Arterial stiffness and endothelial dysfunction in diabetes mellitus

Table 1 Association between pulse wave velocity and prognosis in populations with a high prevalence of diabetes

Ref.	Population	Diabetes proportion	Outcomes assessed	Follow-up duration	Summary
Aortic PWV
Cruickshank et al[29]	Diabetes and glucose intolerance	DM and control	All-cause and cardiovascular mortality	10.7 years	PWV independently predicted all-cause and cardiovascular mortality (HR = 1.08, 95%CI: 1.03-1.14 per 1 m/second increase)
Cardoso et al[30]	High-risk type 2 diabetes	100% T2DM	Major adverse cardiovascular events and all-cause mortality	5.75 years (median)	PWV was a predictor of total cardiovascular events, with a 13% excess risk per 1 m/second increase in a PWV (32% excess risk for a 1-SD increment) and a nearly twofold higher risk among patients with aortic stiffness ≥ 10 m/second)
Levisianou et al[31]	T2DM after STEMI	100% T2DM	Recurrent cardiovascular events	Approximately 3 years	A cf-PWV cutoff of 12 m/second was associated with higher risk of recurrent cardiovascular events
baPWV
Katakami et al[33]	T2DM without cardiovascular events	100% T2DM	Cardiovascular events	7.5 years (median)	baPWV (HR = 1.30, 95%CI: 1.07-1.57) was an independent predictor for cardiovascular events
Kim et al[34]	T2DM and without documented cardiovascular disease and stroke	100% T2DM	Composite cardiovascular events	3.84 years (median)	Higher baPWV (≥ 1672 cm/second) was associated with composite events
Lin et al[35]	T2DM	100% T2DM	All-cause and expanded CVD mortality	8.4 years (mean)	Highest baPWV quartile (2070 cm/second) was independently associated with all-cause (HR = 1.63, 95%CI: 1.16-2.27) and expanded CVD mortality (HR = 1.75, 95%CI: 1.09-2.83)
Wu et al[36]	DM without a history of HF or valvular or congenital heart disease	100% DM	Onset of heart failure	4.19 years (median)	The risk of heart failure was 2.25-fold higher in the elevated-baPWV group (> 18 m/second) than in the normal-baPWV group (95%CI: 1.24-4.11)

PWV: Pulse wave velocity; DM: Diabetes mellitus; HR: Hazard ratio; CI: Confidence interval; T2DM: Type 2 diabetes mellitus; STEMI: ST-elevation myocardial infarction; cf-PWV: Carotid-femoral pulse wave velocity; baPWV: Brachial-ankle pulse wave velocity; CVD: Cardiovascular disease.

Table 2 Association between cardio-ankle vascular index and prognosis in populations with a high prevalence of diabetes

Ref.	Population	Diabetes proportion	Outcome assessed	Follow-up duration	Summary
Bäck et al[22]	Outpatient clinics for prevention, check-up, and/or monitoring of CV risk factors	23%-24% DM	CV morbidity and mortality	3.82 years (median)	The optimal CAVI thresholds for predicting outcomes differed among age groups, with thresholds of 9.25 for CV morbidity and mortality and 9.95 for all-cause mortality in subjects aged ≥ 60 years
Suwannasom et al[47]	Patients with diabetes, aged 40-69 years	100% DM	All-cause death and CV events	59.9 months (median)	CAVI, whether analyzed as a continuous variable or by risk group, did not predict the primary outcomes
Miyoshi et al[19]	Patients with CV risk	≥ 72% DM	CV death and CV events	4.9 years (median)	A CAVI > 9.5 was significantly associated with higher risks of cardiovascular death and nonfatal stroke (crude HR = 3.83, 95%CI: 1.28-11.40; crude HR = 2.07, 95%CI: 1.07-3.91)
Kario et al[20]	Patients with CV risk	32.4% DM	CV death and CV events	5.0 years (median)	The group with CAVI > 10.0 had the highest risk of a cardiovascular event (HR = 1.74, 95%CI: 1.08-2.81)

CV: Cardiovascular; DM: Diabetes mellitus; CAVI: Cardio-ankle vascular index; HR: Hazard ratio; CI: Confidence interval.

Table 3 Comparison of pulse wave velocity, cardio-ankle vascular index, flow-mediated dilation, and reactive hyperemia-peripheral arterial tonometry

	Physiological target	Vascular territory assessed	Most informative stage of diabetic vascular dysfunction	Prognostic evidence in diabetes	Advantages	Limitations
PWV	Arterial stiffness (mainly structural arterial changes)	Large elastic and muscular arteries (cfPWV: Aorta; baPWV: Central and peripheral arteries)	Intermediate to advanced stage (arterial stiffening and vascular remodeling)	Strong; multiple prospective studies demonstrate associations with CVD events, CVD mortality, and all-cause mortality	Well validated; extensive prognostic evidence; cfPWV regarded as gold standard for arterial stiffness assessment	Influenced by blood pressure at measurement; reflects relatively late vascular changes
CAVI	Arterial stiffness corrected for blood pressure effects; ventricular-arterial coupling	Arterial tree from the aortic root to the ankle	Intermediate stage; potentially sensitive to both functional and structural vascular alterations	Moderate to strong; several prospective cohort studies report associations with CVD events and mortality	Less influenced by blood pressure; highly reproducible; may reflect therapeutic responses and overall cardiovascular phenotype	Evidence base smaller than for PWV; most data derived from Japanese and Asian populations
FMD	Endothelium-dependent vasodilation (nitric oxide bioavailability)	Conduit arteries (typically brachial artery)	Early stage (endothelial dysfunction preceding structural vascular damage)	Limited in diabetes-specific cohorts; evidence mainly from high-risk or mixed populations	Detects early vascular abnormalities; extensively studied endothelial function test	Operator-dependent; requires technical expertise and standardization; limited clinical applicability
RH-PAT	Microvascular endothelial responsiveness	Digital microcirculation (fingertip)	Very early stage (microvascular endothelial dysfunction)	Limited; few studies specifically targeting diabetic populations	Automated measurement; good reproducibility; low operator dependence; suitable for screening	Limited prospective evidence in diabetes; biological mechanisms less well established than in FMD

PWV: Pulse wave velocity; cf-PWV: Carotid-femoral pulse wave velocity; baPWV: Brachial-ankle pulse wave velocity; CVD: Cardiovascular disease; CAVI: Cardio-ankle vascular index; FMD: Flow-mediated dilation; RH-PAT: Reactive hyperemia-peripheral arterial tonometry.