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

Kuan-Hung Yeh; Lung-An Hsu; Jyh-Ming Jimmy Juang; Fu-Tien Chiang; Ming-Sheng Teng; I-Shiang Tzeng; Semon Wu; Jeng-Feng Lin; Yu-Lin Ko

doi:10.4103/tcmj.tcmj_219_21

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

Tzu Chi Med J. 2022 Jan 31;34(4):423-433. doi: 10.4103/tcmj.tcmj_219_21. eCollection 2022 Oct-Dec.

Authors

Kuan-Hung Yeh^{1

2}, Lung-An Hsu³, Jyh-Ming Jimmy Juang⁴, Fu-Tien Chiang⁵, Ming-Sheng Teng⁶, I-Shiang Tzeng⁶, Semon Wu⁷, Jeng-Feng Lin^{1

8}, Yu-Lin Ko^{1

2

7}

Affiliations

¹ Cardiovascular Center and Division of Cardiology, Department of Internal Medicine, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei, Taiwan.
² School of Medicine, Tzu Chi University, Hualien, Taiwan.
³ The First Cardiovascular Division, Department of Internal Medicine, Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Taoyuan, Taiwan.
⁴ Cardiovascular Center and Division of Cardiology, Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.
⁵ Division of Cardiology, Department of Internal Medicine, National Taiwan University Hospital and Fu-Jen Catholic University Hospital, Fu-Jen Catholic University, Taipei, Taiwan.
⁶ Department of Research, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei, Taiwan.
⁷ Department of Life Science, Chinese Culture University, Taipei, Taiwan.
⁸ School of Post-Baccalaureate Chinese Medicine, Tzu Chi University, Hualien, Taiwan.

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.

Keywords: Coronary artery disease; Genome-wide association study; Long-term outcomes; SAA1 gene; Serum amyloid A.