Large and Small Vessels Atherosclerosis: Similarities and Differences

doi:10.1016/j.pcad.2007.04.001

Progress in Cardiovascular Diseases

Volume 50, Issue 2, September–October 2007, Pages 112-125

https://doi.org/10.1016/j.pcad.2007.04.001 Get rights and content

Atherosclerosis is a systemic, multifocal disease leading to a various symptoms and clinical events. Beyond disparities related to the organs involved, some differences might exist according to whether the lesions occur in the large (proximal) or small (distal) arteries. Atherosclerotic lesions occur predominantly in the large vessels first, and more distal lesions occur with aging. Proximal lesions are usually more evolving, especially with higher rates of unstable plaques in the proximal segments of coronary arteries. Racial differences regarding lesion distribution exist, with higher rates of distal lesions observed in races other than caucaians. Despite conflicting results found in each vascular territory, there is a suggestion of a stronger association between large vessel disease and smoking and dyslipidemia, whereas diabetes appears more specific for small vessel disease. Hypertension is more frequently reported in intracranial than in extracranial cerebrovascular disease. Preliminary studies report inflammatory markers preferably associated to large-vessel atherosclerosis. Proximal lesions in 1 territory are more frequently associated with concomitant lesions in other territories. Geometric, hemodynamic, and histologic particularities in large and small vessels may at least partially explain these differences, and some recent data point out different biologic properties of the endothelium according to its location.

Section snippets

Large and Small Vessels: Definition

There is little consensus regarding what constitutes a “small” artery. In peripheral arterial disease (PAD) studies, “small vessel” addresses arteries with diameters smaller than 2 to 3 mm,2, 3 corresponding to foot arteries, but many studies actually compared supra- to infragenicular arteries.4, 5, 6, 7, 8 In the field of cerebrovascular diseases (CBVD), some authors9, 10 qualify “small” arteries of 0.1 to 0.4 mm diameter lumen, with internal elastic lamina and a media composed of 3 or 4layers

Cerebrovascular Disease

Because of the several anatomical patterns of cerebral ischemic diseases, including large size infarcts, lacunar lesions, and white matter lesions, studies comparing large vs small or extracranial vs intracranial vessel disease are more frequent in the cerebral territory (Table 2). This review is focused only on atherosclerosis, and nonatherosclerotic small vessel vasculopathies or cerebral microangiopathy as well as different types of chronic small vessel diseases affecting arterioles⁹ are

Peripheral Arterial Disease

Several studies attempted to compare risk factors of PAD affecting proximal and distal arteries (Table 3).

Although the prevalence of PAD increases dramatically with age, the pattern of the disease differs according to age. Aortoiliac disease occurs usually in younger subjects44, 46, 47, 49 and is more rapidly progressive than distal disease.⁷³

Although both diseases are predominant in men, Smith et al found a lower male/female ratio in aortoiliac disease compared to femoropopliteal disease.46, 47

Coronary Artery Disease

In contrast to PAD and CBVD, where small arteries usually correspond to distal branches of larger arteries, studies on distribution of atherosclerotic lesions in coronary arteries are mostly performed on the same 3 major branches, divided on several segments, from the proximal to distal portions (Table 4). In autopsy as well as angiography studies, proximal lesions are more frequent than distal ones39, 43, 37, 90, 91 especially in the LAD and Cx arteries92, 93 because they have more proximal

Association with Other Atherosclerotic Diseases

A trend to higher rates of clinical CAD and PAD was found when comparing stroke³⁴ or TIA²¹ victims with ICA lesions vs MCA lesions. Lawton⁸⁴ reported higher rates of angina in those with angiographic EC stenoses than in IC arteries. Similarly, Heyden et al¹⁵ found that angiographic EC disease was associated to clinical CAD and claudication, and Uehara et al²⁹ reported a 3-fold relative risk of clinical CAD in the presence of EC-ICA lesions on MRA vs IC lesions. Correspondingly, clinical CAD was

Discussion

Although atherosclerosis is considered as a systemic disease affecting different arterial beds with similar lesions, this literature review points out several epidemiologic and some histologic differences in lesions affecting the large and small vessels. Despite some contradictory reports, it appears that atherosclerosis occurs at a younger age in large vessels, and that these lesions are more progressive and are more frequently involved in lesion complications such as plaque rupture and

Conclusions

Beyond the similarities regarding the atherosclerotic nature of occlusive lesions, histologic and epidemiologic studies show consistent differences in the occurrence, progression, and complication rates of these lesions in large and small vessels. Further studies, particularly those focused on the biologic particularities of arterial tissues in different segments, will undoubtedly provide key information about the atherosclerotic process, leading to more specific therapeutic options, especially

References (129)

K.H. Vogelberg et al.
Primary hyperlipoproteinemias as risk factors in peripheralarterial disease documented by arteriography
Atherosclerosis
(1975)
L. Solberg et al.
Cerebral atherosclerosis in Negroes and Caucasians
Atherosclerosis
(1972)
J.S. Hochman et al.
The distribution of atherosclerotic lesions in the coronary arterial tree: relation to cardiac risk factors
Am Heart J
(1988)
K. Yanagi et al.
Characteristics of coronary artery disease and lipoprotein abnormalities in patients with heterozygous familial hypercholesterolemia associated with diabetes mellitus or impaired glucose tolerance
Atherosclerosis
(1997)
P. Pajunen et al.
Quantitative Comparison of angiographic characteristics of coronary artery disease in patients with noninsulin-dependent diabetes mellitus compared with matched nondiabetic control subjects
Am J Cardiol
(1997)
P. Pajunen et al.
Angiographic severity and extent of coronary artery disease in patients with type A diabetes mellitus
Am J Cardiol
(2000)
M.T. Vogt et al.
Segmental arterial disease in the lower extremities: correlates of disease and relationship to mortality
J Clin Epidemiol
(1993)
M.E. Hansen et al.
Age-related differences in the distribution of peripheral atherosclerosis: when atherosclerosis truly premature?
Surgery
(1995)
F.B. Smith et al.
Variation in cardiovascular risk factors by angiographic sites of lower limb atherosclerosis
Eur J Vasc Endovasc Surg
(1996)
N. Diehm et al.
Association of cardiovascular risk factors with pattern of lower limb atherosclerosis in 2659 patients undergoing angioplasty
Eur J Vasc Endovasc Surg
(2006)

J.A. Resch et al.

Pattern ofvessel involvement in cerebral atherosclerosis

J Atheroscler Res

(1969)

J.A. Resch et al.

Comparative autopsy studies on cerebral atherosclerosis in Nigerian and Senegal negroes. American negroes and Caucasians

Atherosclerosis

(1970)

T.S. Huber et al.

Impact of race on the treatment for peripheral arterial occlusive disease

J Vasc Surg

(1999)

Z.J. Zheng et al.

Lower extremity arterial disease assessed by ankle-brachial index in a middle-ages population of African Americans and Whites

Am J Prev Med

(2005)

R. Cooper et al.

Hypertension in blacks

Am J Hypertens

(1997)

A.N. Sidawy et al.

Race as a risk factor in the severity of infragenicular occlusive disease: study of an urban hospital patient population

J Vasc Surg

(1990)

J.P. Strong et al.

Cigarette smoking and atherosclerosis in autopsied men

Atherosclerosis

(1976)

J.O. Menzoian et al.

Symptomatology and anatomic patterns of peripheral arterial disease: differing impact of smoking and diabetes

Ann Vasc Surg

(1989)

C.A. Warnes et al.

Comparison at necropsy by age group of amount and distribution of narrowing by atherosclerotic plaque in 2995 five-mm long segments of 240 major coronary arteries in 60 men aged 31 to 70 years with sudden coronary death

Am Heart J

(1984)

A. Schmermund et al.

Usefulness of topography of coronary calcium by electron-beam computed tomography in predicting the natural history of coronary atherosclerosis

Am J Cardiol

(2000)

M. Valgimigli et al.

Plaque composition in the left main stem mimics the distal but not the proximal tract of the left coronary artery: influence of clinical presentation, length of the left main trunk, lipid profile, and systematic levels of C-reactive protein

J Am Coll Cardiol

(2007)

M.K. Hong et al.

The site of plaque rupture in native coronary arteries. A three-vessel intravascular ultrasound analysis

J Am Coll Cardiol

(2005)

Q. Rasheed et al.

Correlation of intracoronary ultrasound plaque characteristics in atherosclerotic coronary artery disease patients with clinical variables

Am J Cardiol

(1994)

R.C. Pasternak et al.

AHA conference proceedings. Atherosclerotic Vascular Disease Conference. Writing group: I. Epidemiology

Circulation

(2004)

M.H. Criqui et al.

Peripheral arterial disease in large vessels is epidemiologically distinct from small vessel disease

Am J Epidemiol

(1989)

V. Aboyans et al.

Risk factors for progression of peripheral arterial disease in large and small vessels

Circulation

(2006)

H. Haimovici

Patterns of arteriosclerotic lesions of the lower extremity

Arch Surg

(1967)

D.E. Strandness et al.

Combined clinical and pathological study on non-diabetic and diabetic vascular disease

Diabetes

(1964)

C. van der Feen et al.

Angiographic distribution of lower extremity atherosclerosis in patients with and without diabetes

Diabetes Med

(2002)

N.S. Weiss

Cigarette smoking and peripheral arteriosclerosis obliterans: an epidemiological approach

Am J Epidemiol

(1972)

M.G. Bousser et al.

Small vessel vasculopathies affecting the central nervous system

J Neuroophthalmol

(2004)

G.A. Lammie et al.

Nonhypertensive cerebral small-vessel disease. An autopsy study

Stroke

(1997)

D.M. Reed et al.

A prospective study of cerebral artery atherosclerosis

Stroke

(1988)

L.R. Caplan et al.

Race, sex and occlusive cerebrovascular disease: a review

Stroke

(1986)

C.M. Fisher et al.

Atherosclerosis of the carotid and vertebral arteries—extracranial and intracranial

J Neuropathol Exp Neurol

(1965)

S.A. Kieffer et al.

Racial differences in cerebrovascular disease: angiographic evaluation of Japanese and American populations

AJR

(1967)

S. Heyden et al.

Nonembolic occlusion of the middle cerebral and carotid arteries. A comparison of predisposing factors

Stroke

(1970)

A. Heyman et al.

Joint study of extracranial arterial occlusion. VI. Racial differences in hospitalized patients with ischemic stroke

JAMA

(1972)

L. Candelise et al.

Italian Multicenter Study on Reversible Cerebral Ischemic Attacks: III— Influence of age and risk factors on cerebrovascular atherosclerosis

Stroke

(1984)

P.B. Gorelick et al.

Racial differences in the distribution of the anterior circulation occlusive disease

Neurology

(1984)

P.B. Gorelick et al.

Racial differences in the distribution of the posterior circulation occlusive disease

Neurology

(1985)

L. Caplan et al.

Occlusive disease at the middle cerebral artery

Neurology

(1985)

P. McGarry et al.

Cerebral atherosclerosis in New Orleans

Lab Invest

(1985)

G. Weber et al.

Atherosclerosis and aging

Arch Pathol Lab Med

(1988)

E. Feldmann et al.

Chinese-white differences in distribution of occlusive cerebrovascular disease

Neurology

(1990)

D. Inzitari et al.

Racial differences in the anterior circulation in cerebrovascular disease. How much can be explained by risk factors?

Arch Neurol

(1990)

M. Yasaka et al.

Distribution of atherosclerosis and risk factors in atherothrombotic occlusion

Stroke

(1993)

L. Sacco et al.

Race-ethnicity and determinants of intracranial atherosclerotic cerebral infarction. The Northern Manhattan Stroke Study

Stroke

(1995)

R.J. Wityk et al.

Race and sex differences in the distribution of cerebral atherosclerosis

Stroke

(1996)

T. Uehara et al.

Frequency and clinical correlated of occlusive lesions of cerebral arteries in Japanese patients without stroke

Cerebrovasc Dis

(1998)

Cited by (106)

GYY4137, a hydrogen sulfide donor, protects against endothelial dysfunction in porcine coronary arteries exposed to myeloperoxidase and hypochlorous acid
2023, Vascular Pharmacology
Myeloperoxidase (MPO) and its principal reaction product hypochlorous acid (HOCl) are part of the innate immune response but are also associated with endothelial dysfunction, thought to involve a reduction in nitric oxide (NO) bioavailability. We aimed to investigate the effect of MPO and HOCl on vasorelaxation of coronary arteries and to assess directly the involvement of NO. In addition, we hypothesised that the slow release hydrogen sulfide (H₂S) donor GYY4137 would salvage coronary artery endothelial function in the presence of MPO and HOCl.
Contractility of porcine coronary artery segments was measured using isometric tension recording. Incubation with MPO (50 ng/ml) plus hydrogen peroxide (H₂O₂) (30 μM; substrate for MPO) impaired endothelium-dependent vasorelaxation to bradykinin in coronary arteries. HOCl (10–500 μM) also impaired endothelium-dependent relaxations. There was no effect of MPO plus H₂O₂, or HOCl, on endothelium-independent relaxations to 5′-N-ethylcarboxamidoadenosine and sodium nitroprusside. L-NAME (300 μM), a NO synthase inhibitor, attenuated bradykinin relaxations, leaving L-NAME-resistant relaxations to bradykinin mediated by endothelium-dependent hyperpolarization. In the presence of L-NAME, MPO plus H₂O₂ largely failed to impair endothelium-dependent relaxations to bradykinin. Similarly, HOCl failed to inhibit endothelium-dependent relaxations to bradykinin in the presence of L-NAME. GYY4137 (1–100 μM) protected endothelium-dependent relaxations to bradykinin from dysfunction caused by MPO plus H₂O₂, and HOCl, with no effect alone on bradykinin relaxation responses. The specific MPO inhibitor aminobenzoic acid hydrazide (ABAH) (1 and 10 μM) also protected against MPO plus H₂O₂-induced endothelial dysfunction (at 10 μM ABAH), but was less potent than GYY4137.
MPO plus H₂O₂, and HOCl, impair coronary artery endothelium-dependent vasorelaxation via inhibition of NO. GYY4137 protects against endothelial dysfunction in arteries exposed to MPO plus H₂O₂, and HOCl. H₂S donors such as GYY4137 are possible therapeutic options to control excessive MPO activity in cardiovascular diseases.
Pathophysiology, cellular and molecular mechanisms of large and small vessel diseases
2023, Neurochemistry International
Cerebrovascular disease (CVD) is the second most common cause of cognitive impairment and dementia in aged population. CVD presents in a myriad number of clinical ways based on the functional location of pathology. While primary clinical emphasis has been placed on motor, speech and visual deficits, vascular cognitive decline is a vastly under recognized and devastating condition afflicting millions of Americans. CVD, a disease of the blood vessels that supply blood to brain involves an integration between small and large vessels. Cerebral large vessel diseases (LVD) are associated with atherosclerosis, artery-to-artery embolism, intracardiac embolism and a large vessel stroke leading to substantial functional disability. Cerebral small vessel disease (SVD) is critically involved in stroke, brain hemorrhages, cognitive decline and functional loss in elderly patients. An evolving understanding of cellular and molecular mechanisms emphasizes that inflammatory vascular changes contribute to systemic pathologic conditions of the central nervous systems (CNS), with specific clinical presentations including, cognitive decline. Advances in an understanding of pathophysiology of disease processes and therapeutic interventions may help improve outcomes. This review will focus on large and small vessels diseases and their relationship to vascular cognitive decline, atherosclerosis, stroke, and inflammatory neurodegeneration. We will also emphasize the molecular and cellular mechanisms, as well as genetic and epigenetic factors associated with LVD and SVD.
Role of Nrf2 in aging, Alzheimer's and other neurodegenerative diseases
2022, Ageing Research Reviews
Nuclear Factor-Erythroid Factor 2 (Nrf2) is an important transcription factor that regulates the expression of large number of genes in healthy and disease states. Nrf2 is made up of 605 amino acids and contains 7 conserved regions known as Nrf2-ECH homology domains. Nrf2 regulates the expression of several key components of oxidative stress, mitochondrial biogenesis, mitophagy, autophagy and mitochondrial function in all organs of the human body, in the peripheral and central nervous systems. Mounting evidence also suggests that altered expression of Nrf2 is largely involved in aging, neurodegenerative diseases, including Alzheimer’s disease, Parkinson’s disease, Huntington’s diseases, Amyotrophic lateral sclerosis, Stroke, Multiple sclerosis and others. The purpose of this article is to detail the essential role of Nrf2 in oxidative stress, antioxidative defense, detoxification, inflammatory responses, transcription factors, proteasomal and autophagic/mitophagic degradation, and metabolism in aging and neurodegenerative diseases. This article also highlights the Nrf2 structural and functional activities in healthy and disease states, and also discusses the current status of Nrf2 research and therapeutic strategies to treat aging and neurodegenerative diseases.
Atheromatosis of the brain-supplying arteries: Circle of Willis, basilar, vertebral and their branches
2022, Annals of Anatomy
Atherosclerotic plaques in the brain-supplying arteries are slowly-developing alterations of vascular structures that can lead to neurological impairment due to stenosis and insufficient oxygenation of eloquent brain areas. The aim of this study is to provide detailed demographic information related to the incidence of atherosclerotic plaques in the cerebral arteries.
Forty-eight circles of Willis (21 men, 21 women, mean age: 70.26, six samples unknown) were macroscopically analyzed for length, diameter, and presence of atherosclerotic plaques. Statistical analysis was used to identify potential differences in the locations and frequencies of atherosclerotic plaques in relation to age and sex.
The study sample revealed 261 atherosclerotic plaques. The key findings were significant correlations between plaque development and age and between plaque location and age; however, there was no significant sex difference.
The upper and lower branches of the middle cerebral artery (MCA) were novel locations predisposing to plaque development. A cut-off value at 60 years revealed a significant difference in plaque development and distribution. There were no significant sex differences in the occurrence of atherosclerotic plaques.
Characteristics of atherosclerosis in femoropopliteal artery and its clinical relevance
2021, Atherosclerosis
Citation Excerpt :
The mechanical forces exerted on the superficial femoral arteries differ from the coronary arteries. The difference in artery size between the coronary arteries and SFA creates different hemodynamic circumstances [61]. Clinical manifestations of PAD also depend on other comorbidities, particularly diabetes.
Atherosclerosis is a systemic disease with different faces. Despite identical or similar pathogenetic mechanisms, atherosclerotic lesions and their clinical manifestations vary in different parts of the vascular system. Peripheral arterial disease (PAD) represents one of the most frequent clinical manifestations of atherosclerosis with predominant location in the superficial femoral artery (SFA). Morphological characteristics of atherosclerotic plaques in peripheral arteries differ from lesions in the coronary and carotid arteries. Plaques in SFA have more fibrotic components, less lipids and inflammatory cells, which makes them more stable and less prone to rupture. Factors that determine the different structure of plaques in SFA compared to coronary arteries include hemodynamic forces, vasa vasorum and calcification. Low shear stress in SFA in the adductor canal is one of the factors which determines frequent atherosclerotic lesions in this region. Lower lipid content and fewer inflammatory cells explain higher stability of SFA plaques. The specific structure of SFA plaques may require preventive and therapeutic measures, which to some extent differ from prevention of coronary atherosclerosis and may include inhibition of fibrotic proliferation in SFA plaques and calcification. Revascularization of PAD differs from procedures used in coronary arteries and requires specific technical expertise and devices.
Major cerebral vessels involvement in patients with MELAS syndrome: Worth a scan? A systematic review
2021, Journal of Neuroradiology
Major cerebral vessels have been proposed as a target of defective mitochondrial metabolism in patients with mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes syndrome (MELAS). Cerebral angiographic techniques are not routinely performed in MELAS patients. A systematic literature review was performed to identify studies describing major vessel caliber alterations in MELAS. Twenty-three studies reporting on 46 MELAS patients were included. Alterations in major caliber vessels were present in 59% (27/46) of patients. Dilation occurred in 37% (17/46) of patients, and in 88% (15/17) of them during a stroke-like episode (SLE). Stenosis was reported in 24% (11/46) of patients: 36% (4/11) related to an SLE and 64% (7/11) to dissections or degenerative changes.
During an SLE, identification of intracranial vessels dilation or stenosis could be a selection tool for new treatment protocols. Outside SLE, identification of major cerebral vessels dissections and degenerative changes may help to prevent subsequent complications.

View all citing articles on Scopus

View full text

Large and Small Vessels Atherosclerosis: Similarities and Differences

Section snippets

Large and Small Vessels: Definition

Cerebrovascular Disease

Peripheral Arterial Disease

Coronary Artery Disease

Association with Other Atherosclerotic Diseases

Discussion

Conclusions

Atherosclerosis

Atherosclerosis

Am Heart J

Atherosclerosis

Am J Cardiol

Am J Cardiol

J Clin Epidemiol

Surgery

Eur J Vasc Endovasc Surg

Eur J Vasc Endovasc Surg

J Atheroscler Res

Atherosclerosis

J Vasc Surg

Am J Prev Med

Am J Hypertens

J Vasc Surg

Atherosclerosis

Ann Vasc Surg

Am Heart J

Am J Cardiol

J Am Coll Cardiol

J Am Coll Cardiol

Am J Cardiol

AHA conference proceedings. Atherosclerotic Vascular Disease Conference. Writing group: I. Epidemiology

Circulation

Peripheral arterial disease in large vessels is epidemiologically distinct from small vessel disease

Am J Epidemiol

Risk factors for progression of peripheral arterial disease in large and small vessels

Circulation

Patterns of arteriosclerotic lesions of the lower extremity

Arch Surg

Combined clinical and pathological study on non-diabetic and diabetic vascular disease

Diabetes

Angiographic distribution of lower extremity atherosclerosis in patients with and without diabetes

Diabetes Med

Cigarette smoking and peripheral arteriosclerosis obliterans: an epidemiological approach

Am J Epidemiol

Small vessel vasculopathies affecting the central nervous system

J Neuroophthalmol

Nonhypertensive cerebral small-vessel disease. An autopsy study

Stroke

A prospective study of cerebral artery atherosclerosis

Stroke

Race, sex and occlusive cerebrovascular disease: a review

Stroke

Atherosclerosis of the carotid and vertebral arteries—extracranial and intracranial

J Neuropathol Exp Neurol

Racial differences in cerebrovascular disease: angiographic evaluation of Japanese and American populations

AJR

Nonembolic occlusion of the middle cerebral and carotid arteries. A comparison of predisposing factors

Stroke

Joint study of extracranial arterial occlusion. VI. Racial differences in hospitalized patients with ischemic stroke

JAMA

Italian Multicenter Study on Reversible Cerebral Ischemic Attacks: III— Influence of age and risk factors on cerebrovascular atherosclerosis

Stroke

Racial differences in the distribution of the anterior circulation occlusive disease

Neurology

Racial differences in the distribution of the posterior circulation occlusive disease

Neurology

Occlusive disease at the middle cerebral artery

Neurology

Cerebral atherosclerosis in New Orleans

Lab Invest

Atherosclerosis and aging

Arch Pathol Lab Med

Chinese-white differences in distribution of occlusive cerebrovascular disease

Neurology

Racial differences in the anterior circulation in cerebrovascular disease. How much can be explained by risk factors?

Arch Neurol

Distribution of atherosclerosis and risk factors in atherothrombotic occlusion

Stroke