βARKct gene-therapy improves β2-adrenergic receptor-dependent neoangiogenesis following hindlimb ischemia

Following hindlimb ischemia (HI) increased catecholamine levels within the ischemic muscle can cause dysregulation of β2-adrenergic receptor (β2AR) signaling leading to reduced revascularization. Indeed, in vivo β2AR overexpression, via gene therapy, enhances angiogenesis in a rat model of HI. G protein-coupled receptor kinase 2 (GRK2) is a key regulator of βAR signaling, and βARKct, a peptide inhibitor of GRK2, has been shown to prevent βAR down-regulation and to protect cardiac myocytes and stem cells from ischemic injury, through restoration of β2AR protective signaling (i.e. Akt/eNOS). Herein, we tested potential therapeutic effects of adenoviral-mediated βARKct gene transfer in an experimental model of HI and its effects on βAR signaling and on endothelial cell (EC) function in vitro. Accordingly, in this study, we surgically induced HI in rats by femoral artery resection (FAR). Fifteen days of ischemia resulted in significant βAR down-regulation that was paralleled by an about 2-fold increase in GRK2 levels in the ischemic muscle. Importantly, in vivo gene transfer of the βARKct in the hindlimb of rats at the time of FAR resulted in a marked improvement of hindlimb perfusion, with increased capillary and βAR density in the ischemic muscle, compared to control groups. The effect of βARKct expression was also assessed, in vitro in cultured ECs. Interestingly, in ECs expressing the βARKct, fenoterol, a β2AR-agonist, induced enhanced β2AR pro-angiogenic signaling and increased EC function. In conclusion, our results suggest that βARKct gene-therapy and subsequent GRK2 inhibition promotes angiogenesis in a model of HI by preventing ischemia-induced β2AR downregulation

Ischemic preconditioning in the younger and aged heart

: Ischemic preconditioning is the effect of brief ischemic episodes which protect the heart from the following more prolonged ischemic episode. This mechanism is effective in younger but not in aged heart. The age-related reduction of ischemic preconditioning has been demonstrated in experimental models and in elderly patients. Preinfarction angina, a clinical equivalent of ischemic preconditioning, reduces mortality in adult but not in elderly patients with acute myocardial infarction. Physical activity or caloric restriction is partially capable to preserve the cardioprotective effect of ischemic preconditioning in the aging heart. More importantly, physical activity and caloric restriction in tandem action completely preserve the protective mechanism of ischemic preconditioning. Accordingly, the protective mechanism of preinfarction angina is preserved in elderly patients with a high grade of physical activity or a low body-mass index. Thus, both physical activity and caloric restriction are confirmed as powerful anti-aging interventions capable to restore age-dependent reduction of a critical endogenous protective mechanism such as ischemic preconditioning

Charlson Comorbidity Index does not predict long-term mortality in elderly subjects with chronic heart failure

Methods: long-term mortality after 12-year follow-up in 125 subjects with CHF and 1,143 subjects without CHF was studied. Comorbidity was evaluated using CCI.Findings: in elderly subjects stratified for CCI (1-3 and >= 4), mortality was higher in non-CHF subjects with CCI >= 4 (52.4% versus 70%, P < 0.002) but not in those with CHF (75.9% versus 77.6%, P = 0.498, NS). Cox regression analysis on 12 years mortality indicated that both CCI (HR = 1.15; 95% CI = 1.01-1.31; P = 0.035) and CHF (HR = 1.27; 95% CI = 1.04-8.83; P = 0.003) were predictive of mortality. When Cox analysis was performed by selecting the presence and the absence of CHF, CCI was predictive of mortality in the absence but not in the presence of CHF.Conclusion: CCI does not predict long-term mortality in elderly subjects with CHF

Physical activity is inversely related to drug consumption in elderly patients with cardiovascular events

Abstract Elderly patients with cardiovascular events are characterized by high drug consumptions. Whether high drug consumptions are related to physical activity is not known. In order to examine whether physical activity is related to drug consumption in the elderly, patients older than 65 years (n = 250) with a recent cardiovascular event were studied. Physical activity was analyzed according to the Physical Activity Scale for the Elderly (PASE) score and related to drug consumption. PASE score was 72.4 ± 45.0 and drug consumption was 8.3 ± 2.2. Elderly patients with greater comorbidity took more drugs (8.7 ± 2.1) and are less active (PASE = 64.4 ± 50.6) than patients with Cumulative Illness Rating Scale severity score higher than 1.8 than those with a score lower than 1.8 (76.3 ± 41.4, p < 0.05, and 8.0 ± 2.0, p = 0.006, respectively). Multivariate analysis correlation confirmed that PASE score is negatively associated with drug consumption (β = −0.149, p = 0.031), independently of several variables including comorbidity. Thus, physical activity is inversely related to drug consumption in elderly patients with cardiovascular events. This inverse relationship may be attributable to the high degree of comorbidity observed in elderly patients in whom poor level of physical activity and high drug consumption are predominant

Role of permanent atrial fibrillation (AF) on long-term mortality in community-dwelling elderly people with and without chronic heart failure (CHF)

Permanent AF is characterized by an increased mortality in elderly subjects with CHF. Moreover, AF increased the risk of mortality also in elderly subjects without CHF. Thus, we examined long-term mortality in community-dwelling elderly people with and without CHF. A total of 1332 subjects aged 65 and older were selected from the electoral rolls of Campania, a region of southern Italy. The relationship between AF and mortality during a 12-year follow-up in 125 subjects with CHF and in 1.143 subjects without CHF were studied. Elderly subjects showed a higher mortality in those with respect to those without AF (72.1% vs. 51.8%; p &lt; 0.01). Similarly, elderly subjects without CHF showed a higher mortality in those with respect to those without AF (61.8% vs. 49.8%; p &lt; 0.05). In contrast, elderly subjects with CHF showed a similar mortality in those with respect to those without AF (74.7% vs. 82.4%; p = 0.234). Multivariate analysis shows that AF was predictive of mortality in all elderly subjects (Hazard Risk = HR = 1.39, 95% confidence interval (CI) = 1.25-2.82; p &lt; 0.001). When the analysis was conducted considering the presence and the absence of CHF, AF was strongly predictive of mortality in elderly subjects without CHF (HR = 1.95, 95% CI = 1.25-4.51; p &lt; 0.001) but not in those with CHF (HR = 1.12, 95% CI = 0.97-3.69; p = 0.321). We concluded that AF is able to predict long-term mortality in elderly subjects. Moreover, AF is strongly predictive of long-term mortality in the absence but not in the presence of CHF. (C) 2011 Elsevier Ireland Ltd. All rights reserved

Mortality and heart rate in the elderly: role of cognitive impairment

Mortality related to heart rate ( HR) increase in the elderly has not yet been well established. To ascertain the relationships among cognitive impairment ( CI), mortality, and HR increase, the authors prospectively studied a random sample of elderly subjects stratified according to presence or absence of CI. Elderly subjects randomly selected in 1991 ( n = 1332) were followed up for 12 years. Mortality was established in 98.1% of the subjects. When HR was stratified in quartiles (&lt; 69,70-75,76-80, and &gt; 80 bpm), mortality was linearly associated with increased HR in all ( from 47.7 to 57.0; r(2) = .43, p = .019) and in subjects without ( from 41.7 to 51.1%; r(2) = .50, p = .043) but not in those with CI ( from 57.5 to 66.1; r(2) = .20, p = .363). Cox regression analysis, adjusted for several variables, shows that HR doesn't predict mortality in all subjects ( RR 0.69; 95% CI = 0.27-1.73) or in those with CI ( RR 0.91; 95% CI = 0.81-1.02). In contrast, HR predicts mortality in subjects without CI ( RR 1.10; 95% CI = 1.00-1.22). Hence, HR increase is a predictor of mortality in elderly subjects without CI. However, when considering all elderly subjects and those with CI, HR increase seems to have no effect on mortality. Thus, CI should be considered when focusing on HR increase as risk factor for mortality in the elderly

Waist circumference but not body mass index predicts long-term mortality in elderly subjects with chronic heart failure

OBJECTIVESTo examine whether waist circumference (WC) and body-mass index (BMI) can predict long-term mortality in elderly subjects with and without chronic heart failure (CHF).DESIGNLongitudinal evaluation with a 12-year follow-up.SETTINGCampania, a region of southern Italy.PARTICIPANTSOne thousand three hundred thirty-two subjects aged 65 and older selected from the electoral rolls of Campania.MEASUREMENTSThe relationship between WC or BMI and mortality during a 12-year follow-up in 125 subjects with and 1,143 subjects without CHF.RESULTSMortality increased as WC increased in elderly subjects without CHF (from 47.8% to 56.7%, P=.01), and the increase was even greater in patients with CHF (from 58.1% to 82.0%, P=.01). In contrast, mortality decreased as BMI increased in elderly subjects without CHF (from 53.8% to 46.1%, P0 =.046) but not in those with CHF. According to Cox regression analysis, BMI protected against long-term mortality in the absence but not in the presence of CHF. In the absence of CHF, WC was associated with a 2% increased risk of long-term mortality for each 1-cm greater WC (Hazard Ratio (HR)=1.02, 95% confidence interval (CI)=1.01-1.03; P &lt;.001), versus 5% increased in the presence of CHF (HR=1.06, 95% CI=1.02-1.10; P &lt;.001).CONCLUSIONWC, but not BMI, is predictive of long-term mortality in elderly individuals with CHF and to a lesser extent in those without CHF

Unexplained falls are frequent in patients with fall-related injury admitted to Orthopaedic wards: the UFO Study (Unexplained Falls in Older patients)

To evaluate the incidence of unexplained falls in elderly patients affected by fall-related fractures admitted to orthopaedic wards, we recruited 246 consecutive patients older than 65 (mean age 82 \ub1 7 years, range 65-101). Falls were defined "accidental" (fall explained by a definite accidental cause), "medical" (fall caused directly by a specific medical disease), "dementia-related" (fall in patients affected by moderate-severe dementia), and "unexplained" (nonaccidental falls, not related to a clear medical or drug-induced cause or with no apparent cause). According to the anamnestic features of the event, older patients had a lower tendency to remember the fall. Patients with accidental fall remember more often the event. Unexplained falls were frequent in both groups of age. Accidental falls were more frequent in younger patients, while dementia-related falls were more common in the older ones. Patients with unexplained falls showed a higher number of depressive symptoms. In a multivariate analysis a higher GDS and syncopal spells were independent predictors of unexplained falls. In conclusion, more than one third of all falls in patients hospitalized in orthopaedic wards were unexplained, particularly in patients with depressive symptoms and syncopal spells. The identification of fall causes must be evaluated in older patients with a fall-related injury