Clinical impact of high platelet reactivity in patients with atrial fibrillation and concomitant percutaneous coronary intervention on dual or triple antithrombotic therapy.

High platelet reactivity (HPR) on clopidogrel is an established thrombotic risk factor after percutaneous coronary intervention (PCI). The introduction of more potent antiplatelet drugs has partially surpassed this issue. However, in the setting of concomitant atrial fibrillation (AF) and PCI clopidogrel is still the most adopted P2Y12 inhibitor. In the present study all consecutive patients with history of AF discharged from our cardiology ward with dual (DAT) or triple (TAT) antithrombotic therapy after a PCI from April 2018 to March 2021 were enrolled in an observational registry. For all subjects, blood serum samples were collected and tested for platelet reactivity by arachidonic acid and ADP (VerifyNow system) and genotyping of the CYP2C19*2 loss-of-function polymorphism. We recorded at 3 and 12-months follow-up: (1) major adverse cardiac and cerebrovascular events (MACCE), (2) major hemorrhagic or clinically relevant non-major bleeding and (3) all-cause mortality. A total of 147 patients were included (91, 62% on TAT). In 93.4% of patients, clopidogrel was chosen as P2Y12 inhibitor. P2Y12 dependent HPR resulted an independent predictor of MACCE both at 3 and 12 months (HR 2.93, 95% C.I. 1.03 to 7.56, p = 0.027 and HR 1.67, 95% C.I. 1.20 to 2.34, p = 0.003, respectively). At 3-months follow-up the presence of CYP2C19*2 polymorphism was independently associated with MACCE (HR 5.21, 95% C.I. 1.03 to 26.28, p = 0.045). In conclusion, in a real-world unselected population on TAT or DAT, the entity of platelet inhibition on P2Y12 inhibitor is a potent predictor of thrombotic risk, suggesting the clinical utility of this laboratory evaluation for a tailored antithrombotic therapy in this high-risk clinical scenario. The present analysis was performed in patients with AF undergoing PCI on dual or triple antithrombotic therapy. At 1 year follow-up MACCE incidence was consistent, and it was not different in different antithrombotic pattern groups. P2Y12 dependent HPR was a potent independent predictor of MACCE both at 3- and 12-months follow-up. In the first 3 months after stenting the carriage of CYP2C19*2 allele was similarly associated with MACCE. Abbreviation: DAT, dual antithrombotic therapy; HPR, high platelet reactivity; MACCE, major adverse cardiac and cerebrovascular events; PRU, P2Y12 reactive unit; TAT, triple antithrombotic therapy. Created with BioRender.com.

Relationship between hyponatremia at hospital admission and cardiopulmonary profile at follow-up in patients with SARS-CoV-2 (COVID-19) infection.

PURPOSE: Hyponatremia occurs in about 30% of patients with pneumonia, including those with SARS-CoV-2 (COVID-19) infection. Hyponatremia predicts a worse outcome in several pathologic conditions and in COVID-19 has been associated with a higher risk of non-invasive ventilation, ICU transfer and death. The main objective of this study was to determine whether early hyponatremia is also a predictor of long-term sequelae at follow-up. METHODS: In this observational study, we collected 6-month follow-up data from 189 laboratory-confirmed COVID-19 patients previously admitted to a University Hospital. About 25% of the patients (n = 47) had hyponatremia at the time of hospital admission. RESULTS: Serum [Na+] was significantly increased in the whole group of 189 patients at 6 months, compared to the value at hospital admission (141.4 ± 2.2 vs 137 ± 3.5 mEq/L, p < 0.001). In addition, IL-6 levels decreased and the PaO2/FiO2 increased. Accordingly, pulmonary involvement, evaluated at the chest X-ray by the RALE score, decreased. However, in patients with hyponatremia at hospital admission, higher levels of LDH, fibrinogen, troponin T and NT-ProBNP were detected at follow-up, compared to patients with normonatremia at admission. In addition, hyponatremia at admission was associated with worse echocardiography parameters related to right ventricular function, together with a higher RALE score. CONCLUSION: These results suggest that early hyponatremia in COVID-19 patients is associated with the presence of laboratory and imaging parameters indicating a greater pulmonary and right-sided heart involvement at follow-up.

Tenosynovial complications identify TTR cardiac amyloidosis among patients with hypertrophic cardiomyopathy phenotype.

Recent evidence suggests that carpal tunnel syndrome (CTS) and brachial biceps tendon rupture (BBTR) represent red flags for ATTR cardiac amyloidosis (ATTR-CA). The prevalence of upper limb tenosynovial complications in conditions entering differential diagnosis with CA, such as HCM or Anderson-Fabry disease (AFD), and hence their predictive accuracy in this setting, still remains unresolved. OBJECTIVE: To investigate the prevalence of CTS and BBTR in a consecutive cohort of ATTR-CA patients, compared with patients with HCM or AFD and with individuals without cardiac disease history. PARTICIPANTS: Consecutive patients with a diagnosis of ATTR-CA, HCM and AFD were evaluated. A control group of consecutive patients was recruited among subjects hospitalized for noncardiac reasons and no cardiac disease history. The presence of BBTR, CTS or prior surgery related to these conditions was ascertained. RESULTS: 342 patients were prospectively enrolled, including 168 ATTR-CA (141 ATTRwt, 27 ATTRm), 81 with HCM/AFD (N = 72 and 9, respectively) and 93 controls. CTS was present in 75% ATTR-CA patients, compared with 13% and 10% of HCM/AFD and controls (P = 0.0001 for both comparisons). Bilateral CTS was present in 60% of ATTR-CA patients, while it was rare (2%) in the other groups. BBTR was present in 44% of ATTR-CA patients, 8% of controls and 1% in HCM/AFD. CONCLUSIONS: CTS and BBTR are fivefold more prevalent in ATTR-CA patients compared with cardiac patients with other hypertrophic phenotypes. Positive predictive accuracy for ATTR-CA is highest when involvement is bilateral. Upper limb assessment of patients with HCM phenotypes is a simple and effective way to raise suspicion of ATTR-CA.

Clinical aspects and diagnostic relevance of neuroautonomic evaluation in patients with unexplained falls.

OBJECTIVE: To evaluate the diagnostic relevance of neuroautonomic evaluation in patients with unexplained falls compared to those with a syncope etiologically unexplained after initial evaluation. METHODS: It is an observational study, comparing 298 patients with unexplained fall with 989 patients with unexplained syncope. Each patient underwent supine and upright blood pressure measurement, tilt testing (TT) and carotid sinus massage (CSM). RESULTS: Patients with unexplained falls were older (75.3 ± 11.1 vs. 63.2 ± 19.2 years, p < 0.001), were more frequently hypertensive (66.1 vs. 47.2 %, p < 0.001) and more frequently prescribed antihypertensive drugs (62.4 vs. 48.7 %, p < 0.001) or benzodiazepines (15.7 vs. 10.6 %, p = 0.01), and in a greater proportion they experienced major traumatic injuries (77.5 vs. 29.6 %, p < 0.001) as a consequence of falls. The TT was less frequently positive in patients with unexplained falls (36 vs. 51.3 %, p < 0.001), whereas a Carotid Sinus Syndrome as suggested by CSM had a similar prevalence in the two groups (14.3 vs. 10.5 %, p = 0.074). Overall, either TT or CSM were positive in 61 % of patients with unexplained falls, and in 64 % of those with syncope (p = 0.346). After matching by age 298 patients with falls (75.3 ± 11.1 years) and 298 patients with unexplained syncope (75.4 ± 11.1 years), we found that the positivity prevalence of TT and CSM were similar in the two groups. CONCLUSIONS: The positivity prevalence of TT and CSM in patients with unexplained falls compared to patients with unexplained syncope is similar. Given its high diagnostic relevance, the neuroautonomic evaluation should be routinely performed in older patients with unexplained falls.

HbA1c levels and all-cause mortality in type 2 diabetic patients: epidemiological evidence of the need for personalised therapeutic targets.

BACKGROUND AND AIM: The aim of the present case-control study is to explore the effect of case mix on the relationship between glycated haemoglobin (HbA1c) and mortality in type 2 diabetic patients. METHODS AND RESULTS: A nested case-control study data set was generated from the cohort-study data set (n = 4140 type 2 diabetic outpatients) by sampling controls from the risk sets. Cases (n = 427) were compared with an equal number of controls chosen from those members of the cohort who were at risk for the same follow-up time of the case, matched for age (±3 years), sex, body mass index (BMI) (±2 kg m(-2)), duration of diabetes (±5 years), and Charlson's Comorbidity Score (CCS) (±1). The main predefined analysis was the comparison of cases and controls for proportion of patients with each HbA1c class (<6.5%, 6.5-7.4%, 7.5-8.4% and ≥8.5%). During a mean follow-up of 5.7 ± 3.5 years, 427 deaths were recorded. The lowest risk of death was observed in the HbA1c 6.5-7.4% category; a lower HbA1c was associated with a non-significant trend towards a higher risk. The risk associated with a low (<6.5%) HbA1c was significantly greater in patients who were insulin-treated than in the rest of the sample. CONCLUSIONS: The present study suggests that glycaemic targets should be individualised on the basis of the characteristics of each patient, considering age, co-morbidity and duration of diabetes. Caution should be used in prescribing insulin to reach near-normoglycaemia, particularly in older, frail patients.

Prognostic significance of serum uric acid in outpatients with chronic heart failure is complex and related to body mass index: data from the IN-CHF Registry.

BACKGROUND AND AIMS: In the field of cardiovascular diseases, elevated levels of serum uric acid (UA) reflect a marked activation of the xanthine oxidase pathway with increase in free radicals production; it is often associated with an inflammatory state, oxygen consumption and endothelial dysfunction. All these associations have been also confirmed in heart failure (HF) but the pathophysiological role of UA in this setting is not well understood. The aim of this study was to evaluate the prognostic role of UA in outpatients enrolled in the Italian Registry of Congestive Heart Failure (IN-CHF). METHODS AND RESULTS: All patients met the European Society of Cardiology (ESC) criteria for diagnosis of HF. We considered patients with complete clinical data and UA level available at the baseline and at 1-year follow-up. The study population was composed of 877 patients aged 63 ± 12 years. One-year mortality was 10.8% and dead patients had a higher level of UA than survivors (7.1 mg dl⁻¹ vs 6.6 mg dl⁻¹, p < 0.0207). In multivariable full model of analysis, UA did not result in an independent predictor of death in overall population, but only in patients with low body mass index (BMI) (≤22 kg m⁻²) (hazard ratio (HR): 2.38, 95% confidence interval (CI) 1.36-4.18). In this subgroup, a statistically significant gradual relationship between UA and survival was detected starting from values higher than 8 mg dl⁻¹. CONCLUSION: Elevated level of UA is not an independent predictor of mortality in chronic HF, but it markedly worsens outcome if associated with low level of BMI. This association is likely an indicator of chronic inflammatory and catabolic state.

Adiponectin in outpatients with coronary artery disease: independent predictors and relationship with heart failure.

BACKGROUND AND AIMS: Chronic heart failure (HF) is characterised by a neurohormonal dysfunction associated with chronic inflammation. A role of metabolic derangement in the pathophysiology of HF has been recently reported. Adiponectin, an adipose-tissue-derived cytokine, seems to play an important role in cardiac dysfunction. We investigated the variation of circulating adiponectin in patients with coronary artery disease (CAD), with or without HF, in order to identify its independent predictors. METHODS AND RESULTS: A total of 107 outpatients with CAD were enrolled in the study and divided into three groups: CAD without left ventricular systolic dysfunction (group 1); CAD with left ventricular dysfunction without HF symptoms (group 2) and CAD with overt HF (group 3). Plasma adiponectin was determined by enzyme-linked immunosorbent assay. Adiponectin concentrations increased progressively from group 1 (7.6 ± 3.6 ng ml⁻¹) to group 2 (9.1 ± 6.7 ng ml⁻¹) and group 3 (13.7 ± 7.6 ng ml⁻¹), with the difference reaching statistical significance in group 3 versus 1 and 2 (p < 0.001). A multivariable model of analysis demonstrated that the best predictors of plasma adiponectin were body mass index, N-terminal pro-brain natriuretic peptide and high-density lipoprotein cholesterol. However, even after adjusting for all three independent predictors, the increase of adiponectin in group 3 still remained statistically significant (p = 0.015). CONCLUSION: Our data confirm the rise of adiponectin in overt HF. The levels of circulating adipokine seem to be mainly predicted by the metabolic profile of patients and by biohumoral indicators, rather than by clinical and echocardiographic indexes of HF severity.

Effects of antihypertensive treatments on incidence of diabetes: a case-control study.

AIMS: Aim of this case-control study is the assessment of the relationship between antihypertensive treatment and incidence of diabetes in an unselected cohort of subjects participating in a screening program for diabetes. METHODS: A case-control study nested within a cohort of nondiabetic subjects with a mean follow-up of 27.7 ± 11.3 months was performed, comparing 40 cases of incident diabetes and 160 controls matched for age, sex, body mass index, fasting plasma glucose, 2-h post-load glycemia, smoking and alcohol abuse. RESULTS: When considering antihypertensive treatment at enrolment, a lower proportion of cases was exposed to ACE-inhibitors/angiotensin receptor blockers (ACE-i/ARB) in comparison with controls. A non-significant trend toward a higher exposure to diuretics, which were mainly represented by thiazide diuretics, was observed in cases. In a multivariate analysis, including both ACE-i/ARB and diuretics, a protective effect of ACEi/ARB, and an increased risk with diuretics were observed. Similar results were obtained in alternative models, after adjusting for systolic and diastolic blood pressure at enrolment, diagnosis of hypertension, concurrent treatment with ß-blockers or calcium-channel blockers, and number of antihypertensive medications. CONCLUSIONS: Diuretics seem to be associated with a higher incidence of diabetes, whereas treatment with ACEi/ARB could have a protective effect.

Effect of metformin on cardiovascular events and mortality: a meta-analysis of randomized clinical trials.

AIM: Some studies suggested that metformin could reduce cardiovascular risk to a greater extent than that determined by glucose reduction. Aim of the present meta-analysis is to assess the effects of metformin on the incidence of cardiovascular events and mortality. METHODS: An extensive search of Medline, EMBASE and the Cochrane Library (any date up to 31 October 2009) was performed for all trials containing the word 'metformin'. Randomized trials with a duration ≥52 weeks were included. A meta-regression analysis was also performed to identify factors associated with cardiovascular morbidity and mortality in metformin-treated patients. RESULTS: A total of 35 clinical trials were selected including 7171 and 11 301 participants treated with metformin and comparator, respectively, who had 451 and 775 cardiovascular (CV) events, respectively. Overall, metformin was not associated with significant harm or benefit on cardiovascular events (MH-OR 0.94[0.82-1.07], p = 0.34). A significant benefit was observed in trials versus placebo/no therapy (MH-OR 0.79[0.64-0.98], p = 0.031), but not in active-comparator trials (MH-OR 1.03[0.72-1.77], p = 0.89). Meta-regression showed a significant correlation of the effect of metformin on cardiovascular events with trial duration and with minimum and maximum age for inclusion, meaning that the drug appeared to be more beneficial in longer trials enrolling younger patients. It is likely that metformin monotherapy is associated with improved survival (MH-OR: 0.801[0.625-1.024], p = 0.076). However, concomitant use with sulphonylureas was associated with reduced survival (MH-OR: 1.432[1.068-1.918], p = 0.016). CONCLUSION: Available evidence seems to exclude any overall harmful effect of metformin on cardiovascular risk, suggesting a possible benefit versus placebo/no treatment. The observed detrimental effect of the combination with sulphonylureas deserves further investigation.

Is suboptimal prescribing a risk factor for poor health outcomes in community-dwelling elders? The ICARe Dicomano study.

PURPOSE: Mostly because of comorbidity and drugs consumption, older persons are often exposed to an increased risk of sub-optimal prescribing (SP). At present, few studies investigated the association between SP and long-term health outcomes. We examined the relation between SP and the risk of mortality and hospitalization in Italian older community-dwellers. METHODS: Older (65+ years) community-dwelling residents of a small town in Tuscany were enrolled in a longitudinal study. SP was defined as polypharmacy (use of 5+ drugs), prescription of inappropriate drugs (ID) according to Beers' criteria, and of potentially interacting drugs (PID), evaluated in 1995 and 1999. These three forms of SP were entered as time-dependent exposures into multivariable Cox regression analysis models, whose outcomes were mortality and hospitalizations through 2003. RESULTS: Of 1022 participants (mean age 73.0 +/- 6.8, 57% women), 220 were evaluated in 1995, 234 in 1999 and 568 in both waves. In univariate analysis, mortality was two-fold higher in participants with polypharmacy (73.4/1000 person/years, 95% CI 58.2-92.4 vs. 34.1, 95% CI 29.7-39.2; p < 0.001) or PID (72.7/1000 person/years, 95% CI 46.3-113.9 vs. 38.0, 95% CI 33.5-43.1; p < 0.001), whereas it was unrelated to the presence of ID. Hospitalization rates were independent of any form of SP. In multivariable models, polypharmacy, ID, and PID were no longer associated with an increased risk of death, and ID predicted a slightly increased risk of hospitalizations (HR 1.03, 95% CI 1.0-1.06, p = 0.048). CONCLUSIONS: In this cohort, SP was not associated with an excess risk of poor health outcomes.

Dipeptydil peptidase-4 inhibitors in type 2 diabetes: a meta-analysis of randomized clinical trials.

BACKGROUND AND AIM: The role of Dipeptidyl Peptidase-4 (DPP-4) inhibitors in the treatment of type 2 diabetes is debated; many recent trials, which were not included in previous meta-analyses, could add relevant information. METHODS AND RESULTS: All available randomized controlled trials (RCTs), either published or unpublished, performed in type 2 diabetic patients with DPP-4 inhibitors, with a duration >12 weeks were meta-analyzed for HbA1c, BMI, hypoglycemia, and other adverse events. A total of 41 RCTs (9 of which are unpublished) was retrieved and included in the analysis. Gliptins determine a significant improvement of HbA1c in comparison with a placebo (-0.7 [-0.8:-0.6]), with a low risk of hypoglycemia. DPP-4 inhibitors show a similar efficacy in monotherapy and in combination with other agents. The risk of cardiovascular events and all-cause death with DPP-4 inhibitors is 0.76 [0.46-1.28] and 0.78 [0.40-1.51], respectively. CONCLUSIONS: DPP-4 inhibitors reduce HbA1c, although to a lesser extent than sulphonylureas, with no weight gain and no hypoglycemic risk; further data are needed to assess their long-term safety.

Glucagon-like peptide-1 response to meals and post-prandial hyperglycemia in Type 2 diabetic patients.

BACKGROUND: The impaired response of glucagonlike peptide-1 (GLP-1) to meals in diabetic patients can contribute to the pathogenesis of impaired insulin secretion and post-prandial hyperglycemia. This study is aimed at the assessment of the relationship between meal-induced GLP-1 and post-prandial hyperglycemia in Type 2 diabetic patients. METHODS: Twenty-one drug-naïve Type 2 diabetic patients were studied. Blood glucose and active GLP-1 levels were measured 0, 30, 60, 90, and 120 min after a standard test meal. A continuous glucose monitoring (CGM) system was applied for the following 3 days. Nutrient intake at each meal was calculated on the basis of patients' food records. For each patient, post-prandial 120-min glucose incremental area under the curve (iAUC) was included in linear regression model exploring its relationship with total energy and carbohydrate intake, and the angular coefficient for total energy (EAC) and carbohydrate (CAC) was calculated. RESULTS: GLP-1 levels peaked 30 min after the test meal. Logarithmically transformed 60-min GLP-1 iAUC showed a significant inverse correlation with glycated hemoglobin (HbA1c) (p<0.01). A significant inverse correlation of 60-min GLP-1 iAUC was also observed with EAC and CAC (both p<0.01), meaning that patients with a lower GLP-1 response to the test meal had a higher increment of post-prandial glucose for each additional unit of total energy or carbohydrate intake. CONCLUSIONS: In Type 2 diabetic patients, a lower GLP-1 response to meals is associated with a higher HbA1c, and with a greater degree of meal-induced hyperglycemia, both in a meal test and during CGM in "real-life" conditions.

Short-acting insulin analogues vs. regular human insulin in type 2 diabetes: a meta-analysis.

AIM: Short-acting insulin analogues, in comparison with regular human insulin (HRI), provide a greater control of postprandial glucose, while their superiority on haemoglobin A1c (HbA1c) is controversial. METHOD: All randomized controlled trials (RCTs) with a duration >4 weeks comparing short-acting insulin analogues (lispro, aspart or glulisine) with HRI in type 2 diabetic patients were retrieved; data on HbA1c and postprandial glucose et end-point and incidence of severe hypoglycaemia were extracted and meta-analysed. RESULTS: A total of 13 RCTs (7, 4 and 2 with lispro, aspart and glulisine, respectively) were retrieved and included in the analysis. Short-acting analogues reduced HbA1c by 0.4% (0.1-0.6%) (p = 0.027) in comparison with HRI. A significant improvement was observed also in self-monitored 2 h postbreakfast and dinner blood glucose. The overall rate of severe hypoglycaemia was not significantly different with short-acting analogues and HRI [Mantel-Haenszel odds ratio for 95% confidence interval 0.61 (0.25-1.45)]. CONCLUSION: In type 2 diabetic patients, short-acting insulin analogues provide a better control of HbA1c and postprandial glucose than regular human insulin, without any significant reduction of the risk of severe hypoglycaemia.

Long-acting insulin analogues vs. NPH human insulin in type 1 diabetes. A meta-analysis.

AIM: Basal insulin in type 1 diabetes can be provided using either NPH (Neutral Protamine Hagedorn) human insulin or long-acting insulin analogues, which are supposed to warrant a better metabolic control with reduced hypoglycaemic risk. Aim of this meta-analysis is the assessment of differences with respect to HbA1c (Glycated hemoglobin), incidence of hypoglycaemia, and weight gain, between NPH human insulin and each long-acting analogue. METHODS: Of 285 randomized controlled trials with a duration > 12 weeks comparing long-acting insulin analogues (detemir or glargine) with NPH insulin in type 1 diabetic patients identified through Medline search and searches on www.clinicaltrials.gov, 20 met eligibility criteria (enrolling 3693 and 2485 in the long-acting analogues and NPH group respectively). Data on HbA1c and body mass index at endpoint, and incidence of any, nocturnal and severe hypoglycaemia, were extracted and meta-analysed. RESULTS: Long-acting analogues had a small, but significant effect on HbA1c [-0.07 (-0.13; -0.01)%; p = 0.026], in comparison with NPH human insulin. When analysing the effect of long-acting analogues on body weight, detemir was associated with a significantly smaller weight gain than human insulin [by 0.26 (0.06;0.47) kg/m2; p = 0.012]. Long-acting analogues were associated with a reduced risk for nocturnal and severe hypoglycaemia [OR (Odd Ratio, 95% Confidence Intervals) 0.69 (0.55; 0.86), and OR 0.73 (0.60; 0.89) respectively; all p < 0.01]. CONCLUSIONS: The switch from NPH to long-acting analogues as basal insulin replacement in type 1 diabetic patients had a small effect on HbA1c, and also reduced the risk of nocturnal and severe hypoglycaemia.

Prevention of cardiovascular disease through glycemic control in type 2 diabetes: a meta-analysis of randomized clinical trials.

BACKGROUND AND AIMS: Randomized clinical trials (RCTs) aimed at the assessment of the efficacy of lowering blood glucose in the prevention of diabetic complications have always failed to detect a significant effect on cardiovascular events. Aim of this meta-analysis is the assessment of the effects of improvement of glycemic control on the incidence of cardiovascular diseases in patients with type 2 diabetes. METHODS: The RCTs were included in this meta-analysis if: a) the between-group difference in mean HbA1c during the trial was at least 0.5%, b) they had a planned duration of treatment of at least 3 years, c) if they had a cardiovascular endpoint. Data for analysis were extracted independently by two observers and potential contrasts were resolved by a senior investigator. RESULTS: Five studies (17,267 and 15,362 patients in the intensive and conventional therapy groups, respectively) were included. Intensive treatment, which reduced mean HbA1c by 0.9% on average, was associated with a significant reduction of incident cardiovascular events and myocardial infarction (OR 0.89 [0.83-0.95] and 0.86 [0.78-0.93], respectively), but not of stroke or cardiovascular mortality (OR 0.93 [0.81-1.07] and 0.98 [0.77-1.23], respectively). In meta-regression analysis, a higher BMI duration of diabetes, and incidence of severe hypoglycaemia were associated with greater risk for cardiovascular death in intensive treatment groups. CONCLUSION: Intensified hypoglycaemic treatment in type 2 diabetic patients leads to a significant reduction of the incidence of myocardial infarction, while it does not affect the incidence of stroke and cardiovascular mortality. Hypoglycemia induced by intensified treatment could be associated with increased cardiovascular mortality.

The management of syncope in older adults.

Syncope is a frequent symptom in older patients. The diagnostic and therapeutic management may be complex, particularly in older adults with syncope and comorbidities or cognitive impairment. Morbidity related to syncope is more common in older persons and ranges from loss of confidence, depressive illness and fear of falling, to fractures and consequent institutionalization. Moreover, advan-ced age is associated with short and long-term morbidity and mortality after syncope. A standardized approach may obtain a definite diagnosis in more than 90% of the older patients with syncope and may reduce diagnostic tools and hospitalizations. The initial evaluation, including anamnesis, medical examination, orthostatic hypotension test and electrocardiogram (ECG), may be more difficult in the elderly, specially for the limited value of medical history, particularly for the certain diagnosis of neuro-mediated syncope. For this reason neuroautonomic assessment is an essential step to confirm a suspect of neuromediated syncope. Orthostatic blood pressure measurement, head up tilt test, carotid sinus massage and insertable cardiac monitor are safe and useful investigations, particularly in older patients. The most common causes of syncope in the older adults are orthostatic hypotension, carotid sinus hypersensitivity, neuromediated syncope and cardiac arrhythmias. The diagnostic evaluation and the treatment of cardiac syncope are similar in older and young patients and for this reason will not be discussed. In older patients unexplained falls could be related to syncope, particularly in patients with retrograde amnesia. There are no consistent differences in the treatment of syncope between older and younger population, but a specific approach is necessary for orthostatic hypotension, drug therapy and pacemaker implantation.

Pioglitazone and cardiovascular risk. A comprehensive meta-analysis of randomized clinical trials.

AIM: The aim of this meta-analysis of randomized clinical trials (RCT) was to assess whether pioglitazone is also associated with increased cardiovascular risk, as recently reported for rosiglitazone. METHODS: RCT of pioglitazone were retrieved from Medline (any date up to 31 August 2007; English language only). Unpublished RCT were identified through http://www.clinicaltrials.gov or http://www.fda.gov websites, and results on cardiovascular outcomes were retrieved from investigators and/or sponsors, whenever possible. RCT were included in meta-analysis if pioglitazone was compared with other treatments (placebo, active comparators or no treatment) for at least 4 weeks. Ninety-four trials, 10 of which were unpublished, were retrieved; those included in the analysis, which excluded PROspective PioglitAzone Clinical Trial In MacroVascular Events (PROACTIVE), enrolled 11 268 and 9912 patients in the pioglitazone and comparator groups respectively. Data for analysis, extracted independently by two observers, included all-cause and cardiovascular mortality and incidence of non-fatal coronary events and heart failure. Proportions of outcome measures across treatment groups were compared by odds ratios (ORs) and 95% confidence interval. RESULTS: Pioglitazone was associated with reduced all-cause mortality [OR 0.30 (0.14-0.63); p < 0.05], with no relevant effect on non-fatal coronary events. The observed increase in incidence of non-fatal heart failure was not statistically significant [OR 1.38 (0.90-2.12)]. CONCLUSION: The use of pioglitazone does not appear to be harmful in terms of cardiovascular events and all-cause deaths.

Treatment with insulin secretagogues and cancer-related mortality in type 2 diabetic patients a retrospective cohort study.

BACKGROUND: Recent evidence suggests that some hypoglycemic treatments could affect the incidence of malignancies. This study was aimed at the assessment of cancer-related mortality in type 2 diabetic patients treated with different hypoglycemic drugs. METHODS: A retrospective observational cohort study was performed on a consecutive series of 3002 type 2 diabetic outpatients. Cancer-related death was identified through the City Registry Office. For patients visited for the first time after January 1 (st), 2000, information on incidence of cancer was also available. RESULTS: During a mean follow-up of 4.3+/-2.5 years, 87 cases of cancer-related death were recorded, with a yearly incidence rate of 0.70%. Patients receiving secretagogues showed a significantly higher mortality than the rest of the sample (unadjusted OR [95%CI] 1.76 [1.15-2.69], p=0.009), which was maintained after adjustment for confounders (HR 2.29 [1.21-4.02], p=0.003). Conversely, no significant association of cancer-related mortality was observed with insulin sensitizers or exogenous insulin. In comparison with patients receiving no hypoglycemic treatment, those on secretagogue or insulin monotherapy showed a higher cancer-related mortality (HR 2.25 [1.10-4.78], p=0.034 and HR 2.11 [1.01-4.50], p=0.048, respectively). The effect of treatments on incidence of malignancies was similar to that observed on cancer-related death. CONCLUSIONS: Insulin secretagogues and, to a lesser extent, exogenous insulin, appear to be associated with increased mortality for cancer, even after adjustment for multiple confounders. This issue deserves further investigation through epidemiological studies on larger samples of patients.

Prognostic value of International Diabetes Federation and Adult Treatment Panel III definitions of metabolic syndrome in Type 2 diabetic patients: what makes the difference?

AIM: The International Diabetes Federation (IDF) proposed new diagnostic criteria for metabolic syndrome (MS), lowering glucose and waist thresholds, and rendering abdominal adiposity necessary for diagnosis. In Type 2 diabetic patients, IDF-defined MS has a lower prognostic value than Adult Treatment Panel III (ATP-III) criteria; this could depend either on lower thresholds for waist, or on the fact that adiposity was made necessary for diagnosis. METHODS: Information on 3-yr all-cause mortality of a consecutive series of 882 Caucasian Type 2 diabetic outpatients was obtained by the City of Florence Registry Office. Two different modifications of ATP-III criteria were tested: low waist threshold (LWT), with same threshold as IDF, but with abdominal adiposity not considered a necessary condition; and elevated waist as necessary condition (EWNC), with the older ATP-III threshold. RESULTS: Over the follow-up period, 115 (13.6%) deaths were recorded. A significantly higher mortality rate was observed in patients with LWT-, but not EWNC-defined MS, in comparison with the rest of the sample (14.2% vs 13.3%, p=0.705, and 14.7% vs 8.9%, p=0.050, for EWNC and LWT, respectively). Lowering the waist threshold did not reduce prognostic value in comparison with ATP-III definition of MS; conversely, when elevated waist circumference was considered a necessary condition for diagnosis, the predictive value for mortality decreased, irrespective of thresholds used. CONCLUSION: In Type 2 diabetic patients, modification of thresholds for waist circumference does not alter the prognostic value of MS. However, if abdominal adiposity is considered a necessary condition for diagnosis, the ability of MS to predict all-cause mortality is markedly reduced.