Lipoprotein-associated phospholipase A2 (Lp-PLA2), also known as platelet-activating acetylhydrolase (PAF-AH), has been recently proposed as an inflammatory biomarker and independent risk predictor for cardiovascular disease [ [1] Koenig W. Twardella D. Brenner H. Rothenbacher D. Lipoprotein-associated phospholipase a2 predicts future cardiovascular events in patients with coronary heart disease independently of traditional risk factors, markers of inflammation, renal function, and hemodynamic stress. Arterioscler Thromb Vasc Biol. 2006; 26: 1586-1593 Crossref PubMed Scopus (188) Google Scholar ]. Moreover, several studies have demonstrated the clinical significance of several polymorphisms of the Lp-PLA2 gene for the cardiovascular system [ [2] Hou L. Chen S. Yu H. et al. Associations of PLA2G7 gene polymorphisms with plasma lipoprotein-associated phospholipase A2 activity and coronary heart disease in a Chinese Han population: the Beijing atherosclerosis study. Hum Genet. 2009; 125: 11-20 Crossref PubMed Scopus (62) Google Scholar ]. The single nucleotide polymorphism (SNP) Alanine379Valine (Ala379Val) at position 379 at chromosome 6 of the gene encoding Lp-PLA2 has been shown to have an ambiguous role in the onset and development of cardiovascular diseases [ 3 Sutton B.S. Crosslin D.R. Shah S.H. et al. Comprehensive genetic analysis of the platelet activating factor acetylhydrolase (PLA2G7) gene and cardiovascular disease in case–control and family datasets. Hum Mol Genet. 2008; 17: 1318-1328 Crossref PubMed Scopus (62) Google Scholar , 4 Liu P.Y. Li Y.H. Wu H.L. et al. Platelet-activating factor-acetylhydrolase A379V (exon 11) gene polymorphism is an independent and functional risk factor for premature myocardial infarction. J Thromb Haemost. 2006; 4: 1023-1028 Crossref PubMed Scopus (42) Google Scholar , 5 Hoffmann M.M. Winkler K. Renner W. et al. Genetic variants and haplotypes of lipoprotein associated phospholipase A2 and their influence on cardiovascular disease (the Ludwigshafen risk and cardiovascular health study). J Thromb Haemost. 2009; 7: 41-48 Crossref PubMed Scopus (34) Google Scholar , 6 Casas J.P. Ninio E. Panayiotou A. et al. PLA2G7 genotype, lipoprotein-associated phospholipase A2 activity, and coronary heart disease risk in 10 494 cases and 15 624 controls of European ancestry. Circulation. 2010; 121: 2284-2293 Crossref PubMed Scopus (95) Google Scholar ]. However, the prevalence of the Ala379Val polymorphism on Caucasian male hypertensive patients has not been evaluated. Furthermore, correlations of this polymorphism with inflammation and thrombosis in male hypertensive patients have not been investigated. Thus, in the present study, we investigated the association of this polymorphism with arterial hypertension, inflammatory and thrombotic markers.

Kardara, D.; Tousoulis, D.; Antoniades, C.; Koumallos, N.; Xaplanteris, P.; Papageorgiou, N.; Vasiliadou, C.; Stefanadis, C. Author Information

Objective: To investigate the effect of laughter and mental stress on arterial stiffness and central hemodynamics. Arterial stiffness and wave reflections are independent predictors of cardiovascular risk. Chronic psychological stress is an independent risk factor for cardiovascular events, whereas acute stress deteriorates vascular function. Methods: Eighteen healthy individuals were studied' on three occasions, according to a randomized, single-blind, crossover, sham procedure-controlled design. The effects of viewing a 30-minute segment of two films inducing laughter or stress were assessed. Carotid-femoral pulse wave velocity was used as an index of arterial stiffness; augmentation index was used as a measure of wave reflections. Results: Laughter decreased pulse wave velocity (by 0.30 m/sec, p = .01), and augmentation index (by 2.72%, p = .05). Conversely, stress increased pulse wave velocity (by 0.29 m/sec, p = .05) and augmentation index (by 5.1%, p = .005). Laughter decreased cortisol levels by 1.67 mu g/dl (p = .02), soluble P-selectin by 26 ng/ml (p = .02) and marginally von Willebrand factor (by 2.4%, p = .07) and increased total oxidative status (by 61 mu mol/L, p < .001). Stress decreased interleukin-6 (by 0.11 pg/ml, p = .04) and increased total oxidative status (by 44 mu mol/L, p = .007). Soluble CD40 ligand and fibrinogen remained unchanged. Conclusions: Positive (laughter) and negative (stress) behavioral interventions have divergent acute effects on arterial stiffness and wave reflections. These findings have important clinical implications extending the spectrum of lifestyle modifications that can ameliorate arterial function.

Background: Depression has been associated with increased inflammatory process. Although anti-depressive medication has antiinflammatory effect in major depression, its role in patients with heart failure (HF) is unknown. In the present study we evaluated the impact of antidepressive medication on the expression of proinflammatory cytokines and acute phase response proteins, in patients with HF and major depression.Methods: The study population consisted of 250 patients with HF (154 suffering from major depression). Patients with major depression were under selective serotonin reuptake inhibitors (SSRIs, n=120) or tricyclic antidepressants (TCA) and/or serotonin/norepinephrine reuptake inhibitors (SNRIs) (n=34), for at least 6 months.Results: Levels of TNF-alpha, IL-6, CRP and fibrinogen were not significantly different between HF patients with depression under treatment and those without depression (p=NS for all). However, TNF-alpha and CRP levels were significantly lower in patients receiving TCA/SNRI compared to patients receiving SSRIs or those without depression (p < 0.05 for all). Similarly, patients under TCA/SNRI had significantly lower heart rate compared to those treated with SSRIs or those without depression. In multivariate analysis, treatment with SNRI/TCA was an independent predictor for log(TNF-alpha) (beta=0.036(SE:0.016) and log(CRP) (beta=0.099)(SE:0.048), p=0.041).Conclusions: In the present study we demonstrate for the first time that treatment of patients with HF and major depression with TCAs/SNRIs, is associated with lower levels of TNF-alpha and CRP, suggesting that the type of antidepressive treatment may have a significant effect on the underlying inflammatory process. (c) 2008 Elsevier Ireland Ltd. All rights reserved.

Background: Evidence suggests that children with familial hypercholesterolemia (FH) have endothelial dysfunction. Inflammatory and haemostatic abnormalities are associated with advanced atherosclerosis and increased cardiovascular events. However, it is unknown whether these abnormalities present in FH children and contribute to their vascular dysfunction.Methods and results: We studied 38 children with FH (19 males, 19 females aged 14.8 +/- 0.9 years mean +/- S.E.) and 41 healthy children (controls; 22 males, 19 females aged 15.4 +/- 0.7 years). Endothelium-dependent reactive hyperemia (RH%) and endothelium-independent nitrate hyperemia dilatation (NH%) were measured by strain gauge plethysmography. Inflammatory and haemostatic parameters were assessed by ELISA. RH% and NH% were significantly reduced in FH compared to controls (91.3 +/- 9.3% vs. 120.4 +/- 10.6% and 53.6 +/- 3.8% vs. 74.5 +/- 7.4%, p < 0.05 for both), Total cholesterol and lipoprotein (a) were increased in FH children compared to controls (282.3 +/- 8.8 mg/dl vs. 163.8 +/- 4.6 mg/dl and 11.0[4.6, 30.7] mg/dl vs. 5.24[2.63, 11.0] mg/dl median [IQR] respectively; p < 0.001 for both). Intercellular cell adhesion molecule (ICAM-1) and interleukin 1 beta (IL-1 beta) serum levels were increased in FH compared to controls (p < 0.05 and <0.001, respectively). Plasminogen activator inhibitor 1 (PAI-1) levels were also higher in FH children (p < 0.001). Multivariate analysis revealed that reactive hyperemia was independently associated with nitrate-dependent reactive hyperemia (beta = 0.597(0.199), p < 0.01), PAI-1 (beta = -6.78(2.65), p < 0.05), log IL-1 beta (beta = -102.8 (30.2), p<0.01), age (beta = -5.06 (2.35), p < 0.05) and FH status (beta = -25.2(10.6), p < 0.05) (R-2 for the model: 0.63, p = 0.001).Conclusions: Inflammatory and haemostatic abnormalities are present in FH children and contribute to the endothelial dysfunction observed in these children. (C) 2008 Elsevier Ireland Ltd. All rights reserved.

Background Tea consumption is associated with decreased cardiovascular risk. Flow-mediated dilatation (FMD) of the brachial artery is related to coronary endothelial function and it is an independent predictor of cardiovascular risk. Black tea has a beneficial effect on endothelial function; the effect, however, of green tea on brachial artery reactivity has not been defined yet.Design and methods We studied 14 healthy individuals (age 30 3 years) with no cardiovascular risk factors except from smoking (50%) on three separate occasions on which they took: (a) 6 g of green tea, (b) 125 mg of caffeine (the amount contained in 6 g of tea), or (c) hot water. FM D of the brachial artery was measured before each intervention and 30, 90, and 120 min afterward. High-sensitivity C-reactive protein, interleukins 6 (II-6) and 1 b (II-1b), total plasma antioxidative capacity, and total plasma oxidative status/stress were measured at baseline and at 120 min after each intervention.Results Resting and hyperemic brachial artery diameter did not change either with tea or with caffeine. FMD increased significantly with tea (by 3.69%, peak at 30 min, P < 0.02), whereas it did not change significantly with caffeine (increase by 1.72%, peak at 30 min, P=NS). Neither tea nor caffeine had any effect on high-sensitivity C-reactive protein, II-6, II-1b, total plasma antioxidative capacity, or total plasma oxidative status/stress.Conclusion Green tea consumption has an acute beneficial effect on endothelial function, assessed with FMD of the brachial artery, in healthy individuals. This may be involved in the beneficial effect of tea on cardiovascular risk.

BACKGROUNDArterial stiffness is an important determinant of cardiovascular morbidity and mortality. The I/D polymorphism of angiotensin-converting enzyme (ACE) gene is associated with cardiovascular disease. However, the relationship between ACE polymorphism, arterial stiffness, and wave reflections in healthy, low-risk population has not been defined yet.METHODSThe study included 282 apparently healthy, low-risk individuals (mean age 39.7 +/- 8.9 years, 178 males). Carotid-femoral pulse wave velocity (PWV) was measured as an index of aortic stiffness, while wave reflections were assessed by augmentation index (Alx) of the central pressure waveform. I/D polymorphism of the ACE gene was determined in all subjects for the prevalence of the DD, ID, and II genotype (39, 44, and 17%, respectively). C-reactive protein (CRP) levels were determined as a marker of chronic, subclinical inflammation.RESULTSAfter adjustment for potential confounding factors, presence of D allele was associated with lower values of PWV compared to II genotype (P < 0.05), implying lower aortic stiffness for D allele carriers. There was no association between ACE genotype and wave reflections or peripheral and central systolic pressures.CONCLUSIONSIn apparently healthy individuals, D allele is associated with lower aortic stiffness, whereas there is no association of the ACE polymorphism with wave reflections. This finding provides new insights into the possible links between ACE gene, regulation of large artery stiffness, and has implications for cardiovascular risk.

Objective: Homocysteinemia is associated with elevated oxidative stress and impaired endothelial function. In the present study we examined the impact of oxidative stress in the development of endothelial dysfunction in both chronic and acute (methionine-induced) homocysteinemia in humans. We also examined the role of endothelin-1 (ET-1) in the development of endothelial dysfunction in these two conditions.Methods: In this double-blind placebo controlled study, 28 subjects of both genders (14 with homocysteinemia and 14 healthy controls) underwent methionine-loading (100mg/Kg body weight) in a standard juice, containing vitamins C (2g) plus E (800IU) (n = 14) or no vitamins (placebo group, n = 14). Forearm vasodilatory response to reactive hyperemia, plasma total homocysteine (tHcy), oxidized LDL (ox-LDL), ET-1 and soluble vascular cell adhesion molecule (sVCAM-1), were evaluated at baseline and 4 hours post methionine loading (4hPML).Results: Chronic homocysteinemia was associated with increased oxLDL (p < 0.01), higher ET-1 (p < 0.05) and impaired endothelial function (p < 0.01). However, oxLDL (but not ET-1) was increased 4hPML in the placebo group, an effect prevented by antioxidant vitamins. The development of severe endothelial dysfunction 4hPML was not however prevented by antioxidants. In linear regression analysis, fasting tHcy was an independent predictor of baseline oxLDL (p = 0.0001), but not of ET-1 levels. On the contrary, oxLDL was the main predictor of ET-1 (p = 0.008), suggesting that tHcy may increase ET-1 by enhancing the production of oxLDL.Conclusions: Both chronic and acute methionine-induced homocysteinemia are associated with elevated oxidative stress status. Although ET-1 is increased in chronic homocysteinemia, it does not participate in the rapid development of endothelial dysfunction after methionine loading. These findings suggest that despite its potential role in chronic homocysteinemia, ET-1 has a limited contribution to the development of endothelial dysfunction in acute, methionine-induced homocysteinemia in humans.