD is dependent upon inflammation and reduced by immunomodulatory drugs.

Effect of renal artery stenting on left ventricular mass: a randomized clinical trial.

BACKGROUND Whether renal revascularization reduces left ventricular hypertrophy in patients with coronary artery disease is uncertain. STUDY DESIGN Randomized clinical trial testing the effect of renal artery stenting versus medical therapy on left ventricular hypertrophy progression in patients affected by ischemic heart disease and renal artery stenosis. SETTING & PARTICIPANTS Incident patients with ischemic heart disease undergoing cardiac catheterization with renal artery stenosis >50%-≤80%. INTERVENTION Revascularization plus standard medical therapy versus medical therapy alone. OUTCOMES Primary end point was change in echocardiographic left ventricular mass index (LVMI). MEASUREMENTS Clinical and echocardiographic studies were performed at baseline and after 1 year. RESULTS 84 patients were randomly assigned: 43 to revascularization plus standard medical therapy and 41 to medical therapy alone. At baseline, clinical characteristics were similar in the 2 study groups. After 1 year, there was no statistically significant difference between longitudinal change in the medical therapy group versus that in the medical therapy plus revascularization group for LVMI (2.1; 95% CI, -6.1 to 10.3 g/m(2)), blood pressure (systolic, -0.2 [95% CI, -9.1 to 8.8 mm Hg]; diastolic, -3.3 [95% CI, -8.4 to 1.8 mm Hg]), or estimated glomerular filtration rate (1.5; 95% CI, -5.8 to 8.9 mL/min/1.73 m(2)). The number of major cardiovascular events was similar in the 2 groups (revascularization plus standard medical therapy [fatal, n = 2; nonfatal, n = 11] and medical therapy alone [fatal, n = 2; nonfatal, n = 11]). LIMITATIONS Patients with very severe renal artery stenosis were excluded from the study. CONCLUSIONS Our study was unable to detect a clinically significant benefit of renal revascularization on LVMI in patients with coronary artery disease and renal artery stenosis of 50%-80%.

Contrast-enhanced ultrasound (CEUS) in nephrology: Has the time come for its widespread use?

Grey-scale ultrasound has an important diagnostic role in nephrology. The absence of ionizing radiations and nephrotoxicity, rapidity of execution, excellent repeatability, the possibility to perform the test at the patient’s bed and the low cost represent important advantages of this technique. Paired with real-time sonography and colour-power-Doppler contrast-enhanced ultrasound (CEUS) reduces the diagnostic gap with computed tomography (CT) and magnetic resonance (MR) and represents a major step in the evolution of clinical ultrasound. Although there are several situations in which contrast-enhanced CT and MR are indicated (i.e. evaluation of cystic or ischemic lesions, traumatisms and ablative therapies of the native and transplanted kidney), the use of CT contrast media presents a high risk of contrast-induced nephropathy (i.e. in elderly people, subjects with comorbidities and those with renal dysfunction), while gadolinium-based RM contrast agents are contraindicated for the risk of nephrogenic systemic fibrosis (i.e. in patients with severe renal dysfunction). In these situations, CEUS may be a viable alternative, however, as any technique associated with the infusion of pharmacological substances, the potential advantages and risks of CEUS should be critically evaluated. In this regard, the European Federation of Societies for Ultrasound in Medicine and Biology (EFSUMB) has published the guidelines for the use of CEUS for the kidney imaging and the International Contrast Ultrasound Society (ICUS) has been recently founded. The aim of this review is to offer an updated overview of the potential applications of CEUS in nephrology, reporting some indications and possible risks associated to its use.

Arterial structure and function in inflammatory bowel disease.

Inflammatory bowel disease (IBD) is the result of a combination of environmental, genetic and immunologic factors that trigger an uncontrolled immune response within the intestine, which results in inflammation among genetically predisposed individuals. Several studies have reported that the prevalence of classic cardiovascular risk factors is lower among subjects with IBD than in the general population, including obesity, dyslipidaemia, diabetes and hypertension. Therefore, given the risk profile of IBD subjects, the expected cardiovascular morbidity and mortality should be lower in these patients than in the general population. However, this is not the case because the standardized mortality ratio is not reduced and the risk of coronary heart disease is increased in patients with IBD. It is reasonable to hypothesize that other factors not considered in the classical stratification of cardiovascular risk may be involved in these subjects. Therefore, IBD may be a useful model with which to evaluate the effects of chronic low-grade inflammation in the development of cardiovascular diseases. Arterial stiffness is both a marker of subclinical target organ damage and a cardiovascular risk factor. In diseases characterized by chronic systemic inflammation, there is evidence that the inflammation affects arterial properties and induces both endothelial dysfunction and arterial stiffening. It has been reported that decreasing inflammation via anti tumor necrosis factor alpha therapy decreases arterial stiffness and restores endothelial function in patients with chronic inflammatory disorders. Consistent with these results, several recent studies have been conducted to determine whether arterial properties are altered among patients with IBD. In this review, we discuss the evidence pertaining to arterial structure and function and present the available data regarding arterial stiffness and endothelial function in patients with IBD.

Sodium-glucose linked transporter-2 inhibitors in chronic kidney disease.

SGLT2 inhibitors are new antihyperglycaemic agents whose ability to lower glucose is directly proportional to GFR. Therefore, in chronic kidney disease (CKD) the blood glucose lowering effect is reduced. Unlike many current therapies, the mechanism of action of SGLT2 inhibitors is independent of insulin action or beta-cell function. In addition, the mechanism of action of SGLT2 inhibitors is complementary and not alternative to other antidiabetic agents. SGLT2 inhibitors could be potentially effective in attenuating renal hyperfiltration and, consequently, the progression of CKD. Moreover, the reductions in intraglomerular pressure, systemic blood pressure, and uric acid levels induced by SGLT inhibition may potentially be of benefit in CKD subjects without diabetes. However, at present, only few clinical studies were designed to evaluate the effects of SGLT2 inhibitors in CKD. Consequently, safety and potential efficacy beyond blood glucose lowering should be better clarified in CKD. In this paper we provide an updated review of the use of SGLT2 inhibitors in clinical practice, with particular attention on subjects with CKD.

Resistive intrarenal index: myth or reality?

In renal diagnosis, the B-mode ultrasound is used to provide an accurate study of the renal morphology, whereas the colour and power Doppler are of strategic importance in providing qualitative and quantitative information about the renal vasculature, which can also be obtained through the assessment of the resistive index (RI). To date, this is one of the most sensitive parameters in the study of kidney diseases and allows us to quantify the changes in renal plasma flow. If a proper Doppler ultrasound examination is carried out and a critical analysis of the values obtained is performed, the RI measurement at the interlobar artery level has been suggested in the differential diagnosis between nephropathies. The aim of this review is to highlight the pathological conditions in which the study of intrarenal RI provides useful information about the pathophysiology of renal diseases in both the native and the transplanted kidneys.

Increased cardiovascular risk in subjects with a low prevalence of classic cardiovascular risk factors: The inflammatory bowel disease paradox.

lupus erythematosus are characterized by various clusters of these non-traditional cardiovascular risk factors. Apparently, the positive relationship between the burden of the classic cardiovascular risk factors and the risk to develop cardiovascular events has not been confirmed among patients with IBD. Several studies have described a lower prevalence of classic cardiovascular risk factors among patients with IBD compared with the general population, including lower body mass indices and lipid levels [8–11] ,a s well as lower prevalence of diabetes, obesity, and hypertension [11]. Therefore, we would anticipate a decrease in cardiovascular morbidity and mortality in patients with IBD compared with the general population. Surprisingly, it has been reported that in IBD, the standardized mortality ratio is not decreased [12]; Rungoe et al. [7] in this issue of Trends in Cardiovascular Medicine conclude that most studies are indicative of a modestly increased relative risk of coronary artery disease among patients with both ulcerative colitis and Crohns disease; the risk appears to be higher in women. The majority of studies regarding the risk of cardiovascular disease in the setting of IBD did not stratify based on IBD subtypes (ulcerative colitis or Crohns disease). The few that did separately analyze the risk in the setting of ulcerative colitis and Crohns disease determined that the risk was similar between the two groups of patients. Taken together, these results suggest that as an alternative to the traditional cardiovascular risk factors, other factors may be associated with the cardiovascular risk of patients with IBD. Chronic inflammation has recently been linked to an increased risk of cardiovascular disease. In contrast with other chronic

Arterial stiffness in inflammatory bowel disease: a systematic review and meta-analysis.

Background: Arterial stiffness is increased with chronic inflammatory disorders. The reduction of inflammation by immunomodulatory therapy is associated with a restoration of arterial function. The aims of the study were to perform a meta-analysis to determine whether arterial stiffness is increased in patients with inflammatory bowel disease (IBD) and a meta-regression analysis to correlate arterial stiffness with anti-TNF&agr; therapy. Methods: Systematic review registration number: CRD42015017364. A systematic literature search for arterial stiffness in IBD was performed using PubMed, Scopus, and Google Scholar databases (last accessed on 23 September 2015). The search terms were ‘arterial stiffness,’ ‘vascular stiffness,’ or ‘pulse wave velocity’ in combination with ‘inflammatory bowel disease,’ ‘inflammatory bowel diseases,’ ‘Crohns disease,’ or ‘ulcerative colitis.’ Inclusion criteria included peer-reviewed publications reporting original data, a minimum of 20 study participants tested, and pulse wave velocity (PWV) measured via validated devices. Publications with titles or abstracts appearing to meet the inclusion criteria were selected and reviewed by two authors according to PRISMA 2009 guidelines. Results: Carotid–femoral PWV (cf-PWV) was measured in nine cross-sectional studies (234 patients with Crohns disease, 342 with ulcerative colitis, and 435 control study participants). Compared with control patients, cf-PWV was significantly increased in patients with Crohns disease [mean difference 1.34 z-score; 95% confidence interval (CI) 0.71–1.97 z-score; P < 0.0001] and ulcerative colitis (mean difference 1.08 z-score; 95% CI 0.55–1.61 z-score; P < 0.0001). In a meta-regression analysis, cf-PWV was reduced in IBD patients treated with anti-TNF&agr; therapy (&bgr; −2.6 m/s; 95% CI −4.9 to −0.2 m/s; P = 0.03). Conclusion: cf-PWV is increased in both ulcerative colitis and Crohns disease patients.

Incorporating Glomerular filtration rate or creatinine clearance by the modification of diet in renal disease equation or the Cockcroft–Gault equations to improve the Global Accuracy of the Age, Creatinine, Ejection Fraction [ACEF] score in patients undergoing percutaneous coronary intervention

BACKGROUND The aim of the present study was to appraise the comparative ability of different ACEF models incorporating glomerular filtration rate or creatinine clearance estimated by the Modification of Diet in Renal Disease [ACEFMDRD] or Cokcroft-Gault [ACEFCG] equations, respectively, over the original ACEF score (ACEFSrCr) in patients undergoing percutaneous coronary intervention (PCI). METHODS A total of 537 patients were analyzed by different measures of discrimination, calibration and net reclassification improvement (NRI). RESULTS A significant gradient in all-cause mortality was consistently seen with all the models at 30 days, 1 year and 5 years. The comparison of the three models showed that the best balance in terms of discrimination and calibration for all-cause mortality was offered by the ACEFCG at 30 days, the ACEFMDRD at 1 year and similarly by the ACEFCG and ACEFMDRD at 5 years. At 30 days, the NRI was +32.9% for ACEFMDRD over ACEFSrCr and +16% for ACEFCG over ACEFSrCr. At 1 year, the NRI was 13.8% for ACEFMDRD over ACEFSrCr and -7.8% for ACEFCG over ACEFSrCr. At 5 years, the NRI was +7.7% for both the ACEFMDRD and the ACEFCG over the ACEFSrCr. CONCLUSIONS In patients undergoing PCI, the ACEF score is associated with satisfactory early-, mid- and long-term discrimination regardless of the definition of renal function. However, incorporating glomerular filtration rate or creatinine clearance by the MDRD or CG formulas in the ACEF score yields superior calibration compared with the original SrCr-based equation, with the ACEFMDRD displaying superior reclassification ability over the ACEFCG and ACEFSrCr at 30 days and 1 year.

EuroSCORE II Versus Additive and Logistic EuroSCORE in Patients Undergoing Percutaneous Coronary Intervention

The aim of the present study was to externally validate the European System for Cardiac Operative Risk Evaluation (EuroSCORE) II (ESII) in patients undergoing percutaneous coronary intervention (PCI) and to compare its performance with that of its previously released versions, named additive (addES) and logistic EuroSCORE (logES). A total of 537 patients undergoing PCI were analyzed by different measurements of discrimination, calibration, and global accuracy. A significant gradient in all-cause mortality was seen with all the models at 30 days, 1 year, and 5 years, with the exception of the ESII at 30 days. The ESII had the lowest area under the receiver operating characteristic curve at all time points compared with its previous version, being 0.83 (vs 0.90 for both addES and logES) at 30 days, 0.75 (vs 0.82 for both addES and logES) at 1 year, and 0.69 (vs 0.77 for addES and 0.76 for logES) at 5 years. However, the ESII displayed a better calibration than the logES at 30 days, whereas both scores were miscalibrated at 1 and 5 years. The Brier score displayed similar global accuracy between the ESII and logES. In conclusion, the ESII is better calibrated than the logES at 30 days but does not represent a step forward in discrimination and global accuracy compared with its previous versions for predicting early- and long-term mortality of patients undergoing PCI.