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New Studies Show Endothelial Dysfunction Is A Systemic Subclinical Disease

Bottom Line: Endothelial Dysfunction Is A Systemic Subclinical Disease and Should Be Treated Before It Becomes Clinical. (Scroll down to learn more about VENDYS®; the only FDA cleared endothelial function test based on vascular reactivity measurements at fingertips)

Scientific Updates Sponsored by Endothelix Inc. **************************************************** J Cardiol. 2016 67(5):455-62.

Advanced peripheral microvascular endothelial dysfunction and polyvascular disease in patients with high cardiovascular risk

Maeda H1, Sugiyama S2, Jinnouchi H3, Matsuzawa Y4, Fujisue K4, Hirata Y4, Kurokawa H4, Ohba K4, Matsubara J4, Nozaki T4, Konishi M4, Akiyama E4,Sugamura K4, Yamamoto E4, Sumida H4, Ogawa H4.

  • 1Department of Cardiovascular Medicine, Faculty of Life Sciences, Graduate School of Medical Science, Kumamoto University, Kumamoto, Japan; Maeda Clinic of Internal Medicine, Kumamoto, Japan.

  • 2Department of Cardiovascular Medicine, Faculty of Life Sciences, Graduate School of Medical Science, Kumamoto University, Kumamoto, Japan; Diabetes Care Center, Jinnouchi Hospital, Kumamoto, Japan. Electronic address:

  • 3Diabetes Care Center, Jinnouchi Hospital, Kumamoto, Japan.

  • 4Department of Cardiovascular Medicine, Faculty of Life Sciences, Graduate School of Medical Science, Kumamoto University, Kumamoto, Japan



Polyvascular disease (PolyVD) refers to the coexistence of coronary artery disease (CAD), peripheral arterial disease (PAD), and/or cerebrovascular disease (CVD), and carries a high risk of cardiovascular mortality. Endothelial dysfunction plays a crucial role in cardiovascular pathophysiology. This study investigated the association between PolyVD and the presence of microvascular endothelialdysfunction.


Consecutive stable patients (n=533) with diabetes mellitus and/or multiple cardiovascular risk factors were enrolled. Peripheral microvascular endothelial function in the finger microvasculature was assessed using the reactive hyperemia peripheral arterial tonometry index (RHI), and ankle-brachial index was measured for diagnosis of lower-extremity PAD prior to coronary angiography. Diagnosis of CVD was based on clinical symptoms, carotid ultrasound, and magnetic resonance imaging. PolyVD was defined as two or more coexisting vascular diseases from CAD, lower-extremity PAD, and CVD.


Natural logarithmic transformations of RHI (Ln-RHI) were significantly attenuated in 93 patients with PolyVD (0.44±0.20) compared with those in 440 patients without PolyVD (0.56±0.19; p 0.001) or in 299 patients with a single vascular disease (0.54±0.19; p 0.001). There was an independent correlation between Ln-RHI (per 0.1) and the presence of PolyVD in all high-risk patients [odds ratio (OR): 0.724; 95% confidence interval (CI): 0.610-0.859; p 0.001] and one or more vascular diseases (OR: 0.724; 95% CI: 0.605-0.867, p 0.001). Receiver-operating characteristics curve analysis showed that Ln-RHI correlated significantly with PolyVD (area under the curve, 0.682, 95% CI: 0.625-0.740, p 0.001). The optimum cut-off point of Ln-RHI for the existence of PolyVD was 0.479.


Microvascular endothelial dysfunction is significantly associated with the presence of PolyVD. Severe impairment of endothelialfunction in peripheral microvasculature may be an important pathophysiological component of PolyVD.

Skin Endothelial Function: A Window to Heart and Kidney

[Skin] Microvascular endothelial dysfunction is associated with albuminuria and CKD in older adults

Seliger SL, Salimi S, Pierre V, Giffuni J, Katzel L, Parsa A


BACKGROUND: Impairment in glomerular endothelial function likely plays a major role in the development of albuminuria and CKD progression. Glomerular endothelial dysfunction may reflect systemic microvascular dysfunction, accounting in part for the greater cardiovascular risk in patients with albuminuria. Prior studies of vascular function in CKD have focused on conduit artery function or those with ESRD, and have not examined microvascular endothelial function with albuminuria.

METHODS: We conducted a cross-sectional study among older hypertensive male veterans with stage 1-4 CKD, and hypertensive controls without CKD. Microvascular function was quantified by two distinct Laser-Doppler flowmetry (LDF) measures: peak responses to 1) post-occlusive reactive hyperemia (PORH) and 2) thermal hyperemia (TH), measured on forearm skin. Associations of each LDF measure with albuminuria, eGFR, and CKD status were estimated using correlation coefficients and multiple linear regression, accounting for potential confounders.

RESULTS: Among 66 participants (mean age 69.2 years), 36 had CKD (mean eGFR 46.1 cc/min/1.73 m(2); 30.6 % with overt albuminuria). LDF responses to PORH and TH were 43 and 39 % significantly lower in multivariate analyses among those with macroalbuminuria compared to normoalbuminuria, (β= – 0.42, p = 0.009 and β= -0.37, p = 0.01, respectively). Those with CKD had a 23.9 % lower response to PORH compared to controls (p = 0.02 after adjustment). In contrast, TH responses did not differ between those with and without CKD.


Microvascular endothelial function was strongly associated with greater albuminuria and CKD, independent of diabetes and blood pressure. These findings may explain in part the excess systemic cardiovascular risk associated with albuminuria and CKD.

Scientific Updates Sponsored by Endothelix Inc. ****************************************************


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