Newsletter 29 Newsletter 29 Newsletter 29 November 2014
Latest PAT® Publications
Effects of erythritol on endothelial function in
patients with type 2 diabetes mellitus: a pilot
study.
Future non-invasive imaging to detect vascular
plaque instability and subclinical nonobstructive atherosclerosis.
Flint N, Hamburg NM, Holbrook M, G Dorsey P, Leleiko RM, Berger A,
de Cock P, Bosscher D, Vita JA.
Acta Diabetol. 2014 Jun;51(3):513-6
Blum A, Nahir M.
J Geriatr Cardiol. 2013 Jun;10(2):178-85.
Examined the effects of erythritol on vascular function in 24 patients with type
2 diabetes mellitus, who consumed erythritol 36 g/day as an orange-flavored
beverage for 4 weeks and a single dose of 24 g during the baseline and final visits.
Determined vascular function, including Endo PAT-logeRHI, (lnRHI), before and
after acute (2 h) and chronic (4 weeks) erythritol consumption.
RESULTS: Acute erythritol improved lnRHI (0.52 ± 0.48 to 0.87 ± 0.29, P =
0.005). Chronic erythritol decreased central pulse pressure (47 ± 13 to 41 ± 9
mmHg, p=0.02) and tended to decrease carotid-femoral pulse wave velocity
(p=0.06).
CONCLUSION: Erythritol consumption acutely improved lnRHI, and chronic
treatment reduced central aortic stiffness. Erythritol may be a preferred sugar
substitute for patients with diabetes mellitus.
AUTHORS’ ABSTRACT - Atherosclerosis underlies the major causes of death in the
Western World. Our main goal is to detect early changes of atherosclerosis and to
identify subjects at highest cardiovascular risk that may aid in the development of
prevention approaches and better management that will decrease cardiovascular
morbidity and mortality. The new methods that are of interest include the
advanced vascular ultrasound methods, the infra red and near infra red imaging
techniques, the Endo PAT device that reflects peripheral arterial tone, the
electron beam computed tomography, the magnetic resonance imaging, and
the molecular imaging techniques. In this review we will focus on the future of
advanced imaging techniques that are being developed to detect early (preclinical) development of atherosclerosis.
http://www.ncbi.nlm.nih.gov/pubmed/24366423
http://www.ncbi.nlm.nih.gov/pubmed/23888178
The effects of plant stanol ester consumption
on arterial stiffness and endothelial function
in adults: a randomised controlled clinical
trial.
Effects of low-fat dairy intake on blood
pressure, endothelial function, and lipoprotein
lipids in subjects with prehypertension or
stage 1 hypertension.
Gylling H, Halonen J, Lindholm H, Konttinen J, Simonen P, Nissinen MJ,
Savolainen A, Talvi A, Hallikainen M.
BMC Cardiovasc Disord. 2013 Jul 10;13:50
Maki KC, Rains TM, Schild AL, Dicklin MR, Park KM, Lawless AL, Kelley KM.
Vasc Health Risk Manag. 2013;9:369-79.
Studied the effects of 6 months of plant stanol esters (staest) on arterial stiffness
and endothelial function (Endo PAT-RHI), in 92- asymptomatic adults, (35 men)
without lipid medication, mean age 50.8y in a randomized, controlled, doubleblind, parallel trial. The staest group (n=46) consumed rapeseed oil-based spread
enriched with staest (3.0 g of plant stanols/d), and controls (n=46) the same
spread without staest. Endo PAT-RHI, augmentation index (AI), large arterial
stiffness cardio-ankle vascular index (CAVI), and lipids were tested using analysis
of variance for repeated measurements.
RESULTS: Post intervention staest group serum total, LDL, and non-HDL
cholesterol concentrations declined significantly vs. controls (p<0.001 for all).
Both CAVI and AI were unchanged in staest , but increased in control men and
difference in the changes between groups was significant (p=0.023, p=0.046
respectively). The reductions in LDL and non-HDL achieved by staest were both
related to improvement in RHI (r=-0.452, p=0.006 and -0.436, p=0.008).
CONCLUSION: LDL and non-HDL cholesterol lowering with 6 months staest
reduced arterial stiffness in small arteries and had a beneficial effect on large
arterial stiffness and on RHI.
http://www.ncbi.nlm.nih.gov/pubmed/23841572
Compared the effects of 5 weeks of low-fat dairy vs. low-fat nondairy products
on systolic and diastolic blood pressures (SBP and DBP), plasma lipids and Endo
PAT-RHI, and augmentation index (AI), in 62 men and women with untreated
prehypertension or stage 1 hypertension, mean age 54.5 y, tested before and after
a standard breakfast challenge at the end of each treatment period.
RESULTS: No significant differences between dairy and nondairy treatments
in SBP or DBP in the resting postprandial state or from premeal to 3.5 hours
postmeal, or in RHI or AI for premeal to 2 hours postmeal. Among 14 subjects
with endothelial dysfunction (RHI ≤ 1.67), premeal RHI was significantly higher in
the dairy versus nondairy condition (2.32 versus 1.50, p=0.002). Fasting plasma
lipoproteins were not significantly different between treatments.
CONCLUSION: No significant effects of consuming low-fat dairy vs. low-fat
nondairy products were observed for blood pressures, RHI, AI, or plasma lipids
in the overall sample, however dairy foods might improve RHI in those with
endothelial dysfunction.
http://www.ncbi.nlm.nih.gov/pubmed/23901280
Newsletter 29 November 2014
Methodological considerations and practical
recommendations for the application of
peripheral arterial tonometry in children and
adolescents.
Page 2
Effect of orthostasis on endothelial function: a
gender comparative study.
Bruyndonckx L, Radtke T, Eser P, Vrints CJ, Ramet J, Wilhelm M,
Conraads VM.
Int J Cardiol. 2013 Oct 9;168(4):3183-90
Goswami N, Gorur P, Pilsl U, Anyaehie B, Green DA, Bondarenko AI,
Roessler A, Hinghofer-Szalkay HG.
PLoS One. 2013 Aug 2;8(8):e71655. doi: 10.1371/journal.
pone.0071655
Authors allude to Endothelial dysfunction’s recognition as the prime mover in the
development of atherosclerosis and hence its pivotal role in both cardiovascular
morbidity and mortality, and review the clinical utility of invasive and non-invasive
means for assessing it.
They conclude that Endo PAT which assesses microvascular function provides
a non-invasive method which avoids the user dependence of flow-mediated
dilation (FMD), which evaluates nitric oxide dependent vasodilation in large
vessels. Authors further observe that in children and adolescents there is no
consensus with regard to either measuring protocol or data analysis of Endo PAT,
with most studies applying the conventional adult methodology, which may not
be appropriate.
CONCLUSION: While providing a detailed description of Endo-PAT’s
methodology and use, authors allude to differences between children,
adolescents and adults and provide recommendations for a standardized
application of Endo PAT in children and adolescents, as well as for populationspecific data analysis methodology.
Investigated the effect of orthostasis on endothelial function using
Endo PAT-RHI in 11 males and 20 females, and further examined effects of steroid
sex hormones on the RHI response to orthostasis in females at different menstrual
phases (n=11), and on oral contraceptives (n=9). Subjects were tested twice,
two weeks apart; (menstruating females first tested on either days 1-7 or 14-21
of cycle). RHI was assessed at baseline and following a 20-min active orthostatic
challenge.
RESULTS: In females, baseline RHI 1.71 ± 0.09 (mean ± SEM) increased to 2.07
± 0.09 following orthostasis (p<0.001), and from 1.60 ± 0.08 to 1.94 ± 0.13
(p<0.001) in males. There were no significant differences between females and
males, nor in menstrual cycle phases and the usage of oral contraceptive.
CONCLUSION: Increased vasodilatatory endothelial response followed orthostasis
in males and females; the effect of gender and sex hormones appears limited.
Further studies indicated to determine the role of post orthostasis endothelial
response in the pathophysiology of orthostatic intolerance.
http://www.ncbi.nlm.nih.gov/pubmed/23972967
Obesity, hyperglycemia and endothelial function
in inner city Bronx adolescents: a cross-sectional
study.
http://www.ncbi.nlm.nih.gov/pubmed/24147147
EDITOR’S note: An inter-test interval of at least 60 minute between repeat Endo PAT studies
is required. The apparently short time period between tests in this study may possibly have
contributed to the observed increase in RHI following orthostasis.
Automated preoperative assessment of
endothelial dysfunction and risk stratification
for perioperative myocardial injury in patients
undergoing non-cardiac surgery.
Agarwal C, Cohen HW, Muzumdar RH, Heptulla RA, Renukuntla VS,
Crandall J.
Int J Pediatr Endocrinol. 2013 Oct 29;2013(1):18.
McIlroy DR, Chan MT, Wallace SK, Symons JA, Koo EG, Chu LC,
Myles PS.
Br J Anaesth. 2014 Jan;112(1):47-56.
Investigated if childhood obesity is associated with endothelial dysfunction
(Endo PAT-RHI), and if obesity plus impaired glucose regulation further lowers
RHI; in 14 lean and 37 obese 12-18 year olds. The obese group was subdivided
into normal (NGT, n = 22) and impaired glucose regulation (IGR, n = 15).
RESULTS: RHI was lower in obese vs. lean (1.70 +/- 0.02 vs. 1.98 +/- 0.09,
p=0.02), and remained so when adjusted for age, sex and ethnicity (p=0.02).
RHI worsened with increasing metabolic burden in the lean, obese-NGT and
obese-IGR groups, respectively (p trend = 0.03). Obese subjects were significantly
more insulin resistant (p=0.03), had higher levels of leptin (p=0.004), hsCRP
(p=0.0004), and TNF-alpha (p=0.03) vs. lean. Adjusting for insulin resistance and
adipocytokines substantially attenuated the obesity association with RHI.
CONCLUSION: Risk factors for adult cardiovascular disease, including impaired
RHI, insulin resistance and inflammation, are evident in obese adolescents, and
insulin resistance and inflammation may mediate worsening RHI in obesity
Measured preoperative Endo PAT-RHI in 238 subjects before intermediate
or high-risk surgery to determine whether RHI could provide effective risk
stratification for Myocardial injury after non-cardiac surgery (MINS).
RESULTS: Myocardial injury (serum troponin ≥0.04 μg/l within 3 postoperative
days) occurred in 35 subjects (14.7%).Using adjusted for age Lee index, and
a composite measure of the extent of surgery, an RHI threshold of ≤1.22, was
associated with MINS [odds ratio 10.1, 95% confidence interval (CI) 3.3-30.9,
p=0.001] and increased time to discharge (hazard ratio 0.39, 95% CI 0.23-0.65,
p=0.001). RHI identified MINS with a sensitivity of 31%, a specificity of 96%,
and a positive diagnostic likelihood ratio of 8.0. Risk classification for MINS was
improved by adding RHI to the Lee index (c-statistic increased from 0.69 to 0.77,
p=0.003), but prognostic utility varied widely between sites.
CONCLUSION: Assessment of RHI may enhance preoperative risk stratification
for MINS. A large inter-site variation in prognostic utility needs to be further
understood.
http://www.ncbi.nlm.nih.gov/pubmed/24164965
http://www.ncbi.nlm.nih.gov/pubmed/24172055
Newsletter 29 November 2014
Endothelium dependent vasomotion and in
vitro markers of endothelial repair in patients
with severe sepsis: an observational study.
van Ierssel SH, Van Craenenbroeck EM, Hoymans VY, Vrints CJ,
Conraads VM, Jorens PG.
PLoS One. 2013 Aug 6;8(8):e69499. doi: 10.1371/journal.
pone.0069499. Print 2013.
Page 3
Cardiovascular effects of 3 months of football
training in overweight children examined by
comprehensive echocardiography: a pilot study.
Hansen PR, Andersen LJ, Rebelo AN, Brito J, Hornstrup T, Schmidt JF,
Jackman SR, Mota J, Rêgo C, Oliveira J, Seabra A, Krustrup P.
J Sports Sci. 2013;31(13):1432-40
Evaluated endothelial function in 30 patients with severe sepsis and 15
matched healthy controls using cellular endothelial markers (CD34+/KDR+
endothelial progenitor cells (EPC), CD31+ T-cells, and CD31+/CD42b-endothelial
microparticles (EMP)), and Endo PAT-RHI.
RESULTS: In severe sepsis, a lower number of EPC, CD31+ T-cells and a
decreased migratory capacity of CAC coincided with a blunted RHI vs. healthy
controls, while the number of EMP did not differ. The presence of organ failure at
admission (SOFA score) was inversely related with the number of CD31+ T-cells,
and the number of EPC at admission was decreased in progressive organ failure
within the first week.
CONCLUSION: In patients with severe sepsis, Endo PAT-RHI coincides with lower
numbers and reduced function of circulating cells implicated in endothelial repair
suggesting that cellular markers of endothelial repair might be valuable in the
assessment and evolution of organ dysfunction.
Examined effects of a 3-month football training program of 4 weekly 60-90
min sessions with mean heart rate (HR) > 80% of HRmax, in 20 overweight
preadolescents, (17 boys, aged 8-12 yrs; BMI 85th percentile - FG) using
comprehensive echocardiography and Endo PAT-RHI, compared to 11 matched
controls (CG).
RESULTS: After 3 months, systolic blood pressure was unchanged in FG, but
increased in CG (P=0.02). FG demonstrated increased left ventricular (LV)
posterior wall diameter (p< 0.001), improved right ventricular systolic function
determined by tricuspid annular plane systolic excursion (TAPSE- p=0.003) and
increased global isovolumetric relaxation time (IVRTglobal - p<0.001) No ECG
changes were observed in CG. Between-group differences in pre-post delta values
were observed for systolic blood pressure, TAPSE, and IVRTglobal (p=0.02-0.03).
Endo PAT-RHI and AI were similar in both groups at baseline and after 3 months
CONCLUSION: Short-term football training may have positive structural and
functional effects on the cardiovascular system in overweight preadolescents.
http://www.ncbi.nlm.nih.gov/pubmed/23936333
http://www.ncbi.nlm.nih.gov/pubmed/23829576
Nitrosylated Hemoglobin Levels in Human Venous
Erythrocytes Correlate with Vascular Endothelial
Function Measured by Digital Reactive Hyperemia.
Impaired Digital Reactive Hyperemia and the Risk
of Restenosis after Primary Coronary Intervention
in Patients with Acute Coronary Syndrome.
Lobysheva II, Biller P, Gallez B, Beauloye C, Balligand JL.
PLoS One. 2013 Oct 10;8(10):e76457.
Yamamoto M, Hara H, Moroi M, Ito S, Nakamura M, Sugi K.
J Atheroscler Thromb. 2014 Sep 24;21(9):957-65.
Tested whether erythrocyte levels of nitrosylated hemoglobin (HbNO-heme) may
reflect vascular endothelial function (Endo PAT-RHI), in 50 healthy volunteers.
Erythrocyte HbNO levels were measured at baseline and at the peak of
hyperemia.
RESULTS: Overall mean baseline erythrocyte HbNO concentration was 219+/12 nmol/L, with HbNO levels and RHI higher in contraceptive pills free females
than in males. HbNO levels increased at 1-2 min post-occlusion (120+/-8% of
baseline); post-occlusion HbNO levels were correlated with basal levels.
Both basal and post-occlusion HbNO levels were significantly correlated with RHI,
(r = 0.58; P<0.0001 for basal HbNO).
CONCLUSION: Demonstrates quantitative measurements of 5-coordinate
α-HbNO in human venous erythrocytes, its dynamic physiologic regulation and
correlation with Endo PAT-RHI. This opens the way to further understanding of in
vivo determinants of NO bioavailability in human circulation.
Investigated whether impaired Endo PAT-RHI is associated with restenosis
(≥50% at eight months), after percutaneous coronary intervention (PCI) in
patients with acute coronary syndrome (ACS), in 86 ACS patients who underwent
successful primary PCI of native vessels for de novo lesions. RHI was calculated at
three weeks and eight months after ACS.
RESULTS: Restenosis was detected in 17 patients (20%). There were no
differences in RHI at three weeks between patients with and without restenosis,
but RHI at eight months was significantly attenuated in patients with restenosis
(p=0.03). Univariate logistic regression analysis showed that eight-month RHI＜2
was a significant risk factor for restenosis (p=0.02).
CONCLUSION: Impairment of RHI at eight months is associated with restenosis
after primary intervention in patients with ACS, suggesting the potential of Endo
PAT-RHI as a noninvasive test for identifying patients with a high risk of restenosis.
http://www.ncbi.nlm.nih.gov/pubmed/24130774
http://www.ncbi.nlm.nih.gov/pubmed/24814196
Newsletter 29
November 2014
Page 4
Professor Joseph A. Vita 1956-2014
We were deeply saddened by the untimely passing of Professor Joseph A Vita
M.D., a most esteemed colleague and friend, a professor at Boston University,
a renowned cardiologist and scientist, one of the leading investigators in the
area of endothelial function with over 200 peer-reviewed publications and
on the editorial boards of the foremost journals in the cardiovascular field.
Joe was one of the Framingham Heart Study key investigators and was
instrumental in introducing non-invasive endothelial function testing into
this prestigious study.
His pioneering work in this field has been extensive and broached a wide span
of clinical and basic research areas in vascular biology and inflammation, and
particularly on endothelial dysfunction in atherosclerosis and associated risk
factors.
Joe’s publications employing EndoPAT were also broad ranging; from
mitochondrial dysfunction in the impairment of endothelial dysfunction
in T2DM, to clinical intervention studies, and to large community based
epidemiological studies.
The seminal contributions of Joe’s work has indelibly enriched the scientific
base and clinical acceptance of testing endothelial function, and will stand as
an enduring and shining legacy of this great man.
We extend our condolences to his wife and family.