Retinal microvascular dysfunction in heart failure.

Aims: Retinal vessel analysis (RVA) represents a novel, non-invasive, and reliable method to study the microcirculation in the eye. The goal of this study was to assess the extent of retinal microvascular dysfunction in patients with chronic heart failure (CHF) compared to controls and established measures of vascular function. Methods and results: In this prospective, single-centre, observational study, 74 patients with compensated CHF (mean age 63.5 ± 11.2 years, 32% female, mean left-ventricular ejection fraction 37 ± 12.8%), 74 patients with cardiovascular risk factors (CVRF; 64.1 ± 12.7 years, 34% female), and 74 healthy controls (HC; 57.8 ± 14.2 years, 35% female) were included. The primary endpoint, flicker-induced dilatation of retinal arterioles (FIDart), was significantly reduced in patients with CHF compared to CVRF and HC (mean FIDart 0.9 ± 0.2 vs. 2.3 ± 0.3 and vs. 3.6 ± 0.3%, respectively, both P < 0.001 before and after propensity score-weighted analysis). Similar differences were seen for venular FID. FIDart was less impaired in patients with dilated compared to ischaemic cardiomyopathy. No significant differences were observed for arteriovenous ratio and flow-mediated dilatation. Impaired FIDven was associated with echocardiographically estimated systolic pulmonary artery pressure and left atrial volume index. Conclusion: Retinal microvascular dilatation in response to flicker light is impaired in CHF. RVA may represent a new and useful method to non-invasively monitor microvascular abnormalities in heart failure in an easy and standardized way without the use of radiation.

Impact of statin therapy on plasma resistin and visfatin concentrations: A systematic review and meta-analysis of controlled clinical trials.

The beneficial effects of statin therapy in reducing cardiovascular morbidity and mortality is not merely explained by the lipid-modulating effects. Although adipokines levels have been associated with cardiometabolic disorders, a few studies have explored the effect of statin on resistin and visfatin. We aimed to evaluate the impact of statin therapy on levels of resistin and visfatin through a meta-analysis of published studies. A systematic literature search in Medline and SCOPUS databases was conducted up to January 2015 to identify controlled trials assessing changes in plasma concentrations of visfatin and resistin during treatment with statins. Quantitative data synthesis was performed using a random-effects model, with weighed mean difference (WMD) and 95% confidence interval (CI) as summary statistics. 12 eligible studies with 14 treatment arms were included. Overall, 844 participants were studied. No significant change in plasma resistin concentrations was observed following statin therapy (WMD: -0.11ng/mL, CI: -1.94,1.73, p=0.909). This effect was robust and not affected by statin type, treatment duration and LDL-cholesterol concentrations. With respect to visfatin concentrations, there was a marginally significant reduction following statin therapy (WMD: -2.40ng/mL, CI: -4.79,-0.002, p=0.050). However, this effect size was weak and sensitive to three of the trials included in the analysis. This meta-analysis did not suggest any effect of statin therapy on plasma resistin levels, while a slight reduction in visfatin levels was found. The effect of statins on visfatin levels may represent a novel pleiotropic characteristic of these drugs.

Retinal microvascular dysfunction in patients with coronary artery disease with and without heart failure: a continuum?

AIMS: Dynamic retinal vessel analysis is a novel, non-invasive method to assess microvascular function. The primary aim of this study was to investigate whether retinal microcirculation is impaired in patients with stable coronary artery disease (CAD) compared to patients with heart failure due to CAD (ischaemic heart failure, IHF). METHODS AND RESULTS: A total of 150 adults were enrolled to prospectively assess micro- and macrovasculature. The pre-defined primary outcome was flicker-induced arterial dilatation (FIDa) in patients with CAD [n = 40; median age 63 years, interquartile range (IQR) 53-70] and IHF (n = 40; median age 63 years, IQR 59-71) compared to healthy controls (HC, n = 70; median age 57 years, IQR 41-69). Secondary outcomes included arterial stiffness, flow-mediated dilatation, biomarkers, and ergospirometry parameters. Patients with CAD demonstrated impairment in FIDa that was even more pronounced in patients with IHF (CAD: 1.93 ± 0.28% vs. IHF: 0.41 ± 0.28%, P < 0.001; FIDa in HC: 3.69 ± 0.21%, both P < 0.001) adjusting for age, sex, concomitant medication, and co-morbidities. While pulse wave velocity was increased and flow-mediated dilatation reduced in CAD and IHF patients (both P < 0.001 compared to HC), neither differed between CAD and IHF patients. N-terminal pro-B-type natriuretic peptide (r = -0.49, P < 0.001,) and high-sensitivity troponin T (r = -0.28, P = 0.003) correlated with FIDa. Intriguingly, mean metabolic equivalents (5.3 ± 2.3 kcal/kg/h, n = 39) showed a positive correlation with FIDa (r = 0.58, P < 0.001). CONCLUSION: This study demonstrates a decline of retinal arterial function in CAD patients that is significantly more pronounced in the presence of reduced left ventricular ejection fraction, suggesting a continuum of microvascular damage.

Polyphenols: Anti-Platelet Nutraceutical?

BACKGROUND: Coronary artery disease (CAD) is a disease progressing over many years. Genetic factors, as well as the exposure to risk factors, are continuously leading to endothelial dysfunction, vascular alterations and, eventually, organ damage, major cardiovascular events and deaths. Oxidative stress, platelet hyperactivity and low-grade inflammation are important modulators in this context, contributing to plaque formation. Since platelet activation plays a critical role in the development and progression of atherothrombotic events, the inhibition of platelet hyperactivity may contribute to decreased atherothrombotic risk. The consumption of bioactive foods, and plant-derived polyphenols in particular, might impart anti-thrombotic and cardiovascular protective effects. METHODS: Aim of this work is to focus on the potential of dietary derived polyphenols to reduce platelet hyperactivity or hypercoagulability in addition to discussing their possible complementary anti-platelet therapeutic potential. All the relevant publications on this topic were systematically reviewed. RESULTS: Various studies demonstrated that polyphenol supplementation affects platelet aggregation and function in vitro and in vivo, mainly neutralizing free radicals, inhibiting platelet activation and related signal transduction pathways, blocking thromboxane A2 receptors and enhancing nitric oxide production. Experimental data concerning the effect of dietary polyphenols on platelet aggregation in vivo are poor, and results are often conflicting. Only flavanols clearly mirrored in vivo showed the efficacy in vitro in modulating platelet function. CONCLUSION: Dietary polyphenols, and above all flavanols contained in cocoa and berries, reduce platelet activation and aggregation via multiple pathways. However, more controlled interventional studies are required to establish which doses are required as well as what circulating concentrations are sufficient to induce functional antiplatelet effects.

Retinal microvascular dysfunction in hypercholesterolemia.

BACKGROUND: Hypercholesterolemia is one of the most important contributors to atherosclerosis. Whether hypercholesterolemia also affects the retinal microcirculation is unclear. OBJECTIVE: The goal of our study was to assess the association of cholesterol levels with retinal microvascular function using dynamic and static retinal vessel analysis (RVA) in a primary prevention setting. METHODS: This cross-sectional, observational study prospectively recruited 67 patients with hypercholesterolemia without known cardiovascular disease (mean age 64.4 ± 10.4 years; 45% female) and 78 healthy controls (mean age 61.8 ± 11.2 years; 45% female). The primary end point of the study was flicker-induced dilatation of retinal arterioles (FIDart) with secondary exploratory outcomes including venular FID (FIDven), arteriovenous ratio, flow-mediated dilatation and arterial stiffness as measured with augmentation index and pulse wave velocity. Multiple regression analysis was performed to study the association of cholesterol levels with retinal microvascular function. RESULTS: FIDart was significantly impaired in patients with hypercholesterolemia compared with healthy controls (mean FIDart 2.1 ± 1.8 vs 3.1 ± 1.8%, P = .001). This association remained when analysis was restricted to dyslipidemic patients without coexisting hypertension or lipid-lowering therapy. No significant differences remained for FIDven, flow-mediated dilatation, arteriovenous ratio, or arterial stiffness between the groups. Low-density lipoprotein, but not high-density lipoprotein, cholesterol was a significant negative predictor of FIDart in multiple regression analysis. CONCLUSION: Hypercholesterolemia is associated with significant retinal microvascular dysfunction as evidenced by a reduction in flicker-induced dilatation of retinal arterioles. Dynamic RVA may be a promising method for the study of retinal microvascular dysfunction in populations at elevated cardiovascular risk.

Endothelial dysfunction in cardiovascular disease and Flammer syndrome-similarities and differences.

The endothelium has increasingly been recognized as a smart barrier and a key regulator of blood flow in micro- and macrovascular beds. Endothelial dysfunction marks a stage of atherosclerosis and is an important prognostic marker for cardiovascular disease. Yet, some people who tend to be slim and physically active and with rather low blood pressure show a propensity to respond to certain stimuli such as emotional stress with endothelial-mediated vascular dysregulation (Flammer syndrome). This leads to characteristic vascular symptoms such as cold hands but also a risk for vascular-mediated diseases such as normal-tension glaucoma. It is the aim of this review to delineate the differences between Flammer syndrome and its "counterpart" endothelial dysfunction in the context of cardiovascular diseases.

Cocoa, Blood Pressure, and Vascular Function.

Cardiovascular disease (CVD) represents the most common cause of death worldwide. The consumption of natural polyphenol-rich foods, and cocoa in particular, has been related to a reduced risk of CVD, including coronary heart disease and stroke. Intervention studies strongly suggest that cocoa exerts a beneficial impact on cardiovascular health, through the reduction of blood pressure (BP), improvement of vascular function, modulation of lipid and glucose metabolism, and reduction of platelet aggregation. These potentially beneficial effects have been shown in healthy subjects as well as in patients with risk factors (arterial hypertension, diabetes, and smoking) or established CVD (coronary heart disease or heart failure). Several potential mechanisms are supposed to be responsible for the positive effect of cocoa; among them activation of nitric oxide (NO) synthase, increased bioavailability of NO as well as antioxidant, and anti-inflammatory properties. It is the aim of this review to summarize the findings of cocoa and chocolate on BP and vascular function.