Is reversal of endothelial dysfunction still an attractive target in modern cardiology?

Table 1 Large studies evaluating the prognostic value of flow-mediated dilation

Ref.	Number of patients	Cohort	Asymptomatic Patients?	Length of follow-up (mo)	Outcome	Result	Independent value of FMD?
Rossi et al[45]	2264	Post-menopausal women	Yes	45 ± 13	CV death, MI, revascularisation, TIA, stroke	FMD was a predictor of MACE independently of traditional cardiac risk factors.	Yes
Patti et al[56]	136	Patients with single-vessel coronary artery disease undergoing PCI	No	6	In-stent restenosis	Patients with impaired FMD were more likely to suffer in-stent restenosis.	Yes
Gokce et al[59]	187	Patients undergoing vascular surgery	No	1	CV death, MI, unstable angina, ventricular fibrillation, stroke, raised troponin	FMD was an independent predictor of MACE in the immediate post-operative period.	Yes
Brevetti et al[58]	139	Patients with peripheral arterial disease	No	23 ± 10	CV death, MI, revascularisation, TIA, critical limb ischaemia	FMD was an independent predictor of events over the follow-up period.	Yes
Chan et al[53]	152	Patients with coronary artery disease	No	34 ± 10	CV death, MI, revascularisation, claudication	FMD was a strong independent predictor of risk even accounting for carotid plaque burden.	Yes
Shimbo et al[47]	842	Asymptomatic multi-ethnic cohort	Yes	36	Vascular death, MI, stroke	FMD was able to predict adverse events but not independently.	No
Suzuki et al[43]	819	Asymptomatic multi-ethnic cohort including patients with metabolic syndrome	Yes	81 ± 21	Vascular death, MI, stroke	Patients with the combination of metabolic syndrome and endothelial dysfunction had a significantly worse outcome.	No
Yeboah et al[44]	2792	Mixed cohort of patients > 65 yr	No	60	CVD death, MI, stroke, congestive heart failure, claudication, revascularisation	FMD was an independent predictor of risk but added little to traditional risk stratification.	Yes
Muiesan et al[57]	172	Hypertensive patients	No	95 ± 37	CV death, MI, revascularisation, arrhythmia, TIA, critical limb ischaemia, retinal artery occlusion	FMD below median was independently associated with adverse outcome.	Yes
Shechter et al[46]	618	Healthy subjects (mixed)	Yes	55.2 ± 21.6	CV death, MI, stroke, congestive revascularisation	FMD predicted adverse outcome independently.	Yes
Katz et al[77]	259	Heart failure patients (LVEF < 40% and NYHA class 2-3)	No	28	Death or cardiac transplantation	FMD is associated with increased adverse outcome in ischaemic and non-ischaemic heart failure.	Yes

PCI: Percutaneous coronary intervention; MACE: Adverse major cardiovascular events; MI: Myocardial infarction; TIA: Transient ischaemic attack; FMD: Flow-mediated dilation.