OBJECTIVE:Diagnostic criteria for an exaggerated BP increase in response to standing (ERTS) are still debated making it difficult to interpret data regarding the cardiovascular risk associated with ERTS. The aim of the present study was to identify the ERTS definition that was most strongly associated with cardiovascular disease. DESIGN AND METHODS:The study was conducted within the frame of the PARTAGE study, in 920 individuals aged 80 years or older. BP was measured 1 min and 3 min after standing up. Participants were classified into three groups according to whether they had normal response to standing (reference group), orthostatic hypotension, or ERTS defined using 16 different definitions. The risk of adverse cardiovascular outcomes was explored by means of multivariable survival Cox analyses. RESULTS:ERTS was associated with both cardiovascular events and mortality when it was identified according to three definitions: SBP ≥20 mmHg in either orthostatic measurement [hazard ratios (HRs) (95% confidence interval, CI), 1.45 (1.03-2.03; P  = 0.031)] and 1.71 (1.05-2.77; P  = 0.030), respectively; SBP ≥15 mmHg in either orthostatic measurement ((1.43 (1.03-1.99; P  = 0.032) and 1.82 (1.12-2.94; P  = 0.015)), respectively; and SBP ≥20 mmHg and/or DBP ≥15 mmHg in either orthostatic measurement ((1.42 (1.03-1.98; P  = 0.035) and 1.94 (1.19-3.17; P  = 0.008)), respectively. The best model fit was found for SBP and DBP combined. No independent association with both outcomes was found for other ERTS definitions. CONCLUSIONS:The present results show that an SBP increase of >15-20 mmHg is a more important prognostic indicator than less pronounced increases of SBP. However, associating also an increase in DBP of ≥15 mmHg slightly increased the predictive value of ERTS.

BACKGROUND:Among older adults with frailty, evidence on the benefits and risks of discontinuing antihypertensive drugs is limited. METHODS:In a multicenter, randomized, controlled trial conducted in France, we assigned, in a 1:1 ratio, nursing home residents 80 years of age or older who were receiving more than one antihypertensive drug and had a systolic blood pressure below 130 mm Hg to a protocol-driven strategy of progressive reduction of antihypertensive treatment (step-down group) or to receive usual care (usual-care group). Patients were to be followed for up to 4 years. The primary end point was death from any cause. Secondary end points included the changes in the number of antihypertensive drugs being used from baseline to the last trial visit and the change in systolic blood pressure during the follow-up period. RESULTS:A total of 1048 patients underwent randomization: 528 to the step-down group and 520 to the usual-care group. The estimated median potential follow-up was 38.4 months. Between baseline and the last trial visit, the mean (±SD) number of antihypertensive drugs being used decreased from 2.6±0.7 to 1.5±1.1 in the step-down group and from 2.5±0.7 to 2.0±1.1 in the usual-care group. The adjusted mean between-group difference (step-down group minus usual-care group) in the change in systolic blood pressure during the follow-up period was 4.1 mm Hg (95% confidence interval [CI], 1.9 to 5.7). Death from any cause occurred in 326 patients (61.7%) in the step-down group and in 313 (60.2%) in the usual-care group (adjusted hazard ratio, 1.02; 95% CI, 0.86 to 1.21; P = 0.78). There were no apparent differences in adverse events between the trial groups. CONCLUSIONS:Among older nursing home residents with frailty who were receiving treatment with antihypertensive agents and had a systolic blood pressure below 130 mm Hg, an antihypertensive treatment step-down strategy did not lead to lower all-cause mortality than usual care. (Funded by the French Ministry of Health and others; RETREAT-FRAIL ClinicalTrials.gov number, NCT03453268.).

Background: The cardio-ankle vascular index (CAVI) measure of arterial stiffness is associated with prevalent cardiovascular risk factors, while its predictive value for cardiovascular events remains to be established. The aim was to determine associations of CAVI with cardiovascular morbimortality (primary outcome) and all-cause mortality (secondary outcome), and to establish the determinants of CAVI progression. Methods: TRIPLE-A-Stiffness, an international multicentre prospective longitudinal study, enrolled >2000 subjects >= 40 years old at 32 centres from 18 European countries. Of these, 1250 subjects (55% women) were followed for a median of 3.82 (2.81-4.69) years. Findings: Unadjusted cumulative incidence rates of outcomes according to CAVI stratification were higher in highest stratum (CAVI > 9). Cox regression with adjustment for age, sex, and cardiovascular risk factors revealed that CAVI was associated with increased cardiovascular morbimortality (HR 1.25 per 1 increase; 95% confidence interval, CI: 1.03-1.51) and all-cause mortality (HR 1.37 per 1 increase; 95% CI: 1.10-1.70) risk in subjects >= 60 years. In ROC analyses, CAVI optimal threshold was 9.25 (c-index 0.598; 0.542-0.654) and 8.30 (c-index 0.565; 0.512-0.618) in subjects >= or <60 years, respectively, to predict increased CV morbimortality. Finally, age, mean arterial blood pressure, anti-diabetic and lipid-lowering treatment were independent predictors of yearly CAVI progression adjusted for baseline CAVI. Interpretation: The present study identified additional value for CAVI to predict outcomes after adjustment for CV risk factors, in particular for subjects >= 60 years. CAVI progression may represent a modifiable risk factor by treatments.

BACKGROUND:A mismatch between myocardial oxygen supply and demand is the most common cause of ischemic myocardial injury in older persons. The subendocardial viability ratio (SEVR) can usefully estimate the degree of myocardial perfusion relative to left-ventricular workload. The aim of the present study was to evaluate the ability of SEVR to predict long-term mortality in the older population. Additionally, we aimed to identify the SEVR cutoff value best predicting total mortality. METHODS:This is a multicenter, longitudinal study involving a large population of individuals older than 80 years living in nursing homes. Patients with cancer, severe dementia, and very low level of autonomy were excluded from the study. Participants were monitored for 10 years. Adverse outcomes were recorded every 3 months from inclusion to the end of the study. SEVR reflects the balance between subendocardial oxygen supply and demand, and was estimated non-invasively by analyzing the carotid pressure waveform recorded by applanation arterial tonometry. RESULTS:A total of 828 people were enrolled (mean age: 87.7 ± 4.7 years, 78% female). 735 patients died within 10 years and 24 were lost to follow-up. SEVR was inversely associated with mortality at univariate Cox-regression model (risk ratio, 0.683 per unit increase in SEVR; 95% confidence interval (CI) [0.502-0.930], p = 0.015) and in a model including age, sex, body mass index, Activity of Daily Living index and Mini-Mental State Examination score (risk ratio, 0.647; 95% CI [0.472-0.930]). The lowest tertile of SEVR was associated with higher 10-years total mortality than the middle (p < 0.001) and the highest (p < 0.004) tertile. A SEVR cutoff value of 83% was identified as the best predictor of total mortality. CONCLUSIONS:SEVR may be considered as a marker of "cardiovascular frailty." An accurate non-invasive estimation of SEVR could be a useful and independent parameter to assess survival probability in very old adults. TRIAL REGISTRATION:NCT00901355, registered on ClinicalTrials.gov website.

Objective: The subendocardial viability ratio (SEVR), estimate by arterial tonometry, can quantify the degree of myocardial perfusion relative to left-ventricular workload. This study aims to evaluate the ability of SEVR to predict long-term mortality in the older population, in the PARTAGE (Predictive values of blood pressure (BP) and ARTerial stiffness in institutionalized very AGEd population) study. Additionally, we aimed to identify the SEVR cutoff value best predicting mortality. Design and method: Patients were enrolled from the PARTAGE, a multicenter, longitudinal study aimed at determining the predictive value of blood pressure and arterial mechanical parameters in a large population of individuals aged 80 years and over living in nursing homes. Data from central blood pressure derived from arterial tonometry (PulsePen, DiaTecne, Milan) were used to elaborate the SEVR. The mortality over a 10 years follow-up was analyzed according to SEVR, using Kaplan–Meier curves and Cox regression multivariate models. Results: A total of 828 people were enrolled (mean age: 87.7±4.7 years, 78% female). 735 patients died within 10 years and 24 were lost to follow-up. SEVR was inversely associated with mortality at univariate Cox-regression model (risk ratio, 0.683 per unit increase in SEVR; 95% confidence interval (CI) [0.502–0.930], p = 0.015) and in a model including age, sex, body mass index, Activity of Daily Living index and Mini-Mental State Examination score (risk ratio, 0.647; 95% CI [0.472–0.930]). The lowest tertile of SEVR was associated with higher 10-years total mortality than the middle (p < 0.001) and the highest (p < 0.004) tertile. A SEVR cutoff value of 83% was identified as the best predictor of total mortality. Conclusions: SEVR is significantly and independently associated with mortality among nursing home residents aged 80 years and over, with a proposed cutoff value of 83%. An accurate non-invasive estimation of SEVR could be a useful and independent parameter to assess survival probability in very old adults.

Background: Physical activity at high-altitudes is increasingly widespread, both for tourist trekking and for the growing tendency to carry out sports and training activities at high-altitudes. Acute exposure to this hypobaric–hypoxic condition induces several complex adaptive mechanisms involving the cardiovascular, respiratory and endocrine systems. A lack of these adaptive mechanisms in microcirculation may cause the onset of symptoms of acute mountain sickness, a frequent disturbance after acute exposure at high altitudes. The aim of our study was to evaluate the microcirculatory adaptive mechanisms at different altitudes, from 1350 to 5050 m a.s.l., during a scientific expedition in the Himalayas. Methods: The main haematological parameters, blood viscosity and erythrocyte deformability were assessed at different altitudes on eight European lowlanders and on a group of eleven Nepalese highlanders. The microcirculation network was evaluated in vivo by conjunctival and periungual biomicroscopy. Results: Europeans showed a progressive and significant reduction of blood filterability and an increase of whole blood viscosity which correlate with the increase of altitude (p < 0.02). In the Nepalese highlanders, haemorheological changes were already present at their residence altitude, 3400 m a.s.l. (p < 0.001 vs. Europeans). With the increase in altitude, a massive interstitial oedema appeared in all participants, associated with erythrocyte aggregation phenomena and slowing of the flow rate in the microcirculation. Conclusions: High altitude causes important and significant microcirculatory adaptations. These changes in microcirculation induced by hypobaric–hypoxic conditions should be considered when planning training and physical activity at altitude.

Objective: Although the benefits of blood pressure (BP) lowering treatments in patients over 80 years with preserved functional status have been shown, the benefits in treated hypertensive patients of this age-group with several co-morbidities and loss of functionality, remain controversial: data from observational studies show rather inverse relationships between BP and prognosis, whereas there is a total lack of interventional trials in these subjects. Design and method: RETREAT FRAIL is a multicenter randomized controlled trial aiming to evaluate the effect of the step-down of antihypertensive medications on all-cause mortality (mean follow-up, 36 months) in nursing home (NHs) residents over 80 years, treated with >1 antihypertensive drug and presenting an SBP<130 mmHg. The only clinical exclusion criterion was an estimated life expectancy <3 months. Enrolled patients were randomized into one of the 2 groups: treatment step-down or control group. In both groups, the follow-up is performed in the NHs every 2 months, including a comprehensive geriatric assessment every 6 months. Results: Between April 2019 and July 2022, 1048 patients (842 women), mean age 90±5, from 108 NHs were randomized (528 step-down and 520 controls). They were receiving at mean 9.4±3.4 different medications including 2.5±0.7 antihypertensive medications. Mean SBP: 118±11mmHg, DBP: 65±10 mmHg and HR: 71±12 bpm. Based on ADL, MMSE, and mobility criteria, 52% had severe loss of autonomy, 32 % partial loss of functionality and autonomy and 16% had preserved autonomy and functionality. No differences were observed for all these parameters between the 2 randomization groups. The 3-year follow-up of this trial will be completed June 2024. Conclusions: Despite the difficulties in NHs dramatically aggravated during the COVID-19 pandemic, we were able to complete the enrolment of the residents and to respect the follow-up protocol. RETREAT FRAIL will be the first randomized trial to provide information concerning the long-term effects of a progressive standardized down-titration of the BP lowering treatment in very old frail patient i.e. those who have so far been completely excluded from clinical trials.

Does baseline position (lying vs. sitting) influence orthostatic BP changes in adults over 75 years old classified according to their frailty level? In patients with high frailty, orthostatic BP drop was more pronounced from the lying to upright as compared to the sitting to upright position (p < 0.008). No such differences were observed in the individuals with low/medium frailty level. In frail older individuals, baseline position greatly influences the amplitude of orthostatic BP changes, and therefore lying or sitting baseline position should always be clearly stated. To compare blood pressure (BP) values in the lying and sitting positions, and the effect of orthostatism when moving from each of these positions to the upright position in a geriatric population with various frailty levels. In two sub-studies, we included a total of 157 consecutive patients, aged 75+ admitted to the Geriatric Department of Nancy University Hospital. BP and heart rate were sequentially measured three times in 1-min intervals each in lying, sitting and upright positions (Protocol#1, n = 107) or lying and upright positions (Protocol#2, n = 50) with an automatic validated Blood Pressure device. Patients were classified into two increasing frailty status (FS) categories: Low/Moderate (L/M-FS, n = 98) and High (H-FS, n = 59). BP levels were similar in the lying and sitting positions (Protocol#1, SBP 141 ± 22 mmHg vs. 142 ± 21 mmHg, respectively, and DBP 72 ± 12 mmHg vs. 72 ± 12 mmHg, respectively) in both frailty groups. In the H-FS, orthostatic drop of SBP was more pronounced from the lying (22.1 ± 5.8 mmHg, Protocol#2) as compared to the sitting to upright position (9.4 ± 1.9 mmHg, Protocol#1) (p < 0.008), and the same trend was observed for DBP. No such differences were observed in the L-M/FS frailty individuals. Orthostatic BP changes are more pronounced in the frailest patients when going from lying to the upright position than from the sitting to the upright position. Consequently, in these individuals, lying and sitting BP measurements cannot be interchangeable baseline positions to investigate orthostatic BP effects, and therefore, precise patient positioning should be specified when referring to “baseline BP measurements”.

Background: Exposure to high altitudes determines several adaptive mechanisms affecting in a complex way the whole cardiovascular, respiratory, endocrine systems because of the hypobaric hypoxic condition. The aim of our study was to evaluate the circulatory adaptive mechanisms at high altitudes, during a scientific expedition in the Himalayas. Methods: Arterial distensibility was assessed measuring carotid-radial and carotid-femoral pulse wave velocity. Tests were carried out at several altitudes, from 1350 to 5050 m above sea level, on 8 lowlander European researchers and 11 highlander Nepalese porters. Results: In Europeans, systolic blood pressure and pulse pressure increased slightly but significantly with altitude (p < 0.05 and p < 0.001, respectively). Norepinephrine showed a significant increase after the lowlanders had spent some time at high altitude (p < 0.001). With increasing altitude, a progressive increase in carotid-radial and carotid-femoral pulse wave velocity values was observed in lowlanders, showing a particularly significant increase (p < 0.001) after staying at high altitude (carotid-radial pulse wave velocity, median value (interquartile range) from 9.2 (7.9–10.0) to 11.2 (10.9–11.8) m/s and carotid-femoral pulse wave velocity from 8.5 (7.9–9.0) to 11.3 (10.9–11.8) m/s). At high altitudes (3400 and 5050 m above sea level), no significant differences were observed between highlanders and lowlanders in hemodynamic parameters (blood pressure, carotid-radial and carotid-femoral pulse wave velocity). Conclusions: The progressive arterial stiffening with altitude observed in European lowlanders could explain the increase in systolic and pulse pressure values observed at high altitudes in this ethnic group. Further studies are needed to evaluate the role of aortic stiffening in the pathogenesis of acute mountain sickness.

Endothelial dysfunction is a key factor in atherosclerosis. However, the link between endothelial repair and severity of atherosclerotic cardiovascular disease (ASCVD) is unclear. This study investigates the relationship between ASCVD, markers of inflammation, and circulating endothelial progenitor cells, namely hematopoietic cells with paracrine angiogenic activity and endothelial colony forming cells (ECFC). Two hundred and forty-three subjects from the TELARTA study were classified according to the presence of clinical atherosclerotic disease. ASCVD severity was assessed by the number of involved vascular territories. Flow cytometry was used to numerate circulating progenitor cells (PC) expressing CD34 and those co-expressing CD45, CD34, and KDR. Peripheral blood mononuclear cells ex vivo culture methods were used to determine ECFC and Colony Forming Unit- endothelial cells (CFU-EC). The ECFC subpopulation was analyzed for proliferation, senescence, and vasculogenic properties. Plasma levels of IL-6 and VEGF-A were measured using Cytokine Array. Despite an increased number of circulating precursors in ASCVD patients, ASCVD impaired the colony forming capacity and the angiogenic properties of ECFC in a severity-dependent manner. Alteration of ECFC was associated with increased senescent phenotype and IL-6 levels. Our study demonstrates a decrease in ECFC repair capacity according to ASCVD severity in an inflammatory and senescence-associated secretory phenotype context.

Profound T-cell lymphopenia is the hallmark of severe coronavirus disease 2019 (COVID-19). T-cell proliferation is telomere length (TL) dependent and telomeres shorten with age. Older COVID-19 patients, we hypothesize, are, therefore, at a higher risk of having TL-dependent lymphopenia. We measured TL by the novel Telomere Shortest Length Assay (TeSLA), and by Southern blotting (SB) of the terminal restriction fragments in peripheral blood mononuclear cells of 17 COVID-19 and 21 non-COVID-19 patients, aged 87 ± 8 (mean ± SD) and 87 ± 9 years, respectively. TeSLA tallies and measures single telomeres, including short telomeres undetected by SB. Such telomeres are relevant to TL-mediated biological processes, including cell viability and senescence. TeSLA yields 2 key metrics: the proportions of telomeres with different lengths (expressed in %) and their mean (TeSLA mTL), (expressed in kb). Lymphocyte count (109/L) was 0.91 ± 0.42 in COVID-19 patients and 1.50 ± 0.50 in non-COVID-19 patients (p < .001). In COVID-19 patients, but not in non-COVID-19 patients, lymphocyte count was inversely correlated with the proportion of telomeres shorter than 2 kb (p = .005) and positively correlated with TeSLA mTL (p = .03). Lymphocyte count was not significantly correlated with SB mTL in either COVID-19 or non-COVID-19 patients. We propose that compromised TL-dependent T-cell proliferative response, driven by short telomere in the TL distribution, contributes to COVID-19 lymphopenia among old adults. We infer that infection with SARS-CoV-2 uncovers the limits of the TL reserves of older persons. Clinical Trials Registration Number: NCT04325646.

BACKGROUND:Lymphopenia due to a plummeting T-cell count is a major feature of severe COVID-19. T-cell proliferation is telomere length (TL)-dependent and TL shortens with age. Older persons are disproportionally affected by severe COVID-19, and we hypothesized that those with short TL have less capacity to mount an adequate T-cell proliferative response to SARS-CoV-2. This hypothesis predicts that among older patients with COVID-19, shorter telomeres of peripheral blood mononuclear cells (PBMCs) will be associated with a lower lymphocyte count.METHODS:Our sample comprised 17 COVID-19 and 21 non-COVID-19 patients, aged 87(8) (mean(SD)) and 87 (9) years, respectively. We measured TL by the Telomere Shortest Length Assay, a novel method that measures and tallies the short telomeres directly relevant to telomere-mediated biological processes. The primary analysis quantified TL as the proportion of telomeres shorter than 2 kilobases. For comparison, we also quantified TL by Southern blotting, which measures the mean length of telomeres.RESULTS:Lymphocyte count (109/L) was 0.91 (0.42) in COVID-19 patients and 1.50(0.50) in non-COVID-19 patients (P < 0.001). In COVID-19 patients, but not in non-COVID-19 patients, lymphocyte count was inversely correlated with the proportion of telomeres shorter than 2 kilobases (P = 0.005) and positively correlated with the mean of telomeres measured by TeSLA (P = 0.03). Lymphocyte counts showed no statistically significant correlations with Southern blotting results in COVID-19 or non-COVID-19 patients.CONCLUSIONS:These results support the hypothesis that a compromised TL-dependent T-cell proliferative response contributes to lymphopenia and the resulting disproportionate severity of COVID-19 among old adults. We infer that infection with SARS-CoV-2 uncovers the limits of the TL reserves of older persons.

Complete List of Authors: Chahine, Mirna; Foundation-Medical Research Institutes; Universite Libanaise, Faculty of medical SciencesMedicine Toupance, Simon; université de Lorraine, Inserm, DCAC, ; Université de Lorraine, CHRU-Nancy, Pôle "Maladies du Vieillissement, Gérontologie et Soins Palliatifs"; Nancyclotep-GIE El-Hakim, Sandy; Université Libanaise , Faculty of Public Health II Labat, Carlos; université de Lorraine, Inserm, DCAC, Gautier, Sylvie; Université de Lorraine, CHRU-Nancy, Pôle "Maladies du Vieillissement, Gérontologie et Soins Palliatifs" Moussallem, Toufic; Universite Libanaise, Faculty of medical SciencesMedicine Yared, Pierre; Universite Libanaise, Faculty of medical SciencesMedicine Asmar, Roland; Foundation-Medical Research Institutes Benetos, Athanase; université de Lorraine, Inserm, DCAC, ; Université de Lorraine, CHRU-Nancy, Pôle "Maladies du Vieillissement, Gérontologie et Soins Palliatifs"

Short telomere length (TL) is associated with atherosclerotic cardiovascular disease (ACVD) and other age-related diseases. It is unclear whether these associations originate from having inherently short TL or a faster TL attrition before or during disease development. We proposed the blood-and-muscle model to assess TL dynamics throughout life course. Our objective was to measure TL in leukocytes (LTL) and in skeletal muscle (MTL), which served as a proxy of TL at birth. The delta (MTL-LTL) represented life-long telomere attrition. Blood draws and skeletal muscle biopsies were performed on 35 Lebanese individuals undergoing surgery. Following DNA extraction, LTL and MTL were measured by Southern blot. In every individual aged between 30 and 85 years, MTL was longer than LTL. With age, MTL and LTL decreased, but the delta (MTL-LTL) increased by 14 bp/year. We validated the blood-and-muscle model that allowed us to identify TL, TL at birth, and lifelong TL attrition in a cross-sectional study. This model can be used in larger cross-sectional studies to evaluate the association of telomere dynamics with age-related diseases onset and progression.

Objective: The aim of the Advanced Approach to Arterial Stiffness study was to compare arterial stiffness measured simultaneously with two different methods in different age groups of middle-aged and older adults with or without metabolic syndrome (MetS). The specific effects of the different MetS components on arterial stiffness were also studied. Methods: This prospective, multicentre, international study included 2224 patients aged 40 years and older, 1664 with and 560 without MetS. Patients were enrolled in 32 centres from 18 European countries affiliated to the International Society of Vascular Health & Aging. Arterial stiffness was evaluated using the cardio-ankle vascular index (CAVI) and the carotid–femoral pulse wave velocity (CF-PWV) in four prespecified age groups: 40–49, 50–59, 60–74, 75–90 years. In this report, we present the baseline data of this study. Results: Both CF-PWV and CAVI increased with age, with a higher correlation coefficient for CAVI (comparison of coefficients P < 0.001). Age-adjusted and sex-adjusted values of CF-PWV and CAVI were weakly intercorrelated (r2 = 0.06, P < 0.001). Age-adjusted and sex-adjusted values for CF-PWV but not CAVI were higher in presence of MetS (CF-PWV: 9.57 ± 0.06 vs. 8.65 ± 0.10, P < 0.001; CAVI: 8.34 ± 0.03 vs. 8.29 ± 0.04, P = 0.40; mean ± SEM; MetS vs. no MetS). The absence of an overall effect of MetS on CAVI was related to the heterogeneous effects of the components of MetS on this parameter: CAVI was positively associated with the high glycaemia and high blood pressure components, whereas lacked significant associations with the HDL and triglycerides components while exhibiting a negative association with the overweight component. In contrast, all five MetS components showed positive associations with CF-PWV. Conclusion: This large European multicentre study reveals a differential impact of MetS and age on CAVI and CF-PWV and suggests that age may have a more pronounced effect on CAVI, whereas MetS increases CF-PWV but not CAVI. This important finding may be due to heterogeneous effects of MetS components on CAVI. The clinical significance of these original results will be assessed during the longitudinal phase of the study.

We aimed to identify trajectories of nutrition, cognitive function, and autonomy over time among very old adults and to assess their impact on mortality. A cohort of subjects aged ≥80 years (in 2007-2008) who were followed for 5 years in 72 Italian and French nursing homes was used for post hoc analyses. Body mass index (BMI; weight (kg)/height (m)2), Mini-Mental State Examination (MMSE) score, and Katz Index of Independence in Activities of Daily Living (ADL) score were assessed at 4 time points. Information on vital status was collected during follow-up. Latent trajectory and Cox models were used. In the 710 subjects included, the mean age at inclusion was 88.0 (standard deviation, 4.8) years, and 78.9% were female. We identified 7 composite trajectories based on BMI, MMSE, and ADL values. As compared with the reference group (trajectory 7-stable overweight; preserved cognitive function and autonomy), 2 trajectories presented increased hazards of dying: trajectory 1 (stable overweight; moderately impaired, then declining, cognitive function and autonomy (adjusted hazard ratio = 1.79, 95% confidence interval (CI): 1.26, 2.55)) and trajectory 6 (stable normal BMI; slight cognitive decline; and moderate, then degrading, loss of autonomy (adjusted hazard ratio = 1.67, 95% CI: 1.15, 2.44)). The C-index was 0.81 (95% CI: 0.72, 0.88). Repeated monitoring of BMI, MMSE score, and ADL in very old adults provides trajectories that produce better prognostic information than simple baseline assessment.

BACKGROUND Several clinical studies have shown that blood pressure (BP) measurements in very old frail individuals are of limited interest due to the fact that several age-related alterations and geriatric syndromes may modify BP. We studied in persons over 80-year old living in nursing homes the combined effects of 3 BP patterns on total mortality and major cardiovascular (CV) events: (i) low pulse pressure amplification (L-PPA) between carotid and brachial artery, (ii) systolic BP (SBP) <130 mm Hg (L-SBP), under >1 antihypertensive drugs, and (iii) changes in SBP between supine and upright position of >20 mm Hg in both directions (hypotension/hypertension, orthostatic SBP [O-SBP]). METHODS This analysis was performed in subjects of the PARTAGE study presenting all these 3 measurements (n = 883). The combined effects of L-PPA, L-SBP, and O-SBP were studied during the 2 years followed-up period. RESULTS After adjusting for age, sex, and history of CV events, all 3 BP patterns were independent determinants of major CV events (L-PPA, (P = 0.023); L-SBP, (P = 0.050); O-SBP, (P = 0.015)), whereas L-PPA (P = 0.012) and L-SBP (P = 0.006) were also independent determinants of total mortality. Compared with the subjects without any BP pattern, the presence of 2 or 3 BP patterns was associated with an increase in total mortality and major CV events greater than 2 and 2.5 times, respectively. CONCLUSIONS In very old frail subjects, there is a particular interest for using different BP measurement approaches, than in younger populations, in order to evaluate the risks related to the BP levels. CLINICAL TRIALS REGISTRATION Trial Number: NCT00901355 (Clinical Trials.gov).

Background: The relation between telomere dynamics and obesity remains unclear. Cross-sectional studies found associations between short leukocyte telomere length (LTL) and high body mass index (BMI) but longitudinal studies did not find any association between LTL attrition and BMI. In two parallel studies, we aimed to assess the relationship between obesity and telomere dynamics in different tissues. Methods: Study 1: Measurements of LTL and TL in skeletal muscle (MTL) were performed in 53 subjects with severe obesity (BMI > 35) and in 53 age- and sex-matched without obesity (21 < BMI < 30). MTL is a proxy of TL at birth and the LTL/MTL ratio represents life-long telomere attrition. Study 2: Measurements of TL in subcutaneous fat (SCF), a high proliferative adipose tissue, and visceral fat (VF), a low proliferative one in 50 severe obese bariatric patients. TL measurements were performed by Southern blot. Results: Study 1: In younger (<55 years), but not in older, LTL and LTL/MTL were shorter in obese patients vs controls (7.16 kb vs 7.54 kb, p < 0.05 for LTL and 81% vs 84%, p < 0.05 for LTL/MTL). Study 2: Within obese bariatric patients, SCF/VF TL ratio was lower in those with early onset obesity (96% for obesity since childhood vs 97% since adolescence vs 100% for adult development of obesity; p < 0.05). Conclusions: Early life obesity is associated with higher TL attrition leading to shorter TL in high proliferative tissues.

The physiological relevance of slow-wave vasomotion is still unclear, even though it has been hypothesized that it could be a compensatory mechanism for enhancing tissue oxygenation in conditions of reduced oxygen supply. The aim of our study was to explore the effects of hypoxia and ischemia on slow-wave vasomotion in microcirculation. Peripheral oxygen saturation and forearm microcirculation flow (laser-Doppler flowmetry) were recorded at baseline and during postocclusive reactive hyperemia in the Himalaya region from 8 European lowlanders (6 men; aged 29-39 yr) at 1,350, 3,400, and 5,050 m and from 10 Nepalese male highlanders (aged 21-39 yr) at 3,400 and 5,050 m of altitude. The same measurements were also performed at sea level in 16 healthy volunteers (aged 23-61 yr) during a short-term exposure to normobaric hypoxia. In lowlanders, exposure to progressively higher altitude under baseline flow conditions progressively increased 0.06-0.15 Hz vasomotion amplitude [power spectral density % was expressed as geometric means (geometric standard deviation) = 14.0 (3.6) at 1,350 m; 87.0(2.3) at 3,400 m and 249.8 (3.6) at 5,050 m; P = 0.006 and P < 0.001 vs. 1,350 m, respectively]. In highlanders, low frequency vasomotion amplitude was similarly enhanced at different altitudes [power spectral density % = 183.4 (4.1) at 3,400 m vs. 236.0 (3.0) at 5,050 m; P = 0.139]. In both groups at altitude, it was further increased after ischemic stimulus ( P < 0.001). At baseline, acute short lasting normobaric hypoxia did not induce low frequency vasomotion, which was conversely induced by ischemia, even under normal oxygenation and barometric pressure. This study offers the demonstration of a significant increase in slow-wave vasomotion under prolonged hypobaric-hypoxia exposure at high altitude, with a further enhancement after ischemia induction. NEW & NOTEWORTHY This study offers the demonstration in humans of the occurrence of enhanced slow-wave vasomotion in microcirculation induced by exposure to hypobaric hypoxia, ischemia, and their combination. This phenomenon, where vasomotion can be hypothesized to behave as a "peripheral heart," may represent a compensating adaptive change aimed at improving peripheral flow and tissue oxygenation in conditions of reduced oxygen supply, such as altitude-induced hypobaric hypoxia and postocclusion ischemia.