Work

Negative impact of low IGF-1 levels and hypovitaminosis D on coronary artery disease severity and prognosis in patients with AMI

Year: 2025

Type: article

Abstract: Background Low IGF-1 levels, low-grade inflammation and Vitamin D (VitD) are implicated in the pathogenesis of coronary heart disease (CHD). While hypovitaminosis D (HypoD) and low-grade inflammation are associated with presence of CHD and its severity, there are limited data on IGF-1 in this setting. Purpose To investigate the association between IGF-1 and the severity of CHD, as well as the combined effects of IGF-1 and VitD on outcome of patients with acute myocardial infarction (AMI). Also, to analyze the impact of HypoD on systemic markers of inflammation (CRP and IL-1β). Methods Blood samples were collected at fasting state from 685 AMI patients. Definitions: 1) HypoD: VitD levels ≤20 ng/ml; 2) severe CHD: left main disease and/or three-vessel disease. The combined endpoint comprised all-cause mortality, re-infarction, and heart failure development. Results The mean age of cohort was 66(11) years and 73.1% were male. Overall, 28% patients had severe CHD and 72% had STEMI presentation. The median concentration of IGF-1 and VitD were 539 [290 – 824]pg/ml and 18.7 [11.8 – 25.9]ng/ml, respectively. HypoD was present in 56.1% of patients, who had higher levels of inflammatory makers (CRP 6 [2.1– 15.8] vs 3.4 [1.3 – 9.3] mg/l, and IL-1β 0.46 [0.19-0.71] vs 0.35[0.14 – 0.61] pg/ml, both p<0.01) and lower IGF-1 levels (500.8 [261.2 – 793.5] vs 577 [342.5 – 867] pg/ml, p<0.01, respectively) compared to those with VitD >20 ng/ml. Low IGF-1 values were predictive of severe CHD (OR 1.80,p<0.01), along with older age, male gender and GFR <60 mL/min/1.73m2, after correction for VitD, CRP, IL-1β, diabetes mellitus, smoking and LDL levels. During the median follow-up time of 45-months, 249 (36%) patients reached the composite endpoint. There was a linear association between the risk of reaching the endpoint and IGF-1 levels below the cut-off level 539 pg/ml (identified by continuous hazard ratio analysis, Fig. 1a). Subsequently, in order to analyze the impact of IGF-1 and VitD on outcome of patients, we divided the cohort into 4 groups according to IGF-1 levels under/over the cut-off value 539 pg/ml and the presence/absence of HypoD, Fig.1b. At Kaplan-Meier analysis, among 4 groups of patients, the group with IGF-1 levels below the cut-off level 539 pg/ml and HypoD had the worse prognosis (p<0.01; Fig. 1c). The multivariable Cox regression confirmed that the co-existence of low IGF-1 levels and HypoD was associated with an increased risk of adverse outcome when compared to patients with only HypoD (HR 1.52 [1.04-2.2], p=0.03), along with older age, CRP, lower LVEF and worse renal function. Conclusions In AMI patients, low levels of IGF-1 are associated with CHD severity and higher risk of events during the long-term follow-up. In addition, the co-presence of low IGF-1 levels and HypoD is associated with an even worse prognosis.

Source: European Heart Journal Acute Cardiovascular Care

DOI: 10.1093/ehjacc/zuaf044.078