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Background: The timely identification of traditional and non-traditional precursors and risk factors for chronic kidney disease (CKD) (a common systemic disease defined as a decreased kidney function documented by reduced glomerular filtration rate, or markers of kidney damage, or both) is relevant in clinical practice, as CKD increases the risk of end-stage renal disease and other serious comorbidities. A possible relationship between non-alcoholic fatty liver disease (NAFLD) (which is to date the most common chronic disease worldwide) and CKD has recently gained significant attention of researchers. Methods: A systematic literature search using appropriate keywords was made in order to identify relevant articles that have investigated the association between NAFLD and CKD. Results: Several observational studies and meta-analyses have reported the existence of an independent association between NAFLD and risk of CKD in patients with and without diabetes. However, whilst the association between NAFLD and risk of prevalent CKD is strong across various patient populations, whether NAFLD is independently associated with the development and progression of CKD is still debatable. Moreover, emerging evidence now suggests a potential association between patatin-like phospholipase domain-containing protein-3 (PNPLA3) rs738409 genotype (the most important genetic variant associated to NAFLD) and decreasing kidney function, independent of NAFLD. Conclusion: Convincing evidence now indicates that CKD is increased among patients with NAFLD. For this reason, patients with NAFLD should be regularly monitored for renal function and, on the other hand , NAFLD should be considered in all patients with CKD, especially if they are obese or have type 2 diabetes.

Speckle-tracking echocardiography allows early detection of subclinical left ventricular systolic dysfunction (LVSD) in patients with rheumatoid arthritis (RA). In this prospective study, we assessed the prevalence and the prognostic role of subclinical LVSD detected by speckle-tracking echocardiography in RA patients.

Objectives Ascending aorta has an increased stiffness (AoSI) in rheumatoid arthritis (RA) patients due to their chronic inflammatory status. We assessed prevalence and factors associated with increased AoSI and its prognostic role in a large cohort of RA patients.Methods We prospectively analysed 226 RA patients without overt cardiac disease compared with 226 non-RA patients matched for cardiovascular risk factors (non-RA controls). Abnormally high AoSI was diagnosed if AoSI > 6.07% (95th percentile of the AoSI detected in our reference healthy population). AoSI was assessed at the level of the aortic root by two-dimensional guided M-mode evaluation as part of a thorough echocardiography performed in all patients.Results AoSI was significantly higher in the RA patients than non-RA controls (6.3 ± 4.5% vs. 4.6 ± 3.5%, p< 0.001); it was related to older age, higher systolic blood pressure and RA disease. Predictors of AoSI in RA patients were older age, higher systolic blood pressure and the non-prescription of non-steroidal anti-inflammatory drug and/or immunomodulatory/anti-cytotoxic agents. Abnormally high AoSI was diagnosed in 41% RA patients and 21% non-RA controls (p< 0.001). The RA phenotype with abnormally high AoSI was a > 60 years old subject with systolic blood pressure > 129 mmHg, mitral annular calcification who was not receiving non-steroidal anti-inflammatory drug. By multivariate Cox regression analysis abnormally high AoSI independently predicted death or all-cause hospitalization (hazard ratio 2.85 (95% confidence interval 1.03–7.85)) at 12-month follow-up.Conclusions Increased AoSI is common, can be predicted by an ordinary clinical assessment and is a strong predictor of adverse clinical outcome at mid-term follow-up in patients with RA.

Patients with rheumatoid arthritis have an increased risk for cardiovascular disease. Because of accelerated atherosclerosis and changes in left ventricular (LV) geometry, circumferential and longitudinal (C&L) LV systolic dysfunction (LVSD) may be impaired in these patients despite preserved LV ejection fraction. The aim of this study was to determine the prevalence of and factors associated with combined C&L LVSD in patients with rheumatoid arthritis.

IMPORTANCE: Low levels of vitamin D are associated with elevated blood pressure (BP) and future cardiovascular events. Whether vitamin D supplementation reduces BP and which patient characteristics predict a response remain unclear. OBJECTIVE: To systematically review whether supplementation with vitamin D or its analogues reduce BP. DATA SOURCES: We searched MEDLINE, CINAHL, EMBASE, Cochrane Central Register of Controlled Trials, and http://www.ClinicalTrials.com augmented by a hand search of references from the included articles and previous reviews. Google was searched for gray literature (ie, material not published in recognized scientific journals). No language restrictions were applied. The search period spanned January 1, 1966, through March 31, 2014. STUDY SELECTION: We included randomized placebo-controlled clinical trials that used vitamin D supplementation for a minimum of 4 weeks for any indication and reported BP data. Studies were included if they used active or inactive forms of vitamin D or vitamin D analogues. Cointerventions were permitted if identical in all treatment arms. DATA EXTRACTION AND SYNTHESIS: We extracted data on baseline demographics, 25-hydroxyvitamin D levels, systolic and diastolic BP (SBP and DBP), and change in BP from baseline to the final follow-up. Individual patient data on age, sex, medication use, diabetes mellitus, baseline and follow-up BP, and 25-hydroxyvitamin D levels were requested from the authors of the included studies. For trial-level data, between-group differences in BP change were combined in a random-effects model. For individual patient data, between-group differences in BP at the final follow up, adjusted for baseline BP, were calculated before combining in a random-effects model. MAIN OUTCOMES AND MEASURES: Difference in SBP and DBP measured in an office setting. RESULTS: We included 46 trials (4541 participants) in the trial-level meta-analysis. Individual patient data were obtained for 27 trials (3092 participants). At the trial level, no effect of vitamin D supplementation was seen on SBP (effect size, 0.0 [95% CI, −0.8 to 0.8] mm Hg; P = .97; I2 = 21%) or DBP (effect size, −0.1 [95% CI, −0.6 to 0.5] mm Hg; P = .84; I2 = 20%). Similar results were found analyzing individual patient data for SBP (effect size, −0.5 [95% CI, −1.3 to 0.4] mm Hg; P = .27; I2 = 0%) and DBP (effect size, 0.2 [95% CI, −0.3 to 0.7] mm Hg; P = .38; I2 = 0%). Subgroup analysis did not reveal any baseline factor predictive of a better response to therapy. CONCLUSIONS AND RELEVANCE: Vitamin D supplementation is ineffective as an agent for lowering BP and thus should not be used as an antihypertensive agent.

Background: Aortic stiffness index (AoSI) has to be considered a proxy outcome measure in patients with rheumatoid arthritis (RA). The aim of this study was to comparatively describe AoSI progression in two groups of RA patients on long-term treatment with conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) with or without tumour necrosis factor inhibitors (TNFi). Methods: AoSI was evaluated by Doppler echocardiography at the level of the aortic root, using a two-dimensional guided M-mode evaluation. Eligible participants were assessed at baseline and after 12 months. Changes in serum lipids, glucose and arterial blood pressure were assessed. All patients who did not change DMARD treatment during follow-up were consecutively selected for this study. Results: We included 107 (64 TNFi and 43 csDMARDs) RA patients. Most patients (74%) were in remission or low disease activity and had some CVD risk factors (45.8% hypertension, 59.8% dyslipidaemia, 45.3% smoking). The two groups did not differ significantly for baseline AoSI (5.95±3.73% vs 6.08±4.20%, p=0.867). Follow-up AoSI was significantly increased from baseline in the csDMARDs group (+1.00%; p&lt;0.0001) but not in the TNFi group (+0.15%, p=0.477). Patients on TNFi had significantly lower follow-up AoSI from baseline than the csDMARDs group (−1.02%, p&lt;0.001; ANCOVA corrected for baseline AoSI, age and systolic blood pressure). Furthermore, follow-up AoSI was significantly lower in TNFi than in csDMARDs users with an increasing number of CVD risk factors. Conclusion: Long-term treatment with TNFi was associated with reduced aortic stiffness progression in patients with established RA and several CVD risk factors.

Background: Several studies on community populations found that metabolic syndrome (MetS) is associated with higher risk for total incident cancer with a predisposition for specific types of cancer. These findings have never been analyzed in patients with chronic inflammatory rheumatic and musculoskeletal diseases (RMD). We assessed prevalence/incidence and factors related to the development of cancer in a large cohort of these patients and evaluate whether MetS and its components were associated with cancer independent of traditional markers of inflammation. Methods: Between March 2014 and April 2016, 474 patients with RMD involved in a cardiovascular primary prevention program were consecutively recruited into this ambispective (combination of retrospective/prospective) study. They underwent clinical, laboratory, and echocardiographic evaluations. MetS was diagnosed according to the ATPIII criteria. Results: Duration of follow-up was 42 [18–60] months. Patients with a diagnosis of cancer (made before recruitment or during follow-up) were 46 (9.7%). Cancer was diagnosed in 22/76 patients (29%) with MetS and in 24/398 patients (6%, p&lt; 0.001) without MetS; nearly two thirds of malignancies belonged to those traditionally related to MetS. MetS was the strongest cancer risk factor. Cancer was positively associated with the number of MetS components identified in each patient. Beyond MetS, cancer was associated to older age and increased inflammatory disease activity; this information allowed to build a simple performance indicator highly sensitive for cancer development. Conclusion: In light of our results, an increasingly accurate assessment of MetS would be required in patients with RMD as potential measure of clinical outcomes including the risk of cancer.