Dataset Information

Circulating serum amyloid A levels but not SAA1 variants predict long-term outcomes of angiographically confirmed coronary artery disease.

ABSTRACT:

Objectives

Circulating serum amyloid A (SAA) levels are strongly associated with atherosclerotic cardiovascular disease risk and severity. The association between SAA1 genetic variants, SAA levels, inflammatory marker levels, and coronary artery disease (CAD) prognosis has not been fully understood.

Materials and methods

In total, 2199 Taiwan Biobank (TWB) participants were enrolled for a genome-wide association study (GWAS), and the long-term outcomes in 481 patients with CAD were analyzed. The primary endpoint was all-cause mortality, and the secondary endpoint was the combination of all-cause death, myocardial infarction, stroke, and hospitalization for heart failure.

Results

Through GWAS, SAA1 rs11024600 and rs7112278 were independently associated with SAA levels (P = 3.84 × 10^-145 and P = 1.05 × 10^-29, respectively). SAA levels were positively associated with leukocyte counts and multiple inflammatory marker levels in CAD patients and with body mass index, hemoglobin, high-density lipoprotein cholesterol, and alanine aminotransferase levels in TWB participants. By stepwise linear regression analysis, SAA1 gene variants contributed to 27.53% and 8.07% of the variation of the SAA levels in TWB and CAD populations, respectively, revealing a stronger influence of these two variants in TWB participants compared to CAD patients. Kaplan-Meier survival analysis revealed that SAA levels, but not SAA1 gene variants, were associated with long-term outcomes in patients with CAD. Cox regression analysis also indicated that high circulating SAA levels were an independent predictor of both the primary and secondary endpoints.

Conclusion

SAA1 genotypes contributed significantly to SAA levels in the general population and in patients with CAD. Circulating SAA levels but not SAA1 genetic variants could predict long-term outcomes in patients with angiographically confirmed CAD.

SUBMITTER: Yeh KH

PROVIDER: S-EPMC9791857 | biostudies-literature | 2022 Oct-Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Circulating serum amyloid A levels but not SAA1 variants predict long-term outcomes of angiographically confirmed coronary artery disease.

Yeh Kuan-Hung KH Hsu Lung-An LA Juang Jyh-Ming Jimmy JJ Chiang Fu-Tien FT Teng Ming-Sheng MS Tzeng I-Shiang IS Wu Semon S Lin Jeng-Feng JF Ko Yu-Lin YL

Tzu chi medical journal 20220131 4

<h4>Objectives</h4>Circulating serum amyloid A (SAA) levels are strongly associated with atherosclerotic cardiovascular disease risk and severity. The association between <i>SAA1</i> genetic variants, SAA levels, inflammatory marker levels, and coronary artery disease (CAD) prognosis has not been fully understood.<h4>Materials and methods</h4>In total, 2199 Taiwan Biobank (TWB) participants were enrolled for a genome-wide association study (GWAS), and the long-term outcomes in 481 patients with ...[more]

PMID: 36578646

Similar Datasets

Project description:BackgroundMore than a million diagnostic cardiac catheterizations are performed annually in the US for evaluation of coronary artery anatomy and the presence of atherosclerosis. Nearly half of these patients have no significant coronary lesions or do not require mechanical or surgical revascularization. Consequently, the ability to rule out clinically significant coronary artery disease (CAD) using low cost, low risk tests of serum biomarkers in even a small percentage of patients with normal coronary arteries could be highly beneficial.MethodsSerum from 359 symptomatic subjects referred for catheterization was interrogated for proteins involved in atherogenesis, atherosclerosis, and plaque vulnerability. Coronary angiography classified 150 patients without flow-limiting CAD who did not require percutaneous intervention (PCI) while 209 required coronary revascularization (stents, angioplasty, or coronary artery bypass graft surgery). Continuous variables were compared across the two patient groups for each analyte including calculation of false discovery rate (FDR ≤ 1%) and Q value (P value for statistical significance adjusted to ≤ 0.01).ResultsSignificant differences were detected in circulating proteins from patients requiring revascularization including increased apolipoprotein B100 (APO-B100), C-reactive protein (CRP), fibrinogen, vascular cell adhesion molecule 1 (VCAM-1), myeloperoxidase (MPO), resistin, osteopontin, interleukin (IL)-1β, IL-6, IL-10 and N-terminal fragment protein precursor brain natriuretic peptide (NT-pBNP) and decreased apolipoprotein A1 (APO-A1). Biomarker classification signatures comprising up to 5 analytes were identified using a tunable scoring function trained against 239 samples and validated with 120 additional samples. A total of 14 overlapping signatures classified patients without significant coronary disease (38% to 59% specificity) while maintaining 95% sensitivity for patients requiring revascularization. Osteopontin (14 times) and resistin (10 times) were most frequently represented among these diagnostic signatures. The most efficacious protein signature in validation studies comprised osteopontin (OPN), resistin, matrix metalloproteinase 7 (MMP7) and interferon γ (IFNγ) as a four-marker panel while the addition of either CRP or adiponectin (ACRP-30) yielded comparable results in five protein signatures.ConclusionsProteins in the serum of CAD patients predominantly reflected (1) a positive acute phase, inflammatory response and (2) alterations in lipid metabolism, transport, peroxidation and accumulation. There were surprisingly few indicators of growth factor activation or extracellular matrix remodeling in the serum of CAD patients except for elevated OPN. These data suggest that many symptomatic patients without significant CAD could be identified by a targeted multiplex serum protein test without cardiac catheterization thereby eliminating exposure to ionizing radiation and decreasing the economic burden of angiographic testing for these patients.

Dataset Information

Circulating serum amyloid A levels but not SAA1 variants predict long-term outcomes of angiographically confirmed coronary artery disease.

Objectives

Materials and methods

Results

Conclusion

Publications

Circulating serum amyloid A levels but not SAA1 variants predict long-term outcomes of angiographically confirmed coronary artery disease.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets