Need for integration of hepatitis C (HCV) services in community-based settings for people who inject drugs: results from a global values and preferences survey.

BACKGROUND: To inform the development of updated World Health Organization (WHO) guidelines on simplified service delivery for HCV infection, a global survey was undertaken among people affected or infected by HCV. The objective of this analysis is to identify specific needs and preferences among people who inject drugs. METHODS: A multi-country, anonymous, self-administered online survey conducted in 2021 was developed by Coalition PLUS and the World Hepatitis Alliance in partnership with the WHO. Preferences for test and treat locations and simplifying HCV care were collected among people affected or infected by HCV. Chi-square tests were used to compare respondents who identified with current or former injection drug users through identification with key population to other respondents who did not identify with this key population. RESULTS: Among 202 respondents, 62 (30.7%) identified with current/former injection drug users. Compared to other respondents, they were: older [median (IQR): 48 (36-57) vs. 39 (31-51) years, p = 0.003]; more likely to have been tested for HCV (90.2% vs. 64.3%, p = 0.001); more likely to prefer testing in a community-based centre (CBC) (55.4% vs. 33.3%, p = 0.005); or in a support centres for people who use drugs (SCPUD)(50.0% vs. 9.8%, p < 0.001). The most important considerations regarding testing locations among people identified with current/former injection drug users (compared to the other respondents) were: non-judgemental atmosphere (p < 0.001), anonymity (p = 0.018) and community worker (CW) presence (p < 0.001). People identified with current/former injection drug users were more likely to prefer to receive HCV treatment in a CBC (63.0% vs. 44.8%, p = 0.028) or in a SCPUD (46.3% vs. 9.5%, p < 0.001), compared to the other respondents. The most important considerations regarding treatment locations among people identified with current/former injection drug users were the non-stigmatising/non-judgemental approach at the site (p < 0.001) and the presence of community-friendly medical personnel or CW (p = 0.016 and 0.002), compared to the other respondents. CONCLUSION: The preferences of people identified with current/former injection drug users indicated specific needs concerning HCV services. Integration of HCV services in community-based risk reduction centres may be an important element in the development of adapted services to increase uptake and retention in HCV care among this population.

Modelling the impacts of pests and diseases on agricultural systems.

The improvement and application of pest and disease models to analyse and predict yield losses including those due to climate change is still a challenge for the scientific community. Applied modelling of crop diseases and pests has mostly targeted the development of support capabilities to schedule scouting or pesticide applications. There is a need for research to both broaden the scope and evaluate the capabilities of pest and disease models. Key research questions not only involve the assessment of the potential effects of climate change on known pathosystems, but also on new pathogens which could alter the (still incompletely documented) impacts of pests and diseases on agricultural systems. Yield loss data collected in various current environments may no longer represent a adequate reference to develop tactical, decision-oriented, models for plant diseases and pests and their impacts, because of the ongoing changes in climate patterns. Process-based agricultural simulation modelling, on the other hand, appears to represent a viable methodology to estimate the impacts of these potential effects. A new generation of tools based on state-of-the-art knowledge and technologies is needed to allow systems analysis including key processes and their dynamics over appropriate suitable range of environmental variables. This paper offers a brief overview of the current state of development in coupling pest and disease models to crop models, and discusses technical and scientific challenges. We propose a five-stage roadmap to improve the simulation of the impacts caused by plant diseases and pests; i) improve the quality and availability of data for model inputs; ii) improve the quality and availability of data for model evaluation; iii) improve the integration with crop models; iv) improve the processes for model evaluation; and v) develop a community of plant pest and disease modelers.

Modelling soil borne fungal pathogens of arable crops under climate change.

Soil-borne fungal plant pathogens, agents of crown and root rot, are seldom considered in studies on climate change and agriculture due both to the complexity of the soil system and to the incomplete knowledge of their response to environmental drivers. A controlled chamber set of experiments was carried out to quantify the response of six soil-borne fungi to temperature, and a species-generic model to simulate their response was developed. The model was linked to a soil temperature model inclusive of components able to simulate soil water content also as resulting from crop water uptake. Pathogen relative growth was simulated over Europe using the IPCC A1B emission scenario derived from the Hadley-CM3 global climate model. Climate scenarios of soil temperature in 2020 and 2030 were compared to the baseline centred in the year 2000. The general trend of the response of soil-borne pathogens shows increasing growth in the coldest areas of Europe; however, a larger rate of increase is shown from 2020 to 2030 compared to that of 2000 to 2020. Projections of pathogens of winter cereals indicate a marked increase of growth rate in the soils of northern European and Baltic states. Fungal pathogens of spring sowing crops show unchanged conditions for their growth in soils of the Mediterranean countries, whereas an increase of suitable conditions was estimated for the areals of central Europe which represent the coldest limit areas where the host crops are currently grown. Differences across fungal species are shown, indicating that crop-specific analyses should be ran.

Metabolically healthy polycystic ovary syndrome (MH-PCOS) and metabolically unhealthy polycystic ovary syndrome (MU-PCOS): a comparative analysis of four simple methods useful for metabolic assessment.

STUDY QUESTION: Is it possible to distinguish metabolically healthy polycystic ovary syndrome (MH-PCOS) from metabolically unhealthy PCOS (MU-PCOS) by simple diagnostic tools such as body mass index (BMI), waist/hip ratio (WHR), at-risk category suggested by Androgen Excess Society (AES) and visceral adiposity index (VAI)? SUMMARY ANSWER: VAI could be an easy and useful tool in clinical practice and in population studies for assessment of MU-PCOS. WHAT IS KNOWN ALREADY: VAI is a good indicator of insulin sensitivity and cardiometabolic risk in oligo-ovulatory women with PCOS. STUDY DESIGN, SIZE, DURATION: We conducted a cross-sectional study of 232 women with PCOS in a university hospital setting. PARTICIPANTS/MATERIALS, SETTING, METHODS: Anthropometric, hormonal and metabolic parameters were evaluated. An oral glucose tolerance test measured areas under the curve (AUC) for insulin (AUC 2h insulin) and for glucose (AUC 2h glucose). Homeostasis model assessment of insulin resistance (HOMA2-IR), the Matsuda index of insulin sensitivity (ISI), the oral dispositional index (DIo) and VAI were determined. MAIN RESULTS AND THE ROLE OF CHANCE: The prevalence of MU-PCOS according to the different criteria was: BMI, 56.0%; WHR, 18.1%; at-risk criteria of AES, 72.0% and VAI, 34.5%. The likelihood that a woman would exhibit MU-PCOS (except when diagnosed by the WHR criterion) showed a significant positive association with high HOMA2-IR [BMI criterion: (odds ratio (OR): 1.86; 95% confidence interval (CI): 1.43-2.41); risk criteria of AES (OR: 1.86; 95% CI: 1.36-2.56); VAI criterion (OR: 1.45; 95% CI: 1.17-1.80)] and a significant negative association with low ISI Matsuda [BMI criterion: (OR: 0.81; 95% CI: 0.72-0.91); risk criteria of AES (OR: 0.78; 95% CI: 0.69-0.89); VAI criterion (OR: 0.82; 95% CI: 0.71-0.94)]. Only MU-PCOS according to the VAI criterion showed a significant association with low DIo (OR: 0.85; 95% CI: 0.75-0.96); these women also showed a significant association with low luteal progesterone levels (OR: 0.97; 95% CI: 0.95-0.99). LIMITATIONS, REASONS FOR CAUTION: The analysis is limited by the lack of a gold standard definition of metabolic health that would have allowed the execution of a receiver operator characteristic analysis of the four proposed criteria. WIDER IMPLICATIONS OF THE FINDINGS: The results will facilitate the early recognition of cardiometabolic risk in women with PCOS before they develop overt metabolic syndrome.

Acute effects of coffee on endothelial function in healthy subjects.

BACKGROUND/OBJECTIVES: Coffee is the most widely consumed beverage in the world, but its effect on the cardiovascular system has not been fully understood. Coffee contains caffeine and antioxidants, which may influence endothelial function, both of which have not yet been investigated. The objective of this study was to investigate the acute effects of coffee on endothelial function measured by brachial artery flow-mediated dilation (FMD). SUBJECTS/METHODS: A total of 20 (10 males and 10 females) healthy non-obese subjects underwent a double-blind, crossover study. Subjects ingested one cup of caffeinated (CC) and one cup of decaffeinated (DC) Italian espresso coffee in random order at 5- to 7-day intervals. RESULTS: Following CC ingestion, FMD decreased progressively and significantly (mean+/-s.e.m.: 0 min, 7.7+/-0.6; 30 min, 6.3+/-0.7; 60 min, 6.0+/-0.8%; ANOVA (analysis of variance), P<0.05), but it did not significantly increase after DC ingestion (0 min, 6.9+/-0.6; 30 min, 8.1+/-0.9; 60 min, 8.5+/-0.9%; P=0.115). Similarly, CC significantly increased both systolic and diastolic blood pressure; this effect was not observed after DC ingestion. Blood glucose concentrations remained unchanged after ingestion of both CC and DC, but insulin (0 min, 15.8+/-0.9; 60 min, 15.0+/-0.8 muU/ml; P<0.05) and C-peptide (0 min, 1.25+/-0.09; 60 min, 1.18+/-0.09 ng/ml; P<0.01) blood concentrations decreased significantly only after CC ingestion. CONCLUSIONS: CC acutely induced unfavorable cardiovascular effects, especially on endothelial function. In the fasting state, insulin secretion is also likely reduced after CC ingestion. Future studies will determine whether CC has detrimental clinically relevant effects, especially in unhealthy subjects.

A low reported energy intake is associated with metabolic syndrome.

BACKGROUND AND AIMS: Metabolic syndrome (MS) may be associated with the presence of an energy-sparing metabolism that predisposes to the excess accumulation of body fat. This study examined the relationship between reported energy intake and obesity in individuals with and without MS. METHODS AND RESULTS: Ninety consecutive non-diabetic obese subjects were divided into 2 groups based on the presence (MS+: no.=50) or absence (MS-: no.=40) of MS. The study design was cross-sectional. The 3-day food record method was used to assess the subjects' usual energy intake and the Diet Readiness Test (DRT) was also administered. Compared to the MS- group, the MS+ group had a significantly higher body weight, body mass index (mean+/-SEM: 39.1+/-1.3 vs 31.5+/-0.9, p<0.001) and fat mass. The absolute energy intake of the MS+ group (8629+/-331 kJ/24h) did not differ from that of the MS- group (8571+/-515 kJ/24h; p=ns). The daily energy intake normalized for the fat-free mass (FFM) size was higher in the MS- group (163+/-8 kJ/kg-FFM x 24h) than in the MS+ group (138+/-4 kJ/kg-FFM x 24h; p<0.03). The DRT test results were similar in both groups except that section 6 (exercise patterns and attitudes) score was lower in the MS+ group (10.0+/-0.5) than in the MS- group (11.9+/-0.5; p<0.01). CONCLUSION: The results of this study support the hypothesis that subjects with MS have an energy-sparing metabolism.

Liver eosinophilic infiltrate is a significant finding in patients with chronic hepatitis C.

Eosinophilic infiltrate of liver tissue is described in primary cholestatic diseases, hepatic allograft rejection and drug-induced liver injury, but its significance and its implications in chronic hepatitis C are unknown. The aim of this study was to investigate the clinical significance of eosinophilic liver infiltrate in patients with chronic hepatitis C. We retrospectively evaluated 147 patients with chronic hepatitis C. The presence of eosinophilic infiltrate was investigated in liver biopsies, and a numeric count of eosinophilic leucocytes in every portal tract was assessed. An eosinophilic infiltrate of liver tissue (> or =3 cells evaluated in the portal / periportal spaces) was observed in 46 patients (31%), and patients who consumed drugs had an odds ratio (OR) of 4.02 (95% CI: 1.62-9.96) to have an eosinophilic infiltrate in liver biopsy. By logistic regression analysis, the presence of steatosis was independently associated with eosinophilic infiltrate (OR 5.86; 95% CI: 2.46-13.96) and homeostasis model assessment-score (OR 1.18; 95% CI: 1.00-1.39). Logistic regression analysis also showed that fibrosis staging > or = 2 by Scheuer score was associated with grading >1 by Scheuer score (OR 6.82; 95% CI 2.46-18.80) and eosinophilic infiltrate (OR 4.00; 95% CI 1.23-12.91). In conclusion, we observed that the eosinophilic infiltrate of liver tissue was significantly more frequent in patients who assumed drugs, and found a significant association between eosinophilic infiltrate, liver steatosis and liver fibrosis. These preliminary data could lead to a constant assumption of drugs as a co-factor of eosinophils-mediated liver injury in chronic hepatitis C.

Effect of dual blockade of renin-angiotensin system on TGFbeta1 and left ventricular structure and function in hypertensive patients.

The effects of 24 weeks losartan and ramipril treatment, both alone and in combination, on left ventricular mass (LVM), circulating transforming growth factor beta1 (TGFbeta1), procollagen type I (PIP) and III (PIIIP), have been evaluated in hypertensive (HT) patients. A total of 57 HT with stage 1 and 2 essential hypertension were included. After 4 weeks run in, a randomized double-blind, three arms, double dummy, independent trial was used. All HT patients were randomly allocated to three treatment arms consisting of losartan (50 mg/daily), ramipril (5 mg/ daily) and combined (losartan 50 mg/daily + ramipril 5 mg/daily) for 24 weeks. TGFbeta1, PIP and PIIIP, LVM, LVM/h(2.7) and other echocardiographic measurements, blood urea nitrogen, creatinine and clearance and potassium were determined after run in and after 24 weeks. All groups were comparable for gender, age, body mass index, blood pressure and LVM. The prevalence of baseline left ventricular hypertrophy (LVH) was not significantly different among three groups. At the end of treatment, a significant (P<0.05) reduction in systolic blood pressure (SBP), diastolic blood pressure (DBP), mean blood pressure (MBP), TGFbeta1, PIP, PIIIP, LVM and LVM/h(2.7) was observed in all groups. The absolute and percent reduction in TGFbeta1 and LVM/h(2.7) were significantly higher in combined than losartan or ramipril groups and also in HT patients with LVH. No significant change in absolute and percent reduction of SBP, DBP and MBP were found. Our data indicate an additional cardioprotective effect of dual blockade of renin-angiotensin in HT patients.

Craniofacial and body growth: a cross-sectional anthropometric pilot study on children during prepubertal period.

AIM: This was to compare craniofacial and body growth during prepubertal period using direct medical anthropometry for body and craniofacial measurements. METHODS: The sample consisted of 100 patients (48 males, 52 females), aged between 7 and 12 years. Thirty craniofacial and body measurements of height, width, length and circumference were made on each subject. STATISTICAL ANALYSIS: Comparisons were made of averages, percentages and standard deviations, for three growth patterns during prepubertal period: cranial, facial and body growth pattern. Linear correlation coefficients (r) were calculated to evaluate the intensity of the interdependence between variables, using BMDP Dynamic software. RESULTS: Skull and face measurements increased less than body dimensions, but those for the face increased more than for skull, which was valid both for males and females. Differences between males and females were determined for standing height, mandibular height (T-Go) and lower facial height (Sto-Gn). CONCLUSIONS: No body parameter was found to be a good indicator of craniofacial growth during this period. The jaw was found to be the facial area that showed the higher development.

Cardiac changes in subclinical and overt hyperthyroid women: retrospective study.

BACKGROUND: This retrospective and descriptive 4-year study was undertaken to describe cardiac changes in subclinical and overt hyperthyroidism. METHODS: We revised the charts of 386 consecutive cardiopathic women whose blood samples were referred to the Radioimmunoassay Laboratory to evaluate thyroid function from 1 January 1997 through 31 December 2000. RESULTS: After excluding women because euthyroid or hypothyroid, or taking amiodarone and women with hypertension, rheumatic disease, myocardial infarction, a total of 31 hyperthyroid women were thus selected for the study: 19 with subclinical hyperthyroidism and 12 with overt hyperthyroidism. The prevalence of atrial fibrillation did not differ between subclinical (48%) and overt (67%) hyperthyroid women, as well as left atrial dimension; the latter was larger in hyperthyroid (27.8+/-7.8 cm(2)/m(2)) than in control women (18.9+/-2.8 cm(2)/m(2)) (P<0.001). In the subclinical and overt hyperthyroidism, the heart rate (HR) was increased and left ventricular end diastolic (LVED) volume was reduced; in addition, only in overt hyperthyroidism, left ventricular (LV) mass was increased. A significant correlation between LV mass and free triiodothyronine was found. CONCLUSION: HR increase and LVED decrease, both in subclinical and overt hyperthyroidism, indicate a global impairment of diastolic heart performance, complicated in overt hyperthyroidism by LV concentric hypertrophy. So, in our opinion, subclinical hyperthyroidism, far from being considered a simple laboratory finding, in clinical practice should be taken into serious consideration.

Effect of aging and hypertension on beta-myosin heavy chain in heart of spontaneously hypertensive rats.

During aging rat myocardium undergoes structural changes characterized by a shift in the synthesis of myosin heavy chain (MHC) from V1 isoform, composed of two alpha-MHC, to V3 isoform, composed of two beta-MHC. In rat, besides ageing, cardiac hypertrophy as adaptive response to a superimposed pressure load (such as hypertension) is characterized by predominance of V3 myosin isoform. The aim of our study was to evaluate the expression of beta-MHC in right (RV) and left (LV) ventricles of spontaneously hypertensive rats (SHRs), a well defined animal model of hypertension, in relation to aging. We used very young (8-week old) and young (15-week old) SHRs and age-matched normotensive Harlan Sprague-Dawley control rats. By Western analysis, we found that beta-MHC is already present in both RV and LV of 8-week old SHRs, and is markedly predominant in RV and LV of 15-week old SHRs, when compared with age-matched control rats. Our study showed that the shift to V3 myosin isoform in SHRs is an early event, resembling accelerated senescence. We have also demonstrated that beta-MHC is actively synthesized also in young (15-week old) normal rats.

Expression of thyroid hormone receptor isoforms in the hypertrophic heart of spontaneously hypertensive rats.

Thyroid hormones (THs) enhance MHC alpha gene- and repress MHC beta gene-transcription in the heart, by interacting with specific nuclear receptors (TRs), that bind to regulatory sequences localized upstream of basal promoter of myosin heavy chain (MHC) genes. The overall effects of THs include an increase in V1- and a decrease in V3-myosin isozyme concentration in the heart. Myosin V1 contains two MHC alpha chains and has a higher ATPase activity than V3 isoform, which contains two beta chains. Previous studies on papillary muscles of spontaneously hypertensive rats (SHRs) showed that heart hypertrophy is accompanied by a shift from alpha to beta MHC accumulation. The present study was aimed at evaluating whether this event relates to differential expression of alpha1, alpha2, and beta1 isoforms of TRs. At the ages of 8 and 15 weeks, SHRs and Harlan Sprague-Dawley control rats were sacrificed under anesthesia and their hearts were dissected into left and right ventricles, free of atria and great vessels. The results of Western blot analyses showed that the levels of the three TR isoforms do not differ significantly between SHRs and control rats of the same age, either in the left or in the right ventricle. Thus, the expression of MHC beta in SHR hypertrophic heart does not seem to depend on changes in TR isoform concentrations.

Toxic adenoma and papillary thyroid carcinoma in a patient with Graves' disease.

A case of a very rare association of toxic adenoma and papillary carcinoma with Graves' disease is presented. A 34-year-old woman developed Graves' disease with mild ophthalmopathy. An ultrasound revealed diffuse thyroid enlargement with a hypoechoic pattern and a hypoechoic nodule with regular edges of 1.6 cm in diameter at the lower pole of the left lobe. A thyroid 131I scintiscan showed a diffuse and homogeneous 131I distribution. The 131I uptake (RAIU) was elevated. One year later, while still on a low dose of methimazole, the patient had a recurrence of hyperthyroidism following an iodine load from a contrast agent. A further thyroid ultrasound confirmed the previously described pattern but showed a new hypoechoic nodule of 1.1 cm with irregular edges in the left lobe. A thyroid 131I scintiscan this time demonstrated a hyperactive area localised in the larger nodule and a lower diffuse uptake of the remaining tissue. Because of the worsening of the symptoms of hyperthyroidism, the patient had a left lobectomy. On histological examination, the larger nodule was well encapsulated and showed the characteristics of a hyperfunctioning follicular adenoma. The smaller nodule was a typically unencapsulated papillary carcinoma. Several other microfoci of papillary carcinoma were also found in the adjacent tissue. Completion of thyroidectomy was therefore performed, followed by 131I ablative therapy and thyroxine suppressive treatment. This observation suggests that the chronic abnormal stimulation of the thyroid gland by the thyroid-stimulating antibody (TSAb) may facilitate the neoplastic transformation of the thyrocytes in individuals with a critical genetic background.

[Atrial fibrillation and hyperthyroidism. The results of a retrospective study]. / Fibrillazione atriale ed ipertiroidismo. Risultati di uno studio retrospettivo.

BACKGROUND: To examine the prevalence of atrial fibrillation (AF) in cardiopathic patients with hyperthyroidism. METHODS: The data concerning the patients had been derived from registers of the Laboratory of Radioimmunoassay where cardiopathic patients' blood samples were referred from the Cardiology Unit to evaluate thyroid function, consecutively from January 1992 to December 1997. Of the 443 patients, 303 (68.4%) were classified as being euthyroid, 23 (5.2%) hypothyroid, 117 (26.4%) hyperthyroid. Thyroid function was diagnosed clinically and confirmed by serum TSH and free thyroid hormone (FT3, FT4), levels. RESULTS: Among hyperthyroid patients, the more frequent arrhythmia was AF (54.7%). After excluding from the study those hyperthyroid patients with rheumatic disease, hypertension, myocardial infarction, 37 hyperthyroid patients were selected; 18 (48.6%), (mean age 63.4 +/- 10.8 yrs), showed sinus rhythm and 19 (51.4%), (mean age 66.0 +/- 12.1 yrs), showed AF. FT3 and FT4 were higher in patients with AF than in those without AF, whereas TSH was not significantly different between the groups. Left ventricular (LV) mass index was significantly increased in hyperthyroid women with AF compared with hyperthyroid women without AF (109.80 +/- 22.33 g/m2 vs 84.50 +/- 6.20 g/m2; p < 0.005). A significant correlation was found between FT3 levels and LV mass index in the hyperthyroid women with and without AF (r = 0.77; p < 0.001). CONCLUSIONS: In this study the prevalence of AF is 51.4% in hyperthyroid patients. FT3 is higher in patients with AF than in those without AF. Finally, the correlation between FT3 and LV mass index suggests that cardiac hypertrophy is associated with thyroid hyperfunction.

Plasma endothelin-1 levels in patients with angina pectoris and normal coronary angiograms.

BACKGROUND: Some patients with typical angina and electrocardiographic evidence of ischemia have normal coronary angiograms. These patients have a reduced coronary flow reserve and abnormal endothelium-dependent vasodilator responses; this syndrome is known as microvascular angina. Among endothelium-derived peptides, endothelin-1 (ET-1) is a potent vasoconstrictor and an important modulator of microvascular function. METHODS: Plasma ET-1 was measured in 13 patients with typical angina, instrumental evidence of ischemia, and normal arteriograms and in 20 normal control subjects. RESULTS: Mean concentration of ET-1 was 2.89+/-1.24 pmol/L in patients with angina and normal angiograms and 1.99+/-0.81 pmol/L in normal control subjects (p < 0.02). Plasma levels of ET-1 values were significantly higher in patients with angina, positive exercise test results for ischemia, and normal coronary arteriograms compared with the group of patients with no clinical or instrumental evidence of ischemia. CONCLUSIONS: This is consistent with the hypothesis that in patients with microvascular angina, an endothelial dysfunction in the coronary vascular area caused by impaired endothelium-derived ET-1 could play an active role in the disease process.

The impact of coexistent diabetes on the prevalence of coronary heart disease.

The increased risk of developing cardiovascular disease in diabetic population has been well documented, but the prevalent mechanism of this susceptibility is still only partly explained. We compared the impact of diabetes on ischemic heart disease in patients hospitalized in a public general hospital over a 10-year period. The prevalence of coronary heart disease (CHD) was consistently higher among diabetic population [namely, among non-insulin-dependent diabetes mellitus (NIDDM) patients] when compared with the nondiabetic population. The prevalence was similar in both genders, increasing with age, and was independent from body-mass index, history of smoking, metabolic control, or lipid pattern. Heart rate and blood pressure levels were significantly higher in NIDDM patients with CHD; similarly, there was a significant association between ischemic heart disease and atherosclerotic peripheral artery disease prevalence, and this trend was observed even in subjects with impaired glucose tolerance. These observations support the evidence that diabetes exerts a deleterious effect on general risk factors of atherosclerosis and increases susceptibility to cardiovascular disease by itself as an "independent" risk factor; on the other hand, the epidemiological evidence of an excessive occurrence of type II diabetes in individuals with pre-existing vascular disease suggests a genetically determined link between metabolic disturbances and cardiovascular disease.

[Cardiovascular "risk" and diabetes mellitus. Results of a retrospective study]. / "Rischio" cardiovascolare e diabete mellito. Risultati di uno studio retrospettivo.

BACKGROUND: To examine the relationship of non-insulin dependent diabetes mellitus (NIDDM) with the prevalence of coronary heart disease (CHD) in a hospitalized population. METHODS AND RESULTS: Diabetes was associated with a markedly increased risk of developing CHD, whose prevalence was of 48.3% in NIDDM subjects (528 males and 661 females). Between the two groups (with and without CHD) of diabetic patients, the mean age was higher in the CHD-group, but no differences were noted with regard to gender distribution, BMI, history of cigarette smoking, alcohol consumption, glycemic control, hypoglycemic treatment, lipid pattern (although a slight increase in mean level of serum total triglycerides was observed in NIDDM subjects with CHD). On the contrary, CHD was significantly associated with a higher prevalence of periferal vascular disease (49.3% vs 32.5%) and with hypertension and renal dysfunction. CONCLUSIONS: These observations support the evidence that diabetes exerts a deleterious effect on general risk factors of atherosclerosis and increases the susceptibility to cardiovascular disease, although the prevalent mechanism of this susceptibility is only partly explained. Because the adverse "independent" effect of diabetes on the risk of cardiovascular disease is amplified in the presence of other cardiovascular risk factors, these data underscore the importance of prevention of diabetes and, once diabetes is clinically established, the need for standard risk factors management (hypertension, obesity, elevated lipid levels) as well as the development of new therapeutic strategies, in order to reduce the progress of macrovascular disease and the hemostatic derangements which may predispose to thrombosis and endothelial cell injury.

Circulating endothelin-1 levels in type 2 diabetic patients with ischaemic heart disease.

To investigate whether circulating endothelin-1 (Et-1) may be related to the increased incidence and severity of ischaemic heart disease in type 2 diabetes mellitus, we compared the concentrations in type 2 diabetic patients and in non-diabetic patients with coronary artery disease (CAD) angiographically documented. Plasma levels of Et-1 were determined in 34 type 2 diabetic patients with CAD (16 with stable angina, 6 with unstable angina, 12 with previous myocardial infarction) and in 19 nondiabetic patients with CAD (4 with stable angina, 5 with unstable angina, 10 with previous myocardial infarction). Fifteen diabetic patients without CAD and 9 healthy volunteers served as control subjects. In the type 2 diabetic patients, the mean Et-1 levels were 3.19 +/- 1.61 pmol/l in those with stable angina, 3.58 +/- 1.92 pmol/l in those with unstable angina, 4.24 +/- 2.53 pmol/l in those with myocardial infarction. These values were not significantly different one another, nor from the values obtained from type 2 diabetic controls (3.64 +/- 2.13 pmol/l). In the non-diabetic patients, the mean Et-1 levels were 3.92 +/- 0.73 pmol/l in those with stable angina, 4.35 +/- 1.67 pmol/l in those with unstable angina, 4.33 +/- 1.66 pmol/l in those with myocardial infarction. These values were not significantly different one another, but significantly higher than those obtained from healthy controls (2.07 +/- 0.67 pmol/l; P < 0.001). No significant differences were found in Et-1 levels between diabetic and non-diabetic patients with stable, unstable angina and previous myocardial infarction. In contrast, a statistically significant difference was found in Et-1 levels between diabetic and non-diabetic control subjects (P < 0.05). In conclusion, similar raised concentrations of Et-1 in diabetic and non-diabetic patients with stable, unstable angina and previous myocardial infarction do not support the hypothesis that higher levels of Et-1 in diabetic patients are responsible for the increased incidence of CAD in diabetes mellitus. However, the raised Et-1 levels found in diabetic patients in the absence of CAD strongly suggest that a generalised endothelial dysfunction, documented in our study by increased levels of Et-1, most probably precedes subsequent cardiovascular diseases.

Central obesity and hypertension. Relationship between fasting serum insulin, plasma renin activity, and diastolic blood pressure in young obese subjects.

This study was designed to evaluate the role of fasting serum insulin and plasma renin activity in obesity-induced hypertension. In view of this, plasma catecholamines, fasting serum insulin (IRI), urinary sodium excretion (NaU), plasma renin activity (PRA), and plasma aldosterone (PA) levels were assessed in young (age less than 40 years) normotensive (n = 27) and hypertensive (n = 14) subjects with central obesity and in lean normotensives (n = 20). Central obesity was evaluated by waist-to-hip ratio (WHR) according to the indication of the Italian Consensus Conference of Obesity. PRA, PA, IRI, and plasma norepinephrine levels were significantly (P < .05) higher in both obese groups than in lean normotensives. PRA was significantly (P < .05) higher and NaU was significantly (P < .05) lower in obese hypertensives than in obese normotensives. Diastolic blood pressure correlated directly with WHR and PRA in normotensive and hypertensive obese subjects and with IRI but only in normotensive obese subjects. Multiple regression analysis indicated that diastolic blood pressure values increased with WHR (P < .05), IRI (P < .005), and PRA (P < .002), but not with body mass index, NaU, and norepinephrine levels. Our results indicated that increased PRA could play an important role in the development of hypertension in subjects with central obesity.

Plasma endothelin levels in NIDDM patients with macroangiopathy.

To determine whether plasma endothelin, a potent vasoconstrictive peptide, is elevated in NIDDM patients, we compared a group of 15 NIDDM patients with macroangiopathy of mean age 60.60 +/- 2.33 years with 15 NIDDM randomly selected matched patients without macroangiopathy. Plasma endothelin levels were significantly increased in NIDDM patients with macroangiopathy (4.22 +/- 0.57 pmol/L) and in NIDDM patients without macroangiopathy (3.81 +/- 0.51 pmol/L). Although endothelin values did not differ between NIDDM groups, both represented significant difference from control values (2.46 +/- 0.24 pmol/L). No significant correlations were found between plasma endothelin and age (rs = 0.11), duration of diabetes mellitus (rs = 0.06), BMI (rs = 0.19), plasma glucose (rs = 0.15), plasma fructosamine (rs = 0.02). These findings confirm that in diabetes mellitus a primary disturbance in endothelin production from vascular endothelium exists as an early phenomenon rather than a result of advanced stage of the disease.