Serum amyloid A-low-density-lipoprotein complex and cause-specific mortality in patients with suspected or known coronary artery disease: The ANOX Study
Authors: Suzuki M , Kotani K , Matsuda M , Ajiro Y , Shinozak T , Sakagami S , Yonezawa K , Shimizu M , Funada J , Unoki T , Takagi D , Abe M , Akao M , Hasegawa K , Wada H 
Published: October 2024

Abstract

Background
Serum amyloid A-low-density-lipoprotein (SAA-LDL) is a complex formed from the oxidative interaction between SAA and LDLs. A relatively small-scale study has shown that circulating SAA-LDL levels may serve as a prognostic marker in patients with stable coronary artery disease (CAD). However, the association between SAA-LDL and cause-specific mortality in patients with suspected or known CAD is unknown.

Methods
Serum SAA-LDL levels were measured in 2416 patients with suspected or known CAD undergoing elective coronary angiography. The outcomes were all-cause death, cardiovascular (CV) death, non-CV death, cancer death, and other non-CV death. Patients were followed up over a 3-year period.

Results
During the follow-up, 254 (10.5%) deaths occurred, including 88 (3.6%) CV deaths, 151 (6.3%) non-CV deaths, 66 (2.7%) cancer deaths, 85 (3.5%) other non-CV deaths, and 15 (0.6%) undetermined deaths. Stepwise regression analysis including baseline data on potential clinical confounders and established CV biomarkers (i.e., N-terminal pro-brain natriuretic peptide, high-sensitivity cardiac troponin I, and high-sensitivity C-reactive protein [hs-CRP]) revealed that the strongest independent determinant of SAA-LDL levels was hs-CRP (partial regression coefficient, 0.248; standard error, 0.010; p&lt;0.001). After adjusting for potential clinical confounders and established CV biomarkers, the highest quartile of SAA-LDL levels (vs. the lowest quartile) was significantly associated with all-cause death (adjusted hazard ratio [aHR], 1.56; 95% confidence interval [CI], 1.05–2.34) and non-CV death (aHR, 1.76; 95% CI, 1.02–3.11), but not with CV death (aHR, 1.16; 95% CI, 0.62–2.20), cancer death (aHR, 1.68; 95% CI, 0.71–4.34), or other non-CV death (aHR, 1.65; 95% CI, 0.82–3.45) in the entire cohort. In patients with low hs-CRP levels (≤1.0 mg/L, n=1253), the highest quartile of SAA-LDL levels was significantly associated with all-cause death (aHR, 2.19; 95% CI, 1.11–4.57), non-CV death (aHR, 2.78; 95% CI, 1.05–8.79), and cancer death (aHR, 4.65; 95% CI, 1.12–31.9), but not with CV death (aHR, 1.22; 95% CI, 0.39–3.92) or other non-CV death (aHR, 1.68; 95% CI, 0.42–8.35). In contrast, the highest quartile of SAA-LDL levels was not significantly associated with all-cause death (aHR, 1.18; 95% CI, 0.72–1.96), CV death (aHR, 1.02; 95% CI, 0.45–2.31), non-CV death (aHR, 1.46; 95% CI, 0.75–2.91), cancer death (aHR, 1.35; 95% CI, 0.43–4.58), or other non-CV death (aHR, 1.38; 95% CI, 0.60–3.25) in patients with high hs-CRP levels (&gt;1.0 mg/L, n=1163).

Conclusions
Elevated SAA-LDL levels were independently associated with all-cause and non-CV mortality, but unexpectedly not with CV mortality, in patients with suspected or known CAD. These associations were pronounced in patients with low hs-CRP levels (≤1.0 mg/L). The association between the SAA-LDL level and cancer mortality suggests its predictive utility in patients with low hs-CRP levels (≤1.0 mg/L).