ISSN (Online): 1876-4401 ISSN (Print): 1872-9312
Journal Home Page: https://www.atlantis-press.com/journals/artres
P6.9: DIETARY NITRATE BY BEETROOT JUICE CAN LOWER
RENAL RESISTIVE INDEX IN PATIENTS WITH CHRONIC
S. Kemmner, K. Burkhardt, U. Heemann, M. Baumann
To cite this article: S. Kemmner, K. Burkhardt, U. Heemann, M. Baumann (2014) P6.9:
DIETARY NITRATE BY BEETROOT JUICE CAN LOWER RENAL RESISTIVE INDEX IN PATIENTS
WITH CHRONIC KIDNEY DISEASE, Artery Research 8:4, 147–148, DOI:
To link to this article: https://doi.org/10.1016/j.artres.2014.09.160
Published online: 7 December 2019
Material and Metho ds: 80 patients with severe untreated p eriodontitis
were subjected to anti-infective periodontal therapy, comprising bacterial
bioﬁlm removal by scaling and root planning either with or without admin-
istration of systemic antibiotics. The following parameters were assessed at
baseline and 12 month post-therapy: periodontal bleeding on probing, rep-
resenting a clinical parameter for a ctive inﬂammation (BoP), pulse wave
velocity (PWV), augmentation index (AIx), central systolic pressure (SBPao)
and central pulse pr essure (PPao) using an oscillometric device
Results: Preliminary data evaluation demonstrated, that 12 months post
therapy reduction of periodontal bleeding on probing correlated signiﬁcantly
with decreased values of PWV, SBPao, PPao, AIx, and AugP (p<0.05, respec-
tively) whereas peripheral blood pressure remained unchanged.
Conclusions: Successful reduction of periodontal inﬂammation is associated
with improved markers of arterial dysfunction.
A DOUBLE BLIND, RANDOMISED TRIAL INVESTIGATING IF ARTERIAL
STIFFNESS CAN BE REDUCED INDEPENDENTLY OF BLOOD PRESSURE IN
PARTICIPANTS WITH OR AT RISK OF TYPE 2 DIABETES
C. Mills, F. Iqbal, H. Crickmore, V. Govoni, A. Webb, J. K. Cruickshank
King’s College London, London, UK
Background: Arterial stiffness (AS) as pulse wave velocity (PWV), is a power-
ful independent predictor of cardiovascular events, and commonly compli-
cates Type 2 diabetes (T2D). The VaSera machine measures cardiac (by
2nd sound phonogram)-ankle PWV, expressed as a cardio-ankle vascular in-
dex (CAVI), aimed to be independent of blood pressure (BP). Our factorial
trial tests whether separately randomised dietary nitrate or placebo, and
an aldosterone antagonist reduce CAVI and PWV in those at risk of or diag-
nosed with T2D.
Method: Double-blind, randomised trial assessing AS at baseline, 3 and 6
months. Target recruitment is 120 patients, 18-90 years, excluding those
with serious illness or eGFR <45mL/min. Daily interventions are spironolac-
tone (50mg) or doxazosin (16mg), to control for BP change, with a nitrate
donor (0.4g nitrate) or an identical nitrate-free juice.
Results: 74 participants are screened, 54 randomised and 34 completed.
MeanSD baseline age and body mass index were 59.712.1 years and
, respectively; 40% female.
No differences in CAVI or PWV were observed between screening and
randomisation (8.301.4 to 7.971.3 units and 9.302.0 to 9.171.8m/s,
respectively). Systolic (S) and diastolic (D) BP dropped between these visits
(13817 to 13317mmHg, p<0.005 and 8112 to 7112mmHg, p<0.001,
respectively). Bland-Altman analysis between screening and randomisation
for CAVI, PWV, SBP and DBP shows <6% of mean differences fall outside of
the 95% limits; mean differencelimits of agreement; -0.132.12,
-0.321.85, -526 and -419, respectively.
Conclusion: A trial focused on PWV is practical and effective within our
target population, with simple recruitment and a low drop-out rate.
SUBLINGUAL NITROGLYCERIN IN PATIENTS WITH HEART FAILURE AND
PRESERVED EJECTION FRACTION: IMPACT ON CENTRAL AND REGIONAL
CAROTID AND RADIAL INPUT IMPEDANCE AND HEMODYNAMICS
, P. Segers
, P. Shiva-Kumar
, S. Peddireddy
, J. Chirinos
Ghent University, Gent, Belgium
UPenn, Philadelphia, USA
VA Medical center, Philadelphia, USA
Background: The systolic blood pressure lowering effect of sublingual nitro-
glycerin (NTG) administration is thought to primarily arise from its action on
wave reﬂection, although recent invasive data indicate that at least part of
the blood pressure reduction can be ascribed to an effect on left ventricular
Methods: Carotid and radial pressure waveforms and aortic, carotid and
radial ﬂow were measured in 19 HFpEF patients using applanation tonometry
and pulsed Doppler ultrasound, respectively. Signals were time-aligned and
global systemic as well as regional impedance and wave reﬂection analysis
Results: NTG lowered carotid systolic (130.826 at baseline vs.
110.418.4mmHg after NTG, P<0.01) and mean (92.518.4 vs.85.414.3)
blood pressure. Global systemic effects included a decrease in systemic
vascular resistance (1.000.32 vs. 0.880.28 mmHg.ml
.s, P<0.05), charac-
teristic impedance (0.1330.089 vs. 0.0890.034 mmHg.ml
.s, P<0.05) and
an increase in total arterial compliance (1.200.58 vs. 1.520.53 ml.mmHg
,P<0.01). NTG had a major impact on the amplitude of the forward pres-
sure wave (5824.3 vs. 40.613.3 mmHg, P<0.01), with no signiﬁcant
change in reﬂection magnitude. Regional analysis demonstrated a large ef-
fect of NTG on carotid input impedance, lowering impedance over the entire
frequency spectrum, with radial artery input impedance did not demon-
strate any signiﬁcant changes (despite large effects on pressure and ﬂow
Conclusions: Our data in patients with HFpEF conﬁrm the absence of impact
of NTG on reﬂection magnitude, and demonstrate large effects of NTG on
the input impedance of the cerebral vascular district, with little effect on
the distal forearm circulation.
EFFECT OF ORGANIC NITRATES ON INTRAVENTRICULAR PRESSURE
GRADIENTS IN HEART FAILURE PATIENTS WITH PRESERVED EJECTION
, B. Meyers
, P. Vlachos
, P. Segers
, J. Chirinos
IBitech-bioMMeda (Ghent University), Ghent, Belgium
Faculty School of Biomedical Engineering and Sciences (Virginia Tech),
Department of Cardiology & Radiology (University of Pennsylvania), PA,
Introduction: Heart Failure with preserved ejection fraction (HFpEF) is a
highly prevalent condition for which no pharmacologic therapy is available.
Diastolic dysfunction is thought to be central to its pathophysiology. Organic
nitrates have pharmacologic effects on preload, afterload and myocardial
contraction/relaxation that may favourably inﬂuence ventricular ﬁlling.
However, the effect of sublingual nitro-glycerine (NTG) on diastolic param-
eters in this population has not been studied. We aimed to assess the effect
of NTG on intraventricular pressure gradients (IVPG) and other measures of
Methods: Colour M-mode Doppler (CMM) is a non-invasive ultrasound tech-
nique used to obtain left ventricular (LV) blood ﬂow velocities during early
ﬁlling and to calculate IVPG. CMM recordings of 20 patients (HFpEF) at
rest and after the administration of 0.4 mg of NTG were obtained and pro-
cessed. Average values of the parameters were calculated and compared
(Wilconox test) at rest and after NTG.
Results: NTG induced a non-signiﬁcant increase in early diastolic IVPG
(pZ0.286) due to a reduction in the early diastolic convective component
(pZ0.026). Similarly, the early diastolic reversal convective component
was reduced (pZ0.009). In contrast, the late diastolic IVPG was increased
(pZ0.017), due to an increased inertial component (pZ0.034). There was
a reduction in peak E wave velocity (pZ0.004), E wave acceleration
(pZ0.003) and deceleration (pZ0), while the acceleration time
(pZ0.034) and the heart rate (HR) (pZ0.016) increased.
Conclusion: Organic nitrates exert effects on diastolic ﬁlling in HFpEF:
increased HR and myocardial contractility and decreased peak E-wave veloc-
ity possibly related to a preload reduction.
DIETARY NITRATE BY BEETROOT JUICE CAN LOWER RENAL RESISTIVE
INDEX IN PATIENTS WITH CHRONIC KIDNEY DISEASE
, K. Burkhardt
, U. Heemann
, M. Baumann
Technical University, Munich, Germany
Nephrological Clinic Weissenburg, Weissenburg, Germany
Introduction: Beetroot has a high concentration of nitrate. In circulation ni-
trate converts to nitrite. Nitrite-derived NO is a potent vasodilatator.
Increased renal resistive index (RI) are associated with higher mortality in
patients with chronic kidney disease (CKD) and predict cardiovascular events
in these patients. Here we investigated if the ingestion of beetroot juice can
Methods: Using a randomized cross-over study design 12 CKD patients were
investigated within 4 hours (h) after one ingestion of dietary nitrate load
(300 mg) by highly concentrated beetroot juice (30g beetroot powder dis-
pended in 200 ml water) versus 200 ml water. Plasma nitrite concentration
as well as renal segemental arterial RI in duplex doppler ultrasonography
was measured before and 4 hours after ingestion of beetroot or water. BP
was measured every 15 minutes within the 4 hours.
Results: In 12 CKD patients (7 females) the eGFR was 40.713.8 ml/min.
Three patients had a hypertensive nephropathy, 2 diabetic nephropathy
and 7 seven patients had a combined hypertensive/diabetic nephropathy.
The RI value was signiﬁcantly reduced by beetroot ingestion (pre-beetroot
RIZ0.750.05 versus post-beetroot RIZ0.720.05; pre-water
RIZ0.750.06 versus post-water RIZ0.760.05; PZ0.02).
Conclusion: Our ﬁndings suggest that the supplementation of pharmacologic
therapy with diatary nitrate through beetroot juice could prevent cardiovas-
cular events and progression of renal disease in CKD patients.
PROPIONYL-L-CARNITINE FOR INTERMITTENT CLAUDICATION. A
T. De Backer
, V. Kamoen
, R. Vander Stichele
, L. Campens
D. De Bacquer
, L. Van Bortel
Heymans Institute of Pharmacology, Ghent, Belgium
Cardiovascular Center, Ghent, Belgium
Dept of Epidemiology and Public Health, Ghent, Belgium
Intermittent claudication (IC) is a symptomatic form of peripheral arterial
disease (PAD) (pain in the lower limbs with walking and relieved by rest).
Propionyl-L-carnitine (PLC) is a drug which may lower the symptoms of PAD.
Is PLC efﬁcacious in improving clinical outcomes in IC patients?
For this Cochrane review randomized controlled trials in patients with IC
receiving PLC compared with placebo or other intervention were selected.
Pain-free and maximal walking performance were analyzed by standardized
exercise test. ABI, quality of life and adverse events were assessed. 13
Studies were included in this review (1423 patients). The results of the
selected trials were brought together in patient pools. For the maximal
walking distance, the mean difference in walking performance after use of
PLC compared to placebo was an absolute increase of 50.86 m (95% CI 50.34
to 51.38) or a 26% relative improvement (23 to 28%). For the pain-free
walking distance, the improvement in walking performance with PLC
compared to placebo was an absolute increase of 32.98 m (32.60 to 33.37)
or a 31 % relative improvement (28 to 34%) . PLCs had an 0.09 (0.08 to 0.09)
improvement in ABI over placebo. The adverse events of PLC were similar as
in the control group and PLC seemed well tolerated and safe. PLC 1-2g a day
costs 0.30 to 0.70 V.
PLC for IC shows a signiﬁcant, though mild to moderate improvement of
walking distances and ABI compared to placebo. The safety of PLC is
comparable to placebo. In practice, PLC could be useful adjuvant to classic
IC-therapies or when these are contra-indicated, not feasible or ineffective.
This work is a Cochrane review. The data presented here presented are
provisional (as the review has not yet been published).
The citation for the Cochrane protocol is: de Backer TLM, Campens L, Vander
Stichele R, Van Bortel L, De Bacquer D. Propionyl-L-carnitine for intermit-
tent claudication (Protocol). Cochrane Database of Systematic Reviews
2012, Issue 9. Art. No.: CD010117. DOI: 10.1002/14651858.CD010117.
The authors acknowledge the Cochrane Peripheral Vascular Diseases Group.
PHOSPHODIESTERASE TYPE-5 INHIBITOR USE IN TYPE 2 DIABETES IS
ASSOCIATED WITH A REDUCTION IN ALL CAUSE MORTALITY
, D. Hutchings
, C. Kwok
, A. Trafford
, A. Heald
University of Manchester, Manchester, UK
Leighton Hospital, Crewe, UK
Background: Phosphodiesterase type-5 inhibitors (PDE5is) exert cardiopro-
tective effects in small mammal models of myocardial ischaemia. There is
currently little data on whether a similar effect exists in humans. We deter-
mined whether PDE5i use in males with type 2 diabetes (T2DM) was associ-
ated with reduced mortality.
Methods: We retrospectively analysed the pseudoanonymised records of 48
GP practices in Cheshire, UK and identiﬁed all 7029 men (mean age 72.8
years) diagnosed with T2DM before 1 January 2007. Baseline clinical charac-
teristics and PDE5i treatment data were obtained. Mean follow-up was 6.4
years (January 31, 2014) and all deaths were ascertained from GP records.
Findings: Of the 1,663 (23.7%) men prescribed a PDE5i, the proportion of
deaths was signiﬁcantly lower than those never prescribed (16.9% versus
29.4%). All-cause mortality rates (per 1000 person-years) were similarly
lower (21.1 (19.1-24.5) versus 34.4 (32.5e36.5); P<0.0001). There was a
38% reduction in all-cause mortality (univariate Cox proportional hazards
HR: 0.62 (0,54-0.71); P<0.0001) in men on a PDE5i over the period. This
reduction remained but was attenuated (HR: 0.80 (0.65, 0.98); P<0.05) after
multivariate regression adjusting for age (1.11 (1.09e1.12); P<0.0001 per
year), smoking history (1.31 (1.16-1.47); P<0.0001), HbA1c, systolic BP,
creatinine levels, prescribed statins, aspirin and beta-blocker use.
Interpretation: Around 70% of deaths in T2DM are attributable to cardiovas-
cular disease. Our data demonstrates that PDE5i use is associated with
signiﬁcantly reduced mortality in men with T2DM at high risk of CVD. Further
evidence is required to elucidate the role of PDE5is in cardioprotection.
ACUTE EFFECTS OF SMOKING OVER THE ENDOTHELIAL FUNCTION AND
CENTRAL ARTERIAL HEMODYNAMICS IN YOUNG HEALTHY PEOPLE
, J. Maldonado
, R. Branda
, J. Conde
´cnico de Coimbra, Coimbra, Portugal
Instituto de Investigac¸a
˜o e Formac¸a
˜o Cardiovascular, Coimbra, Portugal
Introduction: The aim of this study was to assess the acute effects of smok-
ing over the endothelial function and central arterial hemodynamics, in
healthy and young smokers.
Methods: Thirty healthy young individuals, were allocated into two groups,
matched for gender and age, according to their smoking habits: control
group (CG; nZ15 non-smokers) and intervention group (IG; nZ15 smokers).
All the individuals were submitted to two clinical evaluations, basal and
following 30 minutes (after smoking a cigar in the IG). Weight, height,
body mass index (BMI), systolic blood pressure (SBP), diastolic blood pressure
(DBP), heart rate (HR), ﬂow-mediated dilation (FMD), aortic pulse wave ve-
locity (PWV) and pulse wave analysis over the carotid artery (PWA) were
Results: CG and IG groups had similar baseline clinical and demographic
characteristics, although the IG showed lower baseline FMD values
(7.532.80% versus 12.474.63% in the CG; pZ0.001). The pairwise analysis
revealed signiﬁcant variations in the IG, but not in the CG, with an increase
in HR, brachial and central BP and PWV, and a signiﬁcant decrease in FMD,
revealing an important acute compromise of endothelium-dependent vaso-
dilation after the cigar in the IG, with no changes in the CG.
Conclusion: Smoking has an acute and noteworthy pernicious effect over the
vascular function in young and healthy individuals, compromising endothe-
lium-dependent vasodilation, increasing heart rate, blood pressure and
IDENTIFICATION OF VASCULAR AND CIRCULATING BIOMARKERS TO
PREDICT OUTCOME IN PATIENTS AFFECTED BY SEPTIC SHOCK
, O. Belli
, F. Musca
, G. Monti
, L. Bonacchini
, M. Stucchi
, P. Meani
, L. Frigerio
, M. Molteni
, M. Alloni
, R. Fumagalli
, A. De Gasperi
Milano-Bicocca University, Milano, Italy
Cardiologia IV, Ospedale Niguarda Ca’ Granda, Milano, Italy
Intensive Care Unit 2, Ospedale Niguarda Ca’ Granda, Milano, Italy
Intensive Care Unit 3, Ospedale Niguarda Ca’ Granda, MIlano, Italy
Introduction: Cardiovascular dysfunction is a well-recognized early compli-
cation of septic shock (SS). A hallmark of SS is a change in microvascular
function and endothelial cell (EC) activation, contributing to multiple organ
failure. Angiopoietin (Ang1-2) pathway has been reported associated with
severity of illness and mortality.
Aim: to evaluate prognostic and clinical role of functional vascular assess-
ment in patients with SS.
Methods: We enrolled 20 patients from intensive care units with a diagnosis
of SS. Clinical, hemodynamic, instrumental evaluation s and blood sample
collection were obtained at hospitalization (T1), and one week later
(T2). We assessed echo cardiographic left ventricular systolic function
(LVEF) and functional arterie s evaluation with caro tid-femoral PWV
Results: During the follow-up 11 patients survived (S) and 9 died (D). S and D
had similar ages (628vs6611 yrs, meansSD), MAP (8012vs8112 mmHg,
meansSD) and SOFA score (134vs154, meansSD). At T1, D had a signif-
icantly higher cf-PWV than S (123vs92 m/s, meansSD; p0.05). Further-
more considering all patients toghether, we found an inverse correlation
between PWV and LVEF (p<0.01). Finally, S had a signiﬁcant T1-T2 increase
in Ang1 (7339[4587-17010]vs47384[10658-53645] medians[25-75th]; p<0.05)
and a decrease in Ang2 levels (2778317625vs90085565 means+SD;
p<0.01); D patients showed an inverse trend.
Conclusions: In SS endothelial dysfunction caused by EC-activation is
expressed by an increase of PWV, which was signiﬁcantly different depend-
ing on outcome of patients. PWV also has a correlation with LVEF. The values
of PWV could express an alteration of ventricular-vascular coupling, useful