Licia Denti

Aging-related decline of gonadal function in healthy men: correlation with body composition and lipoproteins.

OBJECTIVE: To assess if androgen decline in physiological aging contributes to the concomitant changes in body composition and lipoprotein levels.

The poor outcome of ischemic stroke in very old people: a cohort study of its determinants.

OBJECTIVES: To assess how much of the excess risk of poor outcome from stroke in people aged 80 and older aging per se explains, independent of other prognostic determinants.

Early Recurrence and Cerebral Bleeding in Patients With Acute Ischemic Stroke and Atrial Fibrillation Effect of Anticoagulation and Its Timing: The RAF Study

Background and Purpose— The best time for administering anticoagulation therapy in acute cardioembolic stroke remains unclear. This prospective cohort study of patients with acute stroke and atrial fibrillation, evaluated (1) the risk of recurrent ischemic event and severe bleeding; (2) the risk factors for recurrence and bleeding; and (3) the risks of recurrence and bleeding associated with anticoagulant therapy and its starting time after the acute stroke. Methods— The primary outcome of this multicenter study was the composite of stroke, transient ischemic attack, symptomatic systemic embolism, symptomatic cerebral bleeding and major extracranial bleeding within 90 days from acute stroke. Results— Of the 1029 patients enrolled, 123 had 128 events (12.6%): 77 (7.6%) ischemic stroke or transient ischemic attack or systemic embolism, 37 (3.6%) symptomatic cerebral bleeding, and 14 (1.4%) major extracranial bleeding. At 90 days, 50% of the patients were either deceased or disabled (modified Rankin score ≥3), and 10.9% were deceased. High CHA2DS2-VASc score, high National Institutes of Health Stroke Scale, large ischemic lesion and type of anticoagulant were predictive factors for primary study outcome. At adjusted Cox regression analysis, initiating anticoagulants 4 to 14 days from stroke onset was associated with a significant reduction in primary study outcome, compared with initiating treatment before 4 or after 14 days: hazard ratio 0.53 (95% confidence interval 0.30–0.93). About 7% of the patients treated with oral anticoagulants alone had an outcome event compared with 16.8% and 12.3% of the patients treated with low molecular weight heparins alone or followed by oral anticoagulants, respectively (P=0.003). Conclusions— Acute stroke in atrial fibrillation patients is associated with high rates of ischemic recurrence and major bleeding at 90 days. This study has observed that high CHA2DS2-VASc score, high National Institutes of Health Stroke Scale, large ischemic lesions, and type of anticoagulant administered each independently led to a greater risk of recurrence and bleedings. Also, data showed that the best time for initiating anticoagulation treatment for secondary stroke prevention is 4 to 14 days from stroke onset. Moreover, patients treated with oral anticoagulants alone had better outcomes compared with patients treated with low molecular weight heparins alone or before oral anticoagulants.

Effects of aging on dehydroepiandrosterone sulfate in relation to fasting insulin levels and body composition assessed by bioimpedance analysis.

Insulin can inhibit dehydroepiandrosterone (DHEA) biosynthesis in humans, as suggested by several studies performed in induced or spontaneous hyperinsulinemia. The increased insulin resistance documented throughout aging, with its accompanying hyperinsulinemia, may contribute to the age-related decline in DHEA synthesis. The aim of this study was to assess if the aging-related differences in DHEA sulfate (DHEA-S) serum levels can be associated with differences in fasting insulin levels, as well as body composition. Two hundred fifty-two healthy subjects of both sexes aged 19 to 90 years with a body mass index (BMI) less than 30 (mean +/- SD, 23.5 +/- 2.4) were studied DHEA-S and insulin serum levels were determined by a radioimmunologic procedure; body composition was assessed by anthropometry (fat mass percentage [FM%] estimated from four skinfold thicknesses by Durnin and Womersley and Siri equations [FM%-SKF]) and by bioimpedance analysis (BIA) (FM% estimated by equations developed by Segal et al and Deurenberg et al for subjects < and > 62 years, respectively [FM%-BIA]). DHEA-S levels were significantly and inversely related to age in both sexes. No significant aging-related differences were found in fasting insulin levels, although a trend toward an increase was apparent in the women on simple regression analysis. No significant associations were found between DHEA-S and insulin levels. As for body composition, a positive relationship to age was apparent for FM%-SKF, FM%-BIA, and waist to hip ratio (WHR), whereas BMI and phase angle ([PA] a bioelectric parameter considered an index of the ratio between intracellular and extracellular water) were inversely related to age. Fasting insulin levels were positively related to FM% as estimated by both BIA and anthropometry, independently of age in both sexes; in addition, a positive correlation with WHR and with the subscapular to triceps skinfold thickness ratio (SS/TS) was found in men and women, respectively. No significant correlation was apparent between DHEA-S and body composition indices in men, whereas in women a slight negative correlation between DHEA-S and WHR was documented, and was still significant after adjustment for age and fasting insulin. Stepwise multiple regression analysis confirmed that DHEA-S levels are not related to fasting insulin, but are independently related to age and, in women only, to WHR. Our study suggests that the DHEA-S decline due to aging is independent of fasting insulin, at least in healthy, non-obese people. In addition, it is not related to the aging-dependent changes in body composition in terms of FM% and fat-free mass (FFM) percentage (FFM%). Only in women could changes in fat distribution be slightly associated with DHEA-S decline, although such a relation cannot be accounted for by changes in insulin levels.

The role of lipid profile in determining the risk of ischemic stroke in the elderly: a case–control study

In this study, we investigated the association of lipids with ischemic stroke and its different subtypes in elderly patients. In particular, lipid parameters not extensively investigated so far in previous case-control studies specifically focused in the old population, such as lipoprotein Lp (a) and Apoproteins AI (ApoAI) and B (ApoB), have been taken into account. Seventy nine patients (mean age 83 +/- 7.4, range 67-99), consecutively admitted to a Geriatric Ward between January 1998 and June 2000 with acute stroke (first event) were studied. A complete clinical and laboratory assessment, including neurological evaluation, head CT scan, carotid ultrasonography and ECG, was employed to define the clinical and etiologic stroke subtype, according to standardized criteria. Fasting blood samples were collected within 48 h from admission, for determination of total cholesterol (TC), triglycerides (TG), High Density Lipoprotein-cholesterol (HDL-C), Lp(a), ApoAI and ApoB; Low Density Lipoprotein-Cholesterol (LDL-C) was estimated by Friedwald formula. Eighty eight age and sex-matched outpatients, referred to the hospital for non-inflammatory disorders of joints and musculoskeletal system, served as controls. Patients showed HDL-C and HDL-C/ApoAI ratio significantly lower than controls, with higher LDL-C/HDL-C ratio. Analysis on quartiles of lipoprotein concentrations showed also a significant increase in odds of stroke for LDL-C concentrations over 100 mg/dl, in absence of a linear relationship between LDL-C levels and risk. Multiple logistic regression, adjusting for non-lipid risk factors for stroke, confirmed the independent association of low HDL-C and HDL-C/ApoAI with all strokes, as well as with each subtype. In conclusion, these data suggest that lipids give some contribution to stroke risk even in the elderly, with a more prevalent role for HDL than LDL, and that lipid profile assessment must be taken into account in estimating the individual risk of stroke.

Changes in HDL-cholesterol and lipoprotein Lp(a) after 6-month treatment with finasteride in males affected by benign prostatic hyperplasia (BPH)

Androgen effects on lipoproteins, mainly high density lipoprotein (HDL), could be exerted by a direct interaction of testosterone (T) or dihydrotestosterone (DHT) with liver androgen receptors. To assess if T needs to be converted into DHT to affect lipid metabolism, 13 patients were studied, affected with benign prostatic hyperplasia (BPH) and treated with an inhibitor of 5 alpha-reductase (finasteride). They were compared with 15 untreated controls. At baseline and after 3 and 6 months of therapy, each patient was evaluated as for lipoprotein and hormone concentrations, as well as for nutritional status. Body composition was assessed by anthropometry and bio-impedance analysis (BIA). Treatment was associated with a significant increase of HDL-cholesterol (HDL-C), mainly HDL3 subclass, and lipoprotein(a) (Lp(a)), as well as a decline of DHT, whereas no significant changes were apparent for T, estradiol (E2), sex hormone binding hormone (SHBG) and body composition indexes. However, no significant associations between DHT and lipid relative changes were apparent at bivariate correlation analysis. This finding was confirmed by comparing patient subsets identified by cluster analysis, according to HDL subclass individual responses. Rather, a slight association with E2 for HDL2 (positive) and HDL3 (negative) was found. In conclusion, finasteride can modify HDL and Lp(a) concentrations. However, by the data, these effects cannot be definitively attributed to the changes in DHT synthesis induced by finasteride, since a direct and non-specific interference of the drug on liver metabolism cannot be excluded.

Effects of raloxifene on carotid blood flow resistance and endothelium-dependent vasodilation in postmenopausal women

Raloxifene is one of the most important selective estrogen receptor modulators currently employed for the treatment of postmenopausal osteoporosis. However, it has also been suggested that this compound affects the vascular system. We evaluated both carotid blood flow resistance and endothelium-dependent vasodilation in 50 healthy postmenopausal women randomly assigned to receive, in a double blind design, either raloxifene (60 mg per day; N=25 subjects) or placebo (N=25 subjects) for 4 months. Indices of carotid blood flow resistance, such as the pulsatility index (PI) and resistance index (RI), as well as the flow-mediated brachial artery dilation were measured both at baseline and at the end of treatment. Changes in PI were -1.86+/-2.24 and -2.15+/-2.22% after placebo and raloxifene treatment, respectively, with no significant differences between groups. Changes in RI were -0.77+/-1.72 and -1.81+/-1.54% after placebo and raloxifene treatment, respectively, with no significant differences between groups. At the end of the treatment period, the increments in artery diameter measured after the flow stimulus were 10.79+/-2.39 and 6.70+/-1.23% for placebo and raloxifene, respectively, with no significant differences between groups. These results demonstrate no significant effects of raloxifene on either carotid blood flow resistance or brachial artery flow-mediated dilation in postmenopausal women.

Impact of gender-age interaction on the outcome of ischemic stroke in an Italian cohort of patients treated according to a standardized clinical pathway.

BACKGROUND Stroke outcome has been reported as worse in women, especially in terms of disability. As for mortality, the data are conflicting, with some reports suggesting a female advantage. Our objective was to explore such issues in an Italian cohort of patients managed by a standardized clinical pathway (CPW) and, as such, homogeneous in terms of clinical management. METHODS Data from a cohort of 1993 patients (987 women and 1006 men) with first-ever ischemic stroke, consecutively referred to an in-hospital Clinical Pathway Program from January 1, 2001 to December 31, 2009, were retrospectively analyzed. The relationship between female gender and one-month outcome was assessed with adjustment for age, stroke severity and premorbid disability. RESULTS The outcome was worse in women in terms of disability (age-adjusted odds ratio 2.03, 95% CI 1.69-2.46), while no difference was found for mortality. In multivariate models, female gender turned out to be associated with a lower case-fatality rate (adjusted hazard ratio 0.65, 95% CI 0.48-0.89, P=0.007), whereas the odds ratio for disability decreased but remained significant (OR 1.30; 95% CI 1.01-1.69). We found a significant interaction between gender and age in the case-fatality rate, and a female survival advantage was apparent only below 50 years. CONCLUSIONS Our study confirms the excess risk of disability after stroke in women, although it is mostly explained by the occurrence of the most severe clinical syndromes. As for mortality, female gender seems to play a protective role, at least in the short-term and in younger patients.

Gonadotropin secretion in hyperthyroidism and hypothyroidism

SummaryGonadotropin patterns were evaluated in a group of 70 patients of both sexes with Graves’ disease or primary hypothyroidism. Significant variations were found only in hyperthyroidism where increased basal and stimulated values of both gonadotropins, but particularly LH, occurred. Qualitative and quantitative recovery was seen when euthyroid states were achieved after treatment of hyper and hypothyroid patients. Interactions with gonadotropin behavior were found in both sexes and in women of different ages. Direct interference on the hypothalamo-pituitary system rather than through the modulation of peripheral estrogen metabolism is suggested as the possible pathogenetic mechanism.

The effects of aging on the secretion of the common alpha-subunit of the glycoprotein hormones in men

To investigate the effects of aging on the secretion of the common alpha‐subunit of the glycoprotein hormones, we measured basal levels of luteinizing hormone (LH), testosterone (T) and alpha‐subunit in 176 normal men aged 19 to 89 years. In addition, in two groups of young (<65 years; n = 25) and old (>65 years; n = 15) subjects, the effects of luteinizing hormone‐releasing hormone (LHRH) on LH and alpha‐subunit secretion were determined. Age‐related increases in serum alpha‐subunit and LH were noted only in the oldest men while T levels decreased progressively with advancing age. LHRH stimulation resulted in significantly greater secretion of alpha‐subunit in the old subjects while no difference in LH release between young and old men was observed. Moreover, there was a delay to peak LH and alpha‐subunit levels after LHRH in the old subjects. These data suggest that the aging process in males involves deficits in both testicular and gonadotroph functions as demonstrated by (1) the relative hypogonadotropic hypogonadism seen until the ninth decade; (2) the hypergonadotropic hypogonadism apparent in men >80 years; (3) the delay in the timing of peak responses of LH and alpha‐subunit after LHRH administration; and (4) the disproportionate increase in the secretion of alpha subunit relative to intact LH.