Daniela Balzi

Low Testosterone is Associated with an Increased Risk of MACE Lethality in Subjects with Erectile Dysfunction

INTRODUCTION Although testosterone (T) has been suggested to play a protective role against the development of atherosclerosis, studies demonstrating an association between low T and incident major adverse cardiovascular events (MACE) are scanty in the general population and absent in subjects with erectile dysfunction (ED). AIM To investigate whether low T in subjects with ED predict incident fatal or nonfatal MACE. METHODS This is an observational prospective cohort study evaluating a consecutive series of 1687 patients attending our andrological unit for ED. Patients were interviewed using the structured interview on erectile dysfunction (SIEDY) and ANDROTEST structured interviews measuring components relative to ED and hypogonadal-related symptoms, respectively. MAIN OUTCOME MEASURES Total T was evaluated at baseline. Information on MACE was obtained through the City of Florence Registry Office. RESULTS Among the patients studied, 5.2, 13.8, and 22.4% were hypogonadal according to different thresholds (T < 8, 10.4 and 12 nmol/L or 230, 300 and 350 ng/dL, respectively). During a mean follow-up of 4.3 + or - 2.6 years, 139 MACE, 15 of which were fatal, were observed. Unadjusted incidence of MACE was not associated with T levels. Conversely, the proportion of lethal events among MACE was significantly higher in hypogonadal patients, using either 10.4 nmol/L (300 ng/dL) or 8 nmol/L (230 ng/dL) thresholds. However, after adjustment for age and Chronic Diseases Score in a Cox regression model, only the association between incident fatal MACE and T < 8 nmol/L (230 ng/dL) was confirmed (HR = 7.1 [1.8-28.6]; P < 0.001). Interestingly, measuring hypogonadal-related symptoms and signs through ANDROTEST, only fatal MACE were also associated with a higher score (HR = 1.2 [1.0-1.5] for each ANDROTEST score increment; P = 0.05 after adjustment for age and Chronic Diseases Score). CONCLUSIONS T levels are associated with a higher mortality of MACE. The identification of low T levels should alert the clinician thus identifying subjects with an increased cardiovascular risk.

Bone Fractures and Hypoglycemic Treatment in Type 2 Diabetic Patients A case-control study

OBJECTIVE—Hypoglycemic treatments could modulate the risk for fractures in many ways. Most studies have not explored the effect on the incidence of bone fractures of individual oral hypoglycemic agents, rather all oral treatments as a whole. The aim of this case-control study, nested within a retrospective cohort, is the assessment of the risk for bone fractures associated with exposure to insulin or different oral hypoglycemic agents. RESEARCH DESIGN AND METHODS—A case-control study nested within a cohort of 1,945 diabetic outpatients with a follow-up of 4.1 ± 2.3 years was performed, comparing 83 case subjects of bone fractures and 249 control subjects matched for age, sex, duration of diabetes, BMI, A1C, comorbidity, smoking, and alcohol abuse. Exposure to hypoglycemic drugs during the 10 years preceding the event (or matching index date) was assessed. RESULTS—In a model including treatment with insulin secretagogues metformin and insulin for at least 36 months during the previous 10 years, no significant association was observed between bone fractures and medications. In an alternative model considering treatments at the time of fracture, insulin treatment was significantly associated with bone fractures in men (OR 3.20 [95% CI 1.32–7.74]) but not in women (1.41 [0.73–2.73]). CONCLUSIONS—Insulin-sensitizing treatment with metformin is not associated with a higher incidence of bone fractures, suggesting that the negative effect of thiazolidinediones is due to a specific action on bone metabolism rather a reduction of insulinemia. Conversely, current treatment with insulin increases the risk of fractures; at the same time, exposure to this agent in the longer term does not appear to affect bone frailty.

BONE FRACTURES AND HYPOGLYCAEMIC TREATMENT IN TYPE 2 DIABETIC PATIENTS: A CASE-CONTROL STUDY.

OBJECTIVE—Hypoglycemic treatments could modulate the risk for fractures in many ways. Most studies have not explored the effect on the incidence of bone fractures of individual oral hypoglycemic agents, rather all oral treatments as a whole. The aim of this case-control study, nested within a retrospective cohort, is the assessment of the risk for bone fractures associated with exposure to insulin or different oral hypoglycemic agents. RESEARCH DESIGN AND METHODS—A case-control study nested within a cohort of 1,945 diabetic outpatients with a follow-up of 4.1 ± 2.3 years was performed, comparing 83 case subjects of bone fractures and 249 control subjects matched for age, sex, duration of diabetes, BMI, A1C, comorbidity, smoking, and alcohol abuse. Exposure to hypoglycemic drugs during the 10 years preceding the event (or matching index date) was assessed. RESULTS—In a model including treatment with insulin secretagogues metformin and insulin for at least 36 months during the previous 10 years, no significant association was observed between bone fractures and medications. In an alternative model considering treatments at the time of fracture, insulin treatment was significantly associated with bone fractures in men (OR 3.20 [95% CI 1.32–7.74]) but not in women (1.41 [0.73–2.73]). CONCLUSIONS—Insulin-sensitizing treatment with metformin is not associated with a higher incidence of bone fractures, suggesting that the negative effect of thiazolidinediones is due to a specific action on bone metabolism rather a reduction of insulinemia. Conversely, current treatment with insulin increases the risk of fractures; at the same time, exposure to this agent in the longer term does not appear to affect bone frailty.

Male Sexuality and Cardiovascular Risk. A Cohort Study in Patients with Erectile Dysfunction

INTRODUCTION Although penile blood flow (PBF) has been recommended as an additional diagnostic test in identifying erectile dysfunction (ED) patients at risk for latent cardiovascular disease, no study has ever assessed the possible association of PBF and the relational component of sexual function with incident major cardiovascular events (MACE). AIM The aim of this study is to investigate whether severity of ED, PBF, and other factors related to a couples relationship predict incident MACE. METHODS A consecutive series of 1,687 patients was studied. Different clinical, biochemical, and instrumental (penile flow at color Doppler ultrasound) parameters were evaluated. MAIN OUTCOME MEASURES Information on MACE was obtained through the City of Florence Registry Office. RESULTS During a mean follow-up of 4.3 +/- 2.6 years, 139 MACE, 15 of which were fatal, were observed. Cox regression analysis, after adjustment for age and Chronic Disease Score, showed that severe ED predicted MACE (hazard ratio [HR] 1.75; 95% confidence interval 1.10-2.78; P < 0.05). In addition, lower PBF, evaluated both in flaccid (before) and dynamic (after prostaglandin-E1 stimulation) conditions, was associated with an increased risk of MACE (HR = 2.67 [1.42-5.04] and 1.57 [1.01-2.47], respectively, for flaccid [<13 cm/second] and dynamic [<25 cm/second] peak systolic velocity; both P < 0.05). Reported high sexual interest in the partner and low sexual interest in the patient proved to have a protective effect against MACE. CONCLUSIONS The investigation of male sexuality, and in particular PBF, and sexual desire, could provide insights not only into present cardiovascular status but also into prospective risk.

DOSES OF INSULIN AND ITS ANALOGUES AND CANCER OCCURRENCE IN INSULIN-TREATED TYPE 2 DIABETIC PATIENTS

OBJECTIVE Recent epidemiological studies suggested that some insulin analogues could be associated with increased risk of cancer. The present study is aimed at assessing the long-term association of different insulin analogues with cancer incidence. RESEARCH DESIGN AND METHODS A nested case-control study dataset was generated from the cohort study dataset (n = 1,340 insulin-treated diabetic outpatients) by sampling control subjects from the risk sets. For each case subject, the control subjects (up to five) were chosen randomly from those members of the cohort who are at risk for the same follow-up time of the case subject. Five-year age classes, sex, and BMI classes (<18.5, 18.5–24.9, 25–29.9, and ≥30 kg/m2) were considered as additional categorical matching variables. RESULTS During a median follow-up of 75.9 months (interquartile range 27.4–133.7), 112 case subjects of incident cancer were compared with 370 matched control subjects. A significantly higher mean daily dose of glargine was observed in case subjects than in control subjects (0.24 IU/kg/day [0.10–0.39] versus 0.16 IU/kg/day [0.12–0.24], P = 0.036). Incident cancer was associated with a dose of glargine ≥0.3 IU/kg/day even after adjusting for Charlson comorbidity score, other types of insulin administration, and metformin exposure (odds ratio 5.43 [95% CI 2.18–13.53], P < 0.001). No association between incident cancer and insulin doses was found for human insulin or other analogues. CONCLUSIONS The possibility of association between cancer and higher glargine doses suggests that dosages should always be considered when assessing the possible association of insulin and its analogues with cancer.

Are sulphonylureas all the same? A cohort study on cardiovascular and cancer‐related mortality

Aim of the present study is the comparison of all‐cause, cardiovascular and non‐cardiovascular mortality, and cardiac morbidity, between patients treated with glibenclamide and gliclazide.

METFORMIN AND CANCER OCCURRENCE IN INSULIN-TREATED TYPE 2 DIABETIC PATIENTS.

OBJECTIVE Metformin is associated with reduced cancer-related morbidity and mortality. The aim of this study was to assess the effect of metformin on cancer incidence in a consecutive series of insulin-treated patients. RESEARCH DESIGN AND METHODS A nested case-control study was performed in a cohort of 1,340 patients by sampling, for each case subject, age-, sex-, and BMI-matched control subjects from the same cohort. RESULTS During a median follow-up of 75.9 months, 112 case patients who developed incident cancer and were compared with 370 control subjects. A significantly lower proportion of case subjects were exposed to metformin and sulfonylureas. After adjustment for comorbidity, glargine, and total insulin doses, exposure to metformin, but not to sulfonylureas, was associated with reduced incidence of cancer (odds ratio 0.46 [95% CI 0.25–0.85], P = 0.014 and 0.75 [0.39–1.45], P = 0.40, respectively). CONCLUSIONS The reduction of cancer risk could be a further relevant reason for maintaining use of metformin in insulin-treated patients.

Risk factors for disability in older persons over 3-year follow-up

BACKGROUND the identification of modifiable risk factors for preventing disability in older individuals is essential for planning preventive strategies. PURPOSE to identify cross-sectional correlates of disability and risk factors for the development activities of daily living (ADL) and instrumental ADL (IADL) disability in community-dwelling older adults. METHODS the study population consisted of 897 subjects aged 65-102 years from the InCHIANTI study, a population-based cohort in Tuscany (Italy). Factors potentially associated with high risk of disability were measured at baseline (1998-2000), and disability in ADLs and IADLs were assessed both at baseline and at the 3-year follow-up (2001-03). RESULTS the baseline prevalence of ADL disability and IADL disability were, respectively, 5.5% (49/897) and 22.2% (199/897). Of 848 participants free of ADL disability at baseline, 72 developed ADL disability and 25 of the 49 who were already disabled had a worsening in ADL disability over a 3-year follow-up. Of 698 participants without IADL disability at baseline, 100 developed IADL disability and 104 of the 199 who already had IADL disability had a worsening disability in IADL over 3 years. In a fully adjusted model, high level of physical activity compared to sedentary state was significantly associated with lower incidence rates of both ADL and IADL disability at the 3-year follow-up visit (odds ratio (OR): 0.30; 95% confidence intervals (CI) 0.12-0.76 for ADL disability and OR: 0.18; 95% CI 0.09-0.36 for IADL disability). After adjusting for multiple confounders, higher energy intake (OR for difference in 100 kcal/day: 1.09; 95% CI 1.02-1.15) and hypertension (OR: 1.91; 95% CI 1.06-3.43) were significant risk factors for incident or worsening ADL disability. CONCLUSIONS higher level of physical activity and lower energy intake may be protective against the development in ADL and IADL disability in older persons.

Prognostic Stratification of Older Persons Based on Simple Administrative Data: Development and Validation of the “Silver Code,” To Be Used in Emergency Department Triage

BACKGROUND Prognostic stratification of older patients with complex medical problems among those who access the emergency department (ED) may improve the effectiveness of geriatric interventions. Whether such targeting can be performed through simple administrative data is unknown. METHODS We examined the discharge records for 10,913 patients aged 75 years or older admitted during 2005 to the ED of all public hospitals in Florence, Italy. Using information on demographics, drug treatment, previous hospital admissions, and discharge diagnoses, we developed a 1-year mortality prognostic index. The predictive validity of this index was tested in a subsample of patients independent of the subsample used for its original development. Finally, we tested whether patients stratified by the prognostic index had different mortality when admitted to a geriatrics compared with an internal medicine ward. RESULTS In the validation subsample, patients with scores of 4-6, 7-10, and 11+ compared with those with scores less than 4 had hazard ratios (95% confidence interval) for 1-year mortality of, respectively, 1.5 (1.3-1.7), 2.2 (1.3-1.7), and 3.0 (2.6-3.4). Patients in the worse prognostic stratum experienced 33% higher mortality when admitted to an internal medicine compared with a geriatrics ward, although mortality was not significantly affected by the type of ward of admission in all other risk strata. CONCLUSIONS Simple administrative data provide prognostic information on long-term mortality in older patients hospitalized via ED. Patients with worse prognostic index scores appear to benefit from admission in a geriatrics compared with an internal medicine ward.

Comparison of methods for monitoring residual platelet reactivity after clopidogrel by point-of-care tests on whole blood in high-risk patients.

Cardiovascular events are more frequent in high-risk coronary artery disease (CAD) patients on dual antiplatelet therapy with a residual platelet reactivity (RPR) than in those showing inhibition of ADP-inducible platelet activation. It is known that post-interventional RPR is a clinically important entity confirming it as a risk factor for thrombo-ischaemic events. Multiple electrode platelet aggregometry (MEA) on whole blood has been recently proposed as a rapid tool to evaluate RPR in high-risk CAD patients on clopidogrel therapy. It was the aim of this study to detect RPR in 801 high-risk CAD patients on dual antiplatelet therapy comparing MEA with the VerifyNow P2Y12 assay on whole blood and classical light transmission aggregation (LTA) on platelet-rich plasma. ADP (10 microM) was employed as agonist for MEA and LTA. The prevalence of RPR was 20.6% by MEA, 16.1% by LTA and 30.8% by VerifyNow. MEA showed a significant correlation (rho=0.62, p<0.0001) with VerifyNow and a moderate agreement (k=0.52, p<0.001) with 81.5% of concordant values. A significant correlation was found between MEA and LTA (rho=0.71, p<0.001) with a good agreement (k=0.63, p<0.001) and 88.8% of concordant values. MEA in relation to LTA showed a sensitivity of 80% and a specificity of 91%. MEA might represent a reliable method and valid alternative in comparison with other available platelet function assays. It might help to guide antiplatelet therapy and thus improve clinical outcome of high-risk CAD patients.