Alterations of carotid arterial mechanics preceding the wall thickening in patients with hypertension

doi:10.1016/j.atherosclerosis.2016.02.017

Atherosclerosis

Volume 248, May 2016, Pages 84-90

https://doi.org/10.1016/j.atherosclerosis.2016.02.017 Get rights and content

Highlights

•
Before the progression of carotid IMT, pathologic process ongoing on carotid artery is already underway in patients with hypertension.
•
The carotid artery of hypertensive patients is stiffer than that of controls and positive remodeling precedes the wall thickening independent of covariates.
•
Vascular adaptations are not evident in patients with diabetes on conventional treatment before wall thickening develops.

Abstract

Background and aims

Carotid intima-media thickness (cIMT) is an established surrogate marker of atherosclerosis. However, cIMT may not reflect the whole arterial changes occurring in various pathologic conditions, such as hypertension. The aim of this study was to evaluate whether vascular properties of carotid artery (CA) in patients with hypertension differ from those of patients with diabetes and controls before the progression of cIMT.

Methods

Vascular properties of CA were assessed in 402 consecutive asymptomatic subjects who have normal cIMT (131 with hypertension, 151 with diabetes mellitus, and 120 controls). Conventional carotid stiffness indices calculated from vessel diameter and blood pressure, and parameters from velocity-vector imaging (VVI), including vessel area, fractional area change (FAC), radial velocity, circumferential strain, and strain rate were measured to assess the differences between the groups.

Results

In univariate analysis, both patients with hypertension and diabetes showed higher elastic modulus, lower distensibility coefficients and FAC of VVI than those of controls. However, when adjusting for baseline covariates, only FAC (odds ratio [OR] = 0.82, 95% confidence interval [CI] = 0.70–0.97, p = 0.025) and vessel area (OR = 2.84, 95% CI = 1.64–4.91, p < 0.001) discriminated CA of patients with hypertension from those of controls. Also, patients with hypertension showed larger vessel area than diabetes (OR = 2.58, 95% CI = 1.75–3.80, p < 0.001) independent of baseline covariates. No significant vascular parameter was found to discriminate patients with diabetes from controls after adjustments.

Conclusion

Despite normal cIMT, the CA of hypertensive patients was stiffer than those of controls and positive remodeling preceded the wall thickening independent of baseline covariates.

Introduction

Among the various parameters of vascular properties, carotid intima-media thickness (cIMT) has been suggested as a surrogate measure of vascular alterations, and several studies have shown that increasing cIMT is associated with subsequent coronary heart disease and stroke [1], [2]. Since it is non-invasive, reproducible, and simple, measurement of cIMT with ultrasonography is widely used to quantify the extent of subclinical disease in individuals with cardiovascular (CV) risk factors and to follow up in interventional studies. However, cIMT may not reflect the whole arterial changes occurring in various pathologic conditions, such as hypertension. Before the progression of the intima and media thickening, the carotid artery (CA) may experience functional alterations (such as wall stiffening), of which the occurrence is also associated with an increased risk of CV morbidity or mortality by augmenting arterial impedance and resultant increase in the afterload of the heart [3]. Recently, with advancements in ultrasound (US) techniques, a novel automated speckle-tracking method using velocity-vector imaging (VVI) software has facilitated the instantaneous quantification of CA mechanics and we have shown the altered vascular properties associated with aging [4] and arteriopathies [5], [6] such as Takayasu's arteritis and Marfan syndrome. In this study, we aimed to assess whether vascular properties of CA before the progression of cIMT in patients with hypertension are abnormal and different from those of patients with diabetes and controls using VVI analysis.

Section snippets

Study population

A total of 1024 subjects were recruited from among patients with hypertension or diabetes and healthy subjects. They underwent carotid US for CV risk stratification and general health screening. Among them, 402 asymptomatic subjects were consecutively identified if they had: 1) normal cIMT free from atheromatous plaque on carotid US; 2) hypertension, were normoglycemic, and had no evidence of secondary hypertension; 3) type 2 diabetes mellitus, were normotensive, and were without evidence of

Baseline characteristics

The mean duration of hypertension was 4.1 ± 3.6 years and that of diabetes was 5.3 ± 4.7 years. Among diabetic patients, 16 (11%) were treated with dietary control alone, 113 (75%) with oral hypoglycemic agents (OHA), and 21 (14%) with insulin plus OHA. The mean value of HbA1c was 7.5 ± 1.6%. Table 1 shows the baseline characteristics of the study population according to the subject groups.

Structural and functional characteristics of the carotid artery

Table 2 shows the structural and functional characteristics of the CA. There was no significant difference

Discussion

The principal findings of the current study are: before the development of thickened cIMT, (1) the CA of hypertensive patients was stiffer than that of controls and positive remodeling preceded the wall thickening independent of baseline covariates. (2) the vascular properties of patients with diabetes on conventional treatment were not different from that of controls after adjustments.

To the best of our knowledge, this study is the first to determine the functional and structural alterations

Conclusion

We demonstrated that vascular alterations as arterial stiffening and positive remodeling independently precede the development of wall thickening in patients with hypertension.

On the other hand, vascular properties of patients with diabetes on conventional treatment were not different from that of control before the progression of cIMT. Our results are unique in that they provide earlier detection of arterial changes associated with hypertension, which could be useful for the stratification of

Sources of funding

This work was supported by a Korea Science and Engineering Foundation (KOSEF) grant funded by the Korean government (M10642120001-06N4212-00110).

Disclosures

None.

References (37)

L.E. Chambless et al.
Association of coronary heart disease incidence with carotid arterial wall thickness and major risk factors: the atherosclerosis risk in communities (ARIC) study, 1987-1993
Am. J. Epidemiol.
(1997)
D.H. O'Leary et al.
Carotid-artery intima and media thickness as a risk factor for myocardial infarction and stroke in older adults
N. Engl. J. Med.
(1999)
C. Giannattasio et al.
Increased arterial stiffness in normoglycemic normotensive offspring of type 2 diabetic parents
Hypertension
(2008)
S.A. Kim et al.
Quantitative assessment of aortic elasticity with aging using velocity-vector imaging and its histologic correlation
Arterioscler. Thromb. Vasc. Biol.
(2013)
I.J. Cho et al.
Assessment of mechanical properties of common carotid artery in Takayasu's arteritis using velocity vector imaging
Circ. J.
(2010)
W.I. Yang et al.
Dyssynchronous systolic expansion of carotid artery in patients with marfan syndrome
J. Am. Soc. Echocardiogr.
(2010)
2008 Standards of medical care in diabetes
Diabetes Care
(2008)
C.S. Kim et al.
Normative values of carotid artery intima-media thickness in healthy Korean adults and estimation of macrovascular diseases relative risk using this data in type 2 diabetes patients
Diabetes Res. Clin. Pract.
(2006)
K. Hayashi et al.
Stiffness and elastic behavior of human intracranial and extracranial arteries
J. Biomech.
(1980)
Y.F. Cheung
Arterial stiffness in the young: assessment, determinants, and implications
Korean Circ. J.
(2010)

J.J. van der Heijden-Spek et al.

Effect of age on brachial artery wall properties differs from the aorta and is gender dependent. A population study

Hypertension

(2000)

J.M. Dijk et al.

SMART study group. Carotid stiffness and the risk of new vascular events in patients with manifest cardiovascular disease. The SMART study

Eur. Heart J.

(2005)

M. O'Rourke

Arterial stiffness, systolic blood pressure, and logical treatment of arterial hypertension

Hypertension

(1990)

O. Traub et al.

Laminar shear stress: mechanisms by which endothelial cells transduce an atheroprotective force

Arterioscler. Thromb. Vasc. Biol.

(1998)

G.H. Gibbons et al.

The emerging concept of vascular remodeling

N. Engl. J. Med.

(1994)

C.P. Johnson et al.

Age related changes in the tunica media of the vertebral artery: implications for the assessment of vessels injured by trauma

J. Clin. Pathol.

(2001)

C. Xu et al.

Hypercholesterolemia superimposed by experimental hypertension induces differential distribution of collagen and elastin

Arterioscler. Thromb. Vasc. Biol.

(2000)

R.F.G. Booth et al.

Rapid development of atherosclerotic lesions in the rabbit carotid artery induced by perivascular manipulation

Atherosclerosis

(1989)

Cited by (12)

Age, sex, antihypertensive drugs and the Mediterranean diet on hypertension-related biomarkers: Impact on carotid structure and blood lipids in an Argentinian cross-sectional study
2024, Human Nutrition and Metabolism
Cardiovascular risk is modifiable by changes in lifestyle and pharmacological management, with hypertension being a common pathology worldwide. Its treatment must address multiple metabolic targets. Based on the hypothesis that certain antihypertensive medications, such as the commonly used enalapril and losartan, and dietary habits improve hypertension-related changes in carotid structure and cardiometabolic variables, this work aimed to associate these drugs, as well as the Mediterranean diet adherence and non-modifiable biological factors, with changes in carotid intima-media thickness [cIMT] and blood lipids.
Sociodemographic, clinical, biochemical and lifestyle data were collected in a cross-sectional study of 313 subjects under survey due to cardiovascular risk factors, aged 34–83 years (Cordoba, Argentina). Generalised structural equation models were used for analysis.
A higher cIMT with age and male sex was confirmed. Women had lower triacylglycerols and saturated fatty acids in serum but higher circulating levels of LDL-C, HDL-C and total cholesterol than men. Also, a higher adherence to the Mediterranean diet was associated with lower triacylglycerols, but higher levels of HDL-C cholesterol and ω-3 polyunsaturated fatty acids (ω-3 PUFAs) in serum. A greater adherence to the Mediterranean diet did not affect cIMT. Enalapril was associated with increased serum ω-3 PUFAs levels, but it did not affect other lipid fractions. Moreover, enalapril may control cIMT, whereas losartan may not.
Our data demonstrate that the Mediterranean diet and enalapril are associated with a cardioprotective circulating lipid profile in hypertension. Concerning this, enalapril potentially promotes serum ω-3 PUFAs levels beyond its classical antihypertensive effect, which encourages future clinical studies to confirm it.
Cardiovascular risk assessment in inflammatory bowel disease with metabolic dysfunction-associated steatotic liver disease
2024, Medicina Clinica
Inflammatory bowel disease (IBD) has been reported to increase the risk of early atherosclerosis even in young patients. Moreover, metabolic dysfunction-associated steatotic liver disease (MASLD), which has been linked to IBD, is a well-recognized but underdiagnosis entity related to cardiovascular risk. We analyze the impact of MASLD in IBD patients’ cardiovascular risk through both advanced lipoprotein profile sorted by nuclear magnetic resonance spectroscopy, and carotid artery intima-media thickness (CIMT).
Cross-sectional cohort study which involves 941 IBD adult outpatients. Of them, 50 patients with IBD who met criteria for MASLD and 50 with IBD without MASLD, matched by sex and age were included. Alterations in CIMT were evaluated considering abnormal measures above the 75th percentile adjusted for sex and age. Specific advanced lipoprotein profile was also carried out.
Most of the patients had an abnormal CIMT (58%). MASLD (OR = 5.05, CI 95% = 1.71–14.92) and female sex (OR = 3.32, CI 95% = 1.03–10) were significantly associated with CIMT alterations. Dense LDL particles (with high cholesterol composition in general cohort (OR = 3.62, 95% CI = 1.07–12.19) and high triglycerides density in young subgroup (OR = 6.25, 95% CI = 1.04–50) but not total LDL cholesterol were associated with CIMT alterations.
MASLD and female sex are associated with early atherosclerosis in IBD patients. Dense LDL particle in combination with vascular imaging findings should be evaluated as non-invasive tools in the management of cardiovascular risk in IBD patients.
Se ha descrito que la enfermedad inflamatoria intestinal (EII) incrementa el riesgo de aterosclerosis precoz incluso en pacientes jóvenes. Además, la esteatosis hepática metabólica (MASLD), entidad relacionada con la EII, es una causa reconocida pero infradiagnosticada de riesgo cardiovascular. Hemos analizado el impacto de MASLD en el desarrollo de enfermedades cardiovasculares en los pacientes con EII a través de un estudio avanzado del perfil de lipoproteínas con espectroscopia por resonancia magnética nuclear y el grosor íntima-media carotídeo (GIMc).
Se trata de un estudio de cohortes transversal de 941 pacientes ambulatorios con EII. De ellos, se incluyeron 50 con EII que cumplían criterios de MASLD y otros 50 con EII sin MASLD emparejados por sexo y edad. Se evaluaron las alteraciones de GIMc considerando patológicos aquellos valores por encima del percentil 75 ajustado por sexo y edad. Se analizó también el perfil avanzado de lipoproteínas.
Muchos de los pacientes tuvieron un GIMc alterado (58%). La presencia de MASLD (odds ratio [OR] = 5,05, intervalo de confianza [IC] 95% = 1,71-14,92) y el sexo femenino (OR = 3,32, IC 95% = 1,03-10), se asociaron significativamente a las alteraciones de GIMc. Las partículas de baja densidad (LDL) (con alta concentración de colesterol en la cohorte general [OR = 3,62, IC 95% = 1,07-12,19], así como de de triglicéridos en el subgrupo de pacientes jóvenes [OR = 6,25, IC 95% = 1,04-50]), pero no las cifras de colesterol LDL total, se asociaron a alteraciones en el GIMc.
La presencia de MASLD y el sexo femenino se asocian a aterosclerosis precoz en los pacientes con EII. El estudio de las partículas LDL densas en combinación con los hallazgos en las pruebas de imagen vascular, deberían valorarse como herramientas no invasivas de detección de riesgo cardiovascular en los sujetos con EII.
Ventricular Stiffness and Ventricular-Arterial Coupling in Heart Failure: What Is It, How to Assess, and Why?
2019, Heart Failure Clinics
Citation Excerpt :
It is necessary to simultaneously measure blood pressure. Carotid stiffness index β, recently carotid artery strain, has been used to assess arterial stiffness in various cardiovascular diseases.24–28 To assess ventricular stiffness and VAC, invasive hemodynamic assessment with pressure-volume loop analysis obtained by cardiac catheterization may be most accurate.
Relationship between carotid intima-media thickness and carotid artery stiffness assessed by ultrafast ultrasound imaging in patients with type 2 diabetes
2019, European Journal of Radiology
Citation Excerpt :
One study based on a murine atherosclerosis model showed that aorta stiffening might precede IMT thickening [32]. Another study of carotid properties using speckle-tracking method verified analogous findings in hypertension patients other than T2DM patients [18]. In our study, to elucidate carotid properties for distinguishing diabetic subjects with normal CIMT from controls, potential influence of other atherosclerosis risk factors should be excluded.
To evaluate the relationship between carotid stiffness and carotid intima-media thickness (CIMT) in patients with type 2 diabetes (T2DM).
Carotid properties were evaluated in 317 consecutive subjects (98 volunteers for controls, 105 patients with normal CIMT for T2DM group 1, and 114 patients with thickened CIMT for T2DM group 2). The CIMT and carotid pulse wave velocity at the beginning (PWV-BS) and at the end of systole (PWV-ES) were measured.
Apart from PWV-BS in T2DM group 1, CIMT and PWV-ES were significant higher in patients groups than those of in controls. In multiple regression analysis, diabetes was independently associated with PWV-ES and not with PWV-BS. Moreover, when adjusting for baseline covariates, only PWV-ES (odds ratio = 4.27, P < 0.001) distinguished carotid in T2DM group 1 from that of controls. Concerning the relationship between log(CIMT) and PWV-ES, when adjusting for baseline covariates, the association were still significant in controls and T2DM group 1, whereas it was no longer present in T2DM group 2 (P = 0.091). Additionally, the slope (β) after adjustment for the PWV-ES to log(CIMT) was significantly steeper in T2DM group 1 than that of in controls (β= 8.35 vs. 3.31, P < 0.01).
The PWV-ES seem to be a better biomarker candidate than PWV-BS to assess the carotid stiffness in diabetic patients. Compared with controls, diabetic patients showed more advanced functional changes than morphological changes despite normal CIMT, whereas the relationship trend was not present when thickened CIMT emerged.
A preliminary study of changes in carotid artery elasticity in type 2 diabetes mellitus
2023, Clinical Physiology and Functional Imaging
Multidisciplinary Lifestyle Interventions In The Management of Resistant Hypertension
2022, Research Square

View all citing articles on Scopus

View full text

Alterations of carotid arterial mechanics preceding the wall thickening in patients with hypertension

Highlights

Abstract

Background and aims

Methods

Results

Conclusion

Introduction

Section snippets

Study population

Baseline characteristics

Structural and functional characteristics of the carotid artery

Discussion

Conclusion

Sources of funding

Disclosures

Association of coronary heart disease incidence with carotid arterial wall thickness and major risk factors: the atherosclerosis risk in communities (ARIC) study, 1987-1993

Am. J. Epidemiol.

Carotid-artery intima and media thickness as a risk factor for myocardial infarction and stroke in older adults

N. Engl. J. Med.

Increased arterial stiffness in normoglycemic normotensive offspring of type 2 diabetic parents

Hypertension

Quantitative assessment of aortic elasticity with aging using velocity-vector imaging and its histologic correlation

Arterioscler. Thromb. Vasc. Biol.

Assessment of mechanical properties of common carotid artery in Takayasu's arteritis using velocity vector imaging

Circ. J.

Dyssynchronous systolic expansion of carotid artery in patients with marfan syndrome

J. Am. Soc. Echocardiogr.

2008 Standards of medical care in diabetes

Diabetes Care

Normative values of carotid artery intima-media thickness in healthy Korean adults and estimation of macrovascular diseases relative risk using this data in type 2 diabetes patients

Diabetes Res. Clin. Pract.

Stiffness and elastic behavior of human intracranial and extracranial arteries

J. Biomech.

Arterial stiffness in the young: assessment, determinants, and implications

Korean Circ. J.

Effect of age on brachial artery wall properties differs from the aorta and is gender dependent. A population study

Hypertension

SMART study group. Carotid stiffness and the risk of new vascular events in patients with manifest cardiovascular disease. The SMART study

Eur. Heart J.

Arterial stiffness, systolic blood pressure, and logical treatment of arterial hypertension

Hypertension

Laminar shear stress: mechanisms by which endothelial cells transduce an atheroprotective force

Arterioscler. Thromb. Vasc. Biol.

The emerging concept of vascular remodeling

N. Engl. J. Med.

Age related changes in the tunica media of the vertebral artery: implications for the assessment of vessels injured by trauma

J. Clin. Pathol.

Hypercholesterolemia superimposed by experimental hypertension induces differential distribution of collagen and elastin

Arterioscler. Thromb. Vasc. Biol.

Rapid development of atherosclerotic lesions in the rabbit carotid artery induced by perivascular manipulation

Atherosclerosis