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Background. An active lifestyle is associated with a reduced cardiovascular risk in middle-aged as well as in elderly patients. In the present study, we investigated the association between physical activity habits of elderly participants prior to coronary artery bypass grafting (CABG) and survival free from both all-cause and cardiac death. Methods and Results. Study population consisted of 587 elderly patients ([greater than or equal to]70 years) CABG patients stratified, according to the Physical Activity Scale for the Elderly (PASE), into less active (low PASE) and exercised (high PASE) groups. At follow-up (mean: 44.3 [+ or -] 21.0 months), 33 (37.1%) of 89 total deaths occurred for cardiac causes. Sixty-month survival rate was 65% and 96% for low-PASE and high-PASE groups, respectively (log rank = 49.460. p < .0001). Cox survival analysis indicated a significant (p < .0001) nonlinear association between PASE score increments and improved survival with the most evident differences in the lowest score categories. A robust association was also found between low PASE score and increased cardiac-related mortality (p < .0001). Conclusions. Our data indicate that a more active lifestyle is significantly associated with improved survival in elderly CABG patients. The nonlinearity of the relation suggests that more sedentary patients could have the most benefit on survival by increasing their exercise lifestyle habits. The improved outcome is explained by both cardiac and overall mortality reduction. Key Words: Coronary surgery--Elderly Patients--Physical activity--Prognosis--Physical Activity Scale for the Elderly. doi: 10.1093/gerona/glp216

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±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.

Cardiac [beta]-adrenergic receptor ([beta]-AR) signaling and left ventricular (LV) responses to [beta]-AR stimulation are impaired with aging. It is shown that exercise and [beta]-AR blockade have a favorable effect on cardiac and vascular [beta]-AR signaling in several cardiovascular diseases. In the present study, we examined the effects of these two different strategies on [beta]-AR dysregulation and LV inotropic reserve in the aging heart. Forty male Wistar-Kyoto aged rats were randomized to sedentary, exercise (12 wk treadmill training), metoprolol (250 mg * [kg.sup.-1] * [day.sup.-1] for 4 wk), and exercise plus metoprolol treatment protocols. Ten male WistarKyoto sedentary young rats were also used as a control group. Old trained, old metoprolol-treated, and old trained plus metoprololtreated rats showed significantly improved LV maximal and minimal first derivative of the pressure rise responses to [beta]-AR stimulation (isoproterenol) compared with old untrained animals. We found a significant reduction in cardiac sarcolemmal membrane [beta]-AR density and adenylyl cyclase activity in old untrained animals compared with young controls. Exercise training and metoprolol, alone or combined, restored cardiac [beta]-AR density and G-protein-dependent adenylyl cyclase activation in old rats. Although cardiac membrane G-proteinreceptor kinase 2 levels were not upregulated in untrained old compared with young control rats, both exercise and metoprolol treatment resulted in a dramatic reduction of G-protein-receptor kinase 2 protein levels, which is a further indication of [beta]-AR signaling amelioration in the aged heart induced by these treatment modalities. In conclusion, we demonstrate for the first time that exercise and [beta]-AR blockade can similarly ameliorate [beta]-AR signaling in the aged heart, leading to improved [beta]-AR responsiveness and corresponding LV inotropic reserve. aging; G-protein-coupled receptor kinase 2; [beta]-adrenergic receptor desensitization; heart failure

Downregulation of hypoxia-inducible factor 1 (HIF-1) and vascular endothelial growth factor (VEGF) are shown to be involved in age-dependent impairment of angiogenesis. In this study, we explore whether prior exercise is able to affect these molecular patterns favorably and to enhance neoangiogenesis in old Wistar rats with hind-limb ischemia. At day 7 after surgery, HIF-l[alpha] and VEGF expression increased in the ischemic muscle of trained animals. Exercise increased capillary density and limb perfusion as revealed by histologic, angiographic, and dyed bead techniques. Furthermore, exercise capacity and limb trophism have significantly improved in trained aged rats. In these animals, the reduction of VEGF serum levels has reflected the comprehensive improvement in local ischemia evoked by exercise. In conclusion, prior exercise represents a valid tool to counteract age-related molecular alterations resulting in impaired angiogenesis in response to ischemia.

Background. Heart rate recovery (HRR), defined as the fall in HR during the first minute after exercise, is a marker of vagal tone, which is a powerful predictor of mortality in patients with coronary artery disease and in older patients. Whether exercise training (ET) modifies HRR in elderly patients recovering from acute myocardial infarction (AMI) is still unknown. Therefore, this study aims at evaluating the effect of ET on HRR in elderly AMI patients. Methods. This was a prospective observational study including 268 older patients after AMI (217 men, 51 women), subdivided in two groups: Group A (n = 104), enrolled in an ET program; Group B (n = 164), discharged with generic instructions to continue physical activity. At baseline and at 3-month follow-up, all Group A and 541164 Group B patients underwent a cardiopulmonary exercise stress test, whereas 110/164 Group B patients underwent an exercise stress test. Results. After completion of the ET program, in Group A we observed an improvement in oxygen consumption at peak exercise (V[O.sub.2peak]; from 14.7 [+ or -] 1.3 to 17.6 [+ or -] 1.9 mL/kg/min, p < .001), in the rate of increase of ventilation per unit of increase of carbon dioxide production (VE/VC[O.sub.2slope]; from 34.2 [+ or -] 3.8 to 30.4 [+ or -] 3.0, p < .001), and in HRR (from 13.5 [+ or -] 3.7 to 18.7 [+ or -] 3.5 beats/min, p < .001). The changes in V[O.sub.2peak] and in VE/VC[O.sub.2slope] after ET were correlated with the improvement of HRR (r = -0.865, p < .01; r= -0.594, p < .01, respectively). No changes in these parameters were observed in Group B patients. Conclusions. In older AMI patients, ET results in HRR improvement, which was correlated to the improvement in cardiopulmonary parameters. These findings may shed additional light on the possible mechanisms of the beneficial prognostic effects of ET in this patient population.

Many older patients, because of their high prevalence of coronary artery disease, are candidates for percutaneous coronary interventions (PCI), but the effects of vascular aging on restenosis after PCI are not yet well understood. Balloon injury to the right carotid artery was performed in adult and old rats. Vascular smooth muscle cell (VSMC) proliferation, apoptotic cell death, together with Akt induction, telomerase activity, [p27.sup.kip1], and endothelial nitric oxide synthase (eNOS) expression was assessed in isolated arteries. Neointima hyperplasia and vascular remodeling along with endothelial cell regeneration were also measured after balloon injury. Arteries isolated from old rats exhibited a significant reduction of VSMC proliferation and an increase in apoptotic death after balloon injury when compared with adult rats. In the vascular wall of adult rats, balloon dilation induced Akt phosphorylation, and this was barely present in old rats. In arteries from old rats, Akt-modulated cell cycle check points like telomerase activity and [p27.sup.kip1] expression were decreased and increased, respectively, compared with adults. After balloon injury, old rats showed a significant reduction of neointima formation and an increased vascular negative remodeling compared with adults. These results were coupled by a marked delay in endothelial regeneration in aged rats, partially mediated by a decreased eNOS expression and phosphorylation. Interestingly, chronic administration of L-arginine prevented negative remodeling and improved reendothelialization after balloon injury in aged animals. A decreased neointimal proliferation, an impaired endothelial regeneration, and an increase in vascular remodeling after balloon injury were observed in aged animals. The molecular mechanisms underlying these responses seem to be a reduced Akt and eNOS activity. restenosis; Akt; cell cycle; nitric oxide

Aging is associated with alterations in [beta]-adrenergic receptor ([beta]-AR) signaling and reduction in cardiovascular responses to [beta]-AR stimulation. Because exercise can attenuate age-related impairment in myocardial [beta]-AR signaling and function, we tested whether training could also exert favorable effects on vascular [beta]-AR responses. We evaluated common carotid artery responsiveness in isolated vessel ring preparations from 8 aged male Wistar-Kyoto (WKY) rats trained for 6 wk in a 5 days/wk swimming protocol, 10 untrained age-matched rats, and 10 young WKY rats. Vessels were preconstricted with phenylephrine ([10.sup.-6] M), and vasodilation was assessed in response to the [beta]-AR agonist isoproterenol ([10.sup.-10]-3 x [10.sup.-8] M), the [[alpha].sub.2]-AR agonist UK-14304 ([10.sup.-9]-[10.sup.-6] M), the muscarinic receptor agonist ACh ([10.sup.-9]-[10.sup.-6] M), and nitroprusside ([10.sup.-8]-[10.sup.-5] M). [beta]-AR density and cytoplasmic [beta]-AR kinase ([beta]-ARK) activity were tested on pooled carotid arteries. [beta]-ARK expression was assessed in two endothelial cell lines from bovine aorta and aorta isolated from a 12-wk WKY rat. [beta]-AR, [[alpha].sub.2]-AR, and muscarinic responses, but not that to nitroprusside, were depressed in untrained aged vs. young animals. Exercise training restored [beta]-AR and muscarinic responses but did not affect vasodilation induced by UK-14304 and nitroprusside. Aged carotid arteries showed reduced [beta]-AR number and increased [beta]-ARK activity. Training counterbalanced these phenomena and restored [beta]-AR density and [beta]-ARK activity to levels observed in young rat carotids. Our data indicate that age impairs [beta]-AR vasorelaxation in rat carotid arteries through [beta]-AR downregulation and desensitization. Exercise restores this response and reverts age-related modification in [beta]-ARs and [beta]-ARK. Our data support an important role for [beta]-ARK in vascular [beta]-AR vasorelaxation. aging; beta-adrenergic receptor; exercise

Ischemic preconditioning (PC) has been proposed as an endogenous form of protection against-ischemia reperfusion injury. We have shown that PC does not prevent postischemic dysfunction in the aging heart. This phenomenon, could be due to the reduction of cardiac norepinephrine release, and it has also been previously demonstrated that age-related decrease of norepinephrine release from cardiac adrenergic nerves may be restored by caloric restriction. We investigated the effects on mechanical parameters of PC against 20 min of global ischemia followed by 40 min of reperfusion in isolated hearts from adult (6 mo) and 'ad libitum'-fed and food-restricted senescent (24 mo) rats. Norepinephrine release in coronary effluent was determined by high-performance liquid chromatography. Final recovery of percent developed pressure was significantly improved after PC in adult hearts versus unconditioned controls (85.2 [+ or -] 19% vs. 51.5 [+ or -] 10%, P < 0.01). The effect of PC on developed pressure recovery was absent in ad libitum-fed rats, but it was restored in food-restricted senescent hearts (66.6 [+ or -] 13% vs. 38.3 [+ or -] 11%, P < 0.05). Accordingly, norepinephrine release significantly increased after PC in both adult and in food-restricted senescent hearts, and depletion of myocardial norepinephrine stores by reserpine abolished the PC effect in both adult and in food-restricted senescent hearts. We conclude that PC reduces postischemic dysfunction in the hearts from adult and food-restricted but not in ad libitum-fed senescent rats. Despite the possibility of multiple age-related mechanisms, the protection afforded by PC was correlated with increased norepinephrine release, and it was blocked by reserpine in both adult and food-restricted senescent hearts. Thus caloric restriction may restore PC in the aging heart probably via increased norepinephrine release. aging; caloric restriction; rat heart

Background. A reduction of exercise-induced ischemia in patients with coronary artery disease by means of brief period of exercise followed by resting is called the 'warm-up' phenomenon. This phenomenon may represent a clinical counterpart of 'ischemic preconditioning.' We studied the warm-up phenomenon in both adult and elderly patients with similar angiographic evidence of coronary artery disease, using three exercise tests after excluding the 'training effect.' Methods. In order to verify the presence of 'training effect,' three exercise tests were performed in days l, 2, and 3 ('training' tests). The third test was used as baseline for a successive test, performed after a recovery period of 10 minutes to reestablish baseline electrocardiographic conditions. A third exercise test was performed 30 minutes later ('warm-up' tests). Results. 'Training' tests did not differ in all parameters in both adult and elderly patients. 'Warm-up' tests showed that time to onset l-ram ST depression was significantly higher (p < .001), whereas ST depression and time to recovery was significantly lower in the second and third test in adult but not in elderly patients (p < .001). Difference (in seconds) in the time at which 1-mm ST depression occurred on first warm-up exercise compared with the second was inversely correlated with age (p < .001). Conclusions. Previous exercise followed by resting is able to reduce the successive exercise-induced ischemia ('warm-up' phenomenon) in adult but not in elderly patients with coronary artery disease. This is independent of a greater age-related severity of coronary disease and of 'training effect.' These results confirm the hypothetical age-related reduction of 'ischemic preconditioning' in aging heart.