Studies on arterial endothelial function and intima-media thickness using ultrasound technique

Background: The development of ultrasonographic arterial imaging, high-resolution B-mode ultrasonography, has created a technical basis for a new diagnostic approach to atherosclerotic disease by offering the possibility of accurate and reproducible quantification of the structural and functional changes in the arterial wall. Flow-mediated dilation (FMD) of the brachial artery and carotid intima-media thickness (IMT) have been shown to be good surrogate markers of atherosclerosis. Atherosclerotic lesions detected in the thoracic aorta by transesophageal echocardiography (TEE) are markers of diffuse atherosclerotic disease, often associated with coronary, carotid and peripheral vascular disease.

Aims: The aims of this thesis were to study whether intake of oral moist snuff causes acute endothelial dysfunction in the brachial artery of long-term snuff users; to assess the strength of any relation between walls changes in the thoracic aorta and carotid arteries and the angiographic severity and extent of coronary artery lesions in patients with angiographically verified CAD; to examine the relationship between morphological and functional parameters of the brachial and carotid arteries and the angiographic extent and severity of coronary artery stenosis in patients with severe CAD; and to determine the influence of low-dose prednisolone on atherosclerosis, endothelial function, and risk factors for atherosclerosis in patients with early rheumatoid arthritis (RA).

Methods: The acute effect of 1 g oral snuff on endothelial function in 20 healthy, long-term snuff users was measured by FMD. The effect on heart rate and blood pressure was also measured. The strength of any relation between the angiographic severity and extent of coronary artery lesions on the one hand and ultrasonographically measured walls changes in the thoracic aorta (n=37), carotid arteries and brachial artery and endothelial function in the brachial artery on the other hand was investigated by TEE, carotid and brachial B-mode scanning and FMD in 58 patients who had undergone coronary angiography. In a randomized study 67 patients with early, active rheumatoid arthritis (RA) were randomized to either 7.5 mg prednisolone daily (n=34) or no prednisolone (n=33). The effects of the low-dose treatment with prednisolone on the brachial endothelial function and the carotid wall thickness were studied by FMD and B-mode ultrasonography, respectively, after a mean of 5 years treatment. The relation between risk factors for atherosclerosis and the above mentioned ultrasonographic parameters was investigated.

Results: FMD values declined significantly after the administration of oral moist snuff. Heart rate, systolic and diastolic blood pressure increased significantly after snuff administration. All parameters remained unchanged after placebo. A significant correlation was seen between the extent of coronary artery stenosis and aortic plaques score. Mean carotid IMT was also significantly correlated with coronary artery stenosis extent score. Moreover, a significant correlation was seen between the aortic plaque score and the mean carotid IMT. A significant correlation was seen between the extent of coronary artery stenosis defined as the coronary angiographic score and both the mean brachial artery IMT and intima media area (IMa). There was no significant correlation between FMD and the extent of coronary artery stenosis. A significant correlation was seen between the mean carotid artery IMT and the mean brachial artery IMT. However, there was no significant correlation between FMD and the mean carotid artery IMT or IMa. Carotid IMT and IMa, prevalence of carotid atherosclerotic plaques and FMD in brachial artery did not differ between RA patients treated with and those not treated with prednisolone. Carotid IMT and IMa, but not brachial FMD, were significantly associated with traditional risk factors for atherosclerosis in patients with RA.

Conclusions: Intake of oral moist snuff significantly impaired endothelial function, measured as FMD of the brachial artery, in long-term snuffers. As endothelial dysfunction predicts cardiovascular morbidity, use of oral snuff should be discouraged. Morphological parameters of the carotid arteries and the thoracic aorta were related to severity and extent of coronary artery stenosis in patients with severe CAD. B-mode ultrasonography of the carotid arteries and transesophageal echocardiography of the aorta therefore have a potential for diagnostic evaluation of patients with suspected CAD. Morphological but not functional parameters of the brachial artery were associated with the extent of coronary artery stenosis and atherosclerotic wall changes in the carotid arteries in patients with severe CAD. These findings indicate a potential of B-mode ultrasonography of morphological parameters in the brachial artery in the diagnostic evaluation of patients with suspected CAD. Low-dose prednisolone did not influence endothelial function or subclinical atherosclerosis in patients with RA. The study verifies the relation between risk factors for atherosclerosis and carotid IMT and IMa.

List of scientific papers

I. Rohani M, Agewall S (2004). "Oral snuff impairs endothelial function in healthy snuff users." J Intern Med 255(3): 379-83
https://pubmed.ncbi.nlm.nih.gov/14871462

II. Rohani M, Jogestrand T, Ekberg M, van der Linden J, Källner G, Jussila R, Agewall S (2005). "Interrelation between the extent of atherosclerosis in the thoracic aorta, carotid intima-media thickness and the extent of coronary artery disease." Atherosclerosis 179(2): 311-6. Epub 2004 Dec 8
https://pubmed.ncbi.nlm.nih.gov/15777547

III. Rohani M, Jogestrand T, Källner G, Jussila R, Agewall S (2005). "Morphological changes rather than flow-mediated dilatation in the brachial artery are better indicators of the extent and severity of coronary artery disease." J Hypertens 23(7): 1397-402
https://pubmed.ncbi.nlm.nih.gov/15942463

IV. Hafström I, Rohani M, Deneberg S, Wörnert M, Jogestrand T, Frostegård J (2007). "Effects of low-dose prednisolone on endothelial function, atherosclerosis, and traditional risk factors for atherosclerosis in patients with rheumatoid arthritis--a randomized study." J Rheumatol 34(9): 1810-6. Epub 2007 Aug 1
https://pubmed.ncbi.nlm.nih.gov/17696277