Using measures of sarcopenia to predict recurrent cerebrovascular events in stroke and TIA patients.

PURPOSE: Sarcopenia is associated with poor outcomes, and evidence suggests an inverse relationship between skeletal muscle mass and cardiovascular risk. Sarcopenia has been studied after stroke, but its value as a risk factor for stroke has not been examined. This prospective cohort study measured sarcopenia in stroke/TIA patients at baseline to explore its role in predicting recurrent events. METHOD: The Arterial Stiffness In lacunar Stroke and TIA (ASIST) study included 96 patients with TIA/lacunar stroke, of which 82 patients (mean age 71.2±10.8 years) had bioimpedance analysis to assess body composition. Skeletal Mass Index (SMI) was calculated and parameters of sarcopenia assessed using Davison (1) and Janssen (2) criteria. Recurrent cerebrovascular events were monitored over 5 years. RESULTS: Eighteen patients had recurrent events. On independent samples t test there were significantly more participants with sarcopenia in the recurrent events group (89% vs 56%, p<0.001) using Davison (1) criteria, as well as lower mean SMI, significantly more participants with diabetes and higher arterial stiffness. On binary logistic regression, the only significant predictors of recurrent events were SMI (p=0.036, hazard ratio=0.414, 95% confidence interval 0.195-0.948) and diabetes (p=0.004, hazard ratio=9.06, 95% confidence interval 2.009-40.860) when corrected for age, sex and cardiovascular risk factors. Using Janssen (2) criteria in the regression, severe sarcopenia was a significant predictor of recurrent events (p=0.028). There was a significant association between sarcopenia and recurrent events on Chi square based on Davison (p=0.02) and Janssen (p=0.034) definitions. CONCLUSIONS: The presence of baseline sarcopenia in stroke and TIA patients is an independent predictor of recurrent events.

Implementation of a medicine management plan (MMP) to reduce medication-related harm (MRH) in older people post-hospital discharge: a randomised controlled trial.

BACKGROUND: Medication-related harm (MRH) is an escalating global challenge especially among older adults. The period following hospital discharge carries high-risk for MRH due to medication discrepancies, limited patient/carer education and support, and poor communication between hospital and community professionals. Discharge Medical Service (DMS), a newly introduced NHS scheme, aims to reduce post-discharge MRH through an electronic communication between hospital and community pharmacists. Our study team has previously developed a risk-prediction tool (RPT) for MRH in the 8-weeks period post discharge from a UK hospital cohort of 1280 patients. In this study, we aim to find out if a Medicines Management Plan (MMP) linked to the DMS is more effective than the DMS alone in reducing rates of MRH. METHOD: Using a randomized control trial design, 682 older adults ≥ 65 years due to be discharged from hospital will be recruited from 4 sites. Participants will be randomized to an intervention arm (individualised medicine management plan (MMP) plus DMS) or a control arm (DMS only) using a 1:1 ratio stratification. Baseline data will include patients' clinical and social demographics, and admission and discharge medications. At 8-weeks post-discharge, a telephone interview and review of GP records by the study pharmacist will verify MRH in both arms. An economic and process evaluation will assess the cost and acceptability of the study methods. DATA ANALYSIS: Univariate analysis will be done for baseline variables comparing the intervention and control arms. A multivariate logistic regression will be done incorporating these variables. Economic evaluation will compare the cost-of-service use among the study arms and modelled to provide national estimates. Qualitative data from focus-group interviews will explore practitioners' understanding, and acceptance of the MMP, DMS and the RPT. CONCLUSION: This study will inform the use of an objective, validated RPT for MRH among older adults after hospital discharge, and provide a clinical, economic, and service evaluation of a specific medicines management plan alongside the DMS in the National Health Service (UK).

Are you as old as your arteries? Comparing arterial aging in Japanese and European patient groups using cardio-ankle vascular index.

BACKGROUND: Most comparisons of arterial stiffness between ethnic groups focus on pulse wave velocity. This study used the cardio-ankle vascular index (CAVI) in European compared to Japanese individuals to investigate how cardiovascular risk factors affect arterial aging across geographic regions. METHODS: Four hundred and ninety-four European and 1044 Japanese individuals underwent measurements of CAVI, blood pressure and information on cardiovascular risk factors. Both datasets included individuals with 0-5 cardiovascular risk factors. RESULTS: Average CAVI was higher in the Japanese than the European group in every age category, with significant differences up to 75 years for males and 85 for females. The correlation of CAVI with age, controlled for cardiovascular risk factors, was slightly higher in Japanese females (r = 0.594 vs. Europeans r = 0.542) but much higher in European males (r = 0.710 vs. Japanese r = 0.511). There was a significant correlation between CAVI and total cardiovascular risk factors in the Japanese (r = 0.141, P < 0.001) but not the European group. On linear regression, average CAVI was significantly dependent on age, sex, diabetes, BMI, SBP and geographic region. When divided into 'healthy' vs. 'high risk', the healthy group had a steeper correlation with age for Europeans (r = 0.644 vs. Japanese r = 0.472, Fisher's Z P < 0.001), whereas in the high-risk group, both geographic regions had similar correlations. CONCLUSION: Japanese patient groups had higher arterial stiffness than Europeans, as measured by CAVI, controlling for cardiovascular risk factors. Europeans had greater increases in arterial stiffness with age in healthy individuals, particularly for males. However, cardiovascular risk factors had a greater impact on the Japanese group.

White-coat hypertension/effect is associated with higher arterial stiffness and stroke events.

OBJECTIVES: The risk profile of white-coat hypertension/effect (WCH/E) remains unclear. This study aimed to investigate the relationship between WCH/E, markers of cardiovascular risk and cerebrovascular events. METHODS: This is a sub-group analysis of The Arterial Stiffness In lacunar Stroke and Transient ischemic attack (ASIST) study, which recruited 96 patients aged at least 40 years old with a diagnosis of transient ischemic attack or lacunar stroke in the preceding 14 days. Thirty-two patients with target blood pressure (clinic blood pressure <140/90 mmHg and daytime ambulatory blood pressure <135/85 mmHg) and 30 patients with WCH/E (clinic blood pressure ≥140/90 mmHg and daytime ambulatory blood pressure <135/85 mmHg) were included in the analysis. RESULTS: Patients with WCH/E were older and had a higher BMI. Central SBP (145 ±â€Š13 vs. 118 ±â€Š8 mmHg, P < 0.001) and DBP (82 ±â€Š8 vs. 76 ±â€Š7 mmHg, P = 0.004) were higher in those with WCH/E. They also had higher arterial stiffness measured by carotid-femoral pulse wave velocity (11.9 ±â€Š3.0 vs. 9.6 ±â€Š2.3 m/s, P = 0.002) and cardio-ankle vascular index (10.3 ±â€Š1.3 vs. 9.4 ±â€Š1.7, P = 0.027). Regression analysis showed an independent relationship between WCH/E and both measures of arterial stiffness. Lacunar strokes were more prevalent in those with WCH/E (47 vs. 22%, P = 0.039) and individuals in this group were more likely to have had a lacunar stroke than a transient ischemic attack (odds ratio 9.6, 95% CI 1.5-62.6, P = 0.02). CONCLUSION: In this cohort of patients with lacunar stroke and transient ischemic attack, WCH/E was associated with elevated markers of cardiovascular risk and a higher prevalence of lacunar stroke. These results suggest that WCH/E is associated with adverse cardiovascular risk.

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.

C-Reactive Protein Predicts Further Ischemic Events in Patients With Transient Ischemic Attack or Lacunar Stroke.

Patients who have experienced a first cerebral ischemic event are at increased risk of recurrent stroke. There is strong evidence that low-level inflammation as measured by high sensitivity C-reactive protein (hs-CRP) is a predictor of further ischemic events. Other mechanisms implicated in the pathogenesis of stroke may play a role in determining the risk of secondary events, including oxidative stress and the adaptive response to it and activation of neuroprotective pathways by hypoxia, for instance through induction of erythropoietin (EPO). This study investigated the association of the levels of CRP, peroxiredoxin 1 (PRDX1, an indicator of the physiological response to oxidative stress) and EPO (a neuroprotective factor produced in response to hypoxia) with the risk of a second ischemic event. Eighty patients with a diagnosis of lacunar stroke or transient ischemic attack (TIA) were included in the study and a blood sample was collected within 14 days from the initial event. Hs-CRP, PRDX1, and EPO were measured by ELISA. Further ischemic events were recorded with a mean follow-up of 42 months (min 24, max 64). Multivariate analysis showed that only CRP was an independent predictor of further events with an observed risk (OR) of 1.14 (P = 0.034, 95% CI 1.01-1.29). No association was observed with the levels of PRDX1 or EPO. A receiver operating curve (ROC) determined a cut-off CRP level of 3.25 µg/ml, with a 46% sensitivity and 81% specificity. Low-level inflammation as detected by hs-CRP is an independent predictor of recurrent cerebrovascular ischemic events.

Aortic stiffness and central systolic pressure are associated with ambulatory orthostatic BP fall in chronic kidney disease.

OBJECTIVE: Orthostatic hypotension (OH) has a significant association with cardiovascular disease. OH becomes more common in older age, as does arterial stiffness, shown to be independently associated with impaired baroreflex sensitivity and OH. Measurement of arterial compliance and central blood pressures are increasingly important, with evidence that central BP more closely correlates to end-organ damage and mortality than peripheral measurements. Patients with chronic kidney disease (CKD) are high risk for cardiovascular events, which can be predicted through measures of arterial compliance. We hypothesised that OH is associated with arterial stiffness and central blood pressure in CKD patients. DESIGN/SETTING: We tested this hypothesis within the arterial compliance and oxidant stress as predictors of loss of renal function, morbidity and mortality in chronic kidney disease (ACADEMIC) study, a single-centre prospective observational study of the progression of arterial stiffness and renal function. PARTICIPANTS: One hundred and forty-six patients with CKD 3 or 4. MEASUREMENTS: Twenty-four-hour ambulatory BP monitoring with postural sensing (DIASYS Integra 2, Novacor France); central systolic and diastolic BP (cSBP and cDBP) and aortic Augmentation Index using Sphygmocor® (Atcor, Australia); Carotid-femoral pulse wave velocity (cfPWV) using Complior® (ALAM Medical, France). RESULTS: Twenty-three patients had a postural SBP fall (prevalence 15.8%), with mean drop 7 mmHg. Patients with OH had higher cfPWV (15.2 m/s vs 12.7 m/s in patients without OH, p < 0.001) and central SBP (147.5 vs 135.7, p = 0.012). Regression analysis gave an odds ratio (OR) of orthostatic SBP fall for cfPWV of 1.46 (95% CI 1.16-1.84, p = 0.001) and 1.03 for cSBP (95% CI 1.004-1.06, p = 0.024) after adjustment for cardiovascular risk factors. CONCLUSION: Aortic stiffness and central SBP are independently associated with orthostatic SBP fall in CKD patients. This suggests that enhanced arterial stiffness may be an underlying mechanism in baroreflex dysfunction, and may partly explain the vascular risk in CKD patients.

Independent Association Between Cardio-Ankle Vascular Index and Sarcopenia in Older U.K. Adults.

OBJECTIVES: To investigate the correlation between sarcopenia and arterial stiffness in Caucasians, centering on the relationship between skeletal mass index (SMI) and the cardio-ankle vascular index (CAVI) to assess the use of CAVI in predicting sarcopenia. DESIGN CROSS-SECTIONAL SETTING: United Kingdom. PARTICIPANTS: UK adults aged 45 years and over (N = 366, n = 177 male, n = 189 female). MEASUREMENTS: Bioimpedance analysis was used to derive SMI. CAVI score was calculated using a vascular screening system. Handgrip strength was measured using a standard dynamometer. RESULTS: Average CAVI was significantly correlated with SMI (correlation coefficient (r) = -0.285, p < .001), with higher correlation in women (r = -0.416, p < .001) than men (r = -0.214, p = .01). CAVI had the highest correlation with SMI from appendicular muscle (fat-free mass in men, r = -0.253, p = .002; predicted muscle mass in women, r = -0.436, p < .001). There was a significant difference in average CAVI between groups, with participants who were not sarcopenic having lower CAVI (8.98) than those who were sarcopenic (9.80) (p < .001, t-test). Linear regression was performed using SMI as the dependent variable. After adjustment for age, average CAVI was a significant predictor of SMI in women (beta = -0.332, p < .001) but not men. CONCLUSION: Indices of sarcopenia are independently associated with a higher CAVI, with greater correlation in women than men. The CAVI can be used to assess overall vascular compliance and may be a useful operator-independent tool that can be used to measure sarcopenia and its cardiovascular implications in older adults. J Am Geriatr Soc 67:317-322, 2019.