Impact of chronic kidney disease on the cardiovascular system : studies in non-dialysis patients and healthy people

Abstract: Background: Cardiac and arterial remodeling and stiffening occur in end-stage renal disease. The presence of cardiovascular (CV) alterations in earlier-stage chronic kidney disease (CKD) is less well studied. We evaluated CV structure and function in patients with mild-to-moderate CKD (stages 2–3) compared with healthy people and patients with advanced CKD (stages 4–5). This thesis is based on a prospective study, PROGRESS 2002, which is a collaborative project between the Department of Renal Medicine and the Department of Clinical Physiology at the Karolinska University Hospital, Solna, Sweden. Aims: The aim of this thesis was to study early cardiac and vascular alterations in non-dialysis CKD, with special interest in patients with mild-to-moderate CKD. Aerobic exercise capacity, changes in blood pressure (BP) at rest and during exercise, and arterial and cardiac remodeling and function were assessed to improve understanding of the pathophysiology of CV involvement in renal disease. Methods and results: In Study I, left ventricular (LV) mass index (LVMI) and systolic and diastolic function were evaluated using transthoracic echocardiography, including tissue Doppler imaging, in 103 patients with CKD (stages 2–3 and 4–5) and 53 healthy controls. The peak systolic myocardial velocity (sʹ′), early diastolic myocardial velocity (eʹ′), and early transmitral diastolic flow velocity (E) were measured, and E/eʹ′ was calculated. CKD patients had a higher mean E/eʹ′ and lower longitudinal systolic function, as assessed by atrioventricular plane displacement and sʹ′, than the controls. The prevalence of LV hypertrophy (LVH) was higher in CKD patients than in controls. In Study II, vascular structure and function were studied using carotid ultrasound in 103 nondialysis CKD patients (stages 2–3 and 4–5) and 54 healthy controls. Carotid intima–media thickness (CIMT) and common carotid artery (CCA) diameter were measured. Strain, stiffness, and the pressure–strain elastic modulus (Ep) of the right CCA were calculated. CCA diameter did not differ significantly between CKD 2–3 patients and controls. CCA diameter was larger in CKD 4–5 patients than in CKD 2–3 patients and controls (CKD 4–5, 6.50 ± 0.79 mm versus CKD 2–3, 6.08 ± 0.56 mm, P = 0.003; and versus controls, 5.97 ± 0.53 mm, P < 0.001). However, after adjustment, the difference in CCA diameter was significant only for older patients and was dependent on systolic blood pressure (SBP). CIMT, strain, and stiffness did not differ significantly between groups, but Ep was higher in CKD 4–5 patients than in controls (P = 0.006). In Study III, aerobic exercise capacity was studied in 99 patients with non-dialysis CKD (stages 2–3 and 4–5) and 54 healthy controls. Peak workload, as a measure of aerobic exercise capacity, and peak heart rate (peak HR) were measured during a maximal exercise test on a cycle ergometer. Cardiac and vascular ultrasound examinations were performed, and muscular function, haemoglobin level, and self-reported physical activity were assessed. Peak workload, peak HR, and haemoglobin level were significantly lower in CKD 2–3 patients than in controls and were lower in CKD 4–5 than in CKD 2–3 patients. Multiple regression analysis showed that peak workload was strongly associated with systemic oxygen delivery factors, as indicated by stroke volume, peak HR, and haemoglobin level; together with age, sex, and height2, these factors explained approximately 80% of individual variation in workload in CKD patients, with peak HR contributing most to the variation. Self-reported physical activity level was also an independent determinant of peak workload. In Study IV, 54 patients with CKD stages 2–3 and 54 healthy controls were included and followed for 5 years. Renal function, ambulatory BP monitoring, measurement of ankle– brachial index (ABI), and carotid and cardiac ultrasound examinations were performed at baseline and after 3 and 5 years. CIMT, CCA diameter, elastic properties of the CCA (measured as Ep), and LVMI were evaluated. In the CKD patients, average 24 h SBP and CCA diameter did not increase significantly from the baseline and to year 5, but these both increased in the controls over the same time. The ABI increased significantly between the baseline and year 5 in the CKD patients but not in the controls. LVMI increased significantly between the baseline and year 5 in both groups, but the change over time did not differ significantly between patients and controls. Ep did not change over time in either group.