Circulation. 2008;117:3161-3162
doi: 10.1161/CIRCULATIONAHA.108.189732
doi: 10.1161/CIRCULATIONAHA.108.189732
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(Circulation. 2008;117:3161-3162.)
© 2008 American Heart Association, Inc.
Clinical Summaries
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Tracking of Blood Pressure From Childhood to Adulthood: A Systematic Review and Meta–Regression Analysis |
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Tracking of Blood Pressure...
Prognostic Value and Temporal...Previously, a large number of studies have examined blood pressure (BP) tracking over time among children and adults. Although rich evidence supports BP tracking from childhood to adulthood, the reported findings are inconsistent. No systematic analyses have been conducted to examine the consistency of findings from different studies or to test the differences across populations worldwide. Using a systematic search of PubMed for studies published between 1970 and 2006 that examined BP tracking from childhood to adulthood, we conducted a meta-analysis of findings from 50 cohort studies, which provided
600 data points (ie, correlation coefficients) for systolic BP (SBP) and diastolic BP (DBP) tracking, respectively. BP tracking was stronger for SBP but did not vary significantly by the number of BP measurements taken per visit or across race/populations. SBP tracking did not vary significantly by sex, but women had weaker DBP tracking than men. The reported BP tracking coefficients varied from –0.12 to 0.80 for SBP and from –0.16 to 0.70 for DBP. The average was 0.38 for SBP and 0.28 for DBP. The strength of BP tracking increased with baseline age by 0.012 for SBP and 0.009 for DBP and decreased with follow-up by 0.008 for SBP and 0.005 for DBP. On the basis of studies from diverse populations, our meta-analysis reinforces the concepts that BP tracks from childhood to adulthood and that an elevated BP in childhood is likely to predict adult hypertension. Childhood BP is associated with BP in later life, and early intervention is important. See p 3171. |
Prognostic Value and Temporal Behavior of the Planar QRS-T Angle in Patients With Nonischemic Cardiomyopathy |
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Current recommendations for implantable cardioverter-defibrillator (ICD) implantation for primary prevention of sudden death are neither highly sensitive nor specific. Many patients with ICDs do not receive appropriate shocks, and the majority of patients who experience sudden death do not meet current criteria for ICD implantation. Additional criteria that improve sensitivity and specificity would be beneficial, especially if they were widely available at low cost. The QRS-T angle has been proven to be predictive of outcomes in various populations. We sought to determine the predictive ability of the planar QRS-T angle (the angle between the frontal QRS and T-wave axes) in 455 patients in the Defibrillators in Nonischemic Cardiomyopathy Treatment Evaluation (DEFINITE) trial. The primary end point (a composite of total mortality, appropriate ICD shock, or resuscitated cardiac arrest) occurred nearly twice as often in patients with a QRS-T angle >90° compared with patients with a QRS-T angle
90° (hazard ratio, 1.95; 95% confidence interval, 1.24 to 3.08; P=0.002). A QRS-T angle >90° remained a significant predictor of the primary end point (P=0.039) after adjustment for treatment group, age, gender, QRS duration, left bundle-branch block, left ventricular ejection fraction, New York Heart Association class III, atrial fibrillation, and diabetes mellitus. The secondary end point (total mortality) also occurred more often in patients with a QRS-T angle >90° compared with patients with a QRS-T angle 90° (hazard ratio, 1.81; 95% confidence interval, 1.04 to 3.13; P=0.016). In the present analysis, a planar QRS-T angle >90° was a significant predictor of a composite end point of death, appropriate ICD shock, or resuscitated cardiac arrest in cardiomyopathy patients selected for primary prevention ICDs. Future studies that incorporate QRS-T angle along with other clinical criteria may improve selection of ICD recipients. See p 3181. |
Cardiomyocyte Overexpression of Neuronal Nitric Oxide Synthase Delays Transition Toward Heart Failure in Response to Pressure Overload by Preserving Calcium Cycling |
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Sustained cardiac hypertrophy typically progress to cardiac dilatation and failure, conditions associated with substantial morbidity and mortality. The prevention of this deterioration is a major therapeutic goal. Recent studies have suggested that a critical factor causing cardiac decompensation after pressure overload may be the failure to preserve calcium homeostasis and thus myocardial inotropy. It is well established that the neuronal (NOS1) isoform of nitric oxide synthase facilitates Ca2+ handling that is central to excitation-contraction coupling. However, the impact of NOS1 on myocardial contractility and Ca2+ cycling remains controversial, and the potential relevance of this mechanism in HF is unknown. Here, we generated a transgenic mouse with conditional, cardiomyocyte-specific NOS1 overexpression (DT) and studied cardiac remodeling, myocardial Ca2+ handling, and contractility in DT and control mice subjected to transverse aortic constriction (TAC). After TAC, control mice developed eccentric hypertrophy with evolution toward HF as revealed by a significantly reduced fractional shortening. In contrast, after TAC, DT mice developed a greater increase in wall thickness and less left ventricular dilatation. Thus, DT mice displayed concentric hypertrophy with fully preserved fractional shortening. The improvement in contraction appears to be due mainly to greater sarcoplasmic reticulum Ca2+ loading in the NOS1-overexpressing DT hearts. This enhanced Ca2+ sarcoplasmic reticulum loading was a consequence of a preserved ratio of phospholamban to sarcoplasmic reticulum Ca2+ ATPase2a and an increased level of phosphorylated phospholamban. These findings support the hypothesis that cardiomyocyte NOS1 plays an important role in cardiac protection. They also suggest that NOS1 could represent a new means of targeting Ca2+ regulatory proteins in the setting of chronic pressure-overload HF. See p 3187.
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Renal and Hormonal Responses to Direct Renin Inhibition With Aliskiren in Healthy Humans |
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New pharmacological regimens that interrupt the renin-angiotensin-aldosterone system (RAAS) are being promoted as evidence mounts to suggest that greater blockade results in improved clinical outcomes. Most recently, the direct renin inhibitor aliskiren, which blocks the system at its rate-limiting step, has been approved for the treatment of hypertension. Blockade at the tissue level is important for organ protection; we investigated a measure of RAAS blockade in the kidney. Our model quantifies renal vasodilator responses in subjects in whom the RAAS is activated by restriction of sodium chloride intake to very low levels. We hypothesized that direct renin inhibition would block the RAAS more completely than other available agents, which would manifest as larger renal vasodilator responses. Aliskiren induced a remarkable dose-related renal vasodilation in 20 healthy subjects. The renal plasma flow response was maximal at the 600-mg dose (197±27 mL · min–1 · 1.73 m–2) and exceeded responses to captopril noted in previously performed studies (92±20 mL · min–1 · 1.73 m–2; P<0.01). Significant residual vasodilation was observed 48 hours after each dose along with significant accompanying natriuresis. These results indicate that aliskiren holds the promise of significantly greater blockade of the RAAS than has been possible previously. See p 3199.
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Targeted Molecular Probes for Imaging Atherosclerotic Lesions With Magnetic Resonance Using Antibodies That Recognize Oxidation-Specific Epitopes |
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Oxidized low-density lipoprotein plays a key role in the initiation, progression, and destabilization of atherosclerotic plaques and is present in macrophages and the lipid pool. Development of sensitive molecular imaging probes that target oxidation-specific epitopes in the vessel wall may allow in vivo detection of plaque vulnerability, which can be used as an index of clinical risk. Because of its submillimeter resolution, magnetic resonance imaging has emerged as a promising technique for both direct assessment of plaque burden and evaluation of plaque composition, particularly in large vessels. In the present study, we demonstrated the magnetic resonance imaging efficacy of micelles loaded with gadolinium and unique human (IK17) or murine antibodies (MDA2 and E06), which recognize oxidation-specific epitopes, to image atherosclerotic lesions noninvasively. This approach was highly specific for targeting oxidation-specific epitopes as documented by several control experiments in which injection of unlabeled antibodies prevented MR lesion enhancement. Magnetic resonance imaging with these oxidized low-density lipoprotein–targeted micelles demonstrated excellent image quality of oxidation-rich atherosclerotic lesions. The present study describes a novel method for noninvasively imaging oxidation-specific epitopes within atherosclerotic lesions that builds on the wealth of basic and clinical data on the role of oxidation in mediating cardiovascular disease. If validated and translated to humans, this imaging approach may provide valuable tools to noninvasively detect, quantify, and monitor atherosclerosis in general and potentially image vulnerable plaques locally. See p 3206.
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High-Mobility Group Box-1 in Ischemia-Reperfusion Injury of the Heart |
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One of the major therapeutic goals of modern cardiology is to design strategies aimed at reducing myocardial tissue damage and optimizing cardiac repair after myocardial infarction. It has become apparent in recent years that high-mobility group box-1 (HMGB1) is instrumental in mediating response to tissue damage and infection. HMGB1, a nuclear factor released by necrotic cells and activated immune cells, was recently rediscovered to be a potent innate "danger signal" for the initiation of host defense or tissue repair. Here, we demonstrate that HMGB1 acts as an early mediator of inflammation and organ damage in ischemia/reperfusion injury of the heart. We further provide evidence that HMGB1-induced cell responses are mediated at least in part by the receptor for advanced glycation end products (RAGE), a multiligand receptor of the immunoglobulin superfamily inducibly expressed in most tissues and present on a wide range of cells where it plays a key role in inflammatory processes, especially at sites where its ligands accumulate. Treatment of mice with recombinant HMGB1 worsened ischemia/reperfusion injury, whereas treatment with HMGB1 box A, a functional antagonist of extracellular HMGB1 cytokine activity, and HMGB1 interaction with the receptor for advanced glycation end products significantly reduced infarct size and markers of tissue damage. See p 3216.
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P-Selectin Glycoprotein Ligand-1 Is Highly Expressed on Ly-6Chi Monocytes and a Major Determinant for Ly-6Chi Monocyte Recruitment to Sites of Atherosclerosis in Mice |
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The recruitment of monocytes into the arterial wall plays decisive roles in the initiation and progression of atherosclerosis. In mice, monocytes are divided into Ly-6Chi and Ly-6Clo subsets. Ly-6Chi monocytes are recognized as the key monocyte subset in the development of atherosclerosis, but the mechanisms by which these monocytes selectively accumulate in atherosclerotic lesions are largely unknown. In the present study, we identified that Ly-6Chi monocytes expressed a higher level of P-selectin glycoprotein ligand-1 (PSGL-1) and had enhanced binding to P-, E-, and L-selectin compared with Ly-6Clo monocytes under physiological conditions. ApoE–/– mice lacking PSGL-1 (ApoE–/–/PSGL-1–/–) had impaired Ly-6Chi monocyte recruitment to arterial injuries and exhibited significantly reduced monocyte infiltration in wire injury–induced neointima and in atherosclerotic lesions. Moreover, ApoE–/–/PSGL-1–/– mice also developed smaller neointima and atherosclerotic plaques. These results indicate that PSGL-1 is a new marker for Ly-6Chi monocytes and a major determinant for Ly-6Chi cell recruitment to sites of atherosclerosis in mice. See p 3227.
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