UA Patients Research Articles

AB0194 Scottish early rheumatoid arthritis (sera) at nhs highland - a multi centre scottish project aiming to establish a clinical database and biorepository of newly diagnosed undifferentiated arthritis (ua) and rheumatoid arthritis (ra) patients

BackgroundDepression and anxiety can be prevalent in newly diagnosed UA & RA patients and can be related to either environmental, social or for health reasons. The SERA study has enabled...

FRI0517 Early metacarpal bone mineral density loss is predictive for radiologic joint damage progression after 1 year in patients with early arthritis

BackgroundIn patients with established RA, radiological progression is preceded by metacarpal bone mineral density (mBMD) loss.ObjectivesTo assess whether in early (rheumatoid) arthritis patients, mBMD loss after 4 months is an...

OP0134 Risk stratification in patients with undifferentiated arthritis according to the 2010 ACR/EULAR criteria

BackgroundEarly recognition and treatment of Rheumatoid Arthritis (RA) is associated with an improved outcome. The 2010 ACR/EULAR criteria for RA identify RA patients earlier than the 1987 criteria. Nevertheless, we...

Genetic thrombophilia in patients with ischemic heart disease

In premature IHD, the role of genetic risk factors should be more important than environmental factors. Genetic thrombophilias represent a group of inherited conditions that predispose to thrombosis. Although the association between inherited thrombophilia and some thrombotic diseases as deep venous thrombosis is well-established, controversial data are present on the association between inherited thrombophilia and IHD. To study some genetic thrombophilic variants in patients suffering from ischemic heart disease. 72 subjects: 52 patients with premature ischemic heart disease <40 years. classified into: • Acute M.I. group:(31 patients). • Unstable angina group: (21 patients), and 20 apparently healthy individuals (of matched age and sex as a control group History taking, clinical and E.C.G. and laboratory investigations (cardiac markers, lipogram, lupus anticoagulants screening, antiphospholipids IgG/lgM and anticardiolipin IgG/lgM antibodies). Also, samples were taken for DNA extraction and typing with cardiovascular disease (CVD) StripAssay for the identification of mutations associated with CVD based on polymerase chain reaction (PCR) and reverse-hybridization molecular technique. The assay covers 12 polymorphisms. In UA patients group, the heterozygous (GA) genotype, and the (A) for UA, compared with the control group In addition, there were significant decreases in the frequencies of heterozygous (GT), and T allele of FXIII Val34Leu in UA patients group, compared with the control group assuming a protective role of FXIII 34Leu allele against unstable angina development. The prevalence of other studied polymorphisms; factor V H1299R (R2), Glycoprotein IIIa Leu33Pro,PAI-1 4G/5G, MTHFR C677T polymorphisms, MTHFR A1298C, apo B R3500Q and apo E polymorphisms; did not differ between IHD patients and control subjects. There was a significant positive association between FVL and family history of IHD in AMI patients. In addition, a highest prevalence of Pl A2 in patients <35 years of age surviving a first AMI, so that age-at-onset of AMI was significantly affected by PlA2 (<35 years vs. 35–40). Apo E3/E4 genotype was associated with both high total Cholesterol (TC) and high TC/HDL ratio in UA group, while in AMI patients, Apo E3/E4 genotype was associated with high TC/HDL ratio, and high triglycerides levels. This study has identified a positive association for FV Leiden, Prothrombin G20210A heterozygosity, and ACE (I/D) polymorphism with premature AMI; a positive association for β-fibrinogen 455-GA polymorphism in UA patients; and a negative association (protective role) for FXIII Val34Leu in UA patients. This study may open a dooor to promised goals of new therapeutics and personalised medicine for premature IHD based on single nucleotide polymorphism in well defined groups of high risk patients (<40 years); and their families.

Mitogen-activated protein kinases activation in T lymphocytes of patients with acute coronary syndromes

Current available biomarkers cannot identify myocardial ischemia without necrosis. To overcome this issue and to increase diagnostic power, we evaluated the activation of the three MAPK pathways, ERK1/2, JNK and p38, in T lymphocytes of patients with acute coronary syndromes (ACS). We included sixty consecutive patients affected by either unstable angina (UA, N=22), Non- ST-segment elevation MI (NSTEMI, N=19) or ST-segment elevation MI (STEMI, N=19). Two separate groups of patients were matched as controls: healthy subjects (CTRL, N=20) and patients with stable coronary artery disease (CAD, N=21). MAPK activation in T lymphocytes, measured by phospho-ERK1/2, phospho-JNK and phospho-p38 levels, was assessed by flow cytometry analysis which revealed significantly increased phosphorylated levels of ERK1/2 in patients with UA, compared to controls. In UA patients no significant changes were detected for phospho-JNK compared to both control groups. NSTEMI and STEMI groups showed a statistically significant increase in both phospho-ERK1/2 and phospho-JNK, compared to control groups. All ACS groups demonstrated significantly increased phosphorylation of p38 compared to CTRL, but not CAD. ROC curves showed that a cut-off value of 22.5 intensity of fluorescence for phospho-ERK1/2 was able to significantly discriminate UA patients from patients with stable angina with 78% sensitivity and 90% specificity. Therefore, a differential MAPK activation in T lymphocytes denotes patients with ACS. Indeed, patients with unstable angina are identified with high specificity by activated ERK1/2 and normal JNK levels. These data could represent a valuable new molecular signature to be used as specific biomarkers for the diagnosis of unstable angina within ACS.

Evaluation of the performance of echocardiography in acute coronary syndrome patients during their stay in coronary units

To evaluate the frequency and the factors associated with performance of echocardiography in acute coronary syndrome (ACS) patients during their stay in intensive care units or coronary care units (ICU/CCU). Retrospective cohort study including all patients diagnosed with acute coronary syndrome-unstable angina (UA), acute myocardial infarction (AMI)-included in the 'ARIAM' Spanish multi-centre register. The study period was from June 1996 to December 2005. The follow-up period is limited to the time of stay in the Intensive Care Units or Coronary Care Units (ICUs/CCUs). A univariate analysis was carried out on the patients with UA and AMI according to whether or not echocardiograms were performed during their stay in ICU/CCU. In addition the data was evaluated for any temporal variation in the performance of echocardiography, and two multivariate analyses were carried out to evaluate the factors associated with performance of echocardiography in UA and AMI patients. The study period included 45,688 AMI patients and 17,277 UA patients. Echocardiograms were performed in 26.87% AMI patients and 16.75% UA patients. In total, 15,172 echocardiograms were performed in ACS patients (23.6%). The multivariate analysis demonstrated that the variables associated with the performance of echocardiography in UA were: Killip and Kimball class, cigarette smoking, family history of cardiovascular events, cardiogenic shock, uncontrolled angina, mechanical ventilation and treatment with ACE inhibitors, while the presence of previous AMI was associated with fewer echocardiograms being performed. In AMI, the multivariate analysis showed the following variables to be associated with the performance of echocardiography: Killip and Kimball class, Q-AMI, right heart failure, the need for insertion of Swan-Ganz catheter, cardiogenic shock, high-degree AV block and the administration of ACE inhibitors, while age was associated with fewer being performed. Over the 10 years of the study period, there was a discrete but significant increase in the use of echocardiography in patients in ICU/CCU. Echocardiography is not commonly used in ACS patients while in ICU/CCU. UA and AMI patients who did have echocardiograms during their stay in ICU/CCU were chiefly those presenting heart failure and major complications, and represent a subpopulation with poor prognosis. The performance of echocardiography in ACS patients increased slightly over the length of their stay in ICU/CCU.

Association of Lipoprotein-Associated Phospholipase A2with Characteristics of Vulnerable Coronary Atherosclerotic Plaques

PurposeLipoprotein-associated phospholipase A2 (Lp-PLA2) is an inflammatory enzyme expressed in atherosclerotic plaques. We investigated the association of circulating Lp-PLA2 with characteristics of vulnerable coronary atherosclerotic plaques.Materials and MethodsWe recruited 113 patients with either unstable angina (UA, n=59) and stable angina (SA, n=54) by coronary angiography. Thirty-six healthy subjects served as controls. Intravascular ultrasound (IVUS) was used to evaluate the characteristics of coronary atherosclerotic plaque, and serum Lp-PLA2 concentration was measured as well.ResultsLp-PLA2 concentration was significantly higher in both UA and SA patients [(396±36) µg/L and (321±39) µg/L, respectively] compared with the controls [(127±49) µg/L, p<0.01], and higher in UA than SA group. IVUS findings showed that remodeling index (RI) (0.91±0.15 vs. 0.85±0.11, p=0.005) and eccentricity index (EI) (0.73±0.16 vs. 0.65±0.22, p=0.039) were larger in UA than in SA group, and fibrous caps were thicker in SA than UA group [(0.91±0.23) mm vs. (0.63±0.21) mm, p=0.032]. Moreover, Lp-PLA2 correlated positively with EI (r=0.439, p<0.01) and RI (r=0.592, p<0.05) in UA group. There was an inverse relationship between Lp-PLA2 and fibrous cap thickness in both UA (r=-0.587, p<0.001) and SA (r=-0.318, p<0.05) groups. The independent risk factors in UA group were Lp-PLA2 (OR=1.055, 95% CI: 1.03-1.08, p=0.013), LDL-cholesterol (OR=0.032, 95% CI: 0.00-0.05, p=0.041) and fibrous cap thickness (OR=0.008, 95% CI: 0.00-0.45, p=0.019). Lp-PLA2 was strongly associated with both EI and fibrous cap thickness in both groups.ConclusionSerum level of Lp-PLA2 is associated with both eccentricity index and fibrous cap thickness in both UA and SA groups. Elevated levels of circulating Lp-PLA2 might to be a strong risk factor and more serious for unstable angina than stable angina.

Characterization of Hematopoietic Stem Cell Frequency and Function In Unexplained Anemia of the Elderly

AbstractAbstract 2047Anemia is both a highly prevalent and clinically important condition that causes significant morbidity and mortality in the elderly population. While anemia in the elderly can be attributed to a number of causes, approximately 30% of elderly subjects with anemia have no overt etiology and fall under the category of unexplained anemia of the elderly (UA). There is increasing evidence to suggest that changes in the frequency and/or function of hematopoietic stem and progenitor cells may contribute to the onset and pathophysiology of age-associated hematological conditions, such as UA. Hematopoietic stem cells (HSC) reside at the top of the hematopoietic hierarchy and can differentiate, via increasingly committed downstream progenitors, into all the mature cells of the hematopoietic system. Human myelo-erythroid development proceeds through a set of oligopotent progenitors: HSC give rise to multipotent progenitors (MPP), which give rise to common myeloid progenitors (CMP), which in turn give rise to granulocyte-macrophage progenitors (GMP) and megakaryocyte-erythrocyte progenitors (MEP). We use flow cytometry and in vitro culture of sorted human HSC (Lin-CD34+CD38-CD90+CD45RA-), MPP (Lin-CD34+CD38-CD90-CD45RA-), CMP (Lin-CD34+CD38+CD123+CD45RA-), GMP (Lin-CD34+CD38+CD123+CD45RA+), and MEP (Lin-CD34+CD38+CD123-CD45RA-) from hematologically normal young (23 samples; age 20–35) and elderly (11 samples; age 65+) and UA (5 samples; age 65+) bone marrow samples in order to characterize the changes in the distribution and function of hematopoietic stem and progenitor populations during the aging process and, in particular, in the development of UA. We found that UA patients contain higher frequencies of HSC compared to both elderly normal (1.5-fold; p<0.03) and young normal samples (2.8-fold; p<10-5). We also found increased frequencies of MPP from UA patients compared to MPP from elderly normal (2.6-fold; p<0.002) and young normal samples (5.8-fold; p<0.04). While we observed similar frequencies of CMP among the three groups, we found a notable trend suggesting decreased frequencies of GMP and corresponding increased frequencies of MEP in UA patients. Functionally, HSC from the three groups exhibit statistically insignificant differences in the efficiency of colony formation under the myeloid differentiation-promoting methylcellulose-based in vitro culture conditions; however, on average, HSC from elderly bone marrow samples, regardless of the presence or absence of anemia, tend to form fewer colonies in methylcellulose. Interestingly, HSC from UA patients produce more granulocyte-monocyte (CFU-GM) colonies and fewer erythroid (CFU-E and BFU-E) colonies, compared to HSC from normal samples (p<0.001). Similarly, CMP from UA patients, compared to normal CMP, yield skewed distributions of myeloid-erythroid colonies when plated in methylcellulose, significantly favoring production of CFU-GM colonies over CFU-E and BFU-E colonies (p<0.003). Additionally, MEP from UA patients form both CFU-E and BFU-E colonies in methylcellulose albeit at a significantly lower efficiency than MEP from normal bone marrow samples (p<0.01). This is the first study to examine the changes in hematopoietic stem and progenitor populations in UA patients. The changes in the distribution of hematopoietic stem and progenitor cells in UA patients indicate that the HSC and MPP populations, and possibly also the MEP population, expand in the context of anemia, potentially in response to homeostatic feedback mechanisms. Nevertheless, these expanded populations are functionally impaired in their ability to differentiate towards the erythroid lineage. Our data suggest that there are intrinsic defects in the HSC population of UA patients that lead to poor erythroid differentiation, which can be readily observed even in the earliest committed myelo-erythroid progenitors. We have generated gene expression profiling data from these purified hematopoietic stem and progenitor populations from UA patients to try to identify biological pathways and markers relevant to disease pathogenesis and potential therapeutic targets. Disclosures:Weissman:Amgen, Systemix, Stem cells Inc, Cellerant: Consultancy, Employment, Equity Ownership, Membership on an entity's Board of Directors or advisory committees. Schrier:Celgene: Research Funding.

Urinary matrix metalloproteinase-8 and -9 activities in type 2 diabetic subjects: A marker of incipient diabetic nephropathy?

Matrix metalloproteinases (MMPs) may play a pathophysiological role in the development of diabetic nephropathy (DN). We hypothesized that urinary MMP activity in patients with type 2 diabetes mellitus (T2DM) is related to a decline in renal function. We determined MMP-2, -8 and -9 activity in 24-h urine collections in relation to risk factors for DN in T2DM patients with (UA, n = 27) and without albuminuria (NA, n = 48) and controls (CO, n = 28). MMP-8 and -9 levels were highest in UA patients ( P < 0.01). Of UA patients, 93% had at least one MMP increased, compared to 78% of NA patients and 46% of CO ( P = 0.001). Age, diabetes duration, BMI, systolic blood pressure, fasting plasma glucose, HbA1c and renal function were determinants of MMP-8 and -9 ( P < 0.05). In summary, MMP-8 and -9 are highest in T2DM UA patients. MMP-9, showed the strongest associations with clinical parameters related to DN.

The threshold of admission glycemia as a predictor of adverse events in diabetic and non-diabetic patients with acute coronary syndrome.

Recent studies indicated a high prevalence of hyperglycemia in non-diabetic patients presenting with acute coronary syndrome (ACS). However, the threshold of admission glucose (AG) as a predictor of adverse events in ACS is unclear. The aim of this study was to assess the threshold of admission glucose (AG) as a predictor of adverse events including Major Acute Cardiac Events (MACE) and mortality, during the first week of admitting patients presenting with ACS. The data of 551 patients with ACS were extracted and evaluated. Patients were stratified according to their blood glucose on admission into three groups: group 1: </=7 mmol/L (n = 200, 36.3%) and group 2: >7 mmol/L and <15 mmol/L (n = 178, 32.3%) and group 3: >/=15 mmol/L (n = 173, 31.4%). Stress hyperglycemia was arbitrarily defined as AG levels > 7 mmol/L (group 2 and 3). Patients with ACS were sub-divided into two groups: patients with unstable angina (UA, n = 285) and those with ST segment elevation myocardial Infarction (STEMI, n = 266) and data were analyzed separately using multiple regression analysis. The mean age of patients was 59.7 +/- 14.8 years and 63% were males. The overall mortality in the population was 8.5% (5.4% in STEMI and 3.1% in UA) patients. In STEMI patients, the odds ratio of stress hyperglycemia as predictor of mortality in group 3 compared with group 1 was 3.3 (CI 0.99-10.98, P < 0.05), while in group 2 compared with group 1 was 2.4 (CI: 0.75-8.07, P = 0.065) after adjustment for age and sex. Similarly, in UA patients, the odds ratio of stress hyperglycemia in group 3 compared with group 1 was 2.7 (CI 0.37-18.98, P < 0.05), while in group 2 compared with group 1 was 2.4 (CI: 0.4-15.2, P = 0.344) after adjustment for age and sex. The incidence of more than 2 MACE in both STEMI and UA patients was higher in group 3 compared with the other two groups. Regression analysis showed that history of DM, high level of LDL cholesterol, high level of HbA1c, and anterior infarction were significant predictors of adverse events while other risk factors such as BMI, history of hypertension and smoking were of no significance. This study indicates that the stress hyperglycemia on admission is a powerful predictor of increased major adverse events and hospital mortality in patients with acute coronary syndrome.

Efficacy of methotrexate treatment in patients with probable rheumatoid arthritis: A double‐blind, randomized, placebo‐controlled trial

To determine whether patients with undifferentiated arthritis (UA; inflammatory, nontraumatic arthritis that cannot be diagnosed using current classification criteria) benefit from treatment with methotrexate (MTX). The PRObable rheumatoid arthritis: Methotrexate versus Placebo Treatment (PROMPT) study was a double-blind, placebo-controlled, randomized, multicenter trial involving 110 patients with UA who fulfilled the American College of Rheumatology (ACR) 1958 criteria for probable RA. Treatment started with MTX (15 mg/week) or placebo tablets, and every 3 months the dosage was increased if the Disease Activity Score was >2.4. After 12 months, the study medication was tapered and discontinued. Patients were followed up for 30 months. When a patient fulfilled the ACR criteria for RA (primary end point), the study medication was changed to MTX. Joint damage was scored on radiographs of the hands and feet. In 22 of the 55 patients (40%) in the MTX group, UA progressed to RA compared with 29 of 55 patients (53%) in the placebo group. However, in the MTX group, patients fulfilled the ACR criteria for RA at a later time point than in the placebo group (P = 0.04), and fewer patients showed radiographic progression over 18 months (P = 0.046). This study provides evidence for the efficacy of MTX treatment in postponing the diagnosis of RA, as defined by the ACR 1987 criteria, and retarding radiographic joint damage in UA patients.

The 620W allele is the PTPN22 genetic variant conferring susceptibility to RA in a Dutch population

A missense SNP, C1858T, in PTPN22 has been identified as a genetic risk factor for rheumatoid arthritis (RA). Subsequent work has suggested that other variants in this gene, in particular a haplotype marked by the minor allele of rs3789604, are associated with RA in white North Americans independent of C1858T. We tested this hypothesis in an independent white Dutch study. A total of 667 RA patients and 286 controls were genotyped for 13 PTPN22 single nucleotide polymorphisms (SNPs) by allele-specific kinetic polymerase chain reaction. rs3789604 was genotyped in an additional 410 RA and 270 UA patients participating in the Leiden early arthritis inception cohort. We conducted single-marker and haplotype association tests. The sole haplotype strongly associated with RA in our Dutch population carries the PTPN22 1858T allele. A second haplotype identical at all other SNPs tested except 1858 was not associated with disease. No significant association of the haplotype tagged by the 3' PTPN22 SNP, rs3789604, with RA susceptibility (P = 0.134) was observed in our sample set. We conclude that C1858T is the sole PTPN22 variant predisposing to RA in our white Dutch sample set.

Transcriptional activity of genes encoding Transforming Growth Factor β and its receptors in peripheral blood mononuclear cells from patients with acute coronary syndromes

Background Recent data report altered gene expression of numerous pro- and anti-inflammatory factors involved in pathology of acute coronary syndromes (ACS). Transforming growth factor β (TGFβ) signaling is engaged in a wide range of processes. Its effect on vessels seems to be protective due to its anti-inflammatory and anti-atherogenic action. However, it also seems to be engaged in such negative effects as neointima formation and fibrosis. The aim of the study was to assess the expression of the genes encoding TGFβ and its receptors (type I, II, and III) in patients with ACS. Methods The study was carried out on 24 patients with acute coronary syndrome (7 with unstable angina [UA] and 17 with myocardial infarction [MI]) and 10 age-matched healthy subjects (control). To evaluate gene expression of TGFβ and its receptors total mRNA was extracted from peripheral blood mononuclear cells (PBMC) and the number of mRNA copies were assessed by quantitative reverse transcriptase polymerase chain reaction (QRT-PCR). Results MI and UA patients demonstrated significantly lower TGFβ gene expression compared to control (2789 ± 418 c/μg vs. 20262 ± 2548 c/μg; p < 0.001, and 3390 ± 518 c/μg vs. 20262 ± 2548 c/μg; p < 0.001, respectively), as well as noticeably lower transcriptional activity of genes encoding its type I (3295 ± 447 c/μg vs. 12859 ± 1929 c/μg; p < 0.001, and 3258 ± 721 c/μg vs. 12859 ± 1929 c/μg; p < 0.01, respectively) and type II receptors (2364 ± 346 c/μg vs. 19003 ± 2357 c/μg; p < 0.001, and 2680 ± 522 c/μg vs. 19003 ± 2357 c/μg; p < 0.01, respectively). Also, gene expression of the type III receptor was inferior in the studied group compared to the control, although the difference was significant only for the UA group vs. control. Expressions of the studied genes did not differ between patients with MI and those with UA. Conclusion Our report shows that the decreased activity of TGFβ in patients with ACS is at least partly due altered transcriptional activity of genes encoding both TGFβ and its receptors, what may be responsible for the evolution of atherosclerotic lesions.

Increased soluble glycoprotein V concentration during the acute onset of unstable angina pectoris in association with chronic cigarette smoking

Platelet hyperactivity is important in the pathobiology of acute coronary syndromes. Glycoprotein V (GPV) is an integral membrane protein of platelets in the function of the GPIb-V-IX receptor for vWf/shear-dependent platelet adhesion in arteries. Soluble GPV is a novel marker of platelet activation. The aim of this study is to assess circulating soluble GPV levels in unstable angina pectoris (UA). Twenty-one patients (15 men, six women, aged 52 ± 7 years) with UA pectoris were studied. The inclusion criteria were angina at rest lasting >20 min during the preceding 6 h, with transient ST segment depression and/or T wave inversion and no evidence of myocardial infarction detected with the use of cardiac troponin-T. Coronary artery stenosis was angiographically confirmed in all patients. Twenty age- and sex-matched healthy adults (14 men, six women, aged 48 ± 7 years) served as controls. There were no significant differences among the studied groups with respect to age, sex, obesity, smoking, total cholesterol, LDL-cholesterol, HDL-cholesterol, triglyceride and platelet counts. Plasma-soluble GPV concentrations were higher in the UA patient group (126 ± 46 ng/ml) than those in the healthy controls (82 ± 15 ng/ml) (P = 0.001). There was a significant correlation only between plasma-soluble GPV levels and smoking (r = 0.526, P = 0.0001). Smoker UA patients had higher levels of soluble GPV than the non-smoker patients (139 ± 40 vs. 113 ± 50 ng/ml, respectively, P = 0.02). However, soluble GPV levels were similar in smoker and non-smoker healthy controls (P = 0.2). It is concluded that soluble GPV concentrations are significantly increased during the acute clinical course of unstable angina pectoris, indicating that soluble GPV may be useful marker of platelet activation in those patients. The level of the molecule is significantly affected from smoking in those patients.

Plasma levels of oxidized-low-density lipoproteins are higher in patients with unstable angina and correlated with angiographic coronary complex plaques

Objectives To measure circulating levels of oxidized-low-density lipoproteins (ox-LDL) in patients with stable and unstable angina and controls, and to investigate their correlation with the extent of coronary artery disease (CAD) and the presence of complex plaques at coronary angiography. Methods and results Circulating ox-LDL were assessed, using ELISA, in patients with unstable angina (UA, n = 26), stable angina (SA, n = 29) and in controls (C, n = 27). All patients underwent coronary angiography. The extent of CAD was evaluated using a quantitative score, while the presence of complex, vulnerable plaques was angiographically assessed. Ox-LDL were higher in UA patients than in SA patients and in C subjects, and in SA patients than in C subjects (C, 45.6 ± 12.8 U/L; SA, 58.8 ± 11.0 U/L; UA, 73.7 ± 13.6 U/L; p < 0.001). No correlation was found with the extent of atherosclerotic disease in the coronary tree. Patients with angiographic complex lesions showed significantly higher levels of ox-LDL (68.4 ± 13.9 U/L versus 55.2 ± 16.4 U/L, p < 0.001). Multiple regression analysis showed that ox-LDL were independent predictors of the presence of complex plaques ( p < 0.023). Conclusions Ox-LDL levels are higher in unstable patients and correlate with the presence of angiographically documented complex plaques. Ox-LDL might be markers of destabilization of CAD.

Platelet reactivity in response to mental stress in syndrome X and in stable or unstable coronary artery disease

Introduction Previous studies showed differences in platelet reactivity in response to exercise in patients with syndrome X (SX) and those with obstructive coronary artery disease (CAD). In this study, we investigated whether similar differences could be detectable in response to a mental stressful stimulus. Materials and methods We studied 30 SX patients (60±8 years, 8 men), 20 patients with stable angina and angiographically documented CAD (SA, 66±8 years, 14 men), and 11 patients with unstable angina (UA, 67±8 years, 6 men). A control group of 22 healthy controls (50±7 years, 5 men) was also studied. All subjects underwent a mathematical mental stress test (MST) consisting of rapid consecutive subtractions of number 7 for a period of 5 min. A venous blood sample was collected at baseline and immediately after MST. Platelet reactivity was measured on flowing blood as time necessary to occlude a ring coated with collagen–adenosine diphosphate (ADP; closure time, CT), using the platelet function analyzer (PFA-100) system. Results At rest, CT was lower in UA patients (87±19 s) compared to controls (109±24 s, p=0.02) and SA patients (105±37 s, p=0.055), and also tended to be lower in SX patients (96±18 s) compared to controls ( p=0.07). The CT response to MST differed significantly among groups ( p=0.0009). At peak MST, CT did not change in controls (110±27 s, p=0.88), whereas it decreased in SA patients (96±29 s, p=0.003) and tended to decrease in UA patients (82±15 s, p=0.25). In contrast, a significant increase in CT with MST was shown in SX patients (103±21 s, p=0.007). Conclusions Platelet reactivity is increased by MST in patients with CAD, whereas it paradoxically decreases in SX patients, which may constitute a protective effect against stress-induced events in these patients.

Effect of Xuefu Zhuyu pill on platelet activating factor expression in patients with unstable angina pectoris

To explore the significance of platelet activation (PA) in patients with unstable angina pectoris (UA) and the effect of Xuefu Zhuyu pill (XZP, a Chinese composite recipe) on it, by way of determining platelet membrane glycoprotein CD62P, CD41/CD45 expressions in whole blood of healthy persons and UA patients. XZP was given orally to 45 UA patients for 2 weeks. Their expressions of CD62P and CD41/CD45 in peripheral blood were determined before and after treatment by whole blood flow cytometry with special marked antibody, and compared with those in 10 healthy persons of the same age as a normal control group. Amount of expressions of CD62P and CD41/CD45 (FC%) in UA patients before treatment were 24. 22±7. 92 and 25. 89±8.10 respectively, all higher than those in the control group (P 0.05) . Platelet adhesion rate reduced significantly (P<0.05) at the same time, as compared with that of before treatment. Highly platelet activated state exists in UA patients. XZP could inhibit platelet membrane glycoprotein CD62P and CD41/CD45 expressions, which might be the molecular mechanism of it in antagonizing PA.

Assessing the clinical and economic burden of coronary artery disease: 1986-1998.

The acute phase of coronary artery disease (CAD) is dramatic and receives much attention because of its high mortality and associated treatment cost. However, the acute phase typically resolves within 30 days whereas CAD is a chronic disease, which most patients will live with for more than a decade. We compared the clinical and economic burden of CAD during the acute phase (first 30 days) with that in the postacute phase (31st day through 10 years). We included acute coronary syndrome (ACS) patients with significant CAD receiving an initial cardiac catheterization at Duke University Medical Center between 1986 and 1997 with follow-up continuing through 1998. Inpatient medical costs were estimated from ACS clinical trial and economic study data. Costs were adjusted to 1997 values and discounted at 3% per annum. Our study included 9,876 ACS patients (5,557 with an acute myocardial infarction [MI] and 4,319 with unstable angina [UA]). Acute MI patients had higher 30-day mortality than UA patients (5.6% vs. 2.3%, P <0.001). In addition, acute MI and UA patients had significant 10-year unadjusted and adjusted survival differences (both P <0.001). For patients who survived to 30 days, there was no difference in 10-year survival between acute MI and UA patients before adjustment (P = 0.472). After adjustment, however, unstable angina patients who survived to 30 days had greater survival than myocardial infarction patients (P = 0.011). Mean 10-year discounted ACS inpatient medical costs were $45,253 ($23,510 acute phase and $21,819 postacute phase, P = 0.002). Ten year costs for unstable angina patients were $46,423 ($21,824 acute phase and $24,599 postacute phase, P = 0.003); ten year costs for myocardial infarction patients were $44,663 ($24,823 acute phase and $19,840 postacute phase, P <0.001). We found that the clinical and economic burden of CAD continues long after a patient's acute event has resolved and that postacute CAD cardiac event rates and inpatient medical costs may be higher than previously estimated. With much of all medical costs occurring in the postacute phase, the potential for effective secondary prevention therapies is substantial.

Blood Cell Activation, Coagulation, and Inflammation in Men and Women With Coronary Artery Disease

We investigated in some detail the immunologic and procoagulant activation patterns in men and women with unstable (UA, n=26) versus stable (SA, n=40) coronary artery disease (CAD). Leukocyte activation and platelet–leukocyte complex formation were assessed by flow cytometry. Plasma markers of coagulation and inflammation were analyzed. Unstable patients displayed higher levels of platelet–leukocyte complexes ( P<.001), of leukocyte CD11b ( P<.01), and of T cell HLA-DR ( P<.05) than healthy controls did. Female UA patients presented the highest degree of complexes. SA patients only differed significantly from controls with respect to HLA-DR ( P=.02). UA patients had higher levels of C-reactive protein ( P<.01), IL-6 ( P<.001), IL-10 ( P<.01), and soluble fibrin ( P<.001) than did stable ones. Regarding P-selectin levels, 25% of SA and 50% of UA patients were above normal range. Again, UA women presented the highest marker amounts. As for soluble tissue factor, women had higher levels than men regardless of the severity of disease ( P<.001 in SA). We conclude that in unstable coronary syndromes, there is an activation of both coagulation and inflammation that coincides with an increased activation of platelets and leukocytes. Cellular interactions may contribute to the systemic responses observed. Women have different patterns of cellular activation than men, indicating differences in pathogenetic mechanisms.

Peripheral venous platelet aggregates in patients with unstable angina pectoris and acute myocardial infarction.

In vivo peripheral venous platelet aggregates (PVPA) have been demon strated in patients with myocardial infarction (MI), transient cerebral ischemic attacks (TIAs), and acute arterial insufficiency by the platelet count ratio (PCR) method. But PVPA determinations have not been reported in patients with unstable angina pectoris (UA), controls have not been specified as acutely ill in earlier studies using this technique, and variability of the method has not been presented in detail. Because platelet aggregation has been mentioned as a possible mechanism for perpetuating myocardial ischemia, we studied 21 acutely ill noncardiac control (NC) patients, 17 UA patients, and 13 MI patients for PVPA. PCR represents ratio of platelet counts obtained when identical aliquots of blood were drawn into two syringes containing formalin-EDTA and EDTA respectively. Free flow was demonstrated before blood was drawn. Mean PCR was 0.90 ± 0.01 (SE) in NC, 0.85 ± 0.02 in UA, and 0.85 ± 0.02 in MI. In the subset of 7 patients with acute transmural MI, PCR was 0.83 ± 0.02. Only this subset was significantly different from NC (P &lt; 0.001). PCR did not vary significantly with age or sex. Aspirin history was positive in 25-30% of the patients in each group and raised PCR by an average of 0.04 units. When PCR was repeated after 45 minutes in 6 patients, moderate variability with a mean absolute change in PCR of 0.08 was noted. Our data fail to support an etiologic role for circulating platelet aggre gates in initiating UA. Clinical trials of platelet inhibitors and experimen tal models of arterial insufficiency probably offer the greatest chance of further defining the potential etiologic role of platelet aggregation in initiating or perpetuating myocardial ischemic phenomena.