Amyloid beta 1-40, inflammation, and the IGF-1 axis: unifying metabolic predictors of post-AMI prognosis

Background Accurate risk stratification after acute myocardial infarction (AMI) is crucial to reduce recurrent events. Metabolic dysregulation, inflammation, and insulin resistance accelerate amyloidogenic processes and may identify patients with a metabolically driven high-risk phenotype. However, the intricate relationship among the insulin/IGF-1/GH axis, C-reactive protein (CRP), and Aβ1−40 in cardiovascular (CV) disease remains unclear. Purpose To (1) explore associations among circulating Aβ1−40, IGF-1, CRP, and insulin with glycemic control, and (2) assess the combined long-term prognostic impact of Aβ1−40 and IGF-1. Methods We conducted a prospective cohort study involving 655 AMI patients and biomarkers were measured on fasting state at hospital admission. The cohort was stratified by HbA1c: Group 1 normal (HbA1c<39 mmol/mol, n=205), Group 2 pre-diabetic (HbA1c39−47 mmol/mol, n=300), and Group 3 diabetic (HbA1c≥48 mmol/mol, n=150). Results Mean plasma concentrations of Aβ1-40, insulin, IGF-1 and CRP were 85.75[53.66 - 128.67]pg/mL, 101[56.45 - 174.5] pmol/L, and 539.55[285.05 - 822.98]pg/mL, 4.4[1.6 - 13.3]mg/L, respectively. Poor glycemic control (Group 3) was associated with higher CRP, insulin, and Aβ1−40 levels (all p<0.05), a trend toward low IGF-1 levels (p=0.08, Figure 1), and the highest HOMA-IR and TyG indices (p<0.01). Aβ1−40 correlated positively with HbA1c, HOMA-IR, TyG, and age, whereas IGF-1 decreased with worsening glycemic control (p=0.04) and correlated inversely with age and CRP. In multivariable analysis, the combination of high Aβ1−40 and low IGF-1 independently predicted diabetic status (OR 2.9, p<0.01) after adjustment for age, gender, hypertension, LVEF, smoking, insulin, renal function, statin use, CRP, and TyG index. During a 42-month follow-up, 243 (37.1%) patients reached the combined endpoint of all-cause mortality, recurrent AMI, revascularization, angina, and/or development of heart failure. Crucially, Kaplan-Meier analysis and multivariable Cox regression confirmed that the combination of high Aβ1−40 and low IGF-1 conferred the poorest survival outcome (p=0.04, Figure 2A). This phenotype was an independent predictor of adverse prognosis alongside established risk factors (age, LVEF, and renal function), after correction for HOMA-IR and CRP levels (Figure 2B). Conclusions For the first time we demonstrated that concurrent assessment of Aβ1−40, IGF-1, CRP, and glycemic status provides an effective metabolic–CV risk model in AMI. Beyond the association of Aβ1−40 and IGF-1 with metabolic dysfunction, the combined high Aβ1−40/low IGF-1 profile independently predicted adverse long-term outcomes, highlighting a novel intersection between metabolic and CV pathology.Figure 1For image description, please refer to the figure legend and surrounding text. Figure 2A and BFor image description, please refer to the figure legend and surrounding text.