Clinical aspects of arterial wall stiffness with a focus on abdominal aortic aneurysm

Sammanfattning: Background: Cardiovascular diseases are the most common type of age-related diseases and can affect health in several ways. As a result of increased life expectancy around the world, the prevalence of cardiovascular diseases is expected to increase. Early detection of cardiovascular morbidity is important to reduce mortality and also to improve cardiovascular health. Arterial stiffness is a well-known independent predictor of cardiovascular morbidity and mortality. The central arterial walls become stiffer with age, which has an important impact on cardiac work. The development of arterial stiffness is not an immutable and inexorable process. Instead, it should be seen as a potential target of interventions that aim to slow the vascular ageing process. Arterial stiffness in individuals affected by abdominal aortic aneurysm (AAA) is an understudied area. AAA is a disease that predominantly affects elderly males. The disease is usually asymptomatic, but a rupture of the aneurysm is life threatening. Even without rupture, individuals with an AAA have an increased risk of other major cardiovascular events, but the underlying mechanisms of this increased risk are unclear.Aim: The overall aim of the research in this thesis was to investigate clinical aspects of arterial stiffness with a focus on AAA.Methods: All studies in this thesis used a quantitative and a cross-sectional design. Paper I compared elderly hypertensive females with elderly hypertensive males and examined the effects of FBN1 genotypes within each sex. The study cohort in Paper I underwent physiological cardiovascular examinations with a focus on pulse wave analysis and blood pressure. In addition, blood samples were taken after overnight fasting. The study cohorts in Papers II–IV were males with AAA and age-matched controls without AAA. The participants underwent physiological cardiovascular examinations, and blood samples were taken after overnight fasting. In Paper II, the speed and shape of the pulse wave and blood pressure were studied non-invasively to evaluate the properties of the arterial system. In Paper III, the heart was studied using two-dimensional ultrasound with a focus on evaluation of the function of the left ventricle. In Paper IV, analyses of IL-10 levels were added to the previously performed studies.Results: A sex-related difference was found in the augmentation index (females: 36%; males 33%; p<0.001) and systolic blood pressure (females: 169 mmHg; males: 162 mmHg; p<0.05) of the elderly hypertensive participants in Paper I. In addition, females, but not males, displayed differences in augmentation index and systolic blood pressure among different FBN1 genotypes; females with the FBN1 2/3 genotype had higher augmentation index (p<0.05) and systolic blood pressure (p<0.05) than those with the FBN1 2/2 and 2/4 genotypes. In Paper II, differences in central pulse wave velocity (12.3 m/s versus 10.9 m/s; p<0.001) and peripheral pulse wave velocity (9.4 m/s versus 9.1 m/s; p<0.05) were seen between patients with AAA and controls. In Paper III, patients with AAA had lower left ventricular ejection fraction (55±8% versus 57±7%) and global longitudinal strain (19±3% versus 20±3%) than controls (both p<0.05). Moreover, the patients with AAA had lower mitral annular plane systolic excursion and higher E/e' compared with the controls (both p<0.05). In Paper IV, patients with AAA had higher levels of Interleukin-10 (21.5±14.0 ng/ml versus 16.6±9.3 ng/ml) compared with controls (p<0.01), and within the AAA cohort, patients with diabetes had higher levels of Interleukin-10 than those without diabetes (26.4±17.3 versus 20.4±13.0; p<0.05).Conclusion: The results from this thesis highlight the possibility to use pulse wave velocity and augmentation index for risk stratification in patients already affected by cardiovascular diseases. The results contribute new knowledge about arterial stiffness and left ventricle function in males with AAA. Moreover, they contribute knowledge to support new and individualised treatments for arterial stiffness in males with AAA in the future.