Microvascular dysfunction in cardiac syndrome X: the role of inflammation.
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Biomedical subjects
Publications and source records attributed to Ramón Arroyo-Espliguero.
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BACKGROUND: The role of inflammation in the pathogenesis of acute coronary syndrome (ACS) is established. Little is known however, regarding the use of inflammatory markers as predictors of future cardiovascular events in patients presenting to the emergency department (ED) with suspected ACS. HYPOTHESIS: To assess whether biomarkers that predict cardiovascular risk in apparently healthy individuals and coronary artery disease patients are useful predictors of future cardiovascular events in patients presenting to the ED with chest pain suggestive of ACS. METHODS: We compared the abilities of serum C-reactive protein (hs-CRP), albumin and leukocyte count to identify subjects with ACS and those who are at high risk of developing events during a 30-day follow-up. RESULTS: 144 patients (mean age 62+/-13 years, 45 female) presenting to the ED <3 h after the onset of symptoms suggestive of ACS were evaluated. Final hospital diagnoses were non-ischemic chest pain in 43 (30%) and ACS in 101 (70%) patients. Patients with ACS had significantly higher leukocyte count (p<0.0001) and hs-CRP levels (p<0.02) and lower albumin concentrations, compared to patients with NICP (p<0.0001). Lower albumin concentrations (p=0.03) and hs-CRP (p=0.049) were predictors of recurrent events at 30 days. On multivariate analysis, however, only leukocyte count was a predictor of ACS (OR 20.9; 95% CI: 3.7-19.5; p=0.01) and high hs-CRP levels were a predictor of clinical outcome (OR 2.8; 95% CI: 1.5-5.2; p=0.001). CONCLUSIONS: Leukocyte count is an independent predictor of ACS in patients presenting to the ED with chest pain suggestive of ACS and high hs-CRP levels are an independent predictor of clinical outcome in ACS patients.
A polymorphism of the human angiotensin-converting enzyme (ACE) gene has been identified in which the insertion (I) rather than the deletion (D) variant is associated with lower circulating and tissue ACE activity. ACE I allele is associated with resistance and endurance performance. Skeletal muscle metabolic efficiency is reduced in patients with heart failure and is improved by ACE inhibition. Profound muscle fatigue is a predominant and debilitating symptom in a proportion or patients with angina and normal coronary arteriograms (ANCA), and we postulated that the gene D allele might be associated with the presence of fatigue in ANCA patients. We studied 33 consecutive patients with typical ANCA who completed a validated fatigue questionnaire, and found an excess of the D allele frequency in patients with the highest fatigue scores compared to those with the lowest (64% vs. 36%; p=0.027).
BACKGROUND: Inflammation and infection have been implicated in atherosclerosis and its complications. The CD14 receptor mediates monocyte activation by lipopolysaccharide (LPS) of Gram-negative bacteria. The aim of this study was to assess whether the C(-260)T polymorphism in the promoter of the CD14 receptor gene is associated with a higher prevalence of acute coronary syndromes (ACS) and severity of coronary atherosclerosis. METHODS: We studied 428 patients (mean age: 63+/-10 years, 67% men) consisting of 334 patients with coronary artery disease (CAD) and 94 patients with normal coronary arteriogram. Patients with CAD were subdivided in two groups: (1) no previous history of ACS (n=140; 64+/-9 years; 79% men) and (2) patients with a history of ACS (n=194; 64+/-10 years; 80% men). CD14 genotypes were determined by a Polymerase Chain Reaction (PCR)-Restriction Fragment Length Polymorphism Analysis (RFLP) technique. RESULTS: Patients with a prior ACS had a significantly higher frequency of the T/T genotype than CAD patients without prior ACS (33% vs. 20%; P=0.009), even after multivariate analysis (odd ratio [OR] 1.8 [1.1-3.1]; confidence intervals [CI] 95%; P=0.023). T/T genotype was not significantly different in CAD patients without prior ACS compared to controls (20% vs. 22.3%; P=0.67), and there was no significant association between genotypes, or allele frequencies, and severity of CAD. CONCLUSIONS: The CD14 C(-260)T polymorphism is associated with a history of ACS and it may represent a genetically determined risk factor for the development of ACS and atheromatous plaque vulnerability in angina patients.
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BACKGROUND: Both endothelial cell activation and macrophage activation play a significant role in atherogenesis and atheromatous plaque vulnerability and may determine rapid coronary artery disease (CAD) progression. We sought to assess the association between serum inflammatory markers and rapid CAD progression in patients with chronic stable angina pectoris. METHODS AND RESULTS: We studied 124 chronic stable angina pectoris patients (84 men; mean age, 61+/-10 years) who were on a waiting list for coronary angioplasty for a mean time of 4.8+/-2.4 months. CAD progression was defined as > or =10% diameter reduction of a pre-existing stenosis > or =50%, > or =30% diameter reduction of a stenosis <50%, development of a new stenosis > or =30% in a previously normal segment, or progression of any stenosis to total occlusion. CAD progression occurred in 35 patients (28%). After adjustment with binary logistic regression, neopterin (P<0.001), high-sensitivity C-reactive protein (P=0.017), matrix metalloproteinase-9 (P=0.002), soluble intercellular adhesion molecule 1 (P<0.001), and previous history of unstable angina (P=0.01) were independent predictors of rapid CAD progression. The association between rapid disease progression and inflammatory markers remained significant even when presence of complex lesions was introduced into the multivariate model. CONCLUSIONS: Rapid CAD progression in patients with stable angina pectoris is associated with increased C-reactive protein levels and raised concentrations of biochemical markers of endothelial and macrophage activation.
We sought to assess the relation between circulating levels of inflammation markers, such as neopterin and C-reactive protein, and the development of adverse cardiovascular events in patients with hypertension but without obstructive coronary artery disease. We observed that patients who developed adverse events during follow-up had significantly higher neopterin levels compared with patients without events.
UNLABELLED: Inflammation plays an important role in atherosclerosis and the genesis of acute coronary syndromes, i.e., atheromatous plaque disruption. Neutrophil count and C-reactive protein (CRP) levels are markers of ongoing inflammation and predictors of cardiovascular risk. We sought to assess whether these inflammatory markers are associated with the presence of multiple complex stenoses in patients with chronic stable angina. METHODS AND RESULTS: We assessed 150 patients with chronic stable angina, 121 with significant coronary artery stenosis (> or =50% diameter reduction) and 29 without. CRP levels and neutrophil count were assessed at study entry. Stenoses were classified as "complex" (irregular or scalloped borders, ulceration or filling defects) or "smooth" (absence of complex features). Eighty-eight percent of the complex lesions were of type C according to AHA/ACC classification whereas the rest were type B. Patients with > or =3 complex lesions were considered to have multiple complex stenoses. Extent of coronary artery disease was assessed using a validated score. Baseline neutrophil count (4.39 x 10(9) L (-1) +/- 28 versus 3.82 x 10(9) L (-1) +/- 0.77; P = 0.004) and CRP levels (2.15 mg/L (4.6-1) versus 0.39 mg/L (0.69-0.23); P < 0.0001) were higher in patients with significant stenoses compared to patients without. No association was found between disease extent and CRP levels or neutrophil count. Neutrophil count, however (but not CRP) correlated with stenosis complexity (r = 0.28; P = 0.002 ) and was also an independent predictor of the presence of multiple complex stenoses (OR: 4.05; CI 95% (1.9-10.4); P = 0.038). CONCLUSIONS: CRP levels and neutrophil count are higher in angina patients with coronary stenoses compared to those without. Neutrophil count, but not CRP levels, correlates with angiographic stenosis complexity.
AIMS: We sought to assess (1) whether C-reactive protein (CRP) is an independent predictor of future cardiovascular events after adjustment for coronary artery disease (CAD) severity and (2) whether CRP levels correlate with number of angiographically complex coronary artery stenosis. METHODS AND RESULTS: We studied 825 consecutive angina patients (mean age 63+/-10 years, 74% men), 700 with chronic stable angina (CSA) and 125 with acute coronary syndromes without ST-segment elevation (ACS). The composite endpoint of non-fatal acute myocardial infarction, hospital admission with class IIIb unstable angina and cardiac death was assessed at one year follow-up. Hs-CRP level was higher in CSA patients with the combined end-point (P=0.03) after adjustment for number of diseased coronary arteries. Hs-CRP was also significantly higher in patients with ACS compared to CSA ( P=0.004) and correlated with number of complex angiographic stenoses (r=0.36, P=0.01). Hs-CRP was also increased in patients with NYHA functional class III or IV compared to those in class I or II (p<0.0001). CONCLUSIONS: CRP levels predict future cardiovascular events independently of CAD severity and correlate with number of angiographically complex coronary artery stenosis in patients with ACS. Thus, CRP levels are a marker of atheromatous plaque vulnerability and CAD activity.
BACKGROUND: The diagnosis of myocardial ischemia in patients with acute chest pain at rest but non-diagnostic electrocardiograms (ECG) is problematic. Ischemia Modified Albumin (IMA) is a new biochemical marker of ischemia, which may be useful to characterise acute coronary syndrome (ACS) patients. METHODS: We studied 131 patients (mean age 58.5 years; 95 male) presenting to the emergency department with symptoms suggestive of ACS but with normal or non-diagnostic ECGs. Cardiac troponin T (cTnT) and IMA were measured within 3 h of last chest pain episode. Based on hospital diagnostic test results, patients were classified as having ACS or non-ischemic chest pain (NICP), by two independent cardiologists unaware of IMA results. RESULTS: Mean IMA levels (U/ml) were higher in patients with ACS (98.3+/-11) compared to patients with NICP (85.5+/-15); p<0.0001. IMA levels >93.5 U/ml demonstrated a sensitivity and specificity of 75% for the diagnosis of ACS; area under the receiver operator characteristic curve 0.78 (95% CI: 0.70-0.85). If we applied the manufacturer cutoff point of 85 U/ml, the sensitivity of IMA increased to 90.6% with a specificity of 49.3% (negative predictive value=84.6%). In combination with cTnT (6-12 h) (>0.05 ng/ml), the sensitivity increased to 92.2%. After multivariate analysis, IMA levels >85 U/ml (odds ratio=14.6 [95% CI 4.4-48.4]; p<0.0001), age and prior myocardial infarction were independent predictors of ACS. CONCLUSION: IMA may be a useful biomarker for the identification of ACS in patients presenting with typical acute chest pain but normal or non-diagnostic ECGs.
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AIMS: Endothelial dysfunction and subangiographic atheroma have been reported in patients with cardiac syndrome X (CSX) but little is known regarding chronic inflammation and reduced arterial distensibility as pathogenic mechanisms. We assessed whether markers of inflammation and arterial distensibility differ in CSX patients compared to control subjects. METHODS AND RESULTS: We studied 30 consecutive CSX patients (mean age 57+/-6 years, 25 women) and 30 healthy controls (mean age 54+/-8 years, 25 women). High sensitivity C-reactive protein (hs-CRP) levels were significantly higher in patients with CSX compared to controls (2.6 [1.7-4.5] vs 1.5[0.7-2.7] mg/l, P=0.02). Hs-CRP levels correlated with carotid intima-media thickness (IMT) (Spearman's rho=0.51; P=0.013). CSX patients also had significantly increased mean IMT values than controls (P<0.0001). Arterial stiffness and elastic modulus were also significantly increased in CSX patients compared to control subjects (P=0.04 and P=0.04, respectively). Distensibility tended to be lower in CSX patients than controls although this difference did not reach statistical significance. CONCLUSIONS: This study showed for the first time that compared to control subjects, patients with CSX have higher hs-CRP serum levels, increased mean common carotid artery IMT and increased arterial stiffness. The role of these abnormalities in the pathogenesis of CSX deserves investigation.