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Biomedical subjects

R Antonicelli

Publications and source records attributed to R Antonicelli.

At least 19 recordsLinked to original sources

Interleukin-6-174 G > C polymorphism affects the association between IL-6 plasma levels and insulin resistance in type 2 diabetic patients.

Interleukin-6 (IL-6), a powerful inflammatory mediator, plays a pivotal role in the pathogenesis of insulin resistance and type 2 diabetes. Recently, the IL-6 promoter polymorphism, at position -174 (G > C), has been associated to insulin sensitivity although contrasting data have been reported. The aim of this study was to evaluate the effect of the IL-6-174 G > C polymorphism on insulin resistance. In 238 type 2 diabetic patients without diabetic complications and in 255 control subjects, age and gender-matched, we evaluated the IL-6 -174 G > C genotype, the IL-6 plasma levels and the insulin resistance by the homeostasis model assessment (HOMA). The levels of IL-6 and HOMA were not genotype-dependent and were higher in diabetic patients (p < 0.01). Control subjects, both C+ (CG + CC genotypes) and C- (GG genotype) carriers, showed IL-6 plasma levels significantly related to BMI, fasting insulin and HOMA. The same relationships were found in C+ diabetic carriers. Differently, diabetic C- carriers did not show any relationship between IL-6 levels and all the evaluated variables. Interestingly, all the correlations were dependent on BMI. These findings highlight that IL-6-174 G > C polymorphism affects insulin resistance in type 2 diabetes, where C+ carriers have an insulin resistance "IL-6-sensitive", while C- carriers do not. The identification of two categories of diabetic patients may, therefore, lead to different therapeutic strategies in the management of insulin resistance.

Aged↗

The different apoptotic potential of the p53 codon 72 alleles increases with age and modulates in vivo ischaemia-induced cell death.

A common arginine to proline polymorphism is harboured at codon 72 of the human p53 gene. In this investigation, we found that fibroblasts and lymphocytes isolated from arginine allele homozygote centenarians and sexagenarians (Arg+) undergo an oxidative-stress-induced apoptosis at a higher extent than cells obtained from proline allele carriers (Pro+). At variance, the difference in apoptosis susceptibility between Arg+ and Pro+ is not significant when cells from 30-year-old people are studied. Further, we found that Arg+ and Pro+ cells from centenarians differ in the constitutive levels of p53 protein and p53/MDM2 complex, as well as in the levels of oxidative stress-induced p53/Bcl-xL complex and mitochondria-localised p53. Consistently, all these differences are less evident in cells from 30-year-old people. Finally, we investigated the in vivo functional relevance of the p53 codon 72 genotype in a group of old patients (66-99 years of age) affected by acute myocardial ischaemia, a clinical condition in which in vivo cell death occurs. We found that Arg+ patients show increased levels of Troponin I and CK-MB, two serum markers that correlate with the extent of the ischaemic damage in comparison to Pro+ patients. In conclusion, these data suggest that p53 codon 72 polymorphism contributes to a genetically determined variability in apoptotic susceptibility among old people, which has a potentially relevant role in the context of an age-related pathologic condition, such as myocardial ischaemia.

Adult↗

A gender--dependent genetic predisposition to produce high levels of IL-6 is detrimental for longevity.

Current literature indicates that elevated IL-6 serum levels are associated with diseases, disability and mortality in the elderly. In this paper, we studied the IL-6 promoter genetic variability at -174 C/G locus and its effect on IL-6 serum levels in a total of 700 people from 60 to 110 years of age, including 323 centenarians. We found that the proportion of homozygotes for the G allele at -174 locus decreases in centenarian males, but not in centenarian females. Moreover, we found that, only among males, homozygotes for the G allele at -174 locus have higher IL-6 serum levels in comparison with carriers of the C allele. On the whole, our data suggest that those individuals who are genetically predisposed to produce high levels of IL-6 during aging, i.e. -174 locus GG homozygous men, are disadvantaged for longevity.

Aged↗

Random fasting hyperglycemia as cardiovascular risk factor in the elderly: a 6-year longitudinal study.

A large body of evidence suggests that diabetes increases the risk of coronary heart disease (CHD), but whether fasting hyperglycemia is associated with a major risk for CHD is still under debate. The aim of the present study was to investigate the role played by fasting hyperglycemia in the development of cardiovascular disease (CVD) in an elderly population when associated with common risk factors for CVD (i.e., hypertension, hypercholesterolemia, smoking, etc). We analyzed a sample of 455 subjects aged > or = 60 years. The risk factors taken into account were systolic and diastolic blood pressure levels, use of antihypertensive drugs, total serum cholesterol, serum triglycerides, and smoking habit. Glycemia was measured at entry on a fasting sample. During the follow-up period (mean 6 years), the occurrence of CVD was monitored (criteria for the occurrence of CVD included total cardiovascular mortality, fatal or nonfatal myocardial infarction, symptomatic coronary heart disease [stable and unstable angina], the need for percutaneous transluminal coronary angioplasty or coronary artery bypass graft, fatal or nonfatal stroke, and transient ischemic attack). A total of 427 subjects completed the follow-up. During this period, 73 subjects (17.10%) developed CVD according to the above criteria. A Cox proportional hazard model was designed to evaluate the contribution of variables in predicting CVD. Relative risks and 95% confidence intervals for CVD were calculated from the regression coefficients to study the association between the risk of developing CVD and predicting variables. We found a relation between occurrence of CVD and fasting hyperglycemia: subjects with fasting glycemia, > 126 mg/dl at enrollment, but without previous clinical diagnosis of diabetes, showed a 2.01 times higher risk than those with fasting glycemia < 126 mg/dl. Hence, random fasting hyperglycemia can predict the occurrence of CVD in elderly subjects.

Age Factors↗

Relationship between lipoprotein(a) levels, oxidative stress, and blood pressure levels in patients with essential hypertension.

High plasma levels of lipoprotein(a) [Lp(a)] are considered a risk factor for the development of coronary artery disease. In vitro experiments have shown that oxidized Lp(a) is able to impair the arterial endothelium-dependent dilation, thus suggesting a possible role of Lp(a) in the genesis of essential hypertension. The aim of our work was to investigate the correlation of blood pressure levels with plasma Lp(a) concentration, apo(a) isoform size, and peroxidative stress in patients with essential hypertension. The study was performed in 54 untreated hypertensive patients whose blood pressure was monitored for 24 h by ambulatory blood pressure monitoring. Lp(a) concentration was measured by a double monoclonal antibody-based enzyme immunoassay demonstrated to be insensitive to apo(a) size heterogeneity. Apo(a) isoforms were determined by a high-resolution SDS-agarose gel electrophoresis followed by immunoblotting. A significant correlation was found between Lp(a) levels and the night-time systolic and diastolic pressures (r=0.32, P<0.05 and r=0.30, P<0.05, respectively), as well as with the mean night-time fall in systolic and diastolic blood pressures (r=-0.28, P<0.05 and r=-0.29, P<0.05, respectively). These relationships were further potentiated when peroxidative stress data were taken into consideration (r=0.37 and r=0.40, P<0.01 for the night-time systolic and diastolic pressures, respectively and r=-0.34 and r=-0.38, P<0.01 for the night-time fall in systolic and diastolic blood pressures, respectively). Apo(a) isoform size did not affect these relationships. Our data suggest that Lp(a) and peroxidative stress may be involved as cofactors in essential hypertension, with a mechanism that remains to be elucidated.

Adult↗

Cardiovascular effects of an earthquake: direct evidence by ambulatory blood pressure monitoring.

The increased cardiovascular mortality during an earthquake has been related, among other factors, to a sympathetically mediated increase in heart rate and blood pressure. However, this is supported only by indirect evidence collected after an earthquake, whereas for obvious technical difficulties, no data are available on the acute blood pressure and heart rate effects during an earthquake. In a patient undergoing 24-hour ambulatory blood pressure monitoring (Spacelabs 90207), we had the opportunity to directly record the acute blood pressure and heart rate changes induced by an earthquake (magnitude 4.7 according to the Richter scale) that struck central Italy in March 1998. Systolic blood pressure rose to 150 mm Hg, diastolic blood pressure rose to 122 mm Hg, and heart rate rose to 150 bpm at the time of the strongest tremor. Prequake blood pressure levels were restored only 1 hour later, but blood pressure remained characterized by a pronounced variability throughout the following 6 hours. Thus, a sympathetically mediated combined increase in blood pressure and heart rate may represent an important pathophysiological mechanism responsible for the increased frequency of cardiovascular events during an earthquake. The associated increase in blood pressure variability might further contribute to the increase in cardiovascular risk typical of this condition. Our case report further supports the usefulness of ambulatory blood pressure monitoring to assess the blood pressure and heart rate effects of sudden daily life events, the actual cardiovascular impact of which can hardly be quantified through traditional measurements.

Adult↗

[Acute pulmonary edema with pseudohypotension].

A 69-year-old male was admitted to our Coronary Care Unit because of increasing dyspnea in a non-Q wave myocardial infarction complicated by severe heart failure. Physical examination revealed dyspnea, cyanosis, sweat, bilateral crepitations on the whole chest and severe hypotension (blood pressure 80/40 mmHg on the left arm and 90/55 mmHg on the right arm). A coronarographic examination was performed as the patient's clinical status worsened despite an appropriate treatment of the hemodynamic impairment with vasoactive drugs. It showed no hemodynamically significant coronary stenosis and an elevated left ventricular systolic pressure (180/200 mmHg). An obstruction of the vascular district of both arms was diagnosed as the underlying cause of such relevant difference between the left ventricular and humeral blood pressures. A computed tomographic spiral scan of the chest confirmed the presence of a bilateral subclavian artery from the aortic arch and an atheromatous substenosis of the right subclavian artery. The subsequent evaluation of the blood pressure at the lower limbs showed values of systolic blood pressure > 220 mmHg, while the values at upper limbs were persistently < 90 mmHg. In conclusion, careful evaluation of the blood pressure at all four limbs is necessary in all patients with suspected peripheral vascular disease in which a single determination may be misleading.

Acute Disease↗

Randomized trial of the effects of low-dose calcium-heparin in patients with peripheral arterial disease and claudication. Italian CAP Study Group.

PURPOSE: We performed a long-term, multicenter, randomized, double-blind trial to evaluate the efficacy and tolerability of low-dose, subcutaneous calcium-heparin (12,500 IU/day) in comparison with placebo in patients with stable peripheral arterial disease of the lower extremities. PATIENTS AND METHODS: At the end of a 2-week washout period, during which aspirin placebo was given, 201 patients were randomly assigned to receive either subcutaneous calcium-heparin or placebo for two 3-month treatment periods, each of which was followed by a 6-month period of observation. All of the patients were given low-dose aspirin (50 mg/day) throughout the 18-month study. The main efficacy variables were pain-free and maximum walking time (by standard treadmill test). Patients answered a questionnaire about pain and the limitation of daily activities. Results were analyzed by intention-to-treat. RESULTS: At the end of the study, the estimated increase in pain-free walking time was 39% in the heparin group and 23% in the placebo group (P = 0.09). The estimated increase in maximum walking time was 40% in the heparin group and 16% in the placebo group (P = 0.05). Patients treated with heparin also reported that they had to stop walking because of leg pain, or had daily activities limited by leg pain, less frequently than the placebo group (P <0.01). CONCLUSIONS: Treatment with low-dose subcutaneous calcium-heparin is safe and effective in improving walking performance and reducing physical disability in patients with stable peripheral arterial disease and claudication.

Aged↗

A strong inverse relationship between PAI-1 and Lp(a) in hypertensive Type 2 diabetic patients.

Thrombophilia with a contemporary reduction of fibrinolytic activity has been observed both in diabetes mellitus and hypertension. Previously, we found a relationship between plasminogen activator inhibitor Type 1 (PAI-1) and lipoprotein(a) [Lp(a)] in Type 2 diabetes mellitus patients without complications. We hypothesised that this relationship could be due to a compensatory mechanism able to lower the risk of hypofibrinolysis as found in Type 2 diabetes mellitus. The present work was aimed at investigating the influence of concurrent hypertension and diabetes mellitus on the plasma levels of these two fibrinolytic inhibitors. In addition, other risk factors, known to influence the fibrinolytic parameters, were taken into account. Forty-nine Type 2 nonhypertensive diabetic patients without complications, 47 Type 2 hypertensive diabetic patients without complications, 54 non-diabetic hypertensive subjects without complications as well as 87 control subjects were studied. Plasma concentrations of Lp(a), PAI-1 antigen and activity, and the main parameters of oxidative, lipo- and glycometabolic balance were determined. Significant statistical differences between diabetic and non-diabetic subjects were found concerning triglycerides and antioxidant defence (p<0.01). Analysis of variance showed the F test statistically significant in evaluating the Log PAI-1/Lp(a) (p = 0.02). Correlation analysis between Log PAI-1 antigen and Lp(a) was significant in non-hypertensive diabetic patients, as expected (r = -0.38, p<0.01), and even stronger in hypertensive diabetic patients (r = -O.72,p<0.01). These results allow to hypothesise that the relationship between PAI-1/Lp(a) could be determinant in avoiding vascular complications due to diabetes mellitus and hypertension.

Aged↗

[Analysis of the DRG rate system in cardiology. Results of a comparative study of diverse regions].

Following the introduction of the reimbursement system for services, the use of a different rate system can have a singularly negative effect on the actual clinical activity. A discipline such as cardiology can be particularly exposed to the eventual variation in rates, and we feel it is necessary to introduce appropriate systems of analysis to deal with this problem. In the present study we carried out an analysis of the rate parameters adopted in Italy, by the Ministry and by two Regions: Lombardia and the Marche. The study took into account only the DRGs of cardiological diseases. We found that regional rates differed greatly according to the evaluation given to some diagnostic groups, inevitably determining the under valuation of the clinical complexity of some cases with the risk of a financial squeeze of certain structures. Variations in the composition of rate lists can also lead to distorted behaviour when selecting cases on condition of the quality of services given. The comparison of rates between the Marche and Lombardia regions showed a great difference in the number of subjects hospitalised for critical pathologies and stable ones, putting the wards in the Marche region in potential difficulty as their activity is aimed at more intensive and emergency therapy. The present study aims at underlining these problems, identifying the most evident inconsistencies and opening a debate on the subject.

Diagnosis-Related Groups↗

[Relationship between cholesterol levels and depression in the elderly].

The aim of our study is to evaluate the possible association between lower plasma cholesterol and depression in the elderly. 140 subjects over 65 years old of both sexes were enrolled, of which 60 were affected by depression (DSM-III-R and Hamilton test) and 80 composed a control group homogeneous for sex and age with the previous one. Plasma cholesterol, HLD-cholesterol (HDL-C), LDL-cholesterol (LDL-C) and triglycerides were measured. A statistically significant difference between cholesterol and LDL-C (p < 0.001) was noted in the total group, in both males and females. Such modifications were independent of sex. In the group with lower cholesterol (cut-off < = 160 mg/dl) a prevalence of depression three times greater than subjects with higher cholesterol was found. In conclusion, the authors recommended a prudent use of lipid-lowering medications in the elderly because of its uncertain benefits.

Aged↗

Blood pressure self-measurement in the elderly: differences between automatic and semi-automatic systems.

Arterial hypertension is the most common cardiovascular risk factor in the elderly. Its clinical control emphasises the problem of the systems used for monitoring: clinical measurement by the physician, home self-monitoring, ambulatory monitoring, etc. In particular, in the elderly population, the self-monitoring of blood pressure can present further problems associated with their situation. In our study we evaluated, in an elderly population, the differences in the self-recording of blood pressure with automatic and semi-automatic equipment using a mercury sphygmomanometer by a physician as a 'gold standard' control. We studied 28 elderly subjects using a rigid protocol for the self-measurement of their blood pressure. Our results show that automatic equipment is significantly more precise and easier to use than semiautomatic equipment in home self-measurement of blood pressure in elderly people.

Aged↗

Hemodynamic effects of cadralazine or chlorthalidone in verapamil-treated elderly hypertensives.

Fourteen hypertensives aged > 66-77 years, whose diastolic blood pressure (DBP) was > or = 95 mmHg at the end of 1-month treatment with verapamil 240 mg SR, took part in this clinical-hemodynamic study. Patients were randomized to add the long-acting hydralazine derivative, cadralazine, 10 mg once daily, or chlorthalidone 25 mg once daily for 1 month each, to their previous verapamil regimen, according to a double-blind crossover design. Echo-Doppler hemodynamics were performed before starting verapamil, 1 month after verapamil and then after each phase of the crossover study. A significant reduction in DBP both in supine and upright position was observed with both drugs, while the reduction in systolic blood pressure was not significant. Criteria for a satisfactory response were DBP < or = 90 mmHg or a DBP reduction > or = 10 mmHg; this goal was achieved in 9 patients with cadralazine, 9 patients with chlorthalidone, 5 patients with both. The hemodynamic study in responders showed that both cadralazine and chlorthalidone acted through a reduction of peripheral resistances without inducing reflex tachycardia. Thus, cadralazine and chlorthalidone represent a suitable second-step treatment in elderly hypertensives insufficiently controlled by verapamil monotherapy: both drugs act through a reduction in total peripheral resistance (TPR).

Aged↗

Arterial hypertension and cardiovascular damage in the elderly: focus on arterial stiffness and left ventricular hypertrophy.

Both aging and Arterial Hypertension (AH) cause a series of structural and functional changes in the cardiovascular apparatus. The reduction of aortic distensibility (RAD) and left ventricular hypertrophy (LVH) are, in particular, two significant markers of cardiovascular damage apart from being factors of serious and widespread morphological alterations. In this paper, the Authors analyze the effects of aging and of AH on the cardiovascular apparatus in order to find a possible clinical significance in relation to both RAD and LVH.

Aging↗

Camerano study on hypertension: the problem of blood pressure variability during medical visit.

The Camerano Study on Arterial Hypertension (AH) is a cross-sectional study, carried out on a wide population sample in a small town in Central Italy, and aimed at revealing the prevalence of certain characteristics of AH in the population examined. In particular, we studied some aspects of blood pressure (BP) levels during the medical visits. To evaluate the effects of the medical visit on BP levels, we divided the subjects into 3 groups: I) Hypertensive subjects, II) Treated hypertensive subjects, III) Normotensive subjects (control group). The Systolic Arterial Pressure (SAP) in normotensive subjects reached maximum levels during the first medical visit and then decreased in the following two controls (p < 0.001). The Diastolic Arterial Pressure (DAP) did not show any significant changes during the three measurements (p = n.s.). Instead the maximum level of SAP in the hypertensive group did not appear at the first measurement but only after 5 minutes and was seen to decrease towards the end of the visit (p < 0.001). Even DAP showed different levels compared to the normotensives: a decrease in BP levels was registered after 15 minutes respect to earlier measurements (p < 0.01). The levels of group II were similar to those of normotensive subjects.

Adult↗