Table 1.

Studies on the association or effect of iron measures on atherosclerotic cardiovascular disease

Study	Year	Sample Size	Design	Iron measure	Association with clinical disease
Salonen et al.56	1992	1,931 (men)	Prospective cohort study Endpoint: myocardial infarction	Serum ferritin	Men with high serum ferritin levels had a 2.2-fold (95% CI, 1.2–4.0) higher risk of acute myocardial infarction
Kiechl et al.57	1997	826	Prospective cohort study Endpoint: progression of carotid atherosclerosis	Serum ferritin	Serum ferritin is a strong risk factor for carotid atherosclerosis progression (odds ratio, 1.50 per SD increase in ferritin; P=0.0002)
Salonen et al. 60	1998	2,862	Prospective cohort study Endpoint: risk of myocardial infarction	Iron depletion by blood donation	Frequent blood donation was associated with an 88% reduced risk of acute myocardial infarction (95% CI for hazard ratio, 0.02–0.86)
Duffy et al. 63	2001	54	Acute intervention clinical study with CAD patients and healthy controls. Endpoint: vasomotor function in forearm resistance vessels	Iron depletion by iron chelation	Iron chelation with one dose of deferoxamine improved endothelium-dependent vasodilation in patients with coronary artery disease (p<0.01 by 2-way repeated-measures ANOVA)
Meyers et al.61	2002	2,104	Retrospective cohort study Endpoint: cardiovascular events	Iron depletion by blood donation	Frequent blood donation was associated with reduced risk of cardiovascular events (odds ratio, 0.60; CI 0.43–0.83)
Zacharski et al.65	2007	,277	Multicenter, randomized, controlled, single-blinded clinical trial Endpoint: all-cause mortality	Iron depletion by phlebotomy	Phlebotomy in patients with symptomatic peripheral arterial disease did not decrease all-cause mortality (hazard ratio, 0.85; 95% CI, 0.67–1.08)
Menke et al.58	2009	2,662	Cross-sectional analysis Endpoint: association of ferritin and transferrin saturation with PAD	Serum ferritin and transferrin saturation	Borderline association in men of serum ferritin with peripheral arterial disease (PAD) (men: OR, 1.18; 95% CI, 1.00–1.41; women: OR, 1.04; 95% CI, 0.87–1.25) but not transferrin saturation (men: OR, 1.45; 95% CI, 0.83–2.51; women: OR, 1.55; 95% CI, 0.98–2.45)
Sung et al.59	2012	12,033	Cross-sectional analysis Endpoint: association of ferritin and coronary artery calcium score (marker of atherosclerosis)	Serum ferritin	Increased ferritin levels were associated with the presence of coronary artery calcium (OR, 1.66; 95% CI, 1.3–1.98)
Houschyar et al.62	2012	64	Randomized, controlled, single-blind clinical trial Endpoint: clinical markers of metabolic syndrome	Iron depletion by phlebotomy in metabolic syndrome patients	In patients with metabolic syndrome, phlebotomy reduced systolic blood pressure by 16.6 mmHg compared to the control group (95% CI, −20.7 to −12.5 mmHg)
Kim et al.67	2012	5695	Prospective cohort study Endpoint: all cause-, cancer-, and cardiovascular mortality	Transferrin saturation, serum ferritin	Increasing quintiles of transferrin saturation were associated with reduced all-cause, cancer, and CV mortality, but there was no association with serum ferritin
Bagheri et al.55	2013	337	Cross sectional analysis Endpoint: association of iron levels with severity of coronary artery disease (CAD)	Serum iron	Increased serum iron levels in patients with severe atherosclerosis (p=0.01) compared to those with mild and moderate amounts of coronary disease
Gill et al.64	2017	294,223	Mendelian randomization analysis Endpoint: Coronary artery disease risk	Serum iron, transferrin saturation, and ferritin	Protective effect of higher iron status on risk of coronary artery disease: OR 0.94 per SD increase in iron; 95% CI, 0.88–1.00; OR, 0.95 per SD increase in transferrin saturation; 95% CI, 0.910.99; OR, 0.85 per SD increase in log- transformed ferritin; 95% CI, 0.73–0.98