© 1998 American Heart Association, Inc.
Original Contributions |
Relationship Between Plasma Viscosity and the Severity of Coronary Heart Disease
From the Institut für Klinische Chemie und Laboratoriumsmedizin, Westfälische Wilhelms-Universität Münster (R.J., H.U., G.A.); Städtisches Klinikum Solingen (J.H.); Institut für Arterioskleroseforschung an der Westfälischen Wilhelms-Universität Münster (H.S., G.A.); and LVA-Klinik Salzetal, Bad Salzuflen (R.S., E.K.), Germany.
Correspondence to Ralf Junker, Institut für Klinische Chemie und Laboratoriumsmedizin, Westfälische Wilhelms-Universität Münster, Albert Schweitzer-Straße 33, 48129 Münster, Germany. E-mail junkerr{at}uni-muenster.de
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Abstract |
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Abstract—Several studies have indicated that plasma viscosity contributes to cardiovascular risk in men. So far, a significant relationship between plasma viscosity and the severity of coronary heart disease has not been found. Thus, the present study is the first to report on the relationship of plasma viscosity and the severity of coronary heart disease. In a collective of 1142 male myocardial infarction patients, plasma viscosity and additional laboratory parameters were determined. Atherosclerotic changes were quantified by coronary angiography. Patients were divided into groups without any, and with one to three stenosed vessels. We found a positive relationship between plasma viscosity and the severity of coronary heart disease, even after adjusting groups for age, fibrinogen, and use of diuretics. Mean plasma viscosity ranged from 1.141±0.035 mPa s in patients without stenosed vessels to 1.162±0.044 mPa s in patients who had three coronary vessels with stenoses >50%. Differences between the groups were significant (P<0.001 to 0.05), with two exceptions: differences between patients without any and with one stenosed vessel, as well as between patients with one and two stenosed vessels, did not reach the significance level. On the whole, we can give further support to the hypothesis that cardiovascular risk factors and coronary heart disease may be linked by plasma viscosity.
Key Words: coronary heart disease • myocardial infarction • coronary risk factor • blood rheology • fibrinogen
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Introduction |
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In the prospective Caerphilly and Speedwell studies, as well as in the MONICA project, plasma viscosity was indicated as a predictive risk factor for CHD.1 2 In other studies, high plasma viscosity was shown to lead to an increased risk of acute MI in patients with unstable angina pectoris.3 4 Furthermore, a relationship of an early increase in plasma viscosity during acute MI and reinfarction or death was shown.5 An elevation of plasma viscosity was found in patients with severe unstable angina pectoris compared with patients with stable angina pectoris and to healthy individuals.6 7 8 Additionally, an elevated plasma viscosity in patients with stable angina pectoris,9 even without coronary artery stenosis at angiography,10 could be demonstrated. In the MONICA project, geographical differences in plasma viscosity between populations differing in the CHD event rates were found.11 Evidently, plasma viscosity contributes to the cardiovascular risk and may be of special importance in areas of reduced blood flow, as commonly occurs in patients with advanced atherosclerosis.12
Lowe et al13 suggested that blood viscosity is related to the extension of CHD. The study that proposed this suggestion, however, consisted only of a small group of patients, and therefore the results require further investigation. Moreover, in this study, plasma viscosity was not significantly elevated in patients with extensive CHD compared with a control group and to patients with less severe CHD. Thus, the present study is the first to report on the relationship of plasma viscosity and the severity of CHD in a large collective of 1142 male MI patients.
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Methods |
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Patients
One thousand one hundred forty-two consecutive male MI patients, mean age 50.4±9.7 years, admitted to a coronary rehabilitation unit (LVA-Klinik Salzetal, Bad Salzuflen, Germany), were investigated. MI was diagnosed according to WHO criteria (central breast pain together with typical variations on electrocardiography or at least threefold increase of creatine kinase in the acute phase, or typical contraction disorder on angiography).14 Patients on oral anticoagulation were not included. There was no restriction on the use of antihypertensives, platelet aggregation inhibitors, and antidiabetics. Intake of lipid-lowering drugs was interrupted 2 weeks before blood sampling.
Evaluation of the Vascular Status
Investigation of the vessels and quantification of
atherosclerotic changes were performed by physicians who were unaware
of the laboratory results. Coronary angiography was performed
by the standard femoral or brachial approach according to
Judkins15 or Sones.16 The
left main, as well as the left anterior descending, circumflex, and
right coronary vessels, were studied. The left coronary
artery was examined in several left anterior oblique views, including
the craniocaudal projection, and at least three right anterior
oblique views, including the craniocaudal projection. The right
coronary artery was projected in at least one left anterior
oblique view and two right anterior oblique views. To ensure that all
vessel segments were viewed without an overlap, additional
projections were recorded according to coronary
morphology. Angiograms were recorded on 35-mm cineangiographic
films or on laser discs. A coronary artery was classified to be
affected by CHD if a stenosis of at least 50% of diameter
reduction at any segment was found by at least two observers. The
severity of atherosclerosis was scored from 0 (no CHD)
to 3 (stenosis >50% in three vessels).
Blood Samples
Venous blood was drawn 4 to 6 weeks after MI. Within 2 hours
after venipuncture, citrated plasma was separated by
centrifugation at room temperature for 15 minutes at
2500g. Serum for clinical chemistry was prepared by
centrifugation for 10 minutes at 3000g.
After aliquots were deposited in plastic tubes, plasma and serum were
immediately frozen and stored at -70°C.
Blood Analysis
Laboratory analyses were performed in one series at the
Institute of Arteriosclerosis Research at the
University of Münster, Germany, after having finished blood
sample collection. Plasma viscosity was measured at 37°C using a
falling ball viscosimeter (Microviscosimeter, Haake). Fibrinogen was
determined on a KC10 coagulation analyzer (Amelung), according
to Clauss,17 using thrombin, control plasma (both
Behringwerke), and a plasma pool. D-Dimer concentrations
were measured with an ELISA kit (Boehringer).
Plasminogen and F1+2 were determined using
chromogenic and ELISA kits, respectively, both by
Behringwerke. CRP was measured using an ELISA kit (Eurogenetics).
Measurement of total cholesterol and
triglycerides in serum was performed on a Hitachi 737
autoanalyzer (Boehringer). HDL cholesterol
concentrations were determined after precipitation with phosphotungstic
acid/MgCl2 (Boehringer) and LDL
cholesterol was calculated using the Friedewald formula.
Lp(a) concentrations were determined by means of electroimmunodiffusion
with the use of standards and antiserum by
Immuno.18
Statistical Analysis
Nonnormally distributed variables were logarithmically
transformed. Percentages of men with three and without any stenosed
vessels, referring to the total number of patients within tertiles of
plasma viscosity, were calculated. Age adjustment of patient groups was
performed to minimize the effect of increasing age on the severity of
CHD. Further statistical analysis was carried out after
adjusting for age, levels of fibrinogen, and current use of
diuretics. Age groups were <45, 46 to 50, 51 to 55, 56 to 60,
and >60; cutoff levels for fibrinogen were <2.75, 2.76 to 3.30, and
>3.30 g/L. Comparisons were made using t tests and
analysis of variance. Bivariate correlations were calculated
according to Pearson. An MLRA was performed to examine the effects of
different variables on plasma viscosity. All statistical
analyses were performed using the SPSSx
package.
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Results |
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Population Characteristics
Population characteristics are displayed in Table 1
. Analysis of variance revealed
a significant increase in mean values of different variables
related to the number of stenosed coronary vessels (0 to 3): BP
(systolic BP, 122.1 to 130.2 mm Hg, P<0.001;
diastolic BP, 79.2 to 81.6 mm Hg,
P<0.001), fibrinogen (2.79 to 3.31 g/L,
P<0.001), plasminogen (92.5% to 98.7%,
P<0.05), D-dimer (287.1 to 468.1 ng/mL,
P<0.001), CRP (0.72 to 1.49 mg/L, P<0.001), and
plasma viscosity (1.130 to 1.168 mPa s, P<0.001). In
addition, the BMI was higher according to increasing severity of CHD
(26.3 to 26.8 kg/m2, P<0.05). Levels
of lipids [total cholesterol, LDL and HDL
cholesterol, triglycerides, and Lp(a)], as
well as F1+2, were similar in patient groups. The percentage of smokers
decreased according to an increase in the number of stenosed vessels
(80.5% to 51.7%, P<0.05), whereas the percentage of men
using diuretics was found to be higher with increasing severity
of CHD (8.8% to 32.3%, P<0.001). The percentage of men
using lipid-lowering drugs was similar in all CHD groups (Table 1).
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Plasma Viscosity and Severity of CHD
The percentages of MI patients without any and with three stenosed
vessels, referring to the total number of MI patients within tertiles
of plasma viscosity, are shown in Figure 1. Tertile cutting points of plasma
viscosity were 1.127 mPa s and 1.164 mPa s. The relative number of men
with three stenosed vessels showed an increase according to higher
levels of plasma viscosity (from 16.6% within the lower tertile up to
32.7% within the upper tertile). In contrast, the percentage of
patients without stenosis of the coronary vessels
decreased with higher levels of plasma viscosity (from 10.6% within
the lower tertile to 3.2% within the upper tertile) (Figure 1).
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Mean plasma viscosity was 1.135±0.042/1.141±0.035 mPa s (adjusted for age/age, fibrinogen, and use of diuretics) in MI patients without stenosed vessels (n=72), 1.145±0.041/1.147±0.038 mPa s with one stenosed vessel (n=467), 1.153±0.040/1.151±0.032 mPa s with two stenosed vessels (n=341), and 1.164±0.054/1.162±0.044 mPa s with three stenosed vessels (n=262).
With the exception of no versus one stenosed vessel, differences
between the age-adjusted groups were significant (P<0.05 to
P<0.001). After adjusting for age, fibrinogen, and use of
diuretics, significance was lost for the difference between the
groups with one and with two stenosed vessels (Figure 2).
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Relationship Between Plasma Viscosity and Different Variables
by Means of Bivariate Analysis and MLRA
Significant positive bivariate correlations were found between
plasma viscosity and age, BMI, smoking, systolic BP, LDL
cholesterol, triglycerides, fibrinogen,
plasminogen, D-dimer, and CRP. Plasma
viscosity and HDL cholesterol were negatively correlated.
With the exception of BMI and smoking (P<0.01), probability
was <0.001 in all cases. No significant correlation was found between
plasma viscosity and Lp(a) or F1+2.
An MLRA was performed to consider the independence of the correlation
between plasma viscosity and the variables investigated. All
variables showing a significant bivariate correlation with plasma
viscosity were taken into account. Significance remained for plasma
viscosity and age, smoking, LDL cholesterol,
triglycerides, fibrinogen, plasminogen, and
CRP. With the exception of smoking and plasminogen
(P<0.01), probability was <0.001 in all cases. Correlation
was lost for plasma viscosity and BMI, systolic BP, HDL
cholesterol, and D-dimer (Table 2).
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Discussion |
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This study is the first showing plasma viscosity to be related to the severity of CHD. Plasma viscosity showed a significant increase according to a higher number of stenosed coronary vessels in male MI patients.
In 1980, Lowe et al13 suggested that blood viscosity is related to the extension of CHD. However, in the study proposing this suggestion, no significant relationship was found between plasma viscosity and the extension of CHD. The contrast to our results may be due to the fact that we investigated a larger collective. Geographical differences in plasma viscosity as described by Koenig et al11 may also have contributed to different findings.
The strong positive correlation between plasma viscosity and fibrinogen
found by other authors2 13 19 20 21 22 was confirmed
by our results (Table 2
). Because fibrinogen is the major determinant
of plasma viscosity,23 patient groups were
adjusted not only for age but also for levels of fibrinogen.
Additionally, groups were adjusted for current use of diuretics
to exclude an influence of such drugs. After this, the significant
relationship between plasma viscosity and the severity of CHD remained
and thus cannot be due to increased levels of fibrinogen or use of
diuretics (Figure 2). Plasma viscosity was similar in patients
using lipid-lowering drugs (until 2 weeks before blood collection) and
patients not using these drugs (data not shown).
In our study, the relative number of men with three stenosed vessels
(referring to the total number of MI patients within tertiles of plasma
viscosity) showed an increase according to higher levels of plasma
viscosity, while the opposite was found for MI patients without
stenosis of the coronary vessels (Figure 1). Elevated
plasma viscosity has been shown to have a deleterious effect on oxygen
delivery to the ischemic
myocardium.24 25 An unfavorable blood
flow may also lead to an increase in aggregation of blood cells,
especially in the presence of high levels of
fibrinogen.26 27 We therefore suggest that
ischemia and a tendency to thrombosis in stenosed vessels due
to a decreased blood flow with increasing viscosity contributes on the
one hand to the progress of atherosclerosis. On the
other hand, an increased cardiovascular risk through an
elevated plasma viscosity may be of greater relevance in already
stenosed coronary vessels. Effects of rheological properties of
blood on thrombogenesis and atherosclerosis have been
summarized by several authors.12 28 29 30
Most of our findings concerning the relationship between plasma viscosity and other parameters were consistent with the results of other authors. The positive bivariate correlation between plasma viscosity and the acute-phase protein CRP remained significant in the MLRA. Acute-phase reactions are associated with the release of molecules of high molecular mass, which increase plasma viscosity. Hence, our findings support the assumption that atherosclerosis is a mild chronic inflammatory disease.31
A positive relationship between plasma viscosity and LDL cholesterol, as well as between plasma viscosity and triglycerides, which may be explained by rheological effects of molecules of high molecular mass, are consistent with the results of other studies.19 32 33 34 35 36 37 The negative bivariate correlation between plasma viscosity and HDL cholesterol seems to be equivocal but is nevertheless consistent with the findings of other authors.36 37 38 However, the relationship remained no longer significant after performing the MLRA.
Positive bivariate correlations between plasma viscosity and fibrinogen, as well as between plasma viscosity and plasminogen, remained significant in the MLRA, indicating an elevated hemostatic balance according to an increased plasma viscosity. No bivariate correlation was found between plasma viscosity and F1+2, whereas in the MLRA, significance was lost for the bivariate correlation between plasma viscosity and D-dimer. The latter results partly contrast the findings of Lowe et al,13 who suggested an imbalance of coagulation and fibrinolysis toward coagulation, but in their study fibrinopeptide A and fibrin Bß15–42 were used as markers for coagulation and fibrinolysis. Fibrin Bß15–42 is a degradation product of fibrinogen and non–cross-linked fibrin, whereas D-dimer results from plasmin-mediated fibrinolysis of cross-linked fibrin. As cross-linking is dependent on coagulation factor XIIIa, one may speculate that on the one hand, an increased plasma viscosity may increase factor XIII activity. On the other hand, cross-linking may be enhanced by an increased plasma viscosity. Fibrinopeptide A represents fibrin generation from fibrinogen, whereas F1+2 is a marker for thrombin generation. Levels of fibrinogen (and therefore nonadjusted levels of plasma viscosity) may be more closely related to fibrin generation than levels of thrombin, which might explain the differences in our findings.19
A causal relationship between BP and plasma viscosity may be suggested, but so far evidence has not been found. We can confirm a positive bivariate correlation as previously described,2 19 20 21 39 40 but no significant relationship between BP and plasma viscosity was found in the MLRA.
One of the linking mechanisms between smoking and CHD may be the increase in fibrinogen and white blood cell count in smokers and therefore an increase in plasma viscosity related to cigarette consumption.19 20 28 40 41 42 In our study, the proportion of smokers decreased according to the number of stenosed vessels (from 80.5% in patients without stenosed vessels to 51.7% in patients with three stenosed vessels). Hence, the relationship between smoking and CHD could neither be confirmed nor rejected.
Compared with the relevant literature, plasma viscosity values were low in our study (eg, Lowe et al,13 1.38±0.10 to 1.43±0.10 mPa s; Yarnell et al,2 1.688±0.096 to 1.735±0.099 mPa s; versus our results, 1.130±0.042 to 1.168±0.057 mPa s). Instead of the conventionally used EDTA-plasma, we used 1:10 diluted citrated plasma for measuring plasma viscosity. Therefore, this finding may be attributable to the dilution effect. Another aspect contributing to low plasma viscosity levels may be the storage of frozen plasma, which could lead to a breakdown of molecules of high molecular weight. Furthermore differences in methodology have to be taken into account when comparing results of different studies. However, as the above-mentioned aspects would lead to a systematic shift in the viscosity values, the conclusions of our study are not influenced by them.
On the whole, with our recent findings, we can give further support to the hypothesis that an increased plasma viscosity may be a linking mechanism between cardiovascular risk factors and CHD. Clinical studies will be required to investigate the therapeutic benefit of reducing plasma viscosity in the clinical management of CHD.
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Selected Abbreviations and Acronyms |
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Acknowledgments |
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This study was supported by the Bundesministerium für Forschung und Technologie, the Ministerium für Wissenschaft und Forschung NRW, the Deutsche Forschungsgemeinschaft, the Landesversicherungsanstalt Westfalen, and the Landesversicherungsanstalt Rheinprovinz. The excellent technical cooperation of R. Bäumer, M. Käse, and R. Kokott is gratefully acknowledged. We thank F. Stuhldreher for English editing.
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Footnotes |
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1 Hans Ulbrich died April 25, 1996.
Received July 18, 1997; accepted November 17, 1997.
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References |
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TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
1. Koenig W, Hombach V, Ernst E, Sund M, Mraz W, Keil U. Plasma viscosity as a cardiovascular risk factor. Circulation. 1992;86:1045. Letter.
2.
Yarnell JW, Baker IA, Sweetnam PM, Bainton D, O'Brien
JR, Whitehead PJ, Elwood PC. Fibrinogen, viscosity, and white blood
cell count are major risk factors for ischemic heart disease:
the Caerphilly and Speedwell Collaborative Heart Disease Studies.
Circulation. 1991;83:836–844.
3.
Fuchs J, Pinhas A, Davidson E, Rotenberg Z, Agmon J,
Weinberger I. Plasma viscosity, fibrinogen and haematocrit in the
course of unstable angina. Eur Heart J. 1990;11:1029–1032.
4.
Neumann FJ, Katus HA, Hoberg E, Roebruck P, Braun M,
Haupt HM, Tillmanns H, Kubler W. Increased plasma viscosity and
erythrocyte aggregation: indicators of an unfavourable clinical outcome
in patients with unstable angina pectoris. Br Heart J. 1991;66:425–430.
5. Fuchs J, Weinberger I, Teboul A, Rotenberg Z, Joshua H, Agmon J. Plasma viscosity and haematocrit in the course of acute myocardial infarction. Eur Heart J. 1987;8:1195–1200.
6. Fuchs J, Weinberger I, Rotenberg Z, Erdberg A, Davidson E, Joshua H, Agmon J. Plasma viscosity in ischemic heart disease. Am Heart J. 1984;108:435–439.[Medline] [Order article via Infotrieve]
7. Leschke M, Blanke H, Stellwaag M, Motz W, Strauer BE. Hyperfibrinogenemia and pathological plasma viscosity: pathogenetic factors in unstable angina pectoris? Dtsch Med Wochenschr. 1988;113:1175–1181.[Medline] [Order article via Infotrieve]
8.
Neumann FJ, Tillmanns H, Roebruck P, Zimmermann R,
Haupt HM, Kubler W. Haemorrheological abnormalities in unstable angina
pectoris: a relation independent of risk factor profile and
angiographic severity. Br Heart J. 1989;62:421–428.
9.
Rainer C, Kawanishi DT, Chandraratna PA, Baversachs
KG, Reid CL, Ramitoola SH, Geiselman HJ. Changes in blood rheology in
patients with stable angina pectoris as a result of coronary
artery disease. Circulation. 1987;76:15–20.
10. Larsson H, Gustavsson CG, Odeberg H, Persson S. Increased whole blood and plasma viscosity in patients with angina pectoris and "normal" coronary arteries. Acta Med Scand. 1988;224:109–114.[Medline] [Order article via Infotrieve]
11. Koenig W, Sund M, Lowe GDO, Lee AJ, Resch KL, Tunstall-Pedoe H, Keil U, Ernst E. Geographical variations in plasma viscosity and relation to coronary event rates. Lancet. 1994;344:711–714.[Medline] [Order article via Infotrieve]
12. Becker RC. The role of blood viscosity in the development and progression of coronary artery disease. Cleve Clin J Med. 1993;60:353–358.[Medline] [Order article via Infotrieve]
13. Lowe GDO, Drummond MM, Lorimer AR, Hutton I, Forbes CD, Prentice CRM, Barbenel JC. Relation between extent of coronary artery disease and blood viscosity. BMJ. 1980;290:673–674.
14. World Health Organization Regional Office for Europe. Myocardial infarction community registers. Public Health in Europe. Copenhagen, Denmark: World Health Organization; 1976.
15. Judkins MP. Selective coronary angiography. Radiology. 1967;89:815–819.[Medline] [Order article via Infotrieve]
16.
Sones FM Jr. Cine coronary arteriography.
Anesth Analg. 1967;46:499–508.
17. Clauss A. Gerinnungsphysiologische Schnellmethode zur Bestimmung des Fibrinogens. Acta Haematol. 1957;17:237–246.[Medline] [Order article via Infotrieve]
18.
Heinrich J, Sandkamp M, Kokott R, Schulte H, Assmann G.
Relationship of lipoprotein(a) to variables of coagulation and
fibrinolysis in a healthy population. Clin
Chem. 1991;37:1950–1954.
19. Lowe GD, Wood DA, Douglas JT, Riemersma RA, Macintyre CC, Takase T, Tuddenham EG, Forbes CD, Elton RA, Oliver MF. Relationships of plasma viscosity, coagulation and fibrinolysis to coronary risk factors and angina. Thromb Haemost. 1991;65:339–343.[Medline] [Order article via Infotrieve]
20. Bonithon-Kopp C, Levenson J, Scarabin PY, Guillanneuf MT, Kirzin JM, Malmejac A, Guize L. Longitudinal associations between plasma viscosity and cardiovascular risk factors in a middle-aged French population. Atherosclerosis. 1993;104:173–182.[Medline] [Order article via Infotrieve]
21. Letcher RL, Chien S, Pickering TG, Sealey JE, Laragh JH. Direct relationship between blood pressure and blood viscosity in normal and hypertensive subjects: role of fibrinogen and concentration. Am J Med. 1981;70:1195–1202.[Medline] [Order article via Infotrieve]
22. Lowe GD, McArdle BM, Stromberg P, Lorimer AR, Forbes CD, Prentice CR. Increased blood viscosity and fibrinolytic inhibitor in type II hyperlipoproteinaemia. Lancet. 1982;1:472–475.[Medline] [Order article via Infotrieve]
23. Harkness J. The viscosity of human blood plasma: its measurement in health and disease. Biorheology. 1971;8:171–193.[Medline] [Order article via Infotrieve]
24. Gordon RJ, Snyder GK, Tritel H, Taylor WJ. Potential significance of plasma viscosity and hematocrit variations in myocardial ischemia. Am Heart J. 1974;87:175–182.[Medline] [Order article via Infotrieve]
25. Wells R. Microcirculation and coronary blood flow. Am J Cardiol. 1972;29:847–850.[Medline] [Order article via Infotrieve]
26.
van Breugel HF, de Groot PG, Heethaar RM, Sixma JJ.
Role of plasma viscosity in platelet adhesion. Blood. 1992;80:953–959.
27. Schmid-Schoenbein H. Microrheology of erythrocytes, blood viscosity, and the distribution of blood flow in microcirculation. In: Guyton A, Cowley AW, eds. International Review of Physiology: Cardiovascular Physiology, II. Baltimore, Md: University Park Press; 1976:1–62.
28. Ernst E, Koenig W. Hemorheology, thrombogenesis, and atherosclerosis. Semin Thromb Hemost. 1993;19:99–103.[Medline] [Order article via Infotrieve]
29. Rabbani LE, Loscalzo J. Recent observations on the role of hemostatic determinants in the development of the atherothrombotic plaque. Atherosclerosis. 1994;105:1–7.[Medline] [Order article via Infotrieve]
30. Somer T, Meiselman HJ. Disorders of blood viscosity. Ann Med. 1993;25:31–39.[Medline] [Order article via Infotrieve]
31.
Liuzzo G, Biasucci LM, Gallimore JR, Grillo RL, Rebuzzi
AG, Pepys MB, Maseri A. The prognostic value of C-reactive protein and
serum amyloid a protein in severe unstable angina. N Engl
J Med. 1994;331:417–424.
32. Jay RH, Rampling MW, Betteridge DJ. Abnormalities of blood rheology in familial hypercholesterolaemia: effects of treatment. Atherosclerosis. 1990;85:249–256.[Medline] [Order article via Infotrieve]
33. Jay RH, Jones SL, Hill CE, Richmond W, Viberti GC, Rampling MW, Betteridge DJ. Blood rheology and cardiovascular risk factors in type 1 diabetes: relationship with microalbuminuria. Diabet Med. 1991;8:662–667.[Medline] [Order article via Infotrieve]
34.
de Simone G, Devereux RB, Chien S, Alderman MH, Atlas
SA, Laragh JH. Relation of blood viscosity to demographic and
physiologic variables and to cardiovascular risk
factors in apparently normal adults. Circulation. 1990;81:107–117.
35. Levenson J, Del Pino M, Razavian M, Merli I, Filitti V, Simon A. Hypercholesterolaemia alters arterial and blood factors related to atherosclerosis in hypertension. Atherosclerosis. 1992;95:171–179.[Medline] [Order article via Infotrieve]
36.
Koenig W, Sund M, Ernst E, Mraz W, Hombach V, Keil U.
Association between rheology and components of lipoproteins in human
blood: results from the MONICA project. Circulation. 1992;85:2197–2204.
37. Jung F, Pindur G, Kiesewetter H. Plasma viscosity dependence on proteins and lipoproteins: results of the Aachen Study. Clin Hemorheol. 1992;12:557–571.
38. Koenig W, Sund M, Ernst E, Mraz W, Hombach V, Keil U. Blood lipids and lipoproteins are the main determinants of plasma viscosity: results from the MONICA project Augsburg. Clin Hemorheol. 1992;12:549–555.
39. Koenig W, Sund M, Ernst E, Keil U, Rosenthal J, Hombach V. Association between plasma viscosity and blood pressure: results from the MONICA project Augsburg. Am J Hypertens. 1991;4:529–536.[Medline] [Order article via Infotrieve]
40.
Levenson J, Simon AC, Cambien FA, Beretti C. Cigarette
smoking and hypertension. Factors independently associated with blood
hyperviscosity and arterial rigidity.
Arteriosclerosis. 1987;7:572–577.
41.
Yarnell JW, Sweetnam PM, Rogers S, Elwood
PC, Bainton D, Baker IA, Eastham R, O'Brien JR, Etherington MD. Some
long term effects of smoking on the haemostatic system: a report from
the Caerphilly and Speedwell collaborative surveys. J Clin
Pathol. 1987;40:909–913.
42. Lowe GD, Drummond MM, Forbes CD, Barbenel JC. The effects of age and cigarette-smoking on blood and plasma viscosity in men. Scott Med J. 1980;25:13–17.[Medline] [Order article via Infotrieve]
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