Introduction: Five anti-tumor necrosis factor (anti-TNF) agents have received regulatory approval for use in rheumatology: adalimumab, golimumab, infliximab, certolizumab, and etanercept. Apart from their well-documented therapeutic value, it is still uncertain to what extent they are associated with an increased risk of infectious adverse events. Areas covered: We conducted a systematic review and meta-analysis of published randomized studies to determine the effect of anti-TNF drugs on the occurrence of infectious adverse events (serious infections; tuberculosis; opportunistic infections; any infection). We searched Medline, Embase, and the Cochrane Library up to May 2014 to identify eligible studies in adult patients with rheumatoid arthritis, psoriatic arthritis, or ankylosing spondylitis that evaluated anti-TNF drugs compared with placebo or no treatment. Expert opinion: Our study encompassed data from 71 randomized controlled trials involving 22,760 participants (range of follow-up: 1–36 months) and seven open label extension studies with 2,236 participants (range of follow-up: 6–48 months). Quantitative synthesis of the available data found statistically significant increases in the occurrence of any infections (20%), serious infections (40%), and tuberculosis (250%) associated with anti-TNF drug use, while the data for opportunistic infections were scarce. The quality of synthesized evidence was judged as moderate. Further evidence from registries and long-term epidemiological studies are needed to better define the relationship between anti-TNF agents and infection complications.

Review from JAMA Internal Medicine — Antihypertensive Treatment and Development of Heart Failure in Hypertension — A Bayesian Network Meta-analysis of Studies in Patients With Hypertension and High Cardiovascular Risk

Left ventricular diastolic dysfunction represents a frequent clinical condition and is associated with increased cardiovascular morbidity and mortality. Diastolic dysfunction is the most common cause of HF-PSF (heart failure with preserved ejection fraction). Therefore it becomes important to understand the pathophysiological mechanisms underlying diastolic dysfunction, as well as the effective therapeutic strategies able to antagonize its development and progression. Among the complex pathophysiological factors that may contribute to the development of diastolic dysfunction, the RAAS (renin–angiotensin–aldosterone system) has been shown to play a significant role. Paracrine and autocrine signals of the RAAS promote structural and functional changes in the heart largely linked to increased myocardial fibrosis. Enhanced and dysregulated activity of the RAAS also contributes to the development of volume overload and vasoconstriction with subsequent increases in left ventricular diastolic filling pressures and a higher susceptibility of developing CHF (congestive heart failure). More recently, it has also been suggested that the RAAS may play a role in triggering myocardial and vascular inflammation through the activation of different cell types and the secretion of cytokines and chemokines. RAAS-induced myocardial inflammation leads to perivascular myocardial fibrosis and to the development or progression of diastolic dysfunction. For these reasons pharmacological blockade of the RAAS has been proposed as a rational approach for the treatment of diastolic dysfunction. In fact, ACEIs (angiotensin-converting enzyme inhibitors), ARBs (angiotensin II receptor blockers) and AAs (aldosterone antagonists) have been demonstrated to delay the development and progression from pre-clinical diastolic dysfunction towards CHF, as well as to reduce the morbidity and mortality associated with this condition.

Introduction: Results of previous clinical trials evaluating the effect of resveratrol supplementation on blood pressure (BP) are controversial. Purpose: We aimed to assess the impact of resveratrol on BP through systematic review of literature and meta-analysis of available randomized, controlled clinical trials (RCTs). Methods: Literature search included SCOPUS, PubMed-Medline, ISI Web of Science and Google Scholar databases up to 17th October 2017 to identify RCTs investigating the impact of resveratrol on BP. Two review authors independently extracted data on study characteristics, methods and outcomes. Overall, the impact of resveratrol on BP was reported in 17 trials. Results: Administration of resveratrol did not significantly affect neither systolic BP [weighted mean difference (WMD): −2.5 95% CI:(-5.5, 0.6) mmHg; p=0.116; I²=62.1%], nor diastolic BP [WMD: −0.5 95% CI:(-2.2, 1.3) mmHg; p=0.613; I²=50.8], nor mean BP [MAP; WMD: −1.3 95% CI:(-2.8, 0.1) mmHg; p=0.070; I²=39.5%] nor pulse pressure [PP; WMD: −0.9 95% CI:(-3.1, 1.4) mmHg; p=0.449; I²=19.2%]. However, significant WMDs were detected in subsets of studies categorized according to high resveratrol daily dosage (≥300 mg/day) and presence of diabetes. Meta-regression analysis revealed a positive association between systolic BP-lowering resveratrol activity (slope: 1.99; 95% CI: 0.05, 3.93; two-tailed p= 0.04) and Body Mass Index (BMI) at baseline, while no association was detected neither between baseline BMI and MAP-lowering resveratrol activity (slope: 1.35; 95% CI: −0.22, 2.91; two-tailed p= 0.09) nor between baseline BMI and PP-lowering resveratrol activity (slope: 1.03; 95% CI: −1.33, 3.39; two-tailed p= 0.39). Resveratrol was fairly well-tolerated and no serious adverse events occurred among most of the eligible trials. Conclusion: The favourable effect of resveratrol emerging from the current meta-analysis suggests the possible use of this nutraceutical as active compound in order to promote cardiovascular health, mostly when used in high daily dose (≥300 mg/day) and in diabetic patients.

Heart failure represents a major cause of disease burden worldwide and is expected to further rise in the coming decades. Hypertension is the clinical condition most frequently associated to heart failure. To systematically review the incidence of heart failure compared to coronary heart diseases and stroke in recent hypertension trials. We identified 23 trials concluded within the last decade including 193,424 patients with hypertension or at 'high' cardiovascular risk with a predominant presence of hypertensive patients, and reported incidence of major cardiovascular events, including heart failure, coronary heart disease and stroke. A total of 24 837 major cardiovascular events were recorded in trials performed between 1997 and 2007, of which 7171 (28.9%) were cases of heart failure, 10,223 (41.1%) of coronary heart disease and 7443 (30.0%) of stroke. The rate of heart failure was comparable with that of stroke, accounting for 8.5 and 9.1 events per 1000 patients (P = NS), respectively. Heart failure development was more prevalent in older subjects (>65 years) [odds ratio: 3.08, confidence interval 95% (2.88-3.31); P < 0.0001], in black versus nonblack individuals [odds ratio 1.90, (1.76-2.06); P < 0.0001], in diabetic versus nondiabetic patients [odds ratio 4.91, 95% confidence interval (4.40-5.43); P < 0.0001] and in patients with 'very high' risk versus those with a 'high' risk profile [odds ratio 1.29, 95% confidence interval (1.23-1.36); P < 0.0001]. Our analysis shows that heart failure development remains a major problem in hypertension. In recent trials on hypertension, the development of heart failure was found comparable with that of stroke: it is more prevalent in older, black, diabetic and 'very high' risk individuals. These findings highlight the relevance of heart failure development in hypertension and support the need for optimizing antihypertensive strategies aimed at preventing the progression to overt heart failure, thus reducing the growing burden of disease associated with hypertension.