Smoking induces lipoprotein-associated phospholipase A2 in cardiovascular disease free adults: The ATTICA Study

Objectives: We studied the association of lipoprotein-associated phospholipase A2 (Lp-PLA2) mass and activity with various lifestyle, clinical and biochemical characteristics in cardiovascular disease (CVD) free adults. Background: Lipoprotein-associated phospholipase A2 (Lp-PLA2) is a novel biomarker of inflammation and risk for CVD. The Lp-PLA2 mass and activity are primarily influenced by the plasma levels of low-density lipoprotein (LDL), however the influence of various lifestyle characteristics on Lp-PLA2 have not been adequately studied. Methods and results: In a random sub-sample of 186 subjects, 64 men (52 ± 13 years) and 122 women (48 ± 13 years) from the ATTICA Study (Greece), Lp-PLA2 activity and mass in total plasma as well as the enzyme activity and mass associated with high-density lipoprotein (HDL-Lp-PLA2) were determined using established methods. Several socio-demographic, lifestyle, clinical and biochemical parameters were assessed in all participants. Multiple linear regression analysis revealed that among the lifestyle characteristics, total plasma Lp-PLA2 activity and mass were positively and independently associated with current smoking (p = 0.02 and p = 0.05, respectively), as well as with exposure to second-hand smoke (p = 0.02 and p = 0.01, respectively). Furthermore, HDL-Lp-PLA2 activity and mass were inversely and independently associated with current smoking (p = 0.04 and p = 0.09, respectively). Conclusions: Smoking is associated with and might even induce an increase in proatherogenic total plasma Lp-PLA2, but attenuates antiatherogenic HDL-Lp-PLA2. These results further support the role of smoking as an important avoidable cause of CVD. © 2009 Elsevier Ireland Ltd. All rights reserved

Development of a Novel Apigenin Dosage form as a Substitute for the Modern Triple Antithrombotic Regimen

The simultaneous administration of three antiplatelet agents has been proposed as an efficient strategy for the secondary prevention of atherothrombotic events and is included in the European guidelines. However, this strategy presented an increased risk of bleeding; therefore, the identification of new antiplatelet agents, with improved efficacy and diminished side effects, is of great importance. In silico studies, UPLC/MS Q-TOF plasma stability, in vitro platelet aggregation experiments, and pharmacokinetic studies were exploited. In the present study, it has been predicted that the flavonoid apigenin could target different platelet activation pathways, including P2Y12, protease-activated receptor-1 (PAR-1), and cyclooxygenase 1 (COX-1). To enhance apigenin’s potency, hybridization with docosahexaenoic acid (DHA) was performed, as fatty acids have illustrated potent efficacy against cardiovascular diseases (CVDs). The new molecular hybrid, termed 4′-DHA-apigenin, demonstrated enhanced inhibitory activity against platelet aggregation induced by thrombin receptor activator peptide-6 (TRAP-6), adenosine diphosphate (ADP), and arachidonic acid (AA), with respect to the parent apigenin. The 4′-DHA-apigenin hybrid illustrated an almost 2-fold enhanced inhibitory activity, with respect to apigenin, and an almost 3-fold enhanced inhibitory activity, with respect to DHA, for the ADP-induced platelet aggregation. Additionally, the hybrid presented a more than 12-fold enhanced inhibitory activity with respect to DHA for the TRAP-6 induced platelet aggregation. Furthermore, a 2-fold enhanced inhibitory activity was recorded for the 4′-DHA-apigenin hybrid for the AA-induced platelet aggregation with respect to apigenin. To surmount the reduced LC-MS based plasma stability, a novel dosage form in olive oil has been developed. The 4′-DHA-apigenin olive oil-based formulation presented an enhanced antiplatelet inhibitory effect in three activation pathways. To further explore the pharmacokinetic profile of 4′-DHA-apigenin in olive oil formulations, a UPLC/MS Q-TOF protocol has been established to quantify the serum levels of apigenin after oral administration to C57BL/6J wild type mice. The olive oil-based formulation of 4′-DHA-apigenin demonstrated an increase in apigenin bioavailability of 262 %. This study may offer a new therapeutic strategy tailored to improve the treatment of CVDs. © 2023 by the authors

Amyloid-beta (1-40) and the risk of death from cardiovascular causes in patients with coronary heart disease

Background The amyloid beta peptide is the major protein constituent of neuritic plaques in Alzheimer disease and appears to play a central role in vascular inflammation pathophysiology. Objectives This study sought to determine the clinical value of amyloid-beta 1-40 (Abeta40) measurement in predicting cardiovascular (CV) mortality in patients with coronary heart disease (CHD) and arterial stiffness progression in young healthy subjects. Methods Abeta40 was retrospectively measured in blood samples collected from 3 independent prospective cohorts and 2 case-control cohorts (total N = 1,464). Major adverse cardiac events (MACE) were assessed in the 2 prospective cohorts (n = 877) followed for a median of 4.4 years. To look at effects on subclinical disease, arterial stiffness was evaluated at baseline and after 5-year follow-up (n = 107) in young healthy subjects. The primary endpoint was the predictive value of Abeta40 for CV mortality and outcomes in patients with CHD. Results In Cox proportional hazards models adjusted for age, sex, estimated glomerular filtration rate, left ventricular ejection fraction, high-sensitivity C-reactive protein, and high-sensitivity troponin T, Abeta40 independently predicted CV death and MACE in patients with CHD (p < 0.05 for all). After multivariate adjustment, Abeta40 levels conferred a substantial enhancement of net reclassification index and integrated discrimination improvement of individuals at risk in the total combined CHD cohort over the best predictive model. Further cohort-based analysis revealed that Abeta40 levels were significantly and independently associated with arterial stiffness progression, incident subclinical atherosclerosis, and incident CHD. Conclusions Measuring blood levels of Abeta40 identified patients at high risk for CV death. © 2015 American College of Cardiology Foundation

Persistence of an atherogenic lipid profile after treatment of acute infection with brucella

Serum lipid changes during infection may be associated with atherogenesis. No data are available on the effect of Brucellosis on lipids. Lipid parameters were determined in 28 patients with Brucellosis on admission and 4 months following treatment and were compared with 24 matched controls. Fasting levels of total cholesterol (TC), HDL-cholesterol (HDL-C), triglycerides, apolipoproteins (Apo) A, B, E CII, and CIII, and oxidized LDL (oxLDL) were measured. Activities of serum cholesterol ester transfer protein (CETP), paraoxonase 1 (PON1), and lipoprotein-associated phospholipase A2 (Lp-PLA2) and levels of cytokines [interleukins (IL)-1β, IL-6, and tumor necrosis factor (TNFa)] were also determined. On admission, patients compared with controls had 1) lower levels of TC, HDL-C, LDL-cholesterol (LDL-C), ApoB, ApoAI, and ApoCIII and higher LDL-C/HDL-C and ApoB/ApoAI ratios; 2) higher levels of IL-1b, IL-6, and TNFa; 3) similar ApoCII and oxLDL levels and Lp-PLA2 activity, lower PON1, and higher CETP activity; and 4) higher small dense LDL-C concentration. Four months later, increases in TC, HDL-C, LDL-C, ApoB, ApoAI, and ApoCIII levels, ApoB/ApoAI ratio, and PON1 activity were noticed compared with baseline, whereas CETP activity decreased. LDL-C/HDL-C ratio, ApoCII, and oxLDL levels, Lp-PLA2 activity, and small dense LDL-C concentration were not altered. Brucella infection is associated with an atherogenic lipid profile that is not fully restored 4 months following treatment

Country image and consumer-based brand equity: relationships and implications for international marketing

This paper examines the relationships between consumers' country-level and product-level images of a country, and the equity they associate with a brand from that country, using canonical correlation analysis. Results from mall-intercept surveys conducted in an Australian state capital city indicated that the consumer-based equity of a brand was significantly associated with both the macro and micro images of the country of origin of the brand. The relationship between these two sets of constructs was found to be positive as well as product category specific. Furthermore, each consumer-based brand equity dimension contributed differently to the relationship according to the product category, while the contribution of both country image dimensions (macro and micro) was also product category specific. Results also showed that cars, as a product category, are more sensitive to country image than televisions. These findings have direct and important implications for international marketers.Ravi Pappu, Pascale G Quester and Ray W Cookse