Aortic Stiffness and its Relationship to Kidney Disease, Brain Structure, and Cognition

Among the aging population, chronic kidney disease and cognitive impairment are highly prevalent and account for a significant portion of medical problems and health care costs. Unfortunately, the disease mechanisms are not well understood. Aortic stiffness increases with age and results in transmittance of increased pressures to the microvasculature of both organs. Aortic stiffness has been linked to both diseases, but prior studies have shown mixed results or were performed in select populations. We hypothesized that higher aortic stiffness would be associated with lower kidney function, lower kidney function would be associated with changes in brain structure and impaired cognition, and these latter associations would be attenuated by adjustment for aortic stiffness. We conducted a cross sectional study utilizing data from a subset of the Age, Gene/Environment, Susceptibility-Reykjavik Study, a large community-based prospective cohort study of cardiovascular disease in Iceland. We used linear or logistic regression as appropriate to assess the associations between aortic stiffness [carotid femoral pulse wave velocity (CFPWV) and carotid pulse pressure (CPP)] and kidney function and damage [estimated glomerular filtration rate (eGFR) and urine albumin to creatinine ratio (ACR)] as well as eGFR and ACR and brain structure and cognition. Sequential sets of multivariable models were performed adjusting for demographics and cardiovascular risk factors. We included 940 patients (mean age 75.8 years, mean eGFR 68 ml/min/1.73m2, median UACR 3 mg/g). Age was strongly related to eGFR, ACR, CFPWV, and CPP. Although CFPWV was associated with eGFR [beta (SE)=0.08 (0.02), p-value<0.001] and ACR [beta (SE)=-0.009 (0.002), p-value<0.001], the association was attenuated after adjusting for age and blood pressure. In those patients with CPP greater than 80 mmHg, CPP was associated with eGFR [beta (SE)=-0.22 (0.09), p-value=0.011], but the relationship became nonsignificant after adjustment for cardiovascular disease risk factors. CPP was significantly related to ACR in fully adjusted models [beta (SE)=0.006 (0.003), p-value=0.013]. ACR was significantly associated with all measures of brain structure; effect was minimally attenuated after adjustment for aortic stiffness. In summary, aortic stiffness was not strongly related to eGFR but higher CPP was related to albuminuria. Albuminuria was more strongly associated than eGFR with brain structure but neither were related to cognition. There was no consistent change in effect size after adjustment for aortic stiffness. Adjustment for age attenuated all relationships.