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ObjectivesThis study sought to investigate the interaction between blood pressure (BP) and heart rate (HR) reduction and changes in left ventricular (LV) structure and function following renal sympathetic denervation (RDN).BackgroundHypertension results in structural and functional cardiac changes. RDN reduces BP, HR, and LV mass and improves diastolic dysfunction.MethodsWe evaluated LV size, mass, and function before and 6 months after RDN in 66 patients with resistant hypertension and analyzed results in relation to systolic BP (SBP) and HR.ResultsSBP decreased by 11 ± 3 mm Hg in the first, 18 ± 5 mm Hg in the second, and 36 ± 7 mm Hg in the third tertile of SBP at baseline (p < 0.001). HR decreased by 13 ± 4 beats/min, 8 ± 3 beats/min, and 11 ± 6 beats/min in tertiles of SBP (p for interaction between tertiles = 0.314). In all SBP tertiles, LV mass index (LVMI) decreased similarly (LVMI −6.3 ± 2.2 g/m2.7, −8.3 ± 2.1 g/m2.7, and −9.6 ± 1.9 g/m2.7; p for interaction = 0.639). LVMI decreased unrelated to HR at baseline (p for interaction = 0.471). The diastolic parameters E-wave deceleration time, isovolumetric relaxation time, and E′-wave velocity improved similarly in all tertiles of SBP and HR. Changes in LV mass and function were also unrelated to reduction in SBP or HR. Vascular compliance improved dependently on BP but independently of HR reduction.ConclusionsIn patients with resistant hypertension, LV hypertrophy and diastolic function improved 6 months after RDN, without significant relation to SBP and HR. These findings suggest a direct effect of altered sympathetic activity in addition to unloading on cardiac hypertrophy and function.

Atrial fibrillation (AF) is the most common cardiac rhythm disorder and a major risk factor for ischemic stroke. Antithrombotic therapy using aspirin or vitamin K antagonists (VKA) is currently prescribed for prevention for ischemic stroke in patients with AF. A narrow therapeutic range and the need of regular monitoring of its anticoagulatory effect impair effectiveness and safety of VKA, causing a need for alternative anticoagulant drugs. Recently developed anticoagulants include direct thrombin antagonists such as dabigatran or factor Xa inhibitors such as rivaroxaban, apixaban, betrixaban, and edoxaban. Currently, data from a phase III clinical trial are available for dabigatran only, which show the direct thrombin antagonist to be at least noninferior in efficacy to VKA for the prevention of stroke and systemic embolism in patients with AF. This review focuses on current advances in the development of directly acting oral anticoagulant drugs and their potential to replace the VKA class of drugs in patients with AF.

BackgroundVitamin K–dependent factors protect against vascular and renovascular calcification, and vitamin K antagonists may be associated with a decreased glomerular filtration rate (GFR).ObjectivesThis study analyzed changes in GFR during long-term treatment with warfarin or dabigatran etexilate (DE) in patients enrolled in the RE-LY (Randomized Evaluation of Long Term Anticoagulation Therapy) trial.MethodsOf the 18,113 patients in the RE-LY study randomized to receive DE (110 mg or 150 mg twice daily) or warfarin, 16,490 patients with atrial fibrillation had creatinine values measured at baseline and at least 1 follow-up visit. Changes in GFR for up to 30 months were evaluated.ResultsGFR declined in all treatment groups. After an average of 30 months, the mean ± SE decline in GFR was significantly greater with warfarin (–3.68 ± 0.24 ml/min) compared with DE 110 mg (–2.57 ± 0.24 ml/min; p = 0.0009 vs. warfarin) and DE 150 mg (–2.46 ± 0.23 ml/min; p = 0.0002 vs. warfarin). A decrease in GFR >25% was less likely with DE 110 mg (hazard ratio: 0.81 [95% confidence interval: 0.69 to 0.96]; p = 0.017) or DE 150 mg (hazard ratio: 0.79 [95% confidence interval: 0.68 to 0.93]; p = 0.0056) than with warfarin in the observation period >18 months. Patients with poor international normalized ratio control (i.e., time in therapeutic range

Epidemiologic studies suggest that elevated postprandial triglycerides (ppTG) are associated with future cardiovascular events. Monocyte activation plays an important role in vascular diseases. Omega-3 fatty acids (n3-FA) lower fasting TG levels. The effects of n3-FA on ppTG and the role of ppTG for monocyte activation are insufficiently understood.23 healthy volunteers and 30 non-diabetic patients with documented coronary artery disease were subjected to an oral TG tolerance test (OTTT) consisting of 80 g cream fat or to water as control (H(2)O). Patients were treated with 4 g n3-FA/day or placebo for 3 weeks in a randomized, placebo-controlled, double-blind, crossover study. Relative postprandial TG increase reached its maximum 4 h after fat intake (185.1 ± 10.9% of baseline). n3-FA reduced fasting TG from 137.1 ± 12.9 to 112.2 ± 8.6 mg/dl (p 0.05), and maximum ppTG concentrations from 243.6 ± 24.6 to 205.8 ± 17.1 mg/dl (p 0.05), while relative TG increase (192.8 ± 12.7%) was comparable to placebo. Relative monocytopenia and neutrophilia were detected following fat intake, which was unaffected by n3-FA and also detectable in the H(2)O group. Serum chemotactic cytokine (MCP1 and fractalkine) concentrations and monocyte migration were not affected by fat intake or n3-FA. Monocyte activation markers CD11b and CD14, monocyte subpopulations CD16(+)CD14(high) and CD16(+)CD14(low), sICAM serum levels and markers of oxidative stress remained unchanged by fat intake or n3-FA.The postprandial TG increase does not stimulate monocytes beyond their circadian activation patterns. n3-FA reduce fasting TG and the postprandial TG increase. n3-FA may therefore allow to prospectively study whether selected patients benefit from TG-lowering independent of LDL- and HDL-cholesterol.

This editorial refers to ‘Nitric oxide enhances the anti-inflammatory and anti-atherogenic activity of atorvastatin in a mouse model of accelerated atherosclerosis’ by S. Momi et al ., doi:10.1093/cvr/cvs100. Statins decrease endogenous hepatic cholesterol synthesis by inhibiting 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase and augment systemic clearance of cholesterol-rich lipoproteins by the up-regulation of hepatic LDL receptors. Furthermore, this class of drug exerts a variety of so-called pleiotropic beneficial effects on the cardiovascular system. Atherosclerosis is initiated by impaired endothelial function characterized by a reduction in endothelial nitric oxide (NO) bioavailability. LDL-cholesterol (LDL-C) is an important negative regulator of endothelial NO synthase activity. In addition to their lipid-lowering effects, one central biological action of statins is their ability to ameliorate the impaired bioavailability of NO.1 Mechanistically, this occurs through increased expression (by inhibition of geranylgeranylation of small G-proteins)2 or enhanced activation (phosphorylation, activation of phosphatidylinositol 3-kinase and Akt) of endothelial NO synthase (eNOS).3 Consequently, statins improve vasodilation, exert antioxidative effects, and inhibit platelet aggregation, monocyte adhesion, and smooth muscle proliferation—all processes with disturbed regulation in atherosclerosis ( Figure 1 ). On top of—and through—enhancing NO bioavailability, statins have potent anti-inflammatory effects: they decrease inflammation in the vascular wall, in atherosclerotic plaques, and in circulating mononuclear cells and mobilize endothelial progenitor cells from the bone marrow.4 A complete review of vascular effects of statins can be found elsewhere.5 Figure 1 Both NO and HMG-CoA reductase inhibitors exert a variety of similar vasoprotective, anti-atherosclerotic functions. The eNOS is the predominant NO-producing enzyme in the vasculature. In the physiological ‘coupled’ state, eNOS forms dimers that are stabilized by the cofactor BH4 to generate more NO …