Influence of lipids and obesity on haemorheological parameters in patients with deep vein thrombosis.
ABSTRACT It is not well established whether haemorheological alterations constitute independent risk factors for deep vein thrombosis (DVT). We have determined in 149 DVT patients and in 185 control subjects the body mass index (BMI), the haemorheological profile: blood viscosity (BV), plasma viscosity (PV), fibrinogen (Fg), erythrocyte aggregation (EA), erythrocyte deformability (ED) and plasma lipids. In the crude analysis BMI, Fg, PV, EA, triglycerides (TG) and ApoB were statistically higher and HDL cholesterol (HDL-Chol) statistically lower in DVT patients than in controls. No differences in BV and ED were observed. After BMI adjustment, Fg, PV and EA remained statistically higher in DVT cases than in controls (P = 0.013; P = 0.012; P = 0.013; P = 0.028, respectively). When the risk of DVT associated with these variables (using cut-offs that corresponded to the mean plus one SD of the control group) was estimated, EA > 8.2 and PV > 1.28 mPa . s were significantly associated with DVT even further adjustment for lipids and obesity (OR = 2.78, P = 0.004; OR = 1.91, P = 0.024, respectively). However, PV did not remain statistically significant after additional adjustment for Fg. When we consider together all the analyzed variables in order to control every variable for each other, TG > 175 mg/dl (OR = 3,2, P = 0.004) and BMI > 30 kg/m(2) (OR = 3.5, P = 0.003), were also independently associated with a greater risk of DVT. Our results suggest that increased EA constitute an independent risk factor for DVT. However, when associated to hyperlipidaemia and obesity it further increases thrombotic risk.
- SourceAvailable from: Ralf Kaiser[Show abstract] [Hide abstract]
ABSTRACT: Elevated plasma viscosity (PV) is observed in patients with vascular risk factors, such as diabetes mellitus or arterial hypertension. In this study we investigated the association of plasma viscosity and the different clinical and radiological entities of cerebral ischemia. PV of 465 consecutively admitted patients with clinical symptoms of acute cerebral ischemia without radiological signs of bleeding was measured. Data is expressed as median [range] unless stated otherwise. p<0.05 was considered statistically significant. Patients with acute cerebral ischemia (TIA or Stroke) showed increased PV (TIA 1.27mPas [1.07-1.53], stroke 1.27mPas [1.07-1.56]) compared to patients without cerebral ischemia (Mimics) (1.23mPas [1.06-1.42]). The group with radiologically proven small vessel disease (SVD) had a significantly higher mean values of PV (1.29mPas [1.06-1.54]) compared to those with signs of large vessel disease or cardioembolic events (1.22mPas [1.07-1.56], p<0.001). Patients with chronic heart failure (p=0.007), arterial hypertension (p<0.001) and diabetes mellitus (p=0.002) had higher PV compared to patients without these cardiovascular risk factors. Hyperlipidemia or nicotine abuse showed no relation to PV. Elevated PV is not only associated TIA and Stroke but is also found in patients with radiological signs of cerebral SVD. High levels of PV could be an underestimated risk for TIA and Stroke and participate in the complex pathophysiology of SVD. Prospective observational and interventional studies are warranted for further evaluation of PV in neurological ischemic diseases.Thrombosis Research 10/2013; · 3.13 Impact Factor
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ABSTRACT: Red blood cell aggregation is an important risk indicator of cardiovascular diseases, which can be quantified by dynamical parameters derived from a time-dependent light transmission profile (syllectogram). This study tests the hypothesis that inhibitory factors on the aggregation process of the blood could greatly alter the dynamical information provided by the syllectogram and highlights the possible limitations in utilizing time-dependent photometric methods for quantifying aggregation. The concept of AIwin (aggregation index) that has been used in conventional aggregometers to determine the extent of aggregation within a 12-s standard time period was distinguished from AI (aggregation index) derived from the aggregating phase of syllectogram. Apparent time delays in shape recovery and aggregating phases were observed at high levels of aggregation inhibition (high medium viscosity) which accounted for the discrepancy between AI and AIwin. In the presence of a small shear (3 s−1), this discrepancy diminished. Fractal analysis was used to validate the aggregation results obtained from the syllectogram. AI was found to better depict the extent of aggregation compared to AIwin.International Journal of Precision Engineering and Manufacturing 13(3). · 1.59 Impact Factor
© 2007 Schattauer GmbH, Stuttgart
Influence of lipids and obesity on haemorheological parameters in
patients with deep vein thrombosis
AmparoVayá1, Cristina Falcó1, María Simó1, Fernando Ferrando1,Yolanda Mira1, JoséTodolí2,Francisco España3,
1Haemorheology andThrombosis Unit, Department of Clinical Pathology, La Fe University Hospital,Valencia, Spain;2Internal Medicine
Service, La Fe University Hospital,Valencia, Spain;3Research Centre, La Fe University Hospital,Valencia, Spain;4Genetic and Molecular
Epidemiology Unit, School of Medicine, University ofValencia, Spain;5CIBER Fisiopatología de la obesidad y nutrición, Instituto de Salud
Carlos III, Madrid, Spain
It is not well established whether haemorheological alterations
constitute independent risk factors for deep vein thrombosis
trol subjects the body mass index (BMI),the haemorheological
profile: blood viscosity (BV), plasma viscosity (PV), fibrinogen
(Fg), erythrocyte aggregation (EA), erythrocyte deformability
(ED) and plasma lipids.In the crude analysis BMI,Fg,PV,EA,trig-
lycerides (TG) andApoB were statistically higher and HDL cho-
lesterol (HDL-Chol) statistically lower in DVT patients than in
adjustment,Fg,PV and EA remained statistically higher in DVT
cases than in controls (P=0.013;P=0.012;P=0.013;P=0.028,re-
spectively).When the risk of DVT associated with these vari-
Deep vein thrombosis, lipids, obesity, haemorheology
of the control group) was estimated,EA>8.2 and PV>1.28 mPa.s
were significantly associated with DVT even further adjustment
spectively). However, PV did not remain statistically significant
after additional adjustment for Fg.When we consider together
all the analyzed variables in order to control every variable for
(OR=3.5, P=0.003), were also independently associated with a
greater risk of DVT.Our results suggest that increased EA con-
stitute an independent risk factor for DVT.However,when as-
sociated to hyperlipidaemia and obesity it further increases
Thromb Haemost 2007; 98: 621–626
Blood Coagulation, Fibrinolysis and Cellular Haemostasis
AmparoVayá, MD, PhD
Hemorheology andThrombosis Unit
Department of Clinical Pathology
La Fe University Hospital
Avda. Campanar 21,Valencia 46009, Spain
Tel.: +34 96 3862714, Fax: +34 96 1973109
This study was partially supported by grants from Instituto de Salud Carlos III (CIBER
CB06/03/0035 and Red RECAVA RD06/0014/0004), Spain.
Received February 7, 2007
Accepted after resubmission May 29, 2007
Prepublished onlineAugust 18, 2007
inherited and acquired risk factors play an important pathogenic
role (1). SinceVirchow, it is assumed that blood flow alterations
(haemorheological alterations) may favour the development of
venous thrombus (2). The rheological hypothesis for venous
tors for DVT with systemic rheological alterations (3, 4) and the
trol studies (5–10). However, there is not enough evidence to
prove that haemorheological alterations constitute independent
phase, when the temporary fibrinogen increase (the protein
which modulates most of the haemorheological parameters) is
strongly marked. Moreover, studies conducted so far consist
mainly of a small sample size (6, 7, 9, 11, 12), do not determine
all the rheological parameters (5–8, 10), do not exclude patients
with malignant, inflammatory, autoimmune or infectious dis-
dition, they do not always consider the presence of concomitant
classical cardiovascular risk factors, i.e. obesity, hypertension,
be overlooked as they affect rheological blood behaviour, acting
as confounders. In particular, both obesity (13–18) and hyper-
lipidaemia (16, 19–26) appear to be associated with a two- to
four-fold increased risk of DVT. The prothrombotic pathogenic
Vayá et al. Lipids, obesity and haemorheology in DVT
blood flow characteristics, given that lipids and fibrinogen,
which are increased in both conditions, may modulate most of
the haemorheological parameters.
The aim of the present study was to assess the overall hae-
patients with DVT, i.e. blood viscosity (BV), plasma viscosity
(PV) and erythrocyte aggregation (EA) and deformability (ED),
to find out whether some haemorheological parameters consti-
tute independent risk factors for DVT and to determine whether
the lipid alterations themselves or those due to obesity could
modify rheological parameters and thus promote DVT.
Materials and methods
One hundred and forty-nine patients with previously docu-
mented DVT (86 male, 63 female) aged 42 ± 12 years were re-
ferred to our Haemorheology andThrombosis Unit between Ja-
nuary 2003 and October 2006. They all had experienced a first
DVT episode six to 12 months before sampling (mean, 9 ± 3
autoimmune or inflammatory diseases, i.e. those pathologies
rheological drugs. Those patients with inherited (antithrombin,
protein C or protein S deficiency, factorV Leiden, prothrombin
diolipin antibodies) thrombophilic risk factors were also ex-
cluded as their thromboembolic episodes could be explained by
years, 89 male, 96 female) undergoing a routine check up at our
hospital, without a previous history of DVT confirmed with a
validated questionnaire (27). Cardiovascular risk factors were
(body mass index [BMI] >30 kg/m2), current tobacco use (>1
cigarette/day), hypertension (diastolic blood pressure >90
mmHg), hyperlipidaemia (total cholesterol >220 mg/dl and/or
triglycerides >175 mg/dl), fasting glucose >126 mg/dl, or were
receiving any pharmacological treatment for hypertension, hy-
to participate in the study, which was approved by the Hospital
Circumstantial patient thrombotic risk factors, i.e. medical
(oral contraceptives, varicose veins, pregnancy, bed rest >1
week, heart failure, chronic obstructive pulmonary disease,
(secondary DVT), and those thrombotic events that occurred
without any circumstantial risk factor were considered sponta-
neous DVT. From the 149 DVT patients, 111 showed some cir-
cumstantial risk factors (75%) and 38 did not (25%). In the 111
as follows: medical 41.7%, surgical 17.5%, immobilisation
20.5% and trauma 20.3%. In addition, 16 of the 149 DVT pa-
tients had a pulmonary embolism (PE). DVT was documented
with ultrasonography or venography, and PE with ventilation
perfusion scanning, pulmonary angiography, or helicoidal com-
Blood was collected at least six months after the acute event
(range 6–12 months; mean: 9 ± 3 months).After a 12-hour over-
night fast, blood was drawn between 8 and 10 a.m. by venipunc-
ture into standard vacuum tubes containing EDTA K3for rheo-
logical and haematological measurements, 0.1 vol of 0.129 M
trisodium citrate as an anticoagulant for fibrinogen measure-
ment, or into plain tubes for glucose and lipids determination.
Rheological parameters were examined within 2 hours of blood
cosimeter (Engineering, Stougthon MA, USA) at native and
45% corrected hematocrit with autologous plasma, at two shear
rates of 230 s-1and 23 s-1, at 37ºC. Plasma viscosity (PV) was
measured in a capillary plasma viscosimeter (Fresenius GmbH,
mined in a Myrenne MA1aggregometer (Myrenne, GmbH,
Roetgen, Germany) (30) after adjusting the haematocrit to 45%
with autologous plasma, during completed stasis (EA0) and
The greater the tendency of red blood cell to aggregate, the
higher the aggregability index. Erythrocyte deformability (ED)
was determined in a Rheodyn shear stress diffractometer (My-
renne GmbH) at 12, 30 and 60 Pascals (31).The higher the ery-
throcyte elongation index (EEI), the more deformable the red
techniques on anACL7000 autoanalyser (Instrumentation Lab-
oratory, Milan, Italy). Haematocrit was measured by microcen-
trifugation at 15,000 x g for 10 minutes.
rol (LDL-Chol), high-density lipoprotein-cholesterol (HDL-
Chol), triglycerides, and glucose were measured by enzymatic
techniques, using a DAX 72 autoanalyser (Bayer Diagnostics
Division,Tarrytown, NY, USA).ApolipoproteinsAIand B were
quantified by immunonephelometry (Dade Behring, Marburg
Basic haematological parameters and red cell indices, in-
cluding mean cell volume (MCV), mean haemoglobin concen-
tration (MHC), and mean corpuscular haemoglobin concen-
lyser (TOA Medical Electronics, Kobe, Japan).
controls and ED in 40 cases and 59 controls. Cases and controls
were processed simultaneously.
All continuous variables were checked for normal distribution.
TG, glucose and Fg values were log-transformed for statistical
(SD). Student's t-test was used to assess the mean differences in
continuous variables between patients and control subjects, and
Chi2-tests were used to compare differences in percentages be-
tween patients and controls. Pearson correlation coefficients
Vayá et al. Lipids, obesity and haemorheology in DVT
ables. Multiple lineal regression analysis (covariance method)
was used to adjust for the influence of BMI or the other param-
eters on the unadjusted differences of means in lipids, fibri-
nogen, plasma viscosity and erythrocyte aggregation between
DVT patients and controls. In these analyses, we used different
models depending on the adjusted variable. First, we adjusted
for all the other variables that were statistically significant in the
unadjusted analysis. Taking into account that after these adjust-
ment BMI was the only variable that remained highly signifi-
and haemorheological parameters were only adjusted for BMI.
Logistic regression models (crude and adjusted for potential
confounders) were fitted to estimate the odds ratio (OR) and
95% confidence interval (CI) of DVT associated with the pres-
these analyses, dichotomised variables according to cut-off
points that corresponded to the mean plus one SD of the control
group were used. Standard regression diagnostic procedures
were used to ensure the appropriateness of the models.
For statistical inference, a bilateral p-value <0.05 was con-
sidered statistically significant. All analyses were calculated
using the Statistical Package for Social Sciences (SPSS, version
14) for Windows.
Table 1 shows the percentage of DVT patients and controls with
cardiovascular risk factors. DVT patients showed a higher per-
(23% vs. 6%, P=0.001) than controls. When hypercholesterole-
mia (T-Chol >220 mg/dl) and hypertriglyceridemia (TG
borderline increased percentage of hypercholesterolemia
(P=0.040) and a higher percentage of hypertriglyceridemia
(P=0.001). The percentage of hypertensives, diabetics and
smokers was similar in DVT patients and control subjects.
Table 2 shows BMI, glucose, lipids and haemorheological
parameters in the 149 DVT patients and 185 control subjects.
nificantly higher and HDL-Chol lower in cases than in controls.
After multivariate adjustment for the potential confounding fac-
adjusting for BMI, only Fg, PV, EA0and EA1remained signifi-
cantly different between patients and controls.
No statistical differences in rheological parameters were ob-
patients and controls (MCV: 91 ± 10 vs. 90 ± 5 fl, P= 0.782;
P=0.875). The Pearson bivariate correlations between haemor-
heological and lipid parameters were statistically significant
(P<0.01) between EA1and BMI (r=0.334), T-Chol (r=0.268),
LDL-Chol (r=0.269), Apo B (r=0.344), TG (r=0.356), Fg
tween EA1and HDL-Chol (r=-0.152) (P<0.05 in all cases). In
addition, PV correlated with BMI (r=0.196), Apo B (r=0.186),
Given the multiple correlations between the rheological pa-
rameters, lipids and BMI, to estimate the risk of obesity associ-
ated with these parameters, a logistic regression analysis was
carried out. Instead of continuous variables, dichotomized vari-
ables (according to cut-off points that corresponded to the mean
rameters to better estimate the risk associated with high values.
rameters (EA1>8.2, PV>1.28 mPa.s, Fg>320 mg/dl) and obesity
(BMI>30 kg/m2). In the crude Model I all parameters were sig-
nificantly associated with a higher risk of DVT.This association
remained statistically significant even further adjustment for li-
tically significant in Model IV.
tained that TG >175 mg/dl (OR=3.2, 95% CI=1.4–7.3,
P=0.004), Fg>320 mg/dl (OR=2.7, 95% CI=1.3–5.6, P=0.008),
EA1>8.2 (OR=2.8, 95% CI=1.3–5.9, P=0.007) and BMI >30
kg/m2(OR=3.5, 95% CI=1.5–8.1, P=0.003), but not PV >1.28
mPa.s norT-Chol >220 mg/dl remained significantly associated
with DVT. Therefore TG, Fg, EA1and BMI constitute indepen-
dent risk factors for DVT when they reach high values (higher
than mean plus one SD).
The results obtained in the present study indicate that DVT pa-
tients do not show a higher BV compared to the control group,
Table 1:Age, gender, BMI and incidence (%) of cardiovascular
risk factor in DVT patients and controls.
42 ± 12
27.6 ± 4.23
42 ± 13
24.5 ± 3.5
Age (mean ± SD)
*T-Chol>220 mg/dl and/orTG>175 ml/dl or were receiving any pharmacological treatment.
**T-Chol >220 mg/dl or were receiving any pharmacological treatment.
***TG>175 ml/dl or were receiving any pharmacological treatment.
Vayá et al. Lipids, obesity and haemorheology in DVT
is available on DVT case-control studies regarding BV evalu-
ation. Our results agree with those previously reported (5, 6, 9,
bal rheological parameter, depending on haematocrit, Fg con-
centration and ED. Given that DVT patients in the present study
did not show a lower ED either, it is reasonable that, at the shear
the former did not show any significant difference with respect
to the control group. The significant increase in Fg observed in
produce significant increases in BV. Our results agree with sev-
eral studies where DVT patients show significant Fg increases
even three months or more after the acute event (5, 6, 8–12). In
Table 2: BMI, glucose, li-
pids and haemorheological
parameters in DVT pa-
tients and controls.
Plasma viscosity (mPa.s)
Erythrocyte aggregation 3s-1
Native bloodViscosity 230s-1(mPa.s)
Native Blood viscosity 23s-1(mPa.s)
Corrected BloodViscosity 230s-1(mPa.s)
Corrected blood viscosity 23s-1(mPa.s)
Erythrocyte elongation index 12 Pa (%)
Erythrocyte elongation index 30 Pa (%)
Erythrocyte elongation index 60 Pa (%)
043 ± 4
001.25 ± 0.07
003.85 ± 1.28
042 ± 4
001.22 ± 0.06
003.46 ± 1.02
007.58 ± 1.36
004.34 ± 0.58
006.61 ± 1.0
004.63 ± 0.39
007.09 ± 0.69
047 ± 3
053 ± 3
056 ± 3
006.99 ± 1.17
004.29 ± 0.52
006.43 ± 1
004.61 ± 0.31
007.06 ± 0.61
047 ± 4
054 ± 4
057 ± 3
Values expressed as mean ± SD. *The corresponding P-value of each variable was adjusted for the other variables that were statistically significant in the un-
adjusted analysis. **The corresponding P-value was adjusted only for BMI.
BMI (kg/m2)027.6 ± 4.23 024.5 ± 3.5
Glucose (mg/dl)091 ± 14 090 ± 14.34
Total cholesterol (mg/dl)211 ± 47 203 ± 37
HDL-Cholesterol (mg/dl)050 ± 15055 ± 13
LDL-Cholesterol (mg/dl)133 ± 38130 ± 34
Triglycerides (mg/dl)127 ± 91094 ± 48
ApoAI(mg/dl)144 ± 32145 ± 25
Apo B (mg/dl)103 ± 30095 ± 23
B/AI000.74 ± 0.26 000.67 ± 0.21
Fibrinogen (mg/dl) 282 ± 72252 ± 46
Table 3: Risk of DVT associated with haemorheological parameters and BMI. Crude and adjusted models.
Model IV adjusted***
Units: PV: mPa.s; Fg: mg/dl; BMI: kg/m2. * Model II.Adjusted for lipids:T-Chol > 220 mg/dl andTG > 175 mg/dl. ** Model III.Adjusted for lipids and BMI > 30 kg/m2.*** Model IV.Adjusted for lipids, BMI > 30 kg/m2
and Fg > 320 mg/dl. +Adjusted for lipids and BMI > 30 kg/m2.++Adjusted for lipids and Fg > 320 mg/dl.
Model I unadjusted
Model II adjusted*
Model III adjusted**
Vayá et al. Lipids, obesity and haemorheology in DVT
conducted by Koster (8), in which 199 patients with a first DVT
episode were compared with 199 healthy subjects, those with
plasma Fg higher than 500 mg/dl had an almost four-fold in-
creased risk of DVT.
With respect to ED, as mentioned, we did not observe differ-
ences between cases and controls at any of the shear stresses
tested. There have been no studies published, so far, where this
rheological parameter has been evaluated using ektacytometric
techniques, as in the present one. Previous studies (32, 33) that
found controversial results regarding ED in DVT patients, used
cytic factors such as remnant leucocytes, red blood cell aggre-
gates or plasma factors (34, 35), whereas ektacytometry does
As regards the other rheological parameters analysed in the
present study, it is important to highlight that DVT patients have
shown increased PV and EA when compared with controls. It is
known that both rheological parameters are influenced by plas-
ma lipids (10, 36–39) and Fg levels (40–42), which have also
shown to be increased in our study.Additionally, obesity is also
associated with increased Fg andTG levels (14, 16, 21, 43–46).
In the present study, the risk associated with obesity (BMI
≥30 kg/m2) was 3.5 (95% CI 1.5–8.1), which is in line with pre-
vious studies carried out by our group where the risk of DVT as-
son, the first question we should consider is: Is the increase in
increase in Fg and lipids or is their increase associated to obes-
ity? In other words, if patients with DVT were not obese:Would
they still have increased PV and EA? Our logistic regression
models (Table 3) indicate that EA1> 8.2 and PV > 1.28 mPa.s
were significantly associated with DVT even further adjustment
for lipids (Model II) and obesity (Model III).These results sug-
statistically significant after additional adjustment for Fg
(Model IV), given the high influence of Fg on this rheological
factor for DVT, increasing the risk even though patients would
not be obese. However, the fact of being obese would further in-
crease the risk.
Several authors have also found EA to be increased in DVT
patients 12 months after the acute event (6, 10–12). Some re-
searchers have found higher EA only in those patients with per-
sistent thrombotic risk factors but not in those with transient
thrombotic risk factors (11). In this sense, we have not observed
any differences in this rheological parameter in connection with
ary DVT. It must be emphasised that some studies include pa-
tients with malignancy (11, 12) where increased Fg could have
been responsible for erythrocyte hyperaggregability. Other au-
thors (7) performed the study six weeks after the acute episode,
tion, most studies did not measure plasma lipids which may also
account for erythrocyte hyperaggregability. In our study, the in-
role played by lipids on EA has also been evaluated, allowing us
to conclude that, according to our logistic regression analysis,
risk almost three times.
As regards PV in DVT patients, only some studies did deter-
increased (5, 6) in association with higher cholesterol and TG
levels (5). Moreover, Balendra et al. (5) reported PV to be an in-
dependent risk factor for DVT. Although the present study has
dent risk factor for DVT (Model IV).This is consistent with the
pathophysiology of the different thrombotic locations, as in-
creases in PV mostly promote thrombus development in the
microcirculatory areas and small arteries, whereas increases in
EA promote thrombus formation in low-shear areas such as
pocket valves in the lower extremities.
In conclusion, the results obtained in the present study, per-
formed in a large group of patients with a DVT episode in the
previous 6–12 months, allow us to conclude that rheological pa-
rameters play a role in the pathogenesis of the thrombotic event.
Increased EA constitute a risk factor for DVT independently of
lipid levels and obesity status. However, when associated with
It is reasonable to advise losing weight and to decrease plasma
lipid levels in order to reduce DVT risk.
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