Erectile Dysfunction as a Predictor of Cardiovascular Events and Death in Diabetic Patients With Angiographically Proven Asymptomatic Coronary Artery Disease A Potential Protective Role for Statins and 5-Phosphodiesterase Inhibitors

ObjectivesWe sought to investigate whether erectile dysfunction (ED) is a predictor of future cardiovascular events and death in diabetic patients with silent coronary artery disease (CAD) and whether there are predictors of cardiovascular events and death among CAD diabetic patients with ED.BackgroundCase-control studies showed that ED is associated with CAD in diabetic patients, but no prospective study is available.MethodsType 2 diabetic men (n = 291) with silent CAD angiographically documented were recruited. Erectile dysfunction was assessed by the International Index Erectile Function-5 questionnaire.ResultsDuring a follow-up period of 47.2 ± 21.8 months (range 4 to 82 months), 49 patients experienced major adverse cardiac events (MACE). The difference in ED prevalence between patients with and those without MACE was significant (61.2% vs. 36.4%; p = 0.001). Cox regression analysis showed that ED predicted MACE (hazard ratio [HR] 2.1; 95% confidence interval [CI] 1.6 to 2.6; p < 0.001). Among patients with CAD and ED, the Kaplan-Meier method showed that the statin (Mantel log-rank test: 3.921; p = 0.048) and 5-phosphodiesterase (5-PDE) inhibitor use (Mantel log-rank test: 4.608; p = 0.032) were associated with a lower rate of MACE. Cox regression analysis showed that statin use (HR 0.66; 95% CI 0.46 to 0.97; p = 0.036) reduced MACE. Treatment with 5-PDE inhibitors did not enter the model, but its p value was very near to the significant level (HR 0.68; 95% CI 0.46 to 1.01; p = 0.056).ConclusionsOur data first show that ED is a powerful predictor of cardiovascular morbidity and mortality in diabetic patients with silent CAD and that the treatment with statins and 5-PDE inhibitors might reduce the occurrence of MACE among CAD diabetic patients with ED

Changes in Endocrine Orcadian Rhythms as Markers of Physiological and Pathological Brain Aging

We studied the circadian rhythm of plasma melatonin, growth hormone (GH), prolactin (PRL), adrenocorticotropic hormone (ACTH), and cortisol in 52 mentally healthy old subjects, 35 old demented patients, and 22 clinically healthy young controls. When compared to young controls, the circadian profile of plasma melatonin of old subjects, both demented or not, was clearly flattened, particularly during the night. The selective impairment of nocturnal melatonin secretion was significantly related to both the age and the severity of mental impairment (Mini Mental State Examination [MMSE] score). The PRL and GH circadian profiles were similar in the three groups during the day, but a significant lowering of the values recorded during the night occurred with aging. The impairment of the nocturnal secretion was related to the subjects' age and, for the GH secretory pattern only, also to the MMSE score. The ACTH circadian profile was similar in the three groups studied, even when old subjects exhibited higher ACTH levels throughout the 24h cycle, compared to young controls. Significantly higher cortisol values at evening- and nighttime occurred in elderly subjects and particularly in the demented group. Both the mean levels and the nadir values of plasma cortisol were positively related to age and negatively to MMSE score. In order to verify the sensitivity of the hypothalamo-pituitary-adrenal (HPA) axis to the steroid feedback, the circadian profile of plasma cortisol was evaluated also after dexamethasone (DXM) administration (1 mg at 23:00h); the sensitivity of the HPA axis was significantly impaired in old subjects and particularly in the demented ones. These findings suggest that the neuroendocrine alterations already present in physiological aging, due to both anatomical damages and unbalanced central neurotransmitters, are enhanced in senile dementia

Age-related changes of the adrenal secretory pattern: possible role in pathological brain aging

The biosynthetic dissociation of the adrenocortical secretion occurring with age may have a pathogenetic role in the pathophysiology of brain aging. We studied cortisol and DHEAS secretion in healthy old and young subjects, in senile dementia, in major depression of elderly subjects and in healthy centenarians. A clear age-related decline of DHEAS secretion was well evident in healthy centenarians, and a further decrease in DHEAS concentration was found in old depressed patients and moreover in the demented ones, by comparison with age-matched controls. The circadian profile of serum cortisol was clearly flattened in old subjects, due to the selective increase in the cortisol nocturnal levels, particularly evident in demented subjects; on the other hand, the morning serum cortisol levels were not significantly different among centenarians, young and old controls. The molar ratio between cortisol and DHEAS showed a significant age-related increase; the occurrence of senile dementia and of major depression played an additive role, by comparison to physiological aging. The qualitative and quantitative modifications of the adrenocortical secretion occurring with aging seem mainly dependent on age itself, but the occurrence of pathological conditions may amplify these changes. Since cortisol and DHEAS play opposite effects on the central nervous system, the evaluation of the ratio between cortisol and DHEAS seems to be a good marker of the neuroendocrine features in old subject

Serum glucacon concentration and hyperinsulinaemia influence renal haemodynamics and urinary protein loss in normotensive patients with central obesity

OBJECTIVES: Insulin-resistance syndrome and hyperinsulinaemia are linked with cardiovascular disease (CVD) in the obese population. In particular, cardiovascular risk is more frequent in central obesity and is associated with microalbuminuria (MA). MA and changes of glomerular permeability to proteins in obesity might be related with renal haemodynamic modifications (that is glomerular hyperfiltration). Since glucagon is physiologically involved in renal haemodynamic regulation, the purpose of this study was to examine whether changes of circulating glucagon levels might haemodynamically induce MA and proteinuria in patients with central obesity. SUBJECTS: Forty normotensive obese out-patients, 22 with central (CO group) and 18 with peripheral (PO group) body fat distribution and 11 healthy subjects. MEASUREMENTS: Serum insulin and glucagon concentrations (fasting and after oral glucose tolerance test (OGTT)) by radio immuno assay (RIA); glomerular filtration rate (GFR, isotopic); total clearances and urinary excretion rates of albumin (AER), IgG (IgGER) and alpha1 microglobulin (computerized immunonephelometry). RESULTS: GFR and insulin concentrations (fasting and during OGTT) were higher in the CO than the PO group. Fasting glucagon concentrations were increased, and not physiologically suppressed during OGTT in patients with CO (fasting, P<0.05; OGTT 60 and 120 min, P<0.001 vs PO group). Moreover, glucagon concentrations were significantly correlated with GFR in the CO group (fasting, r=0.49, P<0.05; 60 min after OGTT, r=0.58, P<0.01); whereas no correlations were found in the PO group. Higher AER (P<0.001), IgGER (P<0.001) and alpha1 microglobulin (P<0.05) urinary concentrations were found in patients with CO than in the PO group. CONCLUSIONS: The increase of serum glucagon concentrations may be associated with the enhancement of GFR in patients with central obesity. Glomerular hyperfiltration might influence the development of MA and of proteinuria by means of a haemodynamic mechanism so contributing to increase the risk of renal microvascular complications and of CVD in central obesity