Age-related Renovascular Changes consequences in late life

This thesis provides new insights in underlying patterns that may be involved in the (accelerated) aging process, in particular in the area of renovascular changes. It hopes to unravel new targets for better diagnostic and therapeutic strategies in an attempt to maintain or even improve quality of late life

Deterioration of Kidney Function Is Affected by Central Arterial Stiffness in Late Life

Cardiovascular diseases affect kidney function. The aim of this study was to investigate the possible associations between hemodynamic parameters and change in kidney function in individuals aged 75 years and older. Data on hemodynamics and blood and urine samples were collected at baseline and during one-year visits. Hemodynamics were split into two groups based on median values. Changes in the estimated glomerular filtration rate (eGFR) were investigated between low and high groups for each hemodynamic parameter using analysis of variance. Changes in the albumin–creatinine ratio (ACR) were examined as binary outcomes (large increase vs. stable) using logistic regression. The population consisted of 252 participants. Participants in the high central systolic blood pressure (cSBP) group had a greater decline in eGFR than participants in the low cSBP group (−6.3% vs. −2.7%, p = 0.006). Participants in the high aortic pulse wave velocity (aPWV) group had a greater decline in eGFR than those in the low aPWV group (−6.8% vs. −2.5%, p = 0.001). Other hemodynamic parameters were not associated with eGFR changes. Hemodynamics were not associated with changes in the ACR; aPWV and cSBP appear to be predictors for eGFR decline in older age; monitoring and treatment of elevated stiffness might be helpful in order to prevent kidney function decline.</p

New horizons in cognitive and functional impairment as a consequence of cerebral small vessel disease

Cerebral small vessel disease (cSVD) is a frequent finding in imaging of the brain in older adults, especially in the concomitance of cardiovascular disease risk factors. Despite the well-established link between cSVD and (vascular) cognitive impairment (VCI), it remains uncertain how and when these vascular alterations lead to cognitive decline. The extent of acknowledged markers of cSVD is at best modestly associated with the severity of clinical symptoms, but technological advances increasingly allow to identify and quantify the extent and perhaps also the functional impact of cSVD more accurately. This will facilitate a more accurate diagnosis of VCI, against the backdrop of concomitant other neurodegenerative pathology, and help to identify persons with the greatest risk of cognitive and functional deterioration. In this study, we discuss how better assessment of cSVD using refined neuropsychological and comprehensive geriatric assessment as well as modern image analysis techniques may improve diagnosis and possibly the prognosis of VCI. Finally, we discuss new avenues in the treatment of cSVD and outline how these contemporary insights into cSVD can contribute to optimise screening and treatment strategies in older adults with cognitive impairment and multimorbidity.</p

The possible impact of aortic stiffness on quality of late life: An exploratory study

Purpose: Aortic stiffness (AS) is associated with cardiovascular events and all-cause mortality in the older population. AS might also influence the health-related quality of life (HRQOL) as a result of the negative effects of AS on cognitive and physical morbidity. We aimed to investigate the possible association between AS and HRQOL in people aged 75 years and over. Patients and Methods: This cross-sectional study was part of the SCOPE study, an international multicenter cohort observational study. The indicators for AS were aortic pulse wave velocity (aPWV) and central pulse pressure (cPP). HRQOL was assessed using the EQ-5D index and the EQ-5D visual analog scale (VAS). ANCOVA and multivariate regression models were used to investigate possible associations. Results: We included 280 Dutch participants of the SCOPE study. Median age was 79 years (IQR 76–83) and 42.1% were women. Participants reporting any problem on the EQ-5D index (n=214) had higher values of aPWV (12.6 vs 12.2 m/s, p = 0.024) than participants not experiencing any problem (n=66) and comparable values of cPP (44.4 vs 42.0 mmHg, p = 0.119). Estimates only slightly changed after adjustments. No association was found between indicators of AS and EQ-5D VAS. Conclusion: Aortic stiffness was associated with impaired quality of late life. This association could be mediated by subclinical vascular pathology affecting mental and physical health

Unraveling the links underlying arterial stiffness, bone demineralization, and muscle loss

The effects of elevated arterial stiffness on cardiovascular outcomes are widely studied, whereas the relation to noncardiovascular outcomes relevant to older persons, such as the effect on bones and muscles, is less well established. Arterial stiffness, bone demineralization, and muscle loss are all age-related processes with common risk factors, however, whether these are just parallel age-related alterations or whether these processes share common pathways is not yet understood. In this review, we outline previous literature using different assessments of arterial stiffness in various populations across the world to produce a comprehensive overview. Although there are many studies showing an association between arterial stiffness and loss of bone and muscle, the majority are cross-sectional and there is limited longitudinal evidence to justify causal conclusions. We also give an in-depth review of hypotheses and possible mechanisms which may underlie these associations including hormone dysregulation, impaired glucose metabolism, and inflammation. This narrative review highlights the associations between vessels, bones, and muscles with aging, offering insights into possible shared pathways

The relevance of geriatric assessments on the association between chronic kidney disease stages and mortality among older people: a secondary analysis of a multicenter cohort study

Background: age-adapted definition of chronic kidney disease (CKD) does not take individual risk factors into account. We aimed at investigating whether functional impairments influence CKD stage at which mortality increases among older people. Methods: our series consisted of 2,372 outpatients aged 75 years or more enrolled in a multicentre international prospective cohort study. The study outcome was 24-month mortality. Kidney function was assessed by estimated glomerular filtration rate (eGFR) and albumin-to-creatinine ratio (ACR). Geriatric assessments included handgrip strength, short physical performance battery (SPPB), cognitive impairment, dependency in basic activities of daily living (BADL) and risk of malnutrition. Analysis was carried out by Cox regression, before and after stratification by individual functional impairments. Survival trees including kidney function and functional impairments were also investigated, and their predictivity assessed by C-index. Results: overall, mortality was found to increase starting from eGFR = 30-44.9 ml/min/1.73 m2 (hazard ratio [HR] = 3.28, 95% confidence interval [CI] = 1.81-5.95) to ACR = 30-300 mg/g (HR = 1.96, 95%CI = 1.23-3.10). However, in survival trees, an increased risk of mortality was observed among patients with impaired handgrip and eGFR = 45-59.9 ml/min/1.73 m2, as well as patients with ACR < 30 mg/g and impaired handgrip and SPPB. Survival tree leaf node membership had greater predictive accuracy (C-index = 0.81, 95%CI = 0.78-0.84 for the eGFR survival tree and C-index = 0.77, 95%CI = 0.71-0.81 for the ACR survival tree) in comparison with that of individual measures of kidney function. Conclusions: physical performance helps to identify a proportion of patients at an increased risk of mortality despite a mild-moderate impairment in kidney function and improves predictive accuracy of individual measures of kidney function

Diabetes, sarcopenia and chronic kidney disease; the screening for CKD among older people across Europe (SCOPE) study

ackground:Sarcopenia may be more present in older adults with diabetes (DM). Accordingly, we evaluated the prevalence of sarcopenia and its associated risk factors among community‑dwelling older adults with DM.Methods:A cross‑sectional analysis of older people living in the community was carried out. Participants (aged 75 years and more) came from an European multicenter prospective cohort (SCOPE study). Global geriatric assess‑ment including short physical performance battery, handgrip strength test and bioelectrical impedance analysis was performed. Sarcopenia was defined by the updated criteria of the European Working Group on Sarcopenia in Older People (EWGSOP2). Estimated glomerular filtration rate (eGFR) was calculated using Berlin Initiative Study (BIS) to define the stages of chronic kidney disease (CKD). Previous known DM was defined as physician‑diagnosed DM reg‑istered in the patient's medical record or the use of DM‑related medications. Hemoglobin A1c levels and specific DM therapies administered were collected. Time elapsed from the first diagnosis of DM was not collected and, therefore, was not included in the analyses.Results:A total of 1,420 subjects were evaluated with a median age of 79.0 (6.0) years, of which 804 (56.6%) were women and 615 (43.3%) men; 315 (22.2%) participants had prior DM diagnosis, with a median age of 80.0 (6.0), 146 (46.3%) were women. Using EWGSOP2 definition, 150 (10.6%) participants in the SCOPE study met diagnostic criteria for sarcopenia. Participants without diabetes had more often normal results in the 3 sarcopenia components than participants with diabetes [887 (80.31%) vs. 227 (72.1%), p=0.002], highlighting higher percentages of severe sarco‑penia in participants with diabetes [27 (8.6%) vs. 58 (5.2%), p=0.028]. Confirmed or severe sarcopenia was detected in 41 (13%) participants with diabetes and 109 (9.8%) participants without diabetes (p=0.108). According to BIS equa‑tion, sarcopenia was not significantly more prevalent in the more advanced stages of CKD (p=0.845). In multivariate analyses, older age (odds ratios [OR], 1.17; 95% confidence interval [CI], 1.08-1.27), and lower body mass index (OR, 0.79; 95% CI, 0.71-0.89 were associated with the presence of sarcopenia.Conclusions:One tenth of all older community‑dwelling subjects have sarcopenia. Older age and being thinner, but not worse renal function, were associated with higher prevalence of sarcopenia in older older adults with diabetes

Clinical implications of estimating glomerular filtration rate with three different equations among older people: preliminary results of the project 'Screening for Chronic Kidney Disease Among Older People Across Europe (SCOPE)'

We aimed at investigating to what extent CKD may be staged interchangeably by three different eGFR equations in older people, and evaluating the source of discrepancies among equations in a population of 2257 patients older than 75 years enrolled in a multicenter observational study. eGFR was calculated by CKD-EPI, BIS and FAS equations. Statistical analysis was carried out by Bland-Altman analysis. κ statistic was used to quantify the agreement between equations in classifying CKD stages. The impact of selected variables on the difference among equations was graphically explored. The average difference between BIS and FAS was -0.24 (95% limits of agreement (95%LA = -4.64-4.14) mL/min/1.73 m2. The difference between CKD-EPI and BIS and between CKD-EPI and FAS was 8.97 (95%LA = -2.90-20.84) and 8.72 (95%LA = -2.11-19.56) mL/min/1.73 m2, respectively. As regards CKD stage classification, κ value was 0.47 for both CKD-EPI vs. FAS and CKD-EPI vs. BIS, while BIS and FAS had similar classificatory properties (κ = 0.90). Muscle mass was found related to the difference between CKD-EPI and BIS (R2 = 0.11) or FAS (R2 = 0.14), but not to the difference between BIS and FAS. In conclusion, CKD-EPI and BIS/FAS equations are not interchangeable to assess eGFR among older people. Muscle mass may represent a relevant source of discrepancy among eGFR equations

Short physical performance battery is not associated with falls and injurious falls in older persons:longitudinal data of the SCOPE project

Introduction: Falls and fall-related injuries in older persons are a major public health problem. Our objective was to study the predictive value of the Short Physical Performance Battery (SPPB) in the cohort of the SCOPE project on falls, injurious falls, and possible difference of prediction between indoors and outdoors falls. Methods: For this sub-study of the SCOPE project participants reporting no falls at baseline, and survey data on falls at the 12-month and 24-month follow-up were included. Participant´s characteristics were assessed during the baseline interview and medical examinations. Falls as well as injurious falls and fall circumstances were obtained self-reported. SPPB and its association with fallers vs. no fallers at 12 and at 24 months were studied with logistic regression models. Results: The 1198 participants had a median age of 79 years (77–82), and a median SPPB of 10 (8–11), with a 52.5% of female. A total of 227 and 277 falls (12- and 24- month visits, respectively) were reported. In the crude model, the SPPB sum scores (p &lt; 0.001) as well as most single item scores were significant different between fallers and non-fallers over time. However, the association was attenuated in models adjusted for age, sex, marital status, number of medications, quality of life, handgrip strength, and muscle mass [e.g., 12 months; OR 0.94 (0.87–1.02)]. While SPPB fails to differentiate between injurious and non-injurious falls (p = 0.48), a lower SPPB score was associated with falls at home (p &lt; 0.01) after 24 months.Conclusion: SBPP was not able to significantly predict the risk of falling as well as experiencing an injurious fall. Trial registration: This study was registered prospectively on 25th February 2016 at clinicaltrials.gov (NCT02691546).</p

Age-Specific Acute Changes in Carotid-Femoral Pulse Wave Velocity With Head-up Tilt

BACKGROUND: Aortic stiffness as measured by carotid-femoral pulse wave velocity (cfPWV) is known to depend on blood pressure (BP), and this dependency may change with age. Therefore, the hydrostatic BP gradient resulting from a change in body posture may elicit a cfPWV change that is age-dependent. We aimed to analyze the relationship between BP gradient-induced by head-up body tilting-and related changes in cfPWV in individuals of varying age. METHODS: cfPWV and other hemodynamic parameters were measured in 30 healthy individuals at a head-up tilt of 0° (supine), 30°, and 60°. At each angle, the PWV gradient and resulting cfPWV were also estimated (predicted) by assuming a global nonlinear, exponential, pressure-diameter relationship characterized by a constant β0, and taking into account that (diastolic) foot-to-foot cfPWV acutely depends on diastolic BP. RESULTS: cfPWV significantly increased upon body tilting (8.0 ± 2.0 m/s supine, 9.1 ± 2.6 m/s at 30°, 9.5 ± 3.2 m/s at 60°, P for trend <0.01); a positive trend was also observed for heart rate (HR; P < 0.01). When the observed, tilt-induced cfPWV change measured by applanation tonometry was compared with that predicted from the estimated BP hydrostatic gradient, the difference in observed-vs.-predicted PWV change increased nonlinearly as a function of age (R2 for quadratic trend = 0.38, P < 0.01, P vs. linear = 0.04). This result was unaffected by HR tilt-related variations (R2 for quadratic trend = 0.37, P < 0.01, P vs. linear = 0.04). CONCLUSIONS: Under a hydrostatic pressure gradient, the pulse wave traveling along the aorta undergoes an age-related, nonlinear PWV increase exceeding the increase predicted from BP dependency