Lipoprotein-associated phospholipase A2 (Lp-PLA2) activity, platelet-activating factor acetylhydrolase (PAF-AH) in leukocytes and body composition in healthy adults.

BACKGROUND: Lipoprotein-associated phospholipase A2 (Lp-PLA2) also known as serum platelet activating factor acetylhydrolase (PAF-AH) activity constitutes a novel risk marker for cardiovascular disease. Leukocytes constitute one main cellular source of circulating Lp-PLA2. The aim of the present study was to evaluate the association of both serum and leukocyte PAF-AH activities with fat distribution and lean tissue. One hundred healthy volunteers without cardiovascular disease history participated in this study (n = 52 men, 44 +/- 13 years and n = 48 women, 43 +/- 13 years). Body composition was assessed with dual-energy X-ray absorptiometry, while anthropometrical indices were also measured. The activity of Lp-PLA2 and levels of lipid and glycemic parameters were determined in fasting samples. RESULTS: Mean Lp-PLA2 activity was 24.8 +/- 4.5 and 19.6 +/- 5.0 nmol/min/mL in men and women, respectively (P < 0.001). Mean activity of PAF-AH in leukocyte homogenates was 386 +/- 127 pmol/min/mg and 292 +/- 92 pmol/min/mg in men and women, correspondingly (P < 0.001). In multiple regression models upper and total adiposity measures were positively associated with Lp-PLA2 activity in men after adjusting for LDL-cholesterol, age, smoking, hs-CRP and physical activity, whereas no associations were found with PAF-AH leukocyte homogenates activity. Hierarchical analysis revealed that the variables with the highest explanatory ability of Lp-PLA2 activity in men, were DXA deriving L1-L4 region of interest and arms fat (increase in R2 = 0.136, P = 0.005 and increase in R2 = 0.118, P = 0.009, respectively), followed by trunk fat and total fat. In women, no association of body composition variables with Lp-PLA2 nor PAF-AH leukocyte homogenates activity was found. CONCLUSION: Lp-PLA2 activity is differentiated across levels of adiposity and topology of adipose tissue, whereas no association was found regarding PAF-AH leukocyte homogenates activity. Our findings suggest that Lp-PLA2 may compensate for the adiposity-associated increases in inflammatory and oxidative burden, in men.

Breast-feeding in Athens, Greece: factors associated with its initiation and duration.

OBJECTIVES: To determine the prevalence, examine the influence of hospital practices and investigate potential determinants of breast-feeding in Athens. PATIENTS AND METHODS: Three hundred twelve mothers provided information regarding feeding practices at certain maternity hospitals in Athens, at 40 days and 6 months postpartum. Multiple logistic regression analysis was performed to evaluate the association between the initiation and maintenance of breast-feeding and potential risk factors. RESULTS: Although almost 90% of newborn infants were given a breast milk substitute one or more times during the first 2 days at the maternity hospital, the exclusive breast-feeding percentage on the last day of hospital stay reached 85%. Breast-feeding and exclusive breast-feeding percentages dropped to 55% and 35%, respectively, at 40 days postpartum and to 16% and 12%, respectively, at 6 months postpartum. While in the hospital, 3% of mothers initiated breast-feeding within 1 hour of labor, only 34% were informed about the advantages of breast-feeding by health professionals and 42% were trained to breast-feed by the midwives. "Rooming-in" was not practiced in the private hospitals. The educational level was positively associated with the initiation of breast-feeding [odds ratio (OR): 1.36, confidence interval (CI): 1.02-1.81], the mother's body mass index was negatively associated with the maintenance of breast-feeding for 40 days (OR: 0.56, CI: 0.32-0.98) and 6 months (OR: 0.28, CI: 0.06-1.26) and a caesarean section was negatively associated with the initiation (OR: 0.24, CI: 0.11-0.49) and maintenance of breast-feeding (OR: 0.42, CI: 0.20-0.89). CONCLUSIONS: Breast-feeding is not appropriately supported in certain maternity hospitals in Athens, and this is probably the cause of observed low breast-feeding prevalence.

Effects of atorvastatin on reactive hyperemia and inflammatory process in patients with congestive heart failure.

Purpose of the study was to investigate whether short-term atorvastatin treatment improves endothelial function and affects inflammatory process in patients with heart failure (HF) and normal cholesterol levels. HF is characterized by endothelial dysfunction and increased inflammatory process, while statins restore endothelial function having also anti-inflammatory effects in hypercholesterolemic patients. We investigated the effect of 4-week atorvastatin treatment (10 mg/day) on endothelial function and inflammatory markers in patients with HF and cholesterol levels <220 mg/dl. Patients were randomly allocated into groups and received atorvastatin (n=19) or no statin (n=19). Forearm blood flow was measured using gauge-strain plethysmography. Serum levels of tumor necrosis factor alpha (TNF-alpha), interleukin 6 (IL-6), and soluble vascular cell adhesion molecule (sVCAM-1) were determined with ELISA. Data are expressed as median [25th-75th percentile]. Forearm vasodilatory response to reactive hyperemia was significantly improved in atorvastatin-treated patients (from 38.1% [32.0-59.1] to 70.0% [61.1-106.3], P<0.01), while it remained unaffected in the control group. Levels of IL-6, TNF-alpha and sVCAM-1 were decreased in atorvastatin-treated group (from 7.8 pg/ml [4.8-9.5], 3.2 pg/ml [2.7-4.8] and 595 ng/ml [440-810] to 5.6 pg/ml [2.5-9.0], 2.8 pg/ml [2.0-3.6] and 289 ng/ml [169-368], respectively, P<0.05 for all) but not in the control group. These findings indicate that atorvastatin may improve forearm vasodilatory response to reactive hyperemia and depress inflammatory process in patients with heart failure and normal baseline cholesterol levels.

Peripheral levels of matrix metalloproteinase-9, interleukin-6, and C-reactive protein are elevated in patients with acute coronary syndromes: correlations with serum troponin I.

BACKGROUND: Acute coronary syndromes (ACS) are characterized by activation of systemic and local inflammatory mediators. The interrelation between these soluble inflammatory markers and their association with markers of myocardial necrosis have not been extensively studied. HYPOTHESIS: The study was undertaken to evaluate the association of the systemic levels of matrix metalloproteinase-9 (MMP-9) and the tissue inhibitor of metalloproteinase-1 (TIMP-1), with C-reactive protein (CRP), interleukin-6 (IL-6), and serum troponin-I in patients admitted with ACS. METHODS: Analysis of serum concentrations of the above inflammatory markers was performed in 53 patients with unstable angina (UA) and in 15 with non-ST-segment elevation myocardial infarction (NSTEMI) within 48 h of admission, and 34 patients with stable coronary artery disease. RESULTS: Compared with patients with stable angina, those with ACS had elevated admission levels of MMP-9 (p = 0.04), CRP (p < 0.001), and IL-6 (p = 0.001), but not TIMP-1 (p = 0.55). Compared with patients with UA, those with NSTEMI also had higher levels of IL-6 (p < 0.001), CRP (p = 0.002), and MMP-9 (p = 0.05). CONCLUSIONS: In patients with ACS, the admission levels of inflammatory mediators, including MMP-9, CRP, and IL-6 are significantly elevated, specifically in association with serum troponin I. Systemic and local markers of inflammatory activity may be directly associated with myocardial injury.

Epidemiology of acute coronary syndromes in the Mediterranean island of Cyprus (CYPACS study, Cyprus study of acute coronary syndromes).

INTRODUCTION: So far, no studies have been performed regarding the epidemiology and management of acute coronary syndromes (ACS) in Cyprus. The aim of the present study was to enroll a representative sample of patients in order to study the epidemiology and management of ACS in the Mediterranean island of Cyprus. METHODS: For a period of 12 months, all patients admitted to Nicosia General Hospital with an ACS were studied. The calculation of the annual incidence of ACS was based on the number of all ACS cases registered during one year in the Nicosia district. The results from the province of Nicosia can be considered as representative of the whole ACS profile in Cyprus. RESULTS: The annual incidence of ACS in the Nicosia district was 160 per 100,000 inhabitants (41 per 100,000 women and 282 per 100,000 men). This percentage translates into 1342 ACS episodes annually among the Cypriot population. The ratio of men to women was 6.8:1. More female ACS patients than men had hypertension (67.3% vs. 46.3%, p=0.005) and were passive smokers (53.8% vs. 47.7%, p=0.4), while male patients with ACS included a significantly greater percentage of smokers compared to women (51.3% vs. 13.5%, p<0.001). Regarding the type of ACS, 45% of patients were diagnosed with STEMI, 41.3% with NSTEMI and 13.7% with unstable angina. The majority of patients with STEMI were treated with medical reperfusion. The in-hospital mortality rate was 3.5%. CONCLUSIONS: The annual incidence of ACS in Cyprus is below the European average. The management of ACS is similar to that in southern Europe. The majority of patients with STEMI are treated with pharmacological reperfusion. The small geographical area of the island provides the advantage of early reperfusion to the majority of patients, which results in very low in-hospital mortality.

Arterial hypertension assessed "out-of-office" in a contemporary cohort of rheumatoid arthritis patients free of cardiovascular disease is characterized by high prevalence, low awareness, poor control and increased vascular damage-associated "white coat" phenomenon.

INTRODUCTION: Rheumatoid arthritis (RA) is associated with a high cardiovascular disease (CVD) risk, whereas arterial hypertension is a major modifiable CVD risk factor with still unclear prevalence in RA disease. We conducted a comprehensive study on hypertension characteristics evaluating for the first time out-of-office blood pressure (BP) in a typical contemporary RA cohort. METHODS: Assessment of office and out-of-office BP (when office systolic/diastolic BP was >129/79) and vascular studies including evaluation of aortic stiffness, carotid hypertrophy/plaques and ankle-brachial index, were performed in 214 consecutive, consenting RA patients free of CVD (aged 58.4 ± 12.3 years, 82% women). As comparators regarding office hypertension measurements, data from 214 subjects (1:1 matched for age and gender with the RA patients) derived from a cohort designed to assess the prevalence of hypertension in the general population were used. RESULTS: The prevalence of declared known hypertension in the RA population was 44%. Of the remaining RA patients, 2 in every 5 individuals had abnormal office BP (systolic/diastolic >139/89 mmHg), contributing to almost double the prevalence of declared/office hypertension compared to the general matched population (67% vs. 34%). Out-of-office (home or ambulatory 24 hour) BP measurements revealed that: (i) a 54% prevalence of actual hypertension in RA, in other words almost 10% of the patients were unaware of having hypertension and (ii) 29% of the RA patients with known hypertension were not well controlled. Actual hypertension was positively associated with age and body mass index, and inversely with the use of biologic drugs. Overall, almost 1 out of 5 presented the 'white coat' phenomenon. An intermediately compromised vascular phenotype was evident in this "white coat" subgroup (lying between patients with sustained normotension and sustained hypertension) in terms of aortic stiffness, carotid hypertrophy and ankle-brachial index, even after adjustment for confounders. CONCLUSION: Beyond any doubt on the basis of out-of-office evaluation, arterial hypertension in RA has a high prevalence, low awareness and poor control, as well as substantial and vascular damage-associated "white coat" phenomenon. Thus, correct diagnosis and effective treatment of hypertension is of key importance in RA for CVD risk reduction.

Inflammatory cytokine gene variants in coronary artery disease patients in Greece.

OBJECTIVE: Abundant evidence supports the central role of inflammatory cytokines in immune responses mediating the pathogenesis of atherosclerosis, coronary artery disease, and its complications, such as myocardial infarction and unstable angina. METHODS: We investigated the association of genetic polymorphisms of the inflammatory cytokines, IL-10, TGF-beta1, IFN-gamma, IL-6, and TNF-alpha with the clinical presentation of coronary artery disease in 26 patients with stable angina, 45 patients with unstable angina and 58 patients who had experienced nonfatal myocardial infarction. Genotyping was performed by the sequence-specific primer polymerase chain reaction method. RESULTS: A significant difference in the frequencies of -174G/C IL-6 alleles was observed, with the low in-vitro producing -174*C allele predominating in patients with myocardial infarction, compared with stable angina and unstable angina patients, after the analysis of genotypes (P=0.024 and 0.022, respectively), phenotypes [P=0.0099, odds ratio (OR)=0.271, 95% confidence interval (CI)=0.1012-0.7292; P=0.03, OR=0.40, respectively] and haplotypes (P=0.007, OR=3.028, 95% CI=1.347-6.806; P=0.0096, OR=2.368, 95% CI=1.262-4.444; respectively). In addition, a predominance of the -1082ACC/ATA IL-10 genotype in the myocardial infarction group compared with the unstable angina group and the -874 A/A IFN-gamma genotype in the stable angina group compared with the unstable angina and the myocardial infarction group, was found. No significant differences in the distribution of genotypes, phenotypes and haplotypes in the three study groups, for the TNF-alpha-308 A/G and TGF-beta1-codon 25 G/C, codon 10 T/C polymorphisms were detected. CONCLUSION: Our data provide evidence that the IL-6-174G/C polymorphism may be involved in the pathogenesis of coronary artery disease, contributing to genetic susceptibility for myocardial infarction.

Genetic polymorphism on endothelial nitric oxide synthase affects endothelial activation and inflammatory response during the acute phase of myocardial infarction.

OBJECTIVES: This study sought to evaluate the effect of genetic polymorphism G894T on endothelial nitric oxide synthase (eNOS); on the risk for myocardial infarction (MI); and on the release of von Willebrand factor (vWF), interleukin (IL)-6, IL-1b, and oxidized low-density lipoprotein (ox-LDL) levels during the acute phase of MI and one year after the event. BACKGROUND: Genetic polymorphism G894T on eNOS has been associated with increased cardiovascular risk. However, its role during the acute phase of MI is unknown. METHODS: The study population consisted of 228 patients with a first event of premature MI and 519 matched control patients. One year after the event, 61 patients and 205 control patients were recalled for the follow-up study. Blood sampling was performed during the acute phase and after one year. RESULTS: The risk for MI in 894TT was 1.992 (95% confidence interval [CI], 1.131 to 3.485), p < 0.05 versus GG+GT; 2.038 (95% CI, 1.125 to 3.695), p < 0.05 versus GG; and 2.009 (95% CI, 1.106 to 3.651), p < 0.05 versus GT. During the acute phase, vWF was higher in GT+TT (121.02 +/- 5.47%) versus GG (84.6 +/- 7.1%, p < 0.01), an effect persisting after one year (90.4 +/- 3.8 vs. 73.1 +/- 4.6%, p < 0.01). During the acute phase, GT+TT had higher ox-LDL and IL-6 (131.2 +/- 6.4 IU/l and 8.5 +/- 0.7 pg/ml) compared with GG (101.7 +/- 9.64 IU/l and 6.2 +/- 0.8 pg/ml, p < 0.05 for both), but no difference was found at one year. CONCLUSIONS: G894T polymorphism on the eNOS gene increases the risk for premature MI and modifies the response of vascular endothelium during the acute phase of MI by affecting the release of vWF, IL-6, and oxidative stress status, an effect diminished one year after the event.