Dataset Information

The novel inflammatory marker GlycA and the prevalence and progression of valvular and thoracic aortic calcification: The Multi-Ethnic Study of Atherosclerosis.

ABSTRACT: BACKGROUND AND AIMS:GlycA is a novel composite biomarker of systemic inflammation reflecting posttranslational glycosylation of acute phase reactants. GlycA has been associated with coronary artery calcium, cardiovascular disease (CVD) events and mortality. Vascular calcifications outside of the coronary arteries are risk markers of CVD and mortality. Whether GlycA is linked to extra-coronary calcifications (ECC) is not well established. METHODS:We studied 6462 MESA participants free of clinical CVD who had plasma GlycA measured at baseline. ECCs [calcification in aortic valve (AVC), mitral annulus (MAC), ascending and descending thoracic aorta (ATAC, DTAC)] were ascertained at baseline and follow-up visit (median 2.3-yrs later) by cardiac CT. Poisson regression models with robust variance estimation assessed associations of GlycA with prevalent and incident ECC. Linear mixed models assessed the cross-sectional and 2-year change in ECC. Models were adjusted for demographic and lifestyle factors. RESULTS:In cross-sectional analysis, GlycA (per SD increment) was positively associated with prevalent AVC, ATAC and DTAC with adjusted prevalence ratios (95% CI) of 1.08 (1.01-1.14), 1.18 (1.03-1.34) and 1.10 (1.06-1.14), respectively. There was also a significant association between GlycA and baseline extent of both ATAC and DTAC. Longitudinally, GlycA was positively associated with incident MAC and DTAC, with adjusted incidence ratios of 1.18 (1.03-1.37) and 1.17 (1.07-1.28), respectively. GlycA was also associated with 2-year change in MAC and DTAC extent. CONCLUSIONS:In this diverse cohort free from clinical CVD, we found GlycA was positively associated with prevalent and incident ECC measures, in particular for progression of MAC and DTAC.

SUBMITTER: Ezeigwe A

PROVIDER: S-EPMC6401213 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

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The novel inflammatory marker GlycA and the prevalence and progression of valvular and thoracic aortic calcification: The Multi-Ethnic Study of Atherosclerosis.

Ezeigwe Angelica A Fashanu Oluwaseun E OE Zhao Di D Budoff Matthew J MJ Otvos James D JD Thomas Isac C IC Mora Samia S Tibuakuu Martin M Michos Erin D ED

Atherosclerosis 20190124

<h4>Background and aims</h4>GlycA is a novel composite biomarker of systemic inflammation reflecting posttranslational glycosylation of acute phase reactants. GlycA has been associated with coronary artery calcium, cardiovascular disease (CVD) events and mortality. Vascular calcifications outside of the coronary arteries are risk markers of CVD and mortality. Whether GlycA is linked to extra-coronary calcifications (ECC) is not well established.<h4>Methods</h4>We studied 6462 MESA participants f ...[more]

PMID: 30716566

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Project description:BackgroundLimited information is available regarding genetic contributions to valvular calcification, which is an important precursor of clinical valve disease.MethodsWe determined genomewide associations with the presence of aortic-valve calcification (among 6942 participants) and mitral annular calcification (among 3795 participants), as detected by computed tomographic (CT) scanning; the study population for this analysis included persons of white European ancestry from three cohorts participating in the Cohorts for Heart and Aging Research in Genomic Epidemiology consortium (discovery population). Findings were replicated in independent cohorts of persons with either CT-detected valvular calcification or clinical aortic stenosis.ResultsOne SNP in the lipoprotein(a) (LPA) locus (rs10455872) reached genomewide significance for the presence of aortic-valve calcification (odds ratio per allele, 2.05; P=9.0×10(-10)), a finding that was replicated in additional white European, African-American, and Hispanic-American cohorts (P<0.05 for all comparisons). Genetically determined Lp(a) levels, as predicted by LPA genotype, were also associated with aortic-valve calcification, supporting a causal role for Lp(a). In prospective analyses, LPA genotype was associated with incident aortic stenosis (hazard ratio per allele, 1.68; 95% confidence interval [CI], 1.32 to 2.15) and aortic-valve replacement (hazard ratio, 1.54; 95% CI, 1.05 to 2.27) in a large Swedish cohort; the association with incident aortic stenosis was also replicated in an independent Danish cohort. Two SNPs (rs17659543 and rs13415097) near the proinflammatory gene IL1F9 achieved genomewide significance for mitral annular calcification (P=1.5×10(-8) and P=1.8×10(-8), respectively), but the findings were not replicated consistently.ConclusionsGenetic variation in the LPA locus, mediated by Lp(a) levels, is associated with aortic-valve calcification across multiple ethnic groups and with incident clinical aortic stenosis. (Funded by the National Heart, Lung, and Blood Institute and others.).

Project description:Thoracic aortic calcification (TAC) and coronary artery calcification (CAC) are markers of subclinical atherosclerosis and are associated with incident major cardiovascular events. We investigated major determinants for incidence and progression of TAC and the association between TAC and CAC incidence and progression. In a population-based cohort study, 3270 participants (aged 45-74 years, 53.1% women) received cardiac computed tomography at baseline and after a mean follow-up of 5.1±0.3 years for quantification of calcification of the ascending (ATAC) and descending thoracic aorta (DTAC) and CAC. Multivariable relative risk regression analysis was used to investigate associations of cardiovascular risk factors with incident TAC, of baseline TAC with incident CAC, and of baseline CAC with incident TAC. Of 1243 participants with baseline TAC of 0, 517 (41.6%) revealed incident TAC after 5 years. Incidence of descending TAC was higher (34.5%) than ascending TAC (23.3%). Incident TAC after 5 years was associated with age (relative risk 1.26 [95% CI 1.21-1.33], per 5 years), blood pressure (relative risk 1.06 [95% CI 1.03-1.10], per 10 mm Hg), low-density lipoprotein cholesterol (relative risk 1.08 [95% CI 1.04-1.12], per 20 mg/dL), and smoking (relative risk 1.28 [95% CI 1.07-1.53]). Among the 1185 participants without CAC at baseline, the risk of developing CAC was 28.3% when baseline TAC was present compared with 22.2% among those without baseline TAC (excess risk 6.1% [95% CI 1.2-11.0%]). The point estimate of excess risk for incident CAC was higher for ascending TAC (10.8% [95% CI 4.8-16.7%]) and low for descending TAC (1.8% [95% CI -3.2% to 6.7%]). Excess risk for developing ascending and descending TAC with present baseline CAC was 16.4% (95% CI 12.7-20.0%) and 15.6% (95% CI 10.8-20.4%), respectively. TAC and CAC share similar major determinants for incident calcification. Participants with TAC, especially ascending TAC, are at elevated risk for development of CAC.

Dataset Information

The novel inflammatory marker GlycA and the prevalence and progression of valvular and thoracic aortic calcification: The Multi-Ethnic Study of Atherosclerosis.

Publications

The novel inflammatory marker GlycA and the prevalence and progression of valvular and thoracic aortic calcification: The Multi-Ethnic Study of Atherosclerosis.

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