Relation of Iron Status to Prognosis After Acute Coronary Syndrome

Abstract

Iron deficiency has been extensively researched and is associated with adverse outcomes in heart failure. However, to our knowledge, the temporal evolution of iron status has not been previously investigated in patients with acute coronary syndrome (ACS). Therefore, we aimed to explore the temporal pattern of repeatedly measured iron, ferritin, transferrin, and transferrin saturation (TSAT) in relation to prognosis post-ACS. BIOMArCS (BIOMarker study to identify the Acute risk of a Coronary Syndrome) is a prospective, multicenter, observational cohort study conducted in The Netherlands between 2008 and 2015. A total of 844 patients with post-ACS were enrolled and underwent high-frequency (median 17) blood sampling during 1 year follow-up. Biomarkers of iron status were measured batchwise in a central laboratory. We analyzed 3 patient subsets, including the casecohort (n = 187). The primary endpoint (PE) was a composite of cardiovascular mortality and repeat nonfatal ACS, including unstable angina pectoris requiring revascularization. The association between iron status and the PE was analyzed using multivariable joint models. Mean age was 63 years; 78% were men, and >50% had iron deficiency at first sample in the case-cohort. After adjustment for a broad range of clinical variables, 1 SD decrease in log-iron was associated with a 2.2-fold greater risk of the PE (hazard ratio 2.19, 95% confidence interval 1.34 to 3.54, p = 0.002). Similarly, 1 SD decrease in log-TSAT was associated with a 78% increased risk of the PE (hazard ratio 1.78, 95% confidence interval 1.17 to 2.65, p = 0.006). Ferritin and transferrin were not associated with the PE. Repeated measurements of iron and TSAT predict risk of adverse outcomes in patients with post-ACS during 1 year follow-up.

Emerging Biomarkers for Predicting Clinical Outcomes in Patients with Heart Disease

“…Iron deficiency is a frequent comorbidity in patients with chronic HF, leading to a decreased quality of life and worse overall clinical prognosis [ 8 ]. A cohort study investigated the prognostic relevance of biomarkers of iron status after an ACS by performing high-frequency blood sampling (a median of 17 determinations) in 844 patients over a one-year follow-up period [ 9 ]. The study revealed a higher incidence of the composite outcome of CV mortality and recurrent nonfatal ACS with decreasing log-iron, as well as with decreasing log-TSAT (transferrin saturation).…”

“…The study revealed a higher incidence of the composite outcome of CV mortality and recurrent nonfatal ACS with decreasing log-iron, as well as with decreasing log-TSAT (transferrin saturation). However, no associations with the composite outcome were recorded for ferritin and transferrin [ 9 ].…”

“…3.9–4.1 g/dL; b. 3.7–3.9 g/dL; c. 3.4–3.7 g/dL; d. <3.4 g/dL a. HR 1.45 [1.24–1.70] [ 7 ] b. HR 1.71 [1.47–1.98] c. HR 2.45 [2.14–2.81] d. HR 4.33 [3.79–4.94] Iron metabolism Post-ACS CV mortality and recurrent nonfatal ACS 1 year 844 log-iron, per 1 SD decrease HR 2.19 [1.34–3.54] [ 9 ] log-TSAT, per 1 SD decrease HR 1.78 [1.17–2.65] Worsening HF and iron deficiency All-cause mortality or HHF 1.8 years 1453 low iron storage (transferrin saturation < 20%; serum ferritin ≤ 128 ng/mL) HR 1.47 [1.26–1.71] [ 10 ] Abbreviations: ACS, acute coronary syndrome; BMI, body mass index; CI, confidence interval; CV, cardiovascular; HF, heart failure; HHF, heart failure hospitalization; HR, hazard ratio; hs-CRP, high-sensitivity C-reactive protein; MACE, major adverse cardiovascular events; MI, myocardial infarction; n, number of participants; PCI, percutaneous coronary intervention; Ref, reference; SAA, serum amyloid A; SD, standard deviation; TSAT, transferrin saturation; UA, unstable angina. …”

The Mutual Relationship among Cardiovascular Diseases and COVID-19: Focus on Micronutrients Imbalance

“…Moreover, in the setting of atherosclerosis and coronary syndromes, iron may have a pivotal role. It is involved in oxidative stress, low-density lipoprotein (LDL) oxidation and inflammation [150]. Meng et al [151] reported that reduced circulating iron values were a predictor of coronary atherosclerosis.…”

Iron Status and Cause-Specific Mortality After Kidney Transplantation

“… 11 Higher iron parameters may protect against incident coronary heart disease, 12 whereas iron deficiency predicts poor outcomes after coronary artery events. 13 , 14 , 15 …”