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Soluble Vascular Cell Adhesion Molecules May be Protective of Future Cardiovascular Disease Risk: Findings from the PREVEND Prospective Cohort Study.

ABSTRACT: Soluble cell adhesion molecules, such as vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1, E-selectin, and P-selectin, have been suggested to be associated with cardiovascular disease (CVD) risk; however, the nature and magnitude of the association between VCAM-1 and CVD risk is uncertain. We aimed to assess the association of VCAM-1 with CVD risk and determine its potential utility for CVD risk prediction.VCAM-1 concentrations were measured at baseline in the PREVEND prospective study of 2,638 participants. Hazard ratios (95% confidence intervals [CI]) and measures of risk discrimination for CVD (e.g., C-index) and reclassification (i.e., net reclassification improvement) of participants were assessed.During a median follow-up of 9.9 years, 614 CVD events occurred. Plasma VCAM-1 was weakly associated with several cardiovascular risk markers. In analyses adjusted for established cardiovascular risk factors, the hazard ratio (95% CI) for CVD per 1 standard deviation increase in loge VCAM-1 was 0.91 (0.84-0.99; P =0.020), which remained consistent after additional adjustment for body mass index, alcohol consumption, triglycerides, renal function, and C-reactive protein; hazard ratio (95% CI) 0.89 (0.82-0.97; P =0.006). Comparing the top versus bottom quintiles of VCAM-1 levels, the corresponding adjusted hazard ratios were 0.74 (0.57-0.96; P =0.023) and 0.70 (0.54-0.91; P =0.007) respectively. Adding VCAM-1 to a CVD risk prediction model containing conventional risk factors did not improve the C-index or net reclassification.Plasma VCAM-1 is inversely and independently associated with CVD. However, VCAM-1 provides no significant improvement in CVD risk assessment beyond conventional CVD risk factors.

SUBMITTER: Kunutsor SK

PROVIDER: S-EPMC5556188 | biostudies-other | 2017 Aug

REPOSITORIES: biostudies-other

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Project description:ObjectiveWhile the role of type 2 diabetes (T2D) in inducing endothelial dysfunction is fairly well-established the etiological role of endothelial dysfunction in the onset of T2D is still a matter of debate. In the light of conflicting evidence in this regard, we conducted a prospective study to determine the association of circulating levels of soluble intercellular adhesion molecule 1 (sICAM-1) and soluble vessel cell adhesion molecule 1 (sVCAM-1) with incident T2D.MethodsData from this study came from 1,269 Mexican Americans of whom 821 initially T2D-free individuals were longitudinally followed up in the San Antonio Family Heart Study. These individuals were followed for 9752.95 person-years for development of T2D. Prospective association of sICAM-1 and sVCAM-1 with incident T2D was studied using Kaplan-Meier survival plots and mixed effects Cox proportional hazards modeling to account for relatedness among study participants. Incremental value of adhesion molecule biomarkers was studied using integrated discrimination improvement (IDI) and net reclassification improvement (NRI) indexes.ResultsDecreasing median values for serum concentrations of sICAM-1 and sVCAM-1 were observed in the following groups in this order: individuals with T2D at baseline, individuals who developed T2D during follow-up, individuals with prediabetes at baseline and normal glucose tolerant (NGT) individuals who remained T2D-free during follow-up. Top quartiles for sICAM-1 and sVCAM-1 were strongly and significantly associated with homeostatic model of assessment--insulin resistance (HOMA-IR). Mixed effects Cox proportional hazards modeling revealed that after correcting for important clinical confounders, high sICAM-1 and sVCAM-1 concentrations were associated with 2.52 and 1.99 times faster progression to T2D as compared to low concentrations, respectively. Individuals with high concentrations for both sICAM-1 and sVCAM-1 progressed to T2D 3.42 times faster than those with low values for both sICAM-1 and sVCAM-1. The results were similar in women in reproductive age group and the remainder of the cohort. Inclusion of sICAM-1 and sVCAM-1 in predictive models significantly improved reclassification and discrimination. The majority of these results were seen even when the analyses were restricted to NGT individuals.ConclusionSerum concentrations of sICAM-1 and sVCAM-1 independently and additively predict future T2D and represent important candidate biomarkers of T2D.

Project description:OBJECTIVE:The objective of this study was to determine the profiles of maternal plasma soluble adhesion molecules in patients with preeclampsia, small-for-gestational-age (SGA) fetuses, acute pyelonephritis, preterm labor with intact membranes (PTL), preterm prelabor rupture of the membranes (preterm PROM), and fetal death. MATERIALS AND METHODS:A cross-sectional study was conducted to determine maternal plasma concentrations of sE-selectin, sL-selectin, and sP-selectin as well as sICAM-1, sVCAM-1, and sPECAM-1 in patients with (1) an uncomplicated pregnancy (control, n?=?100); (2) preeclampsia (n?=?94); (3) SGA fetuses (in women without preeclampsia/hypertension, n?=?45); (4) acute pyelonephritis (n?=?25); (5) PTL (n?=?53); (6) preterm PROM (n?=?24); and (7) fetal death (n?=?34). Concentrations of soluble adhesion molecules and inflammatory cytokines (tumor necrosis factor (TNF)-? and interleukin (IL)-8) were determined with sensitive and specific enzyme-linked immunoassays. RESULTS:In comparison to women with a normal pregnancy, (1) women with preeclampsia had higher median concentrations of sE-selectin, sP-selectin, and sVCAM-1, and a lower concentration of sL-selectin (all p values?<?.001); (2) patients with SGA fetuses had higher median concentrations of sE-selectin, sP-selectin, and sVCAM-1 (all p values?<?.05); (3) patients with a fetal death had higher median concentrations of sE-selectin and sP-selectin (all p values?<?.05); (4) patients with acute pyelonephritis had higher median plasma concentrations of sE-selectin, sICAM-1, and sVCAM-1 (all p values?<?.001); (5) patients with preeclampsia and acute pyelonephritis, plasma concentrations of sVCAM-1, sE-selectin, and sP-selectin correlated with those of the proinflammatory cytokines TNF-? and interleukin (IL)-8 (all p values?<?.05); (6) patients with PTL had a higher median concentration of sP-selectin and a lower median concentration of VCAM-1 (all p values <?.05); and (7) women with preterm PROM had lower median concentrations of sL-selectin and sVCAM-1 (all p values?<?.05). CONCLUSIONS:The results of this study show that endothelial cell activation/dysfunction reflected by the plasma concentration of sE-selectin is not specific to preeclampsia but is present in pregnancies complicated by SGA fetuses, acute pyelonephritis, and fetal death. Collectively, we report that each obstetrical syndrome appears to have a stereotypical profile of soluble adhesion molecules in the peripheral circulation.

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Soluble Vascular Cell Adhesion Molecules May be Protective of Future Cardiovascular Disease Risk: Findings from the PREVEND Prospective Cohort Study.

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