Carmine Gazzaruso

Relationship Between Erectile Dysfunction and Silent Myocardial Ischemia in Apparently Uncomplicated Type 2 Diabetic Patients

Background—Erectile dysfunction (ED) is associated with coronary artery disease (CAD). In diabetic patients, CAD is often silent. Among diabetic patients with silent CAD, the prevalence of ED has never been evaluated. We investigated whether ED is associated with asymptomatic CAD in type 2 diabetic patients. Methods and Results—We evaluated the prevalence of ED in 133 uncomplicated diabetic men with angiographically verified silent CAD and in 127 diabetic men without myocardial ischemia at exercise ECG, 48-hour ambulatory ECG, and stress echocardiography. The groups were comparable for age and diabetes duration. Patients were screened for ED using the validated International Index of Erectile Function (IIEF-5) questionnaire. The prevalence of ED was significantly higher in patients with than in those without silent CAD (33.8% versus 4.7%; P =0.000). Multiple logistic regression analysis showed that ED, apolipoprotein(a) polymorphism, smoking, microalbuminuria, HDL, and LDL were significantly associated with silent CAD; among these risk factors, ED appeared to be the most efficient predictor of silent CAD (OR, 14.8; 95% CI, 3.8 to 56.9). Conclusions—Our study first shows a strong and independent association between ED and silent CAD in apparently uncomplicated type 2 diabetic patients. If our findings are confirmed, ED may become a potential marker to identify diabetic patients to screen for silent CAD. Moreover, the high prevalence of ED among diabetics with silent CAD suggests the need to perform an exercise ECG before starting a treatment for ED, especially in patients with additional cardiovascular risk factors.

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.

OBJECTIVES We 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. BACKGROUND Case-control studies showed that ED is associated with CAD in diabetic patients, but no prospective study is available. METHODS Type 2 diabetic men (n = 291) with silent CAD angiographically documented were recruited. Erectile dysfunction was assessed by the International Index Erectile Function-5 questionnaire. RESULTS During 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). CONCLUSIONS Our 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.

Nutritional Supplements with Oral Amino Acid Mixtures Increases Whole-Body Lean Mass and Insulin Sensitivity in Elderly Subjects with Sarcopenia

Decreases in whole-body lean mass can cause sarcopenia, a disease frequently found in the elderly. This condition is frequently associated with frailty and disability in aging as well as the onset and progression of several geriatric syndromes. Sarcopenia therefore must be managed with multidimensional approaches that include physical training, nutritional support, and metabolic and anabolic treatment. The purpose of our study was to assess the effect of an orally administered special mixture of amino acids (AAs) in elderly subjects with reduced lean body mass and sarcopenia. A randomized, open-label, crossover study was conducted in 41 elderly subjects (age range: 66-84 years) with sarcopenia, assigned to 2 distinct treatments (AAs and placebo). All subjects had normal body weight (body mass index within 19-23). The AA treatment consisted of 70.6 kcal/day (1 kcal = 4.2 kJ) of 8 g of essential AA snacks, given at 10:00 am and 5:00 pm. Lean mass was measured with dual-energy x-ray absorptiometry in leg, arm, and trunk tissues. Significant increases in whole-body lean mass in all areas were seen after 6 months and more consistently after 18 months of oral nutritional supplementation with AAs. Fasting blood glucose, serum insulin, and homeostatic model assessment of insulin resistance (an index of insulin resistance) significantly decreased during AA treatment. Furthermore, a significant reduction in serum tumor necrosis factor-alpha (TNF-alpha) and a significant increase in both insulin-like growth factor-1 (IGF-1) serum concentrations and in the IGF-1/TNF-alpha ratio were also found. No significant adverse effects were observed during AA treatment. These preliminary data indicate that nutritional supplements with the oral AA mixture significantly increased whole-body lean mass in elderly subjects with sarcopenia. The improvement in the amount of whole-body lean mass could be linked to increased insulin sensitivity and anabolic conditions related to IGF-1 availability.

Effect of the functional toll-like receptor 4 Asp299Gly polymorphism on susceptibility to late-onset Alzheimer's disease.

Experimental data have shown an upregulated expression of toll-like receptors, particularly toll-like receptor 4 (TLR4), in neurodegeneration. The Asp299Gly polymorphism of the TLR4 gene has been associated with an attenuated receptor signalling and a blunted inflammatory response. In the present study, we sought to determine whether this common genetic variant could influence susceptibility to late-onset Alzheimers disease (LOAD) in an Italian population sample. A cohort of 277 LOAD patients and 300 cognitively healthy controls were genotyped for the TLR4 Asp299Gly polymorphism using restriction isotyping. The frequency of the minor 299Gly allele was significantly higher in the controls than in the LOAD cases (7.2% versus 3.1%, respectively, P=0.003). Additionally, the frequency of the variant genotypes (Asp/Gly and Gly/Gly) was 13.0% in the controls and 5.4% in LOAD patients (P=0.002). After adjustment for age, gender, and the APOE varepsilon4 carrier status, the odds ratio for the development of LOAD associated with the Asp/Gly and Gly/Gly versus Asp/Asp genotype was 0.37 (95% CI: 0.20-0.69, P=0.002). Our data further support a role for innate immunity in neurodegeneration and give the first evidence that the TLR4 Asp299Gly variant may be protective toward the development of LOAD.

Diabetes in Cushing syndrome: basic and clinical aspects.

Diabetes mellitus is a frequent complication of Cushing syndrome (CS) which is caused by chronic exposure to glucocorticoid excess, either endogenous or exogenous, and that is characterized by several clinical symptoms such as central obesity, purple striae, proximal muscle weakness, acne, hirsutism and neuropsychological disturbances. Diabetes occurs as a consequence of an insulin-resistant state together with impaired insulin secretion which are induced by glucocorticoid excess. The management of patients with CS and diabetes mellitus includes the treatment of hyperglycemia and, when possible, the correction of glucocorticoid excess. This review focuses on the disorders of glucose metabolism in patients exposed to glucocorticoid excess, addressing both the pathophysiological aspects and the clinical and therapeutic implications.

Cardiovascular risk in adult patients with growth hormone (GH) deficiency and following substitution with GH--an update.

CONTEXT GH deficiency (GHD) of the adult is a clinical condition characterized by the presence of several traditional and emerging cardiovascular risk factors that can significantly increase cardiovascular morbidity and mortality. It is still an open issue whether GH replacement is able not only to improve cardiovascular risk factors but also to decrease cardiovascular morbidity and mortality. EVIDENCE ACQUISITION The major source of data acquisition included PubMed research strategies. Original articles, systematic reviews and meta-analyses, and included relevant citations were screened. EVIDENCE SYNTHESIS In untreated GHD, cardiovascular risk is increased due to abnormal lipid profile (increased total and low-density lipoprotein cholesterol, increased triglycerides, and reduced high-density lipoprotein cholesterol) and impaired glucose metabolism. Emerging cardiovascular risk factors/markers such as proinflammatory cytokines, C-reactive protein, and adipokines are also increased in GHD patients. Increased cardiovascular morbidity and mortality have also been reported in GHD. GH treatment has been shown to improve both traditional and emerging cardiovascular risk factors and markers. However, evidence on the effects of GH replacement on cardiovascular events and mortality is limited. CONCLUSION The GHD population may be considered at high cardiovascular risk, and GH substitution may be expected to bring an added value to patients with hypopituitarism in terms of cardiovascular protection. However, there is too limited evidence (rarely coming from randomized and controlled studies) to recommend GH treatment based on the cardiovascular status of the patients.

Association between Apolipoprotein(a) phenotypes and coronary heart disease at a young age

OBJECTIVES The purpose of this study was to investigate lipoprotein(a) [Lp(a)] levels and apolipoprotein(a) [apo(a)] phenotypes in relation to age of onset of coronary heart disease (CHD). BACKGROUND Although Lp(a) levels have been extensively analyzed in relation to age of CHD, apo(a) phenotypes have not. METHODS Three hundred and thirty-five consecutive CHD patients were enrolled and grouped according to their age of CHD onset (<45 years; 45 to 54 years; > or = 55 years). RESULTS In each patient group Lp(a) levels were higher than in an age-matched control group, but among the patient groups no differences in Lp(a) levels were observed. Apolipoprotein(a) phenotype distributions showed significant differences between patients and age-matched control subjects. Among the patient groups the difference in percentage of subjects with two apo(a) isoforms of low molecular weight (MW) was highly significant (p < 0.001). Multivariate analysis showed that apo(a) phenotypes were the best predictors of early CHD (p < 0.000001). The age-specific odds ratios (ORs) of the presence of at least one apo(a) isoform of low MW for CHD declined with age; in particular apo(a) phenotypes had their highest predictive value in younger persons (OR: 14.62). The OR for the presence of two isoforms of low MW/presence of only isoforms of high MW was 40.88 in the younger age group, 27.17 in age group of 45 to 54 years and 15.83 in the older age group. CONCLUSIONS The present article reports the first evidence of a strong independent association of apo(a) phenotypes with the age of onset of CHD. Thus, if our data are confirmed by larger studies, apo(a) phenotypes might be used together with Lp(a) levels as powerful genetic markers in assessing the actual risk of developing CHD at a young age.

Improvement of Blood Glucose Control and Insulin Sensitivity During a Long-Term (60 Weeks) Randomized Study with Amino Acid Dietary Supplements in Elderly Subjects with Type 2 Diabetes Mellitus

A decrease in lean muscular mass causes sarcopenia, a disease frequently found in the elderly population. The reduction of muscle mass may be responsible for reduced insulin sensitivity and decreased glucose uptake, thus increasing the risk for hyperglycemia and insulin-resistance syndrome in elderly subjects with type 2 diabetes mellitus. We therefore wanted to determine the effect of a special mixture of oral amino acids (AAs) on elderly subjects with type 2 diabetes. A randomized, open-label, crossover study was conducted in 34 subjects with diabetes (age range, 65-85 years) assigned to 2 distinct treatments (AAs and placebo). In spite of treatment with oral hypoglycemic drugs or insulin, all subjects were in poor metabolic control (glycated hemoglobin [HbA(1c)] >7%). The subjects studied had normal body weight (ie, body mass index within 19-23). AAs consisted of 70.6 kcal/day (1 kcal = 4.2 kJ) of 8 g of AA snacks, given at 10.00 am and 5.00 pm. Fasting and postprandial (1 hour and 2 hours) blood glucose, serum insulin, and homeostatic model assessment of insulin resistance (an index of insulin resistance) significantly decreased during AA treatment. Furthermore, a significant reduction of HbA(1c) levels was found throughout the study. No significant adverse effects were observed during the active treatment. We suggest that nutritional supplementation with a special mixture of oral AAs is safe and significantly improves metabolic control and insulin sensitivity in poorly controlled elderly subjects with type 2 diabetes. This effect was consistent during the long-term observation period of 60 weeks and was also present after the crossover from AAs to placebo.

Relation between serum uric acid and carotid intima-media thickness in healthy postmenopausal women

Objective:Serum uric acid (SUA) is associated with cardiovascular disease (CVD). However it is still disputed whether the relationship is mediated by other risk factors such as obesity, dyslipidaemia, hypertension and insulin resistance. We explored the association of the uric acid level with carotid intima-media thickness (IMT), a well known marker of CVD, in postmenopausal healthy women.Methods:We consecutively enrolled postmenopausal women undergoing a screening for health evaluation. After an accurate clinical examination, and a biochemical evaluation, the enrolled subjects underwent B mode ultrasonography to assess common carotid intima media thickness.Results:Among 234 women aged 45–70 years, the uric acid level is associated with carotid IMT independently of other prognostic factors (p=0.03). In particular, women in the highest tertiles of uric acid level have a greater IMT than women in the lowest tertile (p=0.007).Conclusions:Independently of other cardiovascular risk factors, SUA levels are associated with carotid IMT even in subjects without the metabolic syndrome. This confirms and expands the role of uric acid in the determinism of CVD. Prospective trials would be useful to evaluate interventions aimed at lowering the uric acid level.

Weight loss after Swedish Adjustable Gastric Banding: relationships to insulin resistance and metabolic syndrome.

Background:The metabolic syndrome is a cluster of cardiovascular risk factors (central obesity, hypertension,dyslipidemia, disturbance in glucose metabolism) associated with insulin-resistance. The cluster of risk factors defining the metabolic syndrome increases cardiovascular risk more than each single component. The aim of the present longitudinal study was to evaluate the relationship between weight loss and changes in insulin-resistance and in the prevalence of the metabolic syndrome 1-year after SAGB implantation. Methods: 51 premenopausal severely obese women (mean age 35.2±8.8 years, BMI 43.3±6.9) were enrolled. As a control group, 51 premenopausal nonobese women (BMI<30) were enrolled. All obese subjects underwent successful implantation of the SAGB via videolaparoscopy. In all subjects insulinresistance was estimated by HOMA index and metabolic syndrome was defined according to the criteria of the European Group for the Study of Insulin Resistance. Results: HOMA (4.2±2.0 vs 1.9±0.8, P<0.001) and the prevalence of the metabolic syndrome (58.8% vs 7.8%, P<0.001) were significantly higher in obese than non-obese women. 1 year after SAGB, BMI significantly decreased from 43.3±6.9 to 34.5±7.4 (P<0.001). HOMA index showed a significant dramatic breakdown (4.2±2.0 vs 2.4±1.0, P<0.001). The prevalence of the metabolic syndrome declined significantly (58.8% vs 21.6%, P<0.001). Conclusion: Our study shows that in severely obese women, insulin-resistance and the prevalence of the metabolic syndrome significantly decrease 1 year after SAGB. Our findings indicate that SAGB could be a useful tool to reduce the global cardiovascular risk in severely obese people and to improve their long-term prognosis.