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Background: The relative risk for cardiovascular diseases in passive smokers is similar to that of active smokers despite almost a 100-fold lower dose of inhaled cigarette smoke. However, the mechanisms underlying the surprising susceptibility of the vascular tissue to the toxins in secondhand smoke (SHS) have not been directly investigated. The aim of this study was to investigate directly vascular endothelial cell function in passive smokers., Methods: Using a minimally invasive method of endothelial biopsy, we investigated directly the vascular endothelium in 23 healthy passive smokers, 25 healthy active smokers, and 23 healthy control subjects who had never smoked and had no regular exposure to SHS. Endothelial nitric oxide synthase (eNOS) function (expression of basal eNOS and activated eNOS [phosphorylated eNOS at serine1177 (P-eNOS)]) and expression of markers of inflammation (nuclear factor-κB [NF-κB]) and oxidative stress (nitrotyrosine) were assessed in freshly harvested venous endothelial cells by quantitative immunofluorescence., Results: Expression of eNOS and P-eNOS was similarly reduced and expression of NF-κB was similarly increased in passive and active smokers compared with control subjects. Expression of nitrotyrosine was greater in active smokers than control subjects and similar in passive and active smokers. Brachial artery flow-mediated dilation was similarly reduced in passive and active smokers compared with control subjects, consistent with reduced endothelial NO bioavailability., Conclusions: Secondhand smoking increases vascular endothelial inflammation and reduces active eNOS to a similar extent as active cigarette smoking, indicating direct toxic effects of SHS on the vasculature.

Background: Renal structural alterations have been partially uncovered in cardiorenal syndrome (CRS). Patients with CRS may have evidence of tubular damage, but markers of glomerular damage other than proteinuria have not been thoroughly investigated. The nature of renal damage in CRS may have therapeutic implications, as glomerular damage requires tight blood pressure control and renin-angiotensin-aldosterone system (RAAS) inhibition. The present investigation evaluates patients with CRS type 2 (CRS-2) for direct evidence of glomerular damage as evidenced by the presence of urinary podocin., Methods: The presence of glomerular damage was assessed in acutely decompensated patients with CRS-2 and healthy controls. Urinary podocin was determined by quantification of a tryptic peptide of podocin with high-performance liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS). Morning urine samples were collected for podocin, creatinine (Cr), and protein. Urinary podocin was expressed in femtomoles of podocin/milligram of Cr., Results: The urinary podocin/Cr ratio was greater in patients than in controls (0.37 ± 0.77 vs. 0.06 ± 0.05 fmol podocin/mg Cr, p = 0.04). A total of 40% of the patients had a urinary podocin/Cr ratio greater than the upper limit of normal (>0.2 fmol podocin/mg Cr). Patients with an elevated podocin/Cr ratio were more likely to have received ≤50% of the maximum dose of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (p = 0.04) than patients with a podocin/Cr ratio in the normal range., Conclusions: CRS-2 may be associated with glomerular damage as evidenced by an elevated urinary podocin/Cr ratio. Modulators of RAAS may have a protective effect on urinary podocin loss.

Background: Pulmonary hypertension (PH) is prevalent in decompensated heart failure with preserved ejection fraction (HFpEF). We investigated the effect of a return to a compensated state on pulmonary artery systolic pressure (PASP) and functional mitral regurgitation (FMR)., Methods and Results: Two-dimensional Doppler echocardiography was prospectively performed before initiation of standard therapy and 48 hours later in 37 patients hospitalized for HFpEF-related dyspnea and in 26 patients hospitalized for non-HFpEF-related dyspnea. Left atrial volume index, and E/e' ratio, and PASP were significantly greater and E-wave deceleration time significantly shorter in HFpEF than in non-HFpEF patients. Thirty-two of the 37 HFpEF had FMR on admission whereas none of the non-HFpEF patients had FMR. After 48 hours of therapy, the reduction in PASP was significantly greater in the 26 HFpEF patients who improved than in the 11 HFpEF patients who did not (-24 vs -9 mm Hg, respectively; P < .0001), whereas PASP remained unchanged in non-HFpEF patients. The decrease in PASP correlated in HFpEF patients with reductions in blood pressure, heart rate, left ventricular end-diastolic volume, inferior vena cava diameter, E/A ratio, E/e' ratio, mitral effective regurgitant orifice area (EROA), and E-wave deceleration time. The correlation between PASP and mitral EROA was the only one that remained significant by multivariate analysis., Conclusions: Noninvasive monitoring of PASP and FMR during an episode of HFpEF decompensation reveals that the return to a compensated state is associated with a significant reduction in PASP and FMR., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Background: Patients with heart failure with preserved ejection fraction (HFpEF) may present with Pulmonary hypertension (PH) and functional mitral regurgitation (MR). Whether PH is linked to the presence of functional MR has not been investigated in HFpEF patients., Methods and Results: Systolic pulmonary artery pressure (sPAP) and functional MR were assessed by 2-dimensional Doppler echocardiography in 70 ambulatory HFpEF patients and 70 hypertensive control subjects free of organic mitral valve lesions, significant valve disease, and comorbid conditions associated with PH. Whereas none of control subjects had more than trivial MR, 21 patients with HFpEF had functional MR (mean mitral effective regurgitant orifice, regurgitant volume, and regurgitant fraction 7 ± 3 mm,(2) 15 ± 8 mL, and 28 ± 14%, respectively). Pulmonary hypertension (sPAP >35 mm Hg) was significantly more prevalent in HFpEF patients with functional MR than in HFpEF patients without functional MR (62 vs 22%; P = .002). Functional MR remained an independent predictor of PH in HFpEF patients (P = .004) after adjustment on mitral E wave to e' mitral annulus velocity ratio (E/e'; P = .022) and left atrial volume index (P = .025). Systolic PAP and E/e' were greater in HFpEF patients than in control subjects (35 ± 9 vs 29 ± 8 mm Hg [P < .0001] and 13 ± 6 vs 11 ± 5 [P = .018], respectively). Systolic PAP remained greater in HFpEF patients than in control subjects after adjusting for E/e' (P = .002)., Conclusions: Pulmonary hypertension appears to be linked to the presence of functional MR in HFpEF patients., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Anemia is highly prevalent in patients with chronic heart failure (CHF) and is associated with poor clinical outcome. Increased prevalence of anemia in CHF has been linked to advanced age, female gender, renal function impairment, severity of symptoms, and clinical settings. Overall, the anemia of CHF shares many common features with the anemia of chronic disease. Both impaired iron metabolism and inflammatory stress appear to be the key mediators of the anemia of CHF., (Copyright 2010 Elsevier Inc. All rights reserved.)

Obstructive sleep apnea (OSA) affects 25% of the Western adult population. It is an independent but seldom-recognized risk factor for hypertension, myocardial infarction, stroke, and increased mortality. Patients with OSA experience repetitive episodes of hypoxia/reoxygenation during transient cessation of breathing that promote systemic oxidative stress and inflammation. Vascular endothelial inflammation and enhanced oxidative stress that are reversible with therapy for OSA were recently demonstrated directly in patients with OSA who were free of overt cardiovascular conditions. Vascular endothelial inflammation and enhanced oxidative stress may in part explain the accelerated progression of atherosclerosis in patients with untreated OSA. The present review will focus on indirect and direct evidence of vascular endothelial inflammation and enhanced oxidative stress in patients with OSA. The potential utility of venous endothelial biopsy technique in evaluating the mechanisms that mediate the effects of systemic conditions such as diabetes mellitus, sleep apnea, and obesity on the vascular endothelium will also be discussed.

A number of large randomized, placebo-controlled mortality trials provided evidence-based data to guide the treatment of patients with systolic heart failure, but, with one exception, similar trials in patients with diastolic heart failure (DHF) either are not yet completed or have not been conducted at all. However, randomized outcomes trials conducted in patients with hypertension with and without left ventricular hypertrophy and in patients with vascular diseases at high risk for cardiovascular events provide a strong rationale for long-term angiotensin-converting enzyme inhibition or angiotensin receptor blockade in patients with DHF. The treatment of patients with acutely decompensated DHF remains purely empirical. Thus, a pragmatic approach to the treatment of acutely decompensated DHF that includes the use of B-type natriuretic peptide is presented.