Acute Coronary Syndrome ; metabolism ; pathology ; physiopathology ; Cholesterol ; metabolism ; Erythrocyte Membrane ; metabolism ; Humans

Natriuretic peptides (NPs) have been found to be useful markers in differentiating acute dyspneic patients presenting to the emergency department (ED) and emerged as potent prognostic markers for patients with congestive heart failure (CHF). The best-established and widely used clinical application of BNP and NT-proBNP testing is for the emergent diagnosis of CHF in patients presenting with acute dyspnea. Nevertheless, elevated NPs levels can be found in many circumstances involving left ventricular (LV) dysfunction or hypertrophy; right ventricular (RV) dysfunction secondary to pulmonary diseases; cardiac inflammatory or infectious diseases; endocrinology diseases and high output status without decreased LV ejection fraction. Even in the absence of significant clinical evidence of volume overload or LV dysfunction, markedly elevated NP levels can be found in patients with multiple comorbidities with a certain degree of prognostic value. Potential clinical applications of NPs are expanded accompanied by emerging reports regarding screening the presence of secondary cardiac dysfunction; monitoring the therapeutic responses, risk stratifications and providing prognostic values in many settings. Clinicians need to have expanded knowledge regarding the interpretation of elevated NPs levels and potential clinical applications of NPs. Clinicians should recognize that currently the only reasonable application for routine practice is limited to differentiation of acute dyspnea, rule-out-diagnostic-tests, monitoring of therapeutic responses and prognosis of acute or decompensated CHF. The rationales as well the potential applications of NPs in these settings are discussed in this review article.
Acute Coronary Syndrome/metabolism ; Arrhythmias, Cardiac/metabolism ; Heart Failure/*metabolism ; Humans ; Hypertension, Pulmonary/metabolism ; Natriuretic Peptides/*metabolism ; Sepsis/metabolism

Acute Coronary Syndrome ; enzymology ; C-Reactive Protein ; metabolism ; Humans ; Matrix Metalloproteinase 9 ; metabolism

Acute Coronary Syndrome ; blood ; Aged ; Cell Membrane ; metabolism ; Female ; Humans ; Male ; Middle Aged ; Thromboplastin ; metabolism

This study established a population pharmacokinetics-pharmacodynamics model of clopidogrel in patients with acute coronary syndrome. Fifty-nine patients were enrolled. The plasma concentration of clopidogrel active metabolite and vasodilator stimulated phosphoprotein platelet reactivity index (VASP-PRI) were selected as the pharmacokinetics index and the pharmacodynamics index, respectively. The covariates including demographic characteristics, laboratory indexes, combined medication, complications and genetic polymorphisms of related enzymes were screened for their influence on the pharmacokinetic and pharmacodynamics parameters. Population pharmacokinetic and pharmacodynamics data analysis was performed using NONMEM software. The general linear model and the indirectly effect model-turnover model for pharmacokinetic and pharmacodynamic analysis were selected as the basic model, respectively. The population typical values of K12, CL/F, V/F, EC50, K(in), and E(max) were 0.259 h(-1), 179 L x h(-1), 632 L, 1.57 ng x mL(-1), 4.29 and 0.664, respectively. CYP2C19 was the covariate in the final pharmacokinetic model, and the model was to design a prior dosage regimen.
Acute Coronary Syndrome ; metabolism ; Humans ; Polymorphism, Genetic ; Ticlopidine ; analogs & derivatives ; pharmacokinetics

BackgroundAcute coronary syndrome (ACS) is closely related to unstable plaques and secondary thrombosis. The inflammatory cells in plaques and their inflammatory products may be the cause for plaque instability and ruptures. The study aimed to disclose the changes of inflammatory factors including serum intracellular adhesion molecule-1 (ICAM-1), chitinase-3-like protein 1 (YKL-40), and lipoprotein-associated phospholipase A2 (Lp-PLA2) in patients with ACS and its clinical significance.

MethodsA total of 120 patients with coronary heart disease (CHD) were categorized into 2 groups: 69 with ACS and 51 with stable angina pectoris (SAP); 20 patients with chest pain and normal angiography served as a control group. The 120 patients with CHD were categorized into single-vessel disease group, double-vessel disease group, and three-vessel disease group based on the number of coronary artery stenosis. The severity of coronary artery stenosis was quantified based on coronary angiography using Gensini score. They were further divided into mild CHD group with its Gensini score <26 (n = 36), moderate CHD group with its Gensini score being 26-54 (n = 48) and severe CHD group with its Gensini score >54 (n = 36). Serum levels of ICAM-1, YKL-40, and Lp-PLA2 of different groups were determined by enzyme-linked immunosorbent assay. Correlation between ICAM-1, YKL-40, Lp-PLA2, and Gensini score was analyzed.

ResultsThe levels of serum inflammatory factors ICAM-1, YKL-40, and Lp-PLA2 were significantly higher in the ACS group than those in control group and SAP group (all P < 0.05); and compared with control group, no significant difference was observed in terms of the serum ICAM-1, YKL-40, and Lp-PLA2 levels in the SAP group (P > 0.05).The levels of serum ICAM-1, YKL-40, and Lp-PLA2 were not significantly different among control group, single-vessel disease group, double-vessel disease group, and three-vessel disease group (all P > 0.05). The levels of serum ICAM-1, YKL-40, and Lp-PLA2 were not significantly different among control group, mild CHD group (Gensini score <26), moderate CHD group (Gensini score 26-54), and severe CHD group (Gensini score >54) (all P > 0.05). Nonparametric Spearman correlation analysis showed that the levels of serum ICAM-1, YKL-40, and Lp-PLA2 were not correlated with the Gensini score in CHD patients (r = 0.093, r = -0.149, and r = -0.085, all P > 0.05; respectively).

ConclusionsThe serum levels of ICAM-1, YKL-40, and Lp-PLA2 were correlated with different clinical types of CHD, but not well correlated the severity and extent of artery stenosis, suggesting that ICAM-1, YKL-40, and Lp-PLA2 might be involved in occurrence of instability of atherosclerotic plaque, and might reflect the severity of CHD mostly through reflecting the plaque stability.

1-Alkyl-2-acetylglycerophosphocholine Esterase ; metabolism ; Acute Coronary Syndrome ; blood ; immunology ; metabolism ; Adult ; Aged ; Chitinase-3-Like Protein 1 ; metabolism ; Coronary Angiography ; Coronary Disease ; blood ; immunology ; metabolism ; Humans ; Intercellular Adhesion Molecule-1 ; metabolism ; Middle Aged

OBJECTIVETo investigate the prognostic value of ultra-sensitive pregnancy associated plasma protein-A (PAPP-A) level in the early phase of acute coronary syndrome (ACS) attack.

METHODSPatients diagnosed as ACS were enrolled and the level of circulatory PAPP-A was measured within 12 hours after ACS attack. The patients were followed at the time of 1st, 6th, and 12th months post-ACS attack in order to observe the incidence of the cardiovascular adverse events. According to the highest quintile, the patients were divided into 2 groups: high level (≥26.08 μg/L) group and low level (<26.08 μg/L) group, to evaluate the association between the level of PAPP-A and the incidence of the cardiovascular events.

RESULTSCompared with the low level group, the incidence of the composite outcome is significantly increased in the high level group, and the values of OR are 4.76, 4.38, 3.75 for 1st, 6th, 12th months respectively (P=0.000). For myocardial infarction (MI) + cardiac death (CD) the values of OR were 9.81, 6.08, 4.12 (P<0.01). Multivariate logistic regression analysis demonstrates that PAPP-A was an independent risk factor for the cardiovascular adverse events in the early, median, and late phase of ACS (P<0.05).

CONCLUSIONIn the early phase of ACS attack, the elevation of PAPP-A is an independent risk factor for the occurrence of cardiovascular adverse events.

Acute Coronary Syndrome ; blood ; diagnosis ; Aged ; Female ; Humans ; Male ; Middle Aged ; Pregnancy-Associated Plasma Protein-A ; metabolism ; Prognosis ; Risk Factors

OBJECTIVETo study the expression of COX-2 and pregnancy associate plasma protein A (PAPP-A) in coronary arteries and their relationship with acute coronary syndrome.

METHODSTwenty-one autopsy cases with acute coronary syndrome encountered during the period from 2002 to 2007 were enrolled into the study. Another 21 autopsy cases without evidence of acute coronary syndrome were used as the controls. The right and left coronary arteries of each group were dissected, embedded and processed as paraffin sections. Immunohistochemical study for CD68 and alpha-actin was performed to highlight the presence of macrophages and smooth muscle cells, respectively. The expression of COX-2 and PAPP-A was evaluated.

RESULTSIn the acute coronary syndrome group, COX-2 was localized mainly in the cytoplasm of endothelial cells, macrophages and smooth muscle cells. COX-2 expression in the cytoplasm of smooth muscle cells (28.60%) was significantly higher than that in the control group (4.76%, chi(2) = 14.13, P< 0.05). There was a positive correlation on COX-2 and PAPP-A expression in smooth muscle cells of the media layer of coronary arteries in acute coronary syndrome group (r = 0.88, P < 0.05). The expression of PAPP-A in smooth muscle cells of the media layer in coronary arteries not associated with plaque formation, was higher than that when there were atherosclerotic plaques (chi(2) = 10.36, P < 0.05).

CONCLUSIONIn coronary arteries, COX-2 and PAPP-A play certain roles in the pathogenesis of acute coronary syndrome.

Acute Coronary Syndrome ; metabolism ; pathology ; Adult ; Aged ; Autopsy ; Coronary Vessels ; metabolism ; pathology ; Cyclooxygenase 2 ; metabolism ; Female ; Humans ; Middle Aged ; Myocytes, Smooth Muscle ; metabolism ; Plaque, Atherosclerotic ; metabolism ; Pregnancy ; Pregnancy-Associated Plasma Protein-A ; metabolism ; Young Adult

OBJECTIVETo investigate the changes of neutrophil myeloperoxidase (MPO) blood concentration gradient between the systemic circulation and the coronary circulation among patients with acute coronary syndrome and its clinical value.

METHODSFifty patients underwent coronary angiography, which including 10 patients in AMI group, 20 patients in UA group, 10 patients in SA group and 10 subjects served as control. The levels of MPO and hs-CRP were measured in the serum of blood collected from femoral vein, aortic artery root and coronary sinus.

RESULTSCompared with the control, concentrations of LDL in the AMI, UA and SA groups were significantly increased, while the latter three groups did not differ from each other. In the UA patients, the in-gate percentage of MPO decreased in the coronary sinus compared with that in the root of aortic artery (P < 0.01); the in-gate percentage of MPO decreased through coronary circulation more than through systemic circulation (P < 0.001); the average fluorescent intensity of MPO and the concentrations of hs-CRP showed no difference between samples from the coronary sinus and that from the root of aortic artery. In the AMI patients, the average fluorescent intensity of MPO in the coronary sinus was weakened compared with that in the root of aortic artery (P < 0.05); it decreased through coronary circulation more than through systemic circulation (P < 0.001); neither the in-gate percentage of MPO nor the concentrations of hs-CRP showed significant difference between samples from the coronary sinus and that from the root of aortic artery. In the control and SA groups, samples from the femoral vein, the root of aortic artery, and the coronary sinus did not show differences at the serum level of MPO and hs-CRP. In the UA group, the in-gate percentage of MPO correlated positively with the concentration of hs-CRP (r = 0.78, P < 0.01), and with the level of LDL as well (r = 0.52, P < 0.05); In the AMI group, the average fluorescent intensity of MPO correlated negatively with the concentration of hs-CRP (r = -0.80, P < 0.01), and showed no correlation with the level of LDL (r = 0.22, P > 0.05).

CONCLUSIONSMPO is a better marker for inflammation of the local plaques. It may be one of the mechanisms that MPO induces the transforming from LDL to ox-LDL in plaques vulnerability.

Acute Coronary Syndrome ; blood ; metabolism ; physiopathology ; Aged ; Biomarkers ; blood ; Case-Control Studies ; Coronary Circulation ; Female ; Humans ; Male ; Middle Aged ; Neutrophils ; enzymology ; Peroxidase ; blood

OBJECTIVETo determine current density of voltage-gated potassium channels and Kv1.3 express in T-lymphocyte derived from patients with acute coronary syndrome (ACS).

METHODSPeripheral blood mononuclear cells were collected from 12 patients with ACS and 10 control donors. Whole-cell patch clamp technique was used to record the outward K(+) currents (IK) and western blots technique was used to detect the express of Kv1.3 protein in lymphocyte.

RESULTS(1) The current density of voltage-gated potassium channel was significantly higher in ACS patients [(269 +/- 94) pA/pF] than in controls [(191 +/- 64) pA/pF, P < 0.01] while membrane capacitance was similar between the two groups. (2) Kv1.3 protein expression was also significantly increased in ACS patients than in controls (P < 0.01).

CONCLUSIONThe lymphocyte voltage-gated potassium channel is upregulated in patients with ACS suggesting a role of Kv activation in the pathophysiology of ACS.

Acute Coronary Syndrome ; metabolism ; Adult ; Aged ; Female ; Humans ; Kv1.3 Potassium Channel ; metabolism ; Male ; Middle Aged ; Patch-Clamp Techniques ; T-Lymphocytes ; metabolism