Thicker carotid intima layer and thinner media layer in subjects with cardiovascular diseases: An investigation using noninvasive high-frequency ultrasound

doi:10.1016/j.atherosclerosis.2006.02.020

Atherosclerosis

Volume 189, Issue 2, December 2006, Pages 393-400

https://doi.org/10.1016/j.atherosclerosis.2006.02.020 Get rights and content

Abstract

Background

The thickness of the arterial intima increases and that of the media decreases with increasing age and degree of atherosclerosis. Separate estimates of the individual intima and media layers might therefore be more appropriate than the commonly used method estimating the combined intima-media thickness (IMT).

Methods and results

One hundred consecutive 70-year-old subjects from the PIVUS study were investigated. Separate estimates of the thickness of the carotid artery intima and media wall layers were carried out noninvasively using 25 MHz high-frequency ultrasound. Subjects with a diagnosis of cardiovascular disease (CVD), coronary heart disease (CHD), myocardial infarction (MI) or stroke had a significantly thicker intima layer (all P < 0.0001) and a thinner media layer (all P < 0.05) than healthy subjects. The intima/media thickness ratio also differed significantly between subjects with and without a diagnosis of CVD (0.43 ± 0.20 versus 0.75 ± 0.48, P = 0.0002). Subjects with hypertension or hyperlipidemia also had a thicker carotid intima than subjects without these diagnoses (P < 0.0005 for both). None of the corresponding intima + media thickness values differed significantly. Similar results were obtained in women and men.

Conclusion

Separate assessment of carotid artery intima and media thickness using noninvasive high-frequency ultrasound appears to be of potential value, as a striking difference in intima thickness and the intima/media thickness ratio was found between subjects with and without CVD.

Section snippets

Subjects and methods

One hundred consecutive subjects from a cohort of 1016 randomly selected persons, all aged 70 years, living in the Uppsala community and participating in the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS; see http://www.medsci.uu.se/pivus/pivus.htm) study, were included in this evaluation. All subjects underwent a physical examination and recorded any medical history of CHD (myocardial infarction (MI), angina pectoris, coronary by-pass or balloon angioplasty), heart

Results

The study group comprised 100 participants, 56 men and 44 women. The prevalence of cardiovascular disease was fairly similar in men and women. There was a tendency for a higher prevalence of diabetes mellitus in men than in women (10.7% versus 2%, respectively, P = 0.08), Table 1.

Discussion

The main finding of this study was that separate estimates of carotid intima thickness, media thickness, and the resulting intima/media thickness ratio, obtained noninvasively using high-frequency (25 MHz) ultrasound, resulted in highly significant differences between 70-year-old subjects with and without various forms of CVD. These findings were consistent and fairly similar in women and men. In contrast, no significant differences were found when estimates of intima + media thickness were used.

Conclusions

We demonstrated substantial differences in the thicknesses of the artery intima and media layers between groups of subjects with and without CVD. We suggest, therefore, that the use of noninvasive high-frequency ultrasound for separately estimating artery intima and media thickness could be a valuable tool for assessing/monitoring changes caused by aging, atherosclerosis and the effects of medical interventions on the artery wall.

Acknowledgements

The authors thank Marita Larsson, Anna Stenborg, Kerstin Marttala and Jan Hall for excellent technical assistance.

Source of funding: K.A. Rodriguez Macias was supported by funds at Uppsala University.

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It has been suggested for many years that the carotid artery intima thickness and I/M thickness ratio be used for estimating atherosclerosis progression instead of the classical IMT measurement. This approach has yielded logical and significant study group differences and associations that have not been obtained with IMT measurements [9,17–26]. In Swedish 70-year-olds, the CCA intima was significantly thicker in those with prevalent CVD, myocardial infarction, stroke, hypertension, or hyperlipidaemia, and increased intima thickness was significantly associated with higher BMI, larger waist circumference, and increased years of hypertension, years of hyperlipidaemia, and number of cigarettes smoked/week [9].
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The CCA intima thickness was correlated with several RHC variables (all p<0.05). The intima was 56% thicker (+0.05 mm; 95% CI 0.03, 0.06; p<0.0001) and the I/M thickness ratio was 128% greater (+0.21; 95% CI 0.13, 0.28; p<0.0001) in patients with PAH than healthy subjects. These values were also significantly higher than in patients with LVrEF. In ROC curve analysis, the c-values for CCA intima thickness (0.92) and I/M ratio (0.87), but not for IMT, correctly indicated which individuals belonged to the PAH or healthy control groups. The CCA IMT showed no corresponding significant group differences or associations and was of no use according to receiver operating curve analysis.
Patients with PAH displayed signs of peripheral vascular remodelling, challenging the common opinion that vascular changes in PAH are restricted to the lung vasculature. Correlations with cardiopulmonary variables from RHC support peripheral vascular coupling and the association with vascular ageing. Results from this pilot study warrant further confirmation.
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The IMPROVE is a multicenter European study (n = 3,711). The association of plasma IL-8 with c-IMT (mm) was estimated by quantile regression. Genotyping was performed using the Illumina CardioMetabo and Immuno chips. Replication was attempted in three independent studies and a meta-analysis was performed using a random model.
In IMPROVE, each unit increase in plasma IL-8 was associated with an increase in median c-IMT measures (all p<0·03) in multivariable analyses. Linear regression identified rs117518778 and rs8057084 as associated with IL-8 levels and with measures of c-IMT. The two SNPs were combined in an IL-8-increasing genetic risk that showed causality of IL-8 on c-IMT in IMPROVE and in the UK Biobank (n = 22,179). The effect of IL-8 on c-IMT measures was confirmed in PIVUS (n = 1,016) and MDCCC (n = 6,103). The association of rs8057084 with c-IMT was confirmed in PIVUS and UK Biobank with a pooled estimate effect (β) of -0·006 with 95%CI (-0·008- -0·003).
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Men with AAA exhibited smaller radial artery LD (2.34 ± 0.42 mm vs 2.50 ± 0.38 mm; P < .01), thicker intima (0.094 ± 0.024 mm vs 0.081 ± 0.018 mm; P < .001), similar intima-media (0.28 ± 0.05 vs 0.26 ± 0.05 mm; P = NS), and lower CWS (42.9 ± 10.2 kPa vs 48.6 ± 11.4 kPa; P < .001), compared with controls. Subgroup analyses including all patients showed smaller LD and thicker intima in patients on statin therapy versus no statin therapy and current/ex-smoking versus never smoking. Individuals with hypertension versus no hypertension also presented with thicker intima, but with no difference in LD.
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Asymmetric- and symmetric dimethylarginines (ADMA, SDMA) are elevated in cardiovascular disease (CVD). Preeclampsia is a pregnancy-specific syndrome and is an independent risk factor for subsequent CVD. Aims were to investigate whether ADMA, SDMA levels and l-arginine/ADMA and l-arginine/SDMA ratios during pregnancy and their changes from pregnancy to postpartum are associated to arterial wall layer dimensions and cardiovascular risk factors in women with and without preeclampsia.
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View full text

Thicker carotid intima layer and thinner media layer in subjects with cardiovascular diseases: An investigation using noninvasive high-frequency ultrasound

Abstract

Background

Methods and results

Conclusion

Section snippets

Subjects and methods

Results

Discussion

Conclusions

Acknowledgements

Am J Cardiol

Clinics

Ultrasound Med Biol

Atherosclerosis

Atherosclerosis

Atherosclerosis

Atherosclerosis

Ultrasound measurement of wall thickness in the carotid artery: fundamental principles and description of a computerized analysing system

Clin Physiol

Arterial wall thickness is associated with prevalent cardiovascular disease in middle-aged adults. The Atherosclerosis Risk in Communities (ARIC) Study

Stroke

Carotid-artery intima and media thickness as a risk factor for myocardial infarction and stroke in older adults. Cardiovascular Health Study Collaborative Research Group

N Engl J Med