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AASI in Diabetic Pregnancy
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syndrome. Androl Gynecol: Curr Res 2014, 2:4. doi: 10.4172/2327-
4360.1000128.
13. Gade M, Lauszus FF. Hirsutism in PCOS - low satisfaction of treatment
and its background. J Genit Syst Disord 2014; 3:3 doi: 10.4172/2325-
9728.1000127.
14. Lauszus FF. Retinopathy in diabetic pregnancy - IGF and progression.
Prensa Med Argent 2014, 100:4 doi: 10.4172/lpma.1000143.
15. Nielsen HN, Lauszus FF, Trolle B, Ingerslev HJ, Tørring N. Impact of
metformin on Anti-Müllerian Hormone in women with PCOS: a
secondary analysis of a randomized controlled trial. Acta Obstet Gynecol
Scand 2015;94:547-51.doi: 10.1111/aogs.12605.
16. Kruse AR, Darling MS, Hansen MKL, Markman MJ, Lauszus FF,
Wielandt HB. Recurrence of gestational diabetes in primiparous women.
Acta Obstet Gynecol Scand 2015 doi: 10.1111/aogs.12764.
17. Andersen A, Lauszus FF. Vabrasio is a reliable test to rule out
endometrial cancer. Dan Med J 2015;62 (8):A5124 PMID: 26239593
18. Rasmussen OW, Lauszus FF, Løkke M. Telemedicine vs. standard care
in type 2 diabetes mellitus. A randomized trial in an outpatient clinic. J
Telemed Telecare 2015 doi: 10.1177/1357633X15608984.
19. Bue L, Lauszus FF. Moxibustion did not have an effect in a randomised
clinical trial for version of breech position. Dan Med J 2016 Feb;63(2).
pii: A5199.
20. Lauszus FF. Preeclampsia prediction in type 1 diabetes and diurnal blood
pressure methodology. Current Hypertension Reviews 2016.
21. Lauszus FF, Kallfa E, Madsen MR. Fatigue and physical performance
after hysterectomy measured by SF-36, ergometer, and dynamometer.
Arch Obstet Gynecol doi: 201610.1007/s00404-015-3999-0.
22. Lauszus FF, Fuglsang J. IGF-1 is associated with fetal growth and
preterm delivery in type 1 diabetic pregnancy. Gynecol Endocrinol 2016
doi: 10.3109/09513590.2015.1134477.
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In: Advances in Arterial Stiffness Research ISBN: 978-1-63485-838-0
Editor: Becky Chavez © 2016 Nova Science Publishers, Inc.
Chapter 6
PULSE WAVE VELOCITY AND
CARDIOVASCULAR MORBIDITY AND
MORTALITY IN PATIENTS ON RENAL
REPLACEMENT THERAPY
Vaia D. Raikou
1
st
Dept. of Medicine - Propaedaetic, National and Kapodistrian University
of Athens, School of Medicine, Αthens, Greece
ABSTRACT
Introduction-Aim: Large arterial pulse wave velocity (PWV)
demonstrates a predictive value of aortic stiffness for cardiovascular
events in general population and in dialysis patients. We observed the
effect of non-adjusted and adjusted for confounding factors carotid-
femoral pulse wave velocity (c-fPWV) on cardiovascular morbidity and
mortality rate in patients on renal replacement therapy during a median
follow up time of 60 months.
Methods: We studied 73 patients on on-line hemodiafiltration.
Dialysis adequacy was defined by Kt/V for urea. We performed a
Kaplan-Meier curve to examine the impact of high or low c-fPWV
on mortality rate. Additionally, we built Cox regression analyses to
investigate the relationship between both, coronary disease and overall
Corresponding author: VaiaRaikou, Ph.D. Nephrologist. Address: 17 AgiouThoma, Athens,
Greece. Phone: 00302107456261. Fax: 00302107791839. E-mail: vraikou@med.uoa.gr.
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Vaia D. Raikou
120
mortality and non-adjusted and adjusted c-fPWV for confounders. Also,
we examined the relationship between c-fPWV and measured i-PTH,
hsCRP, serum bicarbonate concentrations and hydration status.
Results: Kaplan-Meier analysis for the impact of higher or lower
than the mean value of c-fPWV (11.3 ± 1.83m/s) on overall mortality
was found non-significant. Cox-regression analysis revealed significant
predictive effect of non-adjusted and adjusted for confounders c-fPWV
on coronary disease and overall mortality. c-fPWV was positively
associated with i-PTH, hsCRP and pulse pressure (PP), but inversely with
serum bicarbonate concentrations (r = 0.261, p = 0.02, r = 0.400,
p=0.001, r = 0.346, p = 0.003 and r=-0.719, p = 0.001 respectively).
Conclusion: Carotid-femoral pulse wave velocity was found as
a significant predictor for coronary disease and overall mortality in
dialysis patients. The hydration status, bone disease, inflammation and
uncorrected metabolic acidosis state may be the main variables which
impact on arterial stiffening and mortality of these patients.
Keywords:pulse wave velocity, dialysis, coronary disease, mortality, arterial
stiffening
INTRODUCTION
It has been established that cardiovascular disease is the leading cause of
morbidity and mortality among patients on renal replacement therapies due
mainly to vascular occlusive disease defined by myocardial infarction,
cerebrovascular strokes and ischemic events of the limbs. The underlying
disease that leads to these events, progresses through various mechanisms
including left ventricular hypertrophy, plaque formation, arterial stiffening and
endothelial dysfunction [1].
Although coronary atherosclerosis is a well-known underlying cause of
cardiovascular disease, arterial alterations include more widespread vascular
changes that contribute to stiffening of arteries. Arterial hardening causes
increased pulse wave velocity (PWV), increased pulse pressure (PP), cardiac
overload and left ventricular hypertrophy [2, 3]. Large arterial PWV, which is
a simple, noninvasive and reproducible marker, has been used during the last
decades to quantify regional arterial stiffness and a good number of analyses
have been reported, including longitudinal studies and comparative analyses
between hemodialysis and peritoneal dialysis patients [4].
Carotid-femoral PWV (c-fPWV) has been used in the epidemiological
studies demonstrating the predictive value of aortic stiffness for cardiovascular
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Pulse Wave Velocity and Cardiovascular Morbidity …
121
events in general population and in dialysis patients [5]. However, the research
results regarding with the relationship between renal replacement therapy and
arterial stiffness are controversial [6].
Additionally, the arterial wall stiffening in the end stage of renal disease
(ESRD) patients appears to be multifactorial [7], including a list of factors
involved in arterial wall alterations, such as the used dialysate calcium [8], the
bone disease, the presence or absence of calcinosis of the arterial wall, the
tissue hydration changes [9] and the presence of linked to inflammation and
oxidative stress several bioactive uremic toxins [10, 11].
In this chapter, we observed the relative effect of non-adjusted and
adjusted for confounding factors carotid-femoral pulse wave velocity on
cardiovascular morbidity and mortality rate in patients on renal replacement
therapy during a median follow up time of 60 months.
METHODS
Patients
We included 76 patients on on-line- predilution haemodiafiltration. This is
a dual-center observational longitudinal retrospective study examining the
effect of aortic stiffness on cardiovascular morbidity and overall mortality.The
data collection became during a median time of 60 months.
Figure 1. Study chart. The chart describes the participants’ inclusion-exclusion and
clinical outcomes. PWV indicates pulse wave velocity.
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Vaia D. Raikou
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Three subjects were excluded for missing vascular stiffness, leaving 73
subjects for the study analysis, 46 men and 27women, on mean age 61.6 ± 15
years old (Figure 1). In our data, 8 patients were initiared dialysis treatment
after the starting of this study and 65 patients were already in permanent
dialysis therapy. Patients’ contribution to follow up ended at the time of death,
renal transplantation, renal recovery, or at the past follow up (December
2011).
We excluded patients <18 years of age at initiation of dialysis and patients
that had less than 6 months of follow-up. Patients without regular vascular
hemodialysis access and who had dialysis catheter and those with autoimmune
diseases, infections or malignancy were excluded from our study.The
hemodialysis treatment was performed 3-times weekly with a dialysis time of
3.5-4 h per session, a filter of 1.5-2 m2surface area by high-flux synthetic
membrane, defined by a ultrafiltration coefficient >20 ml/h [12] and a blood
flow of 350-400 ml/min. A bicarbonate-based ultrapure buffer dialysis
solution was used with a dialysate flow rate of 500-600ml/min, a calcium
concentration of 1.50-1.75mmol/L, a sodium concentration of 138-145mmol/L
and low molecular weight heparin as anticoagulant therapy. The final
concentration of bicarbonate in dialysate was 32mEq/L. Dialysis dose was
defined by Kt/V/day for urea, which was calculated according to the formula
of Daugirdas [13]. Patients were excluded if they had Kt/V for urea <1.2.
The enrolled patients had a good status and they did not have interdialytic
peripheral oedema, high blood pressure, interdialytic orthostatic hypotension
or other characteristics of an inaccurate dry body weight.
Cardiovascular disease was represented by the presence of coronary
disease (CD, n = 25, 34.2%), which might be the underlying disease for
heart failure or peripheral arterial disease. At start of study, the coronary
syndrome was documented by history of myocardial infarction, coronary
artery angioplasty or bypass surgery, clinical signs of angina pectoris or
electrocardiographic ischaemic findings. Also, the first and the current
cardiovascular events during the study were written down as one event for the
coronary artery disease manifestation.
28 of the enrolled patients (a ratio of 38.4%) were receiving
anti-hypertensive drugs, such as calcium channel blockers, beta-blockers or
inhibitors of agiotensin II receptors. Another receiving medication included
statin and only calcium-free phosphate binders were prescribed. All of the
studied patients were on erythropoetin-a or-β therapy.
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Pulse Wave Velocity and Cardiovascular Morbidity …
123
19 of the studied patients were current smokers (a ratio of 26%). 20
studied patients disposed urine volume up to 100 ml/day.
In our data, the renal failure was caused by hypertensive nephrosclerosis
at a ratio of 32.9%, chronic glomerulonephritis at a ratio of 30.1%, polycystic
disease at a ratio 11%, diabetic nephropathy at a ratio equal to 9.6% and other
causes at a ratio 16.4%.
APPROVAL AND CONSENT
The study was approved by the ethics committee of the Hospitals “Laiko,
University General Hospital of Athens” and Renal Unit of “Diagnostic and
Therapeutic Center of Athens Hygeia SA”. Written informed consent was
obtained from all subjects.
BLOOD COLLECTION
Blood samples were obtained just before the start of the mean weekly
dialysis session in a twelve hours fasting state from the vascular access.In the
end of the treatment the blood pump speed was reduced to <80ml/min and
blood samples was obtained at 2 min post-dialysis from the arterial dialysis
tubing for the calculation of the adequacy of dialysis by Kt/V for urea.Samples
were centrifuged immediately. Serum was separated and processed for various
assays.
In each subject, three sequences of samples (every month within 3
months) were received for the serum bicarbonate measurements, and their
average was used for statistical analysis. The low serum bicarbonate level was
considered in combination to low arterial pH (acidemia) and decreased PCO2.
LABORATORY MEASURMENTS
Albumin, high density lipoproteins (HDL), low density lipoproteins
(LDL), sodium (Na
+
) levels in the start and Na
+
levels in the end of the
treatment session were measured by biochemical analysis and the ratio of
LDL/HDL was calculated. The sodium removal was determined as percent
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Vaia D. Raikou
124
sodium removal (PSR) using the following formula:(Na
+
pre-Na
+
post/ Na
+
pre)
x 100. Hematocrit and hemoglobin values were also measured.
High sensitivity C-reactive protein (hsCRP) and oxidized LDL (ox-LDL)
serum concentrations were measured using enzyme linked immunoabsorbed
assays (ΕLISA, Immundiagnostik AG., Germany and Immundiagnostik
AG. Stubenwald-Allee, Bensheim respectively) according to manufacturer’s
specifications.
The concentrations of intact-parathormone (i-PTH) were measured by
radioimmunoassay (CIS bio international/France).
Insulin resistance was calculated using the homeostasis model assessment
of insulin resistance (HOMA-IR) [14].
Metabolic acidosis was defined by serum bicarbonate concentrations less
than 22.0mEq/L, which were measured in gas machine (Roche, combas b 121)
taking care of the blood specimens [15].
Normalized protein catabolic rate for dry body mass (nPCR) was
calculated from the urea generation rate [16]. Body mass index (BMI) was
obtained from height and post-dialysis body weight.
HAEMODYNAMICMEASUREMENTS
Predialysis peripheral systolic and diastolic blood pressures
(SBP and DBP respectively) in enrolled patients were calculated as the
mean of 10 measurements during a treatment month using an automatic
sphygmomanometer OMRON M4-I (Co Ltd Kyoto Japan). Mean peripheral
pre-dialysis BP (MBP) was calculated as: MBP = DBP + 1/3 (SBP-DBP).
Electrocardiographical analysis and M-mode echocardiography were
performed the day after dialysis with a Hewlett Packard SONOS 2500 using a
2.25 MHz transducer to estimate the ejection fraction and the ischaemic
findings according to the recommendations of the American Society of
Echocardiography [17].
Arterial stiffness was measured as carotid-femoral pulse wave velocity (c-
f PWV) and carotid augmentation index (AIx) using the SphygmoCor system
®
(AtCor Medical Pty. Ltd, Sydney, Australia).In each subject two sequences
of measurements were performed, and their mean was used for statistical
analysis. We recorded the carotido-femoral PWV by positioning one sensor
over the right femoral artery and a second sensor over the left carotid artery.
The distance between the two sensors was measured with a measuring tape,
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Pulse Wave Velocity and Cardiovascular Morbidity …
125
and three recordings of both pulse wave forms were performed (8-10 heart
beats for each recording). The Complior software automatically detected the
foot of each pulse wave form from the two arterial sites and then measured the
mean distance between the two feet as being the travel time of the wave. PWV
was then computed using the formula: PWV = travel distance/travel time, as
previously validated [18].
Central systolic blood pressure (SBP), diastolic blood pressure (DBP),
mean blood pressure (MBP), PP, and the time of return of the reflected wave
(Tr) were derived. Pressure and time of first peak (P1 and T1) and second peak
(P2 and T2), and central augmented pressure (AP) were obtained. Central
augmentation index (AIx) was computed (AP = P2-P1; AIx = (AP/PP) x 100)
and corrected for a heart rate of 75 beats/minute.
DATA ANALYSIS
Data were analyzed using SPSS 15.0 statistical package for Windows
(SPSS Inc, Chicago, Illinois) and expressed as mean ± standard deviation or as
median value (interquartile range) for data that showed skewed distribution;
Differences between mean values were assessed by using unpaired t-test for
two groups and data that showed skewed distributions were compared with
Mann-Whitney U-test.
Correlations between variables were defined by Pearson and Spearman
coefficient and p values less than .05 were considered significant.
We performed a Kaplan-Meier analysis to examine the impact of high
or low c-fPWV on mortality rate. Additionally, we built a Cox regression
analysis to investigate the relationship between mortality rate and non-adjusted
and adjusted c-fPWV for confounders such as dialysis adequacy defined
by Kt/V for urea, dyslipidemia, hypertension, dialysis vintage, diabetes
mellitus, smoking, age and sex. Because of the follow up time was not the
same for the total of enrolled patients, we also used a Cox regression analysis
to investigatethe relationship between coronary disease manifestation and
adjusted c-fPWV for the above confounders.
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Vaia D. Raikou
126
RESULTS
Characteristics of the studied population at the time of inclusion are listed
in Table 1.
Kaplan-Meier analysis for the impact of higher or lower than the
mean value of c-fPWV (11.3 ± 1.83m/s) on overall mortality was found non-
significant (log-rank = 0.342, p = NS). However, Cox-regression analysis
revealed significant predictive effect of non-adjusted c-fPWV on overall
mortality (p = 0.006, OR = 1.5, 95% CI = 1.12-1.98) (Figure 2). Also, c-fPWV
was found significant independent predictive factor for mortality rate after
adjustment for confounding variables such as dialysis adequacy defined by
Kt/V for urea, dyslipidemia, hypertension, dialysis vintage, diabetes mellitus,
smoking, age and sex (Table 2). In the meantime, built Cox-regression
analysis showed that c-fPWV was a significant factor for coronary disease
manifestation adjusted for the same above confounders during the median
follow up time of 60 months (Table 3).
Table 1. Baseline characteristics
Parameters
N =73
Male
46 (63)
Age (years)
61.6 ±14.9
Dialysis vintage (years)
5 (3-10)
Body mass index (BMI, Kg/m
2
)
24.3 ± 2.9
Kt/V for urea
1.29 (1.25-1.49)
Normalized protein catabolic rate (nPCR, g/Kg/day)
2.4 ±0.5
Serum bicarbonate concentrations (mEq/L)
20.09 ± 2.28
LDL/HDL
2.34 ± 0.8
HOMA-IR (mmol/L x μU/ml)
3.4 (2.08-6.4)
i-PTH(pg/ml)
122.0 (58.3-236.5)
hsCRP(mg/L)
8.05 ± 5.8
oxLDL (ng/ml)
70.6 (50.9-115.9)
Albumin (gr/dl)
3.9 ± 0.4
MBP (mmHg)
98.3 ± 12.6
carotid-femoral pulse wave velocity (c-f PWV, m/s)
11.3 ± 1.83
Carotid augmentation index (AIx, %)
24.1 ± 2.1
Pulse pressure (mmHg)
58.08 ± 19.6
Percent sodium removal (PSR, %)
2.14 (0.7-2.87)
Hemoglobin(gr/dl)
11.8 ± 1.3
Coronary disease
25 (34.2)
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