The Alzheimer's Disease Amyloid-Beta Hypothesis in Cardiovascular Aging and Disease: JACC Focus Seminar.

Aging-related cellular and molecular processes including low-grade inflammation are major players in the pathogenesis of cardiovascular disease (CVD) and Alzheimer's disease (AD). Epidemiological studies report an independent interaction between the development of dementia and the incidence of CVD in several populations, suggesting the presence of overlapping molecular mechanisms. Accumulating experimental and clinical evidence suggests that amyloid-beta (Aβ) peptides may function as a link among aging, CVD, and AD.

Expression of functional tissue factor by neutrophil extracellular traps in culprit artery of acute myocardial infarction.

Aims: Neutrophil extracellular traps (NETs) are chromatin filaments released by activated polymorphonuclear neutrophils (PMNs) and decorated with granule proteins with various properties. Several lines of evidence implicate NETs in thrombosis. The functional significance and the in vivo relevance of NETs during atherothrombosis in humans have not been addressed until now.

Plasma leptin and adiponectin concentrations correlate with cardiometabolic risk and systemic inflammation in healthy, non-obese children.

Background: Plasma adipocytokines are associated with metabolic profile and cardiovascular risk in obese children.

Objective: To investigate the association of plasma leptin and adiponectin concentrations with cardiometabolic risk profile and systemic inflammation in non-obese children.

Subjects: We studied 170 healthy, non-obese children (86 males, mean age 10±2 years).

Regional and overall aortic function in nondiabetic individuals with insulin resistance and normal glucose tolerance.

Context: Insulin resistance is associated with altered vascular function in diabetes.

Objective: The objective of the study was to define the overall and regional aortic function as well as the changes of aortic function over time in nondiabetic individuals with insulin resistance and a normal oral glucose tolerance test (OGTT).

Design: This was a cross-sectional and longitudinal analysis with 12 months follow-up.

Chest pain in patients with arterial hypertension, angiographically normal coronary arteries and stiff aorta: the aortic pain syndrome.

Introduction: Arterial hypertension is often associated with a stiff aorta as a result of collagen accumulation in the aortic wall and may produce chest pain. In the present study, possible interrelationships between aortic function, collagen turnover and exercise-induced chest pain in patients with arterial hypertension and angiographically normal coronary arteries were investigated.

Methods: Ninety-seven patients with arterial hypertension, angiographically normal coronary arteries and no evidence of myocardial ischemia on nuclear cardiac imaging during exercise test were studied.

Platelet microRNAs: From platelet biology to possible disease biomarkers and therapeutic targets.

Although anucleated, platelets contain megakaryocyte-derived messenger ribonucleic acid (mRNA) which can be translated to produce protein molecules. Recently, platelets have been found to contain small (∼23 base pair) non-coding microRNAs (miRNAs) derived from hairpin-like precursors. MiRNAs can specifically silence their mRNA targets regulating mRNA translation.

Statin-induced immunomodulation alters peripheral invariant natural killer T-cell prevalence in hyperlipidemic patients.

Purpose: To assess the difference in the prevalence of invariant Natural Killer T (iNKT) lymphocytes between hyperlipidemic and control individuals and to evaluate changes in iNKT cell levels after 6 months lipid lowering therapy.

Methods: A total of 77 hyperlipidemic individuals (54 ± 5 years) were assigned to simvastatin 40 mg or ezetimibe 10 mg daily for 6 months. Fifty individuals with normal cholesterol levels were used as control.

Mechanisms of platelet activation in acute coronary syndromes.

Platelets are known to play a fundamental role in acute coronary syndromes. After atherosclerotic plaque rupture, platelets can form pathogenic, occlusive thrombi leading to acute ischemic events. Today there are promising results from recently developed antiplatelet agents.

Plasma leptin and adiponectin concentrations in healthy, non-obese children.

Background: Alterations in plasma leptin and adiponectin concentrations are associated with an adverse metabolic profile in obese children.

Objective: To simultaneously assess multiple factors with possible effects on plasma leptin and adiponectin concentrations in healthy, non-obese children.

Subjects: We studied 170 healthy non-obese children (86 males, age 10+1.

Relation of tricuspid annular displacement and tissue Doppler imaging velocities with duration of weaning in mechanically ventilated patients with acute pulmonary edema.

Background: Liberation from the ventilator is a difficult task, whereas early echocardiographic indices of weaning readiness are still lacking. The aim of this study was to test whether tricuspid annular plane systolic excursion (TAPSE) and right ventricular (RV) systolic (Sm) and diastolic (Em & Am) tissue Doppler imaging (TDI) velocities are related with duration of weaning in mechanically ventilated patients with acute respiratory failure due to acute pulmonary edema (APE).

Methods: Detailed quantification of left and right ventricular systolic and diastolic function was performed at admission to the Intensive Care Unit by Doppler echocardiography, in a cohort of 32 mechanically ventilated patients with APE.

Associations between collagen synthesis and degradation and aortic function in arterial hypertension.

Background: Studies have suggested that collagen accumulation in the aortic wall may contribute to the stiff aorta in arterial hypertension. However, data in human hypertension are limited. In this investigation, relations between markers of collagen metabolism and aortic function in patients with arterial hypertension were evaluated.

Resolution of symptoms and serum peptides of collagen type I turnover in acute heart failure patients.

Objectives: Myocardial collagen content as a fundamental component of extracellular matrix, is altered in pathological states including heart failure (HF). Serum peptides related to myocardial collagen synthesis and degregation can be measured and may be used as indices of myocardial collagen turnover. The present study was undertaken to assess the hypothesis that resolution of acute decompensation of chronic HF is associated with changes in serum peptides related to collagen synthesis and degregation.

Oxidised low-density lipoprotein and arterial function in beta-thalassemia major.

Objectives: Vascular abnormalities such as endothelial dysfunction and arterial stiffness have been described in patients with beta-thalassemia major (beta-TM). Increased concentrations of oxidised low-density lipoprotein cholesterol (oxLDL) have been observed in those patients, but possible associations between oxLDL and arterial function in beta-TM have not been defined.

Methods: Twenty-six patients (11 males) with beta-TM (age 23 +/- 4 yr) and 30 age and gender-matched healthy subjects were studied.

Serum levels of collagen type-I degradation markers are associated with vascular stiffness in chronic heart failure patients.

Background: Chronic heart failure (CHF) induces peripheral vasoconstriction, endothelial dysfunction and arterial stiffness by activation of various neurohormonal pathways. The abnormal collagen turnover observed in CHF may be attributed not only to myocardial remodelling, but also to vascular remodelling. However, the effect of collagen metabolism on progressive large artery stiffening in the setting of CHF is understudied.

Effect of statins on collagen type I degradation in patients with coronary artery disease and atrial fibrillation.

The present study was undertaken to assess the effect of statins on collagen type I degradation and C-reactive protein in patients with coronary artery disease and atrial fibrillation. One hundred six patients with coronary artery disease and atrial fibrillation were studied: 40 (36 men, mean age 72 +/- 8 years) treated with a statin and 66 (48 men, mean age 74 +/- 9 years) not treated with a statin. Serum concentrations of carboxy-terminal telopeptide of collagen type I, an index of collagen type I degradation, and high-sensitivity C-reactive protein were measured in all patients.

Effect of angiotensin-converting enzyme insertion/deletion genotype on collagen type I synthesis and degradation in patients with atrial fibrillation and arterial hypertension.

Objective: The present study was undertaken to assess the impact of the angiotensin-converting enzyme (ACE) insertion (I)/deletion (D) polymorphisms on circulating markers of collagen type I synthesis and degradation, and also to study the effect of therapy with ACE inhibitors on these markers in hypertensive patients with atrial fibrillation (AF).

Research Design And Methods: ACE I/D genotypes were assessed in 158 hypertensive patients (71 +/- 9 years; 72 male) with AF and 174 patients with arterial hypertension in sinus rhythm (SR) (71 +/- 9 years; 88 male). Serum concentrations of amino-terminal propeptide of pro-collagen type I (PINP) and of carboxy-terminal telopeptide of collagen type I (CITP), indices of collagen type I synthesis and degradation, respectively, were measured.

Association between glycosylated hemoglobin, left ventricular mass and aortic function in nondiabetic individuals with insulin resistance.

Objective: An association between glycosylated hemoglobin (GHb) and cardiovascular mortality in nondiabetic individuals has recently been reported. Prompt detection of nondiabetic individuals with high-normal GHb and early cardiovascular involvement may be of value for preventive strategies. In this investigation, a possible relationship between GHb, aortic function and left ventricular (LV) mass in nondiabetic individuals has been studied.

Circulating levels of collagen type I degradation marker depend on the type of atrial fibrillation.

Aims: To investigate the hypothesis that circulating levels of collagen type I degradation or synthesis markers are associated with the presence and pattern of atrial fibrillation (AF).

Methods And Results: We assessed the serum concentrations of amino-terminal propeptide of procollagen type I (PINP) and of carboxy-terminal telopeptide of collagen type I (CITP), indexes of collagen type I synthesis and degradation, respectively, in 98 paroxysmal AF (PAF) patients (65 +/- 14 years, 62 men), in 80 persistent AF (PsAF) patients (73 +/- 8 years, 32 men), in 114 permanent AF (PmAF) patients (73 +/- 10 years, 54 men), and in 180 patients in sinus rhythm (SR) (66 +/- 13 years, 88 men) who represented a control group. Serum CITP levels were higher (P < 0.

Leukocyte activation after coronary stenting in patients during the subacute phase of a previous ST-elevation myocardial infarction.

Objective: To study leukocyte activation after percutaneous coronary intervention in patients with previous ST elevation myocardial infarction.

Methods: Neutrophil and monocyte activation (by flow cytometric assessment of the surface expression of CD11b and CD62L adhesion molecules) was assessed in 39 patients during the subacute period of a previous ST elevation myocardial infarction initially treated with fibrinolytic agents, before and after diagnostic coronary angiography (coronary angiography control phase) as well as before and after stent implantation (percutaneous coronary intervention phase). Simultaneous evaluation of C-reactive protein (C-reactive protein immonoturbidimetry) and plasma cytokine levels (interleukins-1, -6, -10 and tumor necrosis alpha by immunoassay) was also performed.

Interleukin-18/interleukin-10 ratio is an independent predictor of recurrent coronary events during a 1-year follow-up in patients with acute coronary syndrome.

Background: The pro-inflammatory cytokine IL-18 has been suggested to play a role in atherogenesis and atheromatous plaque rupture leading to the acute coronary syndrome (ACS). Conversely, the anti-inflammatory cytokine IL-10 seems to have an atheroprotective role. Patients with unstable coronary artery disease show an imbalance between serum levels of pro- and anti-inflammatory cytokines, and studies have shown that IL-18/IL-10 ratio is an independent predictor of adverse in-hospital events in patients with ACS.

Inflammatory and anti-inflammatory variable clusters and risk prediction in acute coronary syndrome patients: a factor analysis approach.

Background: Numerous inflammatory mediators such as C-reactive protein (CRP), fibrinogen, interleukin-18 (IL-18), and inter-cellular adhesion molecule-1 (ICAM-1) have been proposed for risk stratification in acute coronary syndrome (ACS) patients. However, interactions between these markers have made it difficult to assess their true role in risk prediction. Factor analysis is a multivariable statistical technique that reduces a large number of intercorrelated variables to a smaller set of independent clusters, underlining physiological relationships.

Levosimendan use reduces matrix metalloproteinase-2 in patients with decompensated heart failure.

Background: Extracellular matrix metabolism (ECM) has an important role in left ventricular (LV) remodeling in chronic heart failure (CHF). Matrix metalloproteinases (MMPs) are involved in the regulation of extracellular matrix (ECM) metabolism. We investigated the effect of levosimendan, a novel calcium sensitizer, on serum levels of MMP-2.

Comparison of levels of matrix metalloproteinase-2 and -3 in patients with ischemic cardiomyopathy versus nonischemic cardiomyopathy.

It has been reported that circulating matrix metalloproteinase (MMP) levels are upregulated in patients with chronic heart failure. However, experimental studies indicate that differences in the profiles of MMPs and tissue inhibitors of metalloproteinase (TIMPs) may exist in ischemic compared with nonischemic cardiomyopathy. This study examined whether circulating levels of MMPs and TIMP-1 are related to the pathogenesis of heart failure.