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Doppler study of cerebral arteries in hypercholesterolemia.
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MedLine Citation:
PMID:  21490946     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Hypercholesterolemia is one of the major modifiable risk factors for atherosclerosis of the coronary and carotid arteries. Although transcranial Doppler (TCD) studies of the cerebral arteries are indicative of decreased cerebral blood flow velocities in patients with hypercholesterolemia, the number of these studies has been limited. The aim of this study was to assess the hemodynamic status of the cerebral arteries in patients with hypercholesterolemia using TCD.
METHODS: In a case-control study, 60 individuals, including 30 hypercholesterolemic cases (low-density lipoprotein [LDL] > 160 mg/dL) and 30 healthy controls were enrolled. Other arterial risk factors, including diabetes mellitus, hypertension, smoking, and obesity (body mass index > 30), were evaluated and matched as well. TCD was used to assess the hemodynamics of the intracranial arteries as well as the internal carotid arteries. The mean blood flow velocity, pulsatility index, and resistance index were recorded in all the arteries.
RESULTS: The mean blood flow velocity, pulsatility index, and resistance index of the intracranial arteries and internal carotid arteries were not significantly different between the two groups (P > 0.05). However, those with higher levels of LDL (>180 mg/dL) showed significantly lower mean blood flow velocity and resistance index of the internal carotid arteries than the healthy controls. In addition, individuals with high-density lipoprotein (HDL) <35 mg/dL had significantly lower mean blood flow velocity in the internal carotid arteries.
CONCLUSION: Hypercholesterolemia (LDL >160 mg/dL) does not seem to have a detrimental effect on the hemodynamic status of the intracranial arteries and internal carotid arteries. However, in cases of higher LDL (>180 mg/dL) and lower HDL, decreased TCD parameters in the internal carotid arteries, as a surrogate of the peripheral arteries, are prominent.
Authors:
Mehdi Farhoudi; Kaveh Mehrvar; Naser Aslanabadi; Kamyar Ghabili; Nazila Rasi Baghmishe; Farzad Ilkhchoei
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Publication Detail:
Type:  Journal Article     Date:  2011-03-31
Journal Detail:
Title:  Vascular health and risk management     Volume:  7     ISSN:  1178-2048     ISO Abbreviation:  Vasc Health Risk Manag     Publication Date:  2011  
Date Detail:
Created Date:  2011-04-14     Completed Date:  2011-08-09     Revised Date:  2013-06-30    
Medline Journal Info:
Nlm Unique ID:  101273479     Medline TA:  Vasc Health Risk Manag     Country:  New Zealand    
Other Details:
Languages:  eng     Pagination:  203-7     Citation Subset:  IM    
Affiliation:
Neuroscience Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
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MeSH Terms
Descriptor/Qualifier:
Adult
Aged
Biological Markers / blood
Blood Flow Velocity
Carotid Artery, Internal / physiopathology,  ultrasonography
Case-Control Studies
Cerebral Arteries / physiopathology,  ultrasonography*
Cerebrovascular Circulation*
Chi-Square Distribution
Female
Humans
Hypercholesterolemia / blood,  physiopathology,  ultrasonography*
Iran
Lipoproteins, HDL / blood
Lipoproteins, LDL / blood
Male
Middle Aged
Pulsatile Flow
Regional Blood Flow
Ultrasonography, Doppler, Transcranial*
Vascular Resistance
Chemical
Reg. No./Substance:
0/Biological Markers; 0/Lipoproteins, HDL; 0/Lipoproteins, LDL
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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Journal Information
Journal ID (nlm-ta): Vasc Health Risk Manag
Journal ID (publisher-id): Vascular Health and Risk Management
ISSN: 1176-6344
ISSN: 1178-2048
Publisher: Dove Medical Press
Article Information
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© 2011 Farhoudi et al, publisher and licensee Dove Medical Press Ltd.
License:
Received Day: 30 Month: 3 Year: 2011
collection publication date: Year: 2011
Print publication date: Year: 2011
Electronic publication date: Day: 31 Month: 3 Year: 2011
Volume: 7First Page: 203 Last Page: 207
ID: 3072744
PubMed Id: 21490946
DOI: 10.2147/VHRM.S18663
Publisher Id: vhrm-7-203

Doppler study of cerebral arteries in hypercholesterolemia
Mehdi Farhoudi1
Kaveh Mehrvar2
Naser Aslanabadi3
Kamyar Ghabili1
Nazila Rasi Baghmishe4
Farzad Ilkhchoei4
1Neuroscience Research Center
2Razi Hospital
3Department of Cardiology
4Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
Correspondence: Correspondence: Kamyar Ghabili, Neuroscience Research Center, Tabriz University of Medical Sciences, Tabriz, Iran, Tel +98 91 4410 6136, Fax +98 41 1336 1120, Email kghabili@gmail.com

Introduction

Cerebrovascular disease and subsequent stroke is one of the most important neurological diseases. Several modifiable (eg, hypertension, hyperlipidemia, obesity, smoking, and diabetes) and nonmodifiable (eg, gender, age, and race) risk factors for stroke have been established.1 Hypercholesterolemia is one of the major modifiable risk factors for atherosclerosis of the coronary and carotid arteries. However, its role in the pathogenesis of stroke is unknown.24 Although early epidemiological studies failed to find an association between cholesterol levels and overall stroke risk,5,6 later investigations revealed a relationship between dyslipidemia and risk of ischemic stroke.79

Assessments of human and animal arterial vasculature revealed an impaired endothelial function in hypercholesterolemia.1012 In addition, transcranial Doppler (TCD) studies of the major cerebral arteries have shown decreased cerebral blood flow velocities in patients with familial hypercholesterolemia.13 Nonetheless, studies of the hemodynamics of the cerebral vasculature in hypercholesterolemic patients are limited. The present study aimed at assessing the hemodynamic status of the cerebral arteries in patients with hypercholesterolemia using TCD.


Methods

In this case-control study, 60 individuals comprising 30 hypercholesterolemic cases (low-density lipoprotein [LDL] >160 mg/dL) and 30 healthy controls were enrolled in a university-affiliated hospital in Tabriz, Iran. The study was approved by the local ethics committee and written informed consent was obtained for each subject. Both groups were age- and gender-matched. Other arterial risk factors including diabetes mellitus, hypertension, smoking, and obesity (body mass index > 30) were evaluated and matched as well. Individuals who had given up smoking for more than five years were considered to be nonsmokers. TCD was used to assess the hemodynamics of the cerebral arteries (DWL®, Multi-Dop®, Germany). The standard method of using a 2 mHz probe for the intracranial arteries and a 4 mHz probe for the cervical carotids was applied in the present study. The Doppler signals were detected through the temporal window for the middle cerebral artery, anterior cerebral artery and two segments of the posterior cranial artery (PCA1, PCA2), through the suboccipital window for the vertebral arteries and basilar artery, and through the cervical window for the internal carotid arteries.14 Mean blood flow velocity, pulsatility index, and resistance index were recorded in all the arteries.1517

Data were presented as means ± standard deviations. Statistical analysis was performed with SPSS for Windows version 13.0 (Chicago, IL) and by using the Chi-square test, Fisher’s Exact test, and independent-samples t-test wherever appropriate. P < 0.05 was considered statistically significant.


Results

Sixty individuals were included in the study, ie, 30 in the hypercholesterolemic group and 30 in the healthy control group. There were no differences in gender, age, and vascular risk factors, including hypertension, diabetes mellitus, smoking, and obesity between the groups (Table 1, P > 0.05). Moreover, the mean blood flow velocity, pulsatility index, and resistance index of the intracranial arteries and internal carotid arteries were not significantly different between the two groups (Table 2, P > 0.05).

To find out whether higher levels of LDL alter the hemodynamics of the cerebral arteries, individuals with LDL levels of less and more than 180 mg/dL were compared (Table 3). The mean blood flow velocity and resistance index of the internal carotid arteries in those with LDL > 180 mg/dL was significantly lower than that in individuals with LDL < 180 mg/dL (P < 0.05, Table 3). In addition, individuals with high-density lipoprotein (HDL) <35 mg/dL were compared regarding TCD indices in both groups. The analysis revealed a significant difference only in mean blood flow velocity of the internal carotid arteries.


Discussion

The hemodynamics of the cerebral vasculature in both healthy individuals and patients have been of great research interest.18 Impaired cerebral vasomotor reactivity to L-arginine and/or CO2 has been reported in patients with recent stroke,19 severe internal carotid artery stenosis,20 lacunar infarction, and high blood pressure.21 Nonetheless, studies of the hemodynamics of the cerebral vasculature in hypercholesterolemic patients are limited. The current literature mainly focuses on the effect of lipid-lowering methods on hemodynamic alterations in the cranial arteries. Sander et al22 and Sterzer et al23 reported an improvement in cerebral vasoreactivity after statin administration. However, the results of PROSPER (Prospective Study of Pravastatin in the Elderly at Risk) failed to confirm this finding.24 On the other hand, Pfefferkorn et al25 revealed that cholesterol reduction through heparin-mediated extracorporal LDL precipitation resulted in an improvement of cerebrovascular CO2 reactivity in patients with coronary heart disease and hyperlipidemia. Interestingly, Rubba et al13 and Iannuzzi et al26 noted an increasing trend in cerebral blood flow velocities after LDL apheresis in patients with familial hypercholesterolemia.

The present study showed that the hemodynamic status of the cerebral arteries, including the internal carotid arteries, was similar in healthy individuals and those with LDL > 160 mg/dL. Nonetheless, in cases of a higher cholesterol level (LDL > 180 mg/dL), decreased mean blood flow velocity and resistance index of the internal carotid artery were noted, indicating the effect of high LDL levels only on the peripheral arteries. Reduced mean blood flow velocity of the internal carotid arteries was also seen with lower levels of HDL, probably indicative of the protective effect of HDL in prophylaxis of arterial damage. Kerenyi et al27 failed to find any significant difference between healthy controls and hyperlipidemic patients in cerebrovascular reactivity or reserve capacity after intravenous administration of acetazolamide. In a study of stroke-free Chinese individuals, hypercholesterolemia was associated with decreased blood flow velocity in the extracranial arteries, eg, the common carotid artery and internal carotid artery. However, this association was an inverse one in the intracranial arteries.28 Nevertheless, a few studies of patients with familial hypercholesterolemia have reported contrasting results in this regard. Rubba et al13 and Iannuzzi et al26 found an abnormally low cerebral blood flow velocity in the middle cerebral artery prior to LDL apheresis in patients with familial hypercholesterolemia. A later study by Rubba et al29 demonstrated lower diastolic blood flow velocities and a higher pulsatility index in the middle cerebral artery in familial hypercholesterolemic patients compared with control subjects. It seems that higher levels of LDL (about 600 mg/dL) in studies of patients with familial hypercholesterolemia have reported controversial results regarding the hemodynamic status of the cranial arteries.

Although the relationship between hypercholesterolemia and coronary and carotid artery atherosclerosis is established, its role in the pathogenesis of stroke is unknown. An ultrasound study has shown a direct relationship between lipid levels and atherosclerosis of the carotid artery.1,30 Moreover, formation of reactive oxygen species has been deemed to play a role in the pathogenesis of cerebral vascular dysfunction during hypercholesterolemia. Reactive oxygen species impair the response to acetylcholine, enhance superoxide activity, and lead finally to endothelial dysfunction.31

This study has certain limitations. It was a single-center study with a quite small sample size. A multicenter study including a large number of patients may give more concrete results. We did not exclude patients with a drug history of lipid-lowering agents. Further investigations excluding individuals on lipid-lowering agent therapy, eg, statins are recommended. Furthermore, other sources of potential bias, including anxiety disorders, were not controlled for. On the other hand, some advantages of the current study might be highlighted. We matched the hypercholesterolemic and control groups with regard to arterial risk factors, including diabetes mellitus, hypertension, smoking, and obesity. We applied two different definitions of hypercholesterolemia (LDL 160 versus 180 mg/dL) to achieve further results.

In conclusion, hypercholesterolemia (LDL > 160 mg/dL) does not seem to have a detrimental effect on the hemodynamic status of the intracranial arteries and internal carotid arteries. However, in cases of higher cholesterol levels (LDL > 180 mg/dL) and lower levels of HDL, decreased TCD parameters for the internal carotid arteries, as a surrogate for the peripheral arteries, are prominent.


Notes

Disclosure

The authors report no conflicts of interest in this work.

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Article Categories:
  • Original Research

Keywords: hypercholesterolemia, transcranial Doppler, cerebral arteries.

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