Nicola Ferrara

Congestive Heart Failure and Cognitive Impairment in an Older Population

OBJECTIVE: Congestive heart failure (CHF) is potentially preventable, and the identification of modifiable risk factors for cognitive impairment (CI) for older persons is a very important issue. We examined the cross‐sectional relationship between CHF and CI in an older population.

Angina-induced protection against myocardial infarction in adult and elderly patients : A loss of preconditioning mechanism in the aging heart?

OBJECTIVES The present study examined whether angina 48 h before myocardial infarction provides protection in adult and elderly patients. BACKGROUND The mortality rate for coronary artery disease is greater in elderly than in young patients. In experimental studies, ischemic preconditioning affords an endogenous form of protection against ischemia-reperfusion injury in adult but not in senescent hearts. Angina before myocardial infarction, a clinical equivalent of experimental ischemic preconditioning, has a protective effect in adult patients. It is not known whether angina before myocardial infarction is also protective in aged patients. METHODS We retrospectively verified whether antecedent angina within 48 h of myocardial infarction exerts a beneficial effect on in-hospital outcomes in adult (< 65 years old, n = 293) and elderly (> or = 65 years old, n = 210) patients. RESULTS In-hospital death was more frequent in adult patients without than in those with previous angina (10% vs. 2.6%, p < 0.01), as were congestive heart failure or shock (10.7% vs. 3.3%, p < 0.02) and the combined end points (in-hospital death and congestive heart failure or shock) (20.7% vs. 5.9%, p < 0.0003). In contrast, the presence or absence of previous angina before acute myocardial infarction in elderly patients seems not to influence the incidence of in-hospital death (14.4% vs. 15.2%, p = 0.97), congestive heart failure or shock (11.0% vs. 11.9%, p = 0.99) and the combined end points (25.4% vs. 27.1%, p = 0.89). Logistic regression analysis models for in-hospital end points show that previous angina is a positive predictor in adult but not in elderly patients. CONCLUSIONS The presence of angina before acute myocardial infarction seems to confer protection against in-hospital outcomes in adults; this effect seemed to be less obvious in elderly patients. This study suggests that the protection afforded by angina in adult patients may involve the occurrence of ischemic preconditioning, which seems to be lost in senescent patients.

Preconditioning does not prevent postischemic dysfunction in aging heart

OBJECTIVES This study was performed to investigate the effect of single or multiple brief periods of ischemia and the administration of exogenous norepinephrine before a more prolonged ischemic period and after reperfusion in adult and senescent isolated and perfused rat hearts. BACKGROUND The mortality rate for coronary artery disease is greater in the elderly. Ischemic preconditioning has been proposed as an endogenous form of protection against ischemia-reperfusion injury. However, the role of preconditioning in aging heart is unknown. METHODS We compared the protective effect of preconditioning transient ischemic and norepinephrine stimuli against 20 min of global normothermic ischemia and 40 min of reperfusion in isolated perfused hearts of adult (6 months old) and senescent (24 months old) rats. Norepinephrine release in coronary effluent was determined by high performance liquid chromatography. RESULTS Final recovery of percent developed pressure was improved after single preconditioning transient ischemic and norepinephrine stimuli in adult hearts (87.7 +/- 9% and 82.3 +/- 8.7%) versus unconditioned control hearts (50.6 +/- 4.8%, p < 0.01 [mean +/-SD]). The effect of preconditioning on developed pressure recovery was not present in senescent hearts after transient ischemic stimulus (39.8 +/- 4.9% vs. 41.6 +/- 5.8%, p = NS) but was present after norepinephrine stimulus (74.3 +/- 10.5, p < 0.01). Norepinephrine release significantly increased after preconditioning transient ischemic stimulus in adult but not in senescent hearts (p < 0.01 vs. adult). Transient ischemic- and norepinephrine-induced preconditioning was blocked by alpha-adrenergic receptor antagonists in both adult and senescent hearts. Multiple transient ischemic stimuli were able to reduce postischemic dysfunction in adult but not in senescent hearts. CONCLUSIONS Preconditioning transient ischemic stimulus significantly reduces postischemic dysfunction in adult but not in senescent hearts, whereas exogenous norepinephrine is able to mimic preconditioning in both adult and senescent hearts. Ischemic preconditioning induces an increase in norepinephrine release in adult but not in senescent hearts. Preconditioning induced by transient ischemic stimulus and norepinephrine was abolished by alpha-adrenergic receptor blockade in both adult and senescent hearts. Thus, our data demonstrate that preconditioning is absent in aging heart and is probably related to the reduction of norepinephrine release and alpha-adrenergic receptor stimulation in response to ischemic preconditioning.

Safety of intravenous high-dose dipyridamole echocardiography

Abstract Clinical data on 10,451 high-dose (up to 0.84 mg/kg over 10 minutes) dipyridamole-echocardiography tests (DET) performed in 9,122 patients were prospectively collected from 33 echocardiographic laboratories, each contributing >100 tests. All patients were studied for documented or suspected coronary artery disease (1,117 early [

The role of blood pressure in cognitive impairment in an elderly population

Objective The aim of this study was to investigate the cross-sectional relationship between arterial blood pressure and cognitive impairment in a group of elderly subjects, controlling for such confounding variables as age, education, depression, drug use and antihypertensive treatment. Design and setting A cross-sectional survey in Campania, a region in southern Italy. Subjects and methods A random sample of 1339 elderly subjects aged 65–95 years (mean 73.9 ± 6.2 years) selected from the electoral rolls was interviewed by trained physicians. Sociodemographic characteristics, results of Mini-Mental State Examination (MMSE), Geriatric Depression Scale (GDS), blood pressure and whether antihypertensive treatment was being administered were recorded. When subjects with neurological diseases and those under psychotropic therapy were excluded from the analyses, the population numbered 1106. Results The MMSE score was less than 24 for 27.9% of the subjects and the mean GDS score was 10.8 ± 6.3. The mean systolic blood pressure (SBP) was 145.3 ± 19.0 mmHg and the mean diastolic blood pressure (DBP) was 82.0 ± 9.2 mmHg. Logistic regression analysis showed that female sex, age, GDS score and DBP but not SBP were predictive of cognitive impairment. Educational level and antihypertensive treatment, on the contrary, play a protective role. DBP was associated with cognitive impairment in subjects aged 75 years (odds ratio 1.62, 95% confidence interval 1.16–2.25) and over (odds ratio 5.16, 95% confidence interval 1.50–17.71) but not in those aged 65–74 years. Conclusion DBP but not SBP is predictive of cognitive impairment in subjects aged 75 years and over without neurological disorders independently from sex, age, education, GDS and antihypertensive treatment.

High level of physical activity preserves the cardioprotective effect of preinfarction angina in elderly patients.

OBJECTIVES The study investigated the effects of physical activity on preinfarction angina, a clinical equivalent of ischemic preconditioning (PC), in adult and elderly patients with acute myocardial infarction (AMI). BACKGROUND Preinfarction angina seems to confer protection against in-hospital mortality in adult but not in elderly patients. However, it has been experimentally demonstrated that exercise training restores the protective effect of PC in the aging heart. METHODS We retrospectively verified whether physical activity preserved the protective effect of preinfarction angina against in-hospital mortality in 557 elderly patients with AMI. Physical activity was quantified according to the Physical Activity Scale for the Elderly (PASE). RESULTS In-hospital mortality was 22.2% in elderly patients with preinfarction angina and 27.2% in those without (p = 0.20). When the PASE score was stratified in quartiles (0 to 40, 41 to 56, 57 to 90, >90), a high score was strongly associated with reduced in-hospital mortality (30.8%, 32.2%, 17.2% and 15.3%, respectively, p < 0.001 for trend). Interestingly, a high level of physical activity reduced in-hospital mortality in elderly patients with preinfarction angina (35.7%, 35.4%, 12.3% and 4.23%, respectively, p < 0.001 for trend) but not in those without (23.0%, 27.2%, 26.0% and 35.0%, respectively, p = 0.35 for trend). Accordingly, the protective role of preinfarction angina on in-hospital mortality was present only in elderly patients showing a high level of physical activity (adjusted odds ratio, 0.09; 95% confidence interval, 0.01 to 0.57; p < 0.05). CONCLUSIONS Physical activity and not preinfarction angina protects against in-hospital mortality in elderly patients with myocardial infarction. Nevertheless, the protective effect of preinfarction angina is preserved in elderly patients with a high level of physical activity.

Exercise training restores ischemic preconditioning in the aging heart

OBJECTIVES To investigate the effects of ischemic preconditioning in hearts from adult and both sedentary and trained senescent rats. BACKGROUND Ischemic preconditioning does not prevent postischemic dysfunction in the aging heart, probably because of reduction of cardiac norepinephrine release. Exercise training can reverse the age-related decrease of norepinephrine production. METHODS We investigated the effects on mechanical parameters of ischemic preconditioning against 20 min of global ischemia followed by 40 min of reperfusion in isolated perfused hearts from adult (six months) and sedentary or trained (six weeks of graduated swim training) senescent (24 months) rats. Norepinephrine release in coronary effluent was determined by high-performance liquid chromatography. RESULTS Final recovery of percent-developed pressure was significantly improved after preconditioning in adult hearts (91.6+/-9.6%) versus unconditioned controls (54.2+/-5.1%, p<0.01). The effect of preconditioning on developed pressure recovery was absent in sedentary but present in trained senescent hearts (39.6+/-4.1% vs. 64.3+/-7.1%, p<0.05). Norepinephrine release significantly increased after preconditioning in adult and in trained but not in sedentary senescent hearts. The depletion of myocardial norepinephrine stores by reserpine abolished preconditioning effects in adult and trained senescent hearts. CONCLUSIONS In adult and trained but not in sedentary senescent hearts, preconditioning reduces postischemic dysfunction and is associated with an increase in norepinephrine release. Preconditioning was blocked by reserpine in both adult and trained senescent hearts. Thus, exercise training may restore preconditioning in the senescent heart through an increase of norepinephrine release.

The emerging role of microRNAs in Alzheimer's disease

MicroRNAs (miRNAs) are small non-coding RNA which have been shown to regulate gene expression. The alteration ofmiRNAs expression has been associated with several pathological processes, including neurodegeneration. In the search for easily accessible and non-invasive biomarkers for Alzheimers disease (AD) diagnosis and prognosis, circulating miRNAs are among the most promising candidates. Some of them have been consistently identified as AD-specific miRNAs and their targets also seem implicated in pathophysiological processes underlying AD. Here, we review the emerging role for miRNA in AD, giving an overview on general miRNAs biology, their implications in AD pathophysiology and their potential role as future biomarkers.

Social support and long-term mortality in the elderly: Role of comorbidity

Several studies have demonstrated a global increase in morbidity and mortality in elderly subjects with low social support or high comorbidity. However, the relationship between social support and comorbidity on long-term mortality in elderly people is not yet known. Thus, the present study was performed to evaluate the relationship between social support and comorbidity on 12-year mortality of elderly people. A random sample of 1288 subjects aged 65-95 years interviewed in 1992 was studied. Comorbidity by Charlson Comorbidity Index (CCI) score and Social Support by a scale in which total score ranges from 0 to 17, assigning to lowest social support the highest score, were evaluated. At 12-year follow-up, mortality progressively increase with low social support and comorbidity increasing (from 41.5% to 66.7% and from 41.2% to 68.3%, respectively; p<0.001). Moreover, low social support progressively increases with comorbidity increasing (and 12.4±2.5 to 14.3±2.6; p<0.001). Accordingly, multivariate analysis shows an increased mortality risk of 23% for each increase of tertile of social support scale (Hazard ratio=HR=1.23; 95% CI=1.01-1.51; p=0.045). Moreover, when the analysis was performed considering different degrees of comorbidity we found that social support level was predictive of mortality only in subjects with the highest comorbidity (HR=1.39; 95% CI=1.082-1.78; p=0.01). Thus, low social support is predictive of long-term mortality in the elderly. Moreover, the effect of social support on mortality increases in subjects with the highest comorbidity.

Left ventricular diastolic filling in diabetes mellitus with and without hypertension

Left ventricular diastolic filling by Doppler echocardiography was investigated in 84 diabetic patients without evidence of heart disease and in 84 normotensive nondiabetic age- and sex-matched control subjects. Diabetic patients were subdivided into two groups on the basis of the presence of arterial hypertension. Group 1 comprised 41 normotensive diabetic patients (19 men, 22 women, mean age 63.7 +/- 9.1 years); Group 2 comprised 43 hypertensive diabetics (15 men, 28 women, mean age 65.6 +/- 9.6 years). Doppler measures of diastolic filling were significantly altered in the two groups as compared with control subjects. Peak atrial flow velocity, velocity integral for the atrial filling period, and atrial filling fraction were increased, whereas the ratio of peak early to peak atrial flow velocity and the ratio of flow velocity integrals were decreased, especially in Group 2 patients. Thirteen patients in Group 1 (32%) and 17 in Group 2 (40%) had evidence of diastolic dysfunction, as assessed by the presence of at least two independent abnormal indices (outside age-corrected 95% confidence interval). In each group, patients with altered diastolic filling differed slightly from diabetic patients with normal Doppler indices, tending to increased wall thickness and left ventricular mass. In conclusion, diastolic filling of the left ventricle is frequently altered in diabetic patients and is adversely affected by arterial hypertension whose coexistence further impairs left ventricular relaxation.