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Objective: Aberrations in apolipoprotein (apo) metabolism and increased systemic inflammation associate with the metabolic syndrome (MetS) and may contribute to its atherogenicity. We examined whether the association between carotid atherosclerosis and MetS in a population of young adults is mediated by apoB and apoA-I and/or by inflammatory markers C-reactive protein and type II secretory phospholipase A2., Methods and Results: We used cross-sectional and 6-year prospective data from the cardiovascular risk in young Finns study. In young adults (aged 24 to 39 years), apoB, C-reactive protein, and type II secretory phospholipase A2 enzyme activity were significantly higher and apoA-I lower in subjects with MetS (N=325) than in subjects without MetS (N=1858). In prospective analysis (N=1587), both MetS and high apoB predicted (P<0.0001) incident high carotid intima-media thickness, defined as carotid intima-media thickness >90th percentile and/or plaque. The association between MetS and incident high carotid intima-media thickness was attenuated by approximately 40% after adjustment with apoB. Adjustments with apoA-I, C-reactive protein, or type II secretory phospholipase A2 did not diminish the association., Conclusions: High levels of apoB, C-reactive protein, and type II secretory phospholipase A2 and low levels of apoA-I associate with MetS in young adults. The atherogenicity of MetS in this population assessed by incident high carotid intima-media thickness appears to be substantially mediated by elevated apoB but not inflammatory markers.

Objective: To assess the association between secretory phospholipase A2 (sPLA2) activity, which encompasses several types of sPLA2, and cardiovascular disease (CAD) in healthy individuals., Methods and Results: We investigated this association in a nested case-control study among the 25,663 participants in EPIC-Norfolk cohort. Cases (n=991) were subjects in whom CAD developed during the 6 years of mean follow-up. Controls (n=1806) matched by age, sex, and enrollment time remained free of any CAD during follow-up. The risk of incident CAD was associated with increasing quartiles of sPLA2 activity (P<0.001). After adjustment for risk factors, C-reactive protein and sPLA2 type IIA concentration, the odds ratios of incident CAD in the second, third, and fourth quartiles of sPLA2 activity were 1.41, 1.33, and 1.56 (P=0.003), compared with the lowest quartile. sPLA2 activity and CRP were poorly correlated (r=0.15), and their combined values were more informative for incident risk of CAD than either biomarker alone. Subjects in the highest quartiles of sPLA2 activity and CRP had an adjusted odds ratio of 2.89 (95% confidence interval, 1.78 to 4.68; P<0.001) for CAD compared with those with the lowest quartiles of both markers., Conclusions: Measurement of serum sPLA2 activity provides additive prognostic value to traditional risk factors and CRP levels, and identifies a subgroup of individuals at high risk for incident CAD. Measurement of sPLA2 type II concentration had little added prognostic utility.

Objective: Platelet adhesion to the subendothelial tissue via the collagen receptor alpha2beta1 is a crucial event in vascular biology. Although evidence has been provided that the number of platelets alpha2beta1 copies is genetically determined, the molecular change primary responsible has not been yet elucidated. The aim of our present study was to investigate the effect of combined polymorphisms within both regulatory (-52C/T and -92C/G) and coding regions (807C/T and 1648A/G) of the alpha2 subunit gene on human platelets alpha2beta1 receptor density and/or susceptibility to coronary artery disease (CAD)., Methods and Results: Among 254 cardiac surgery patients, no evidence was found for an association between the alpha2 subunit gene polymorphisms and CAD. In contrast, in a subgroup of 113 patients, we observed a significant association between all polymorphisms except -52C/T and alpha2beta1 receptor level. Furthermore, when 3 groups of patients were defined according to the tertiles of platelets alpha2beta1 copies, the -92C/807T haplotype was more frequent in the group of patients with high alpha2beta1 receptor level., Conclusions: These results suggest that an individual effect of each polymorphism located either in the coding or promoter sequence of the alpha2 gene may act in combination to modulate variations in platelets alpha2beta1 receptor density.

Angiotensin II (Ang II) has been reported to modulate cGMP formation in various types of cells. To acquire direct information on the intracellular transduction involved in this mechanism, we tested the effects of Ang II on vascular tone and on cGMP content of in vitro isolated carotid arteries from 12-week-old Wistar-Kyoto rats. Segments of carotid artery 20 mm long (n = 8 for each group) maintained at a transmural pressure of 100 mm Hg were immersed in a bath (38 degrees C) containing oxygenated Tyrode's solution. At the end of each experiment, the vessel diameter was measured, and the wall cGMP content was determined by enzyme immunoassay. Under basal conditions, mean diameter was 968 +/- 19 microns, and mean cGMP carotid artery content was 38.9 +/- 3.5 fmol/mg tissue. Incubation for 20 minutes with Ang II (10(-5) mol/L) significantly increased cGMP wall content, twofold above the basal content (P < .01), and constricted the vessel (60 +/- 2.2% of the control diameter, P < .001). After preincubation with a nonselective antagonist of Ang II receptors, saralasin ([Sar1,Val5,Ala8]Ang II, 5 x 10(-5) mol/L), or with a specific antagonist of Ang II AT1 receptor subtype, losartan (5 x 10(-5) mol/L), carotid diameter and cGMP content were no longer affected by Ang II. Exposure of carotid arteries to a specific antagonist of Ang II AT2 receptor, PD 123319 (10(-7) mol/L), modified neither Ang II-induced diameter decrease nor cGMP content increase. Constriction of the vessel with KCl (26 +/- 3%, P < .001) did not modify the basal cGMP wall content.(ABSTRACT TRUNCATED AT 250 WORDS)