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Background: In patients with Systemic lupus erythematosus (SLE) a greater prevalence of structural and functional cardiovascular (CV) alterations has been described, possibly explaining the higher incidence of CV events, as compared to subjects matched for age and sex. Aim of this study was to analyze the presence of target organ damage in premenopausal women with SLE and in controls matched not only for demographic characteristics but also for other cardiovascular risk factors. Subjects and methods: 4 patients with SLE clinically stable(SLEDAI Score 2.5±1.5)(age 32±7years, range 19-44)and 34 controls matched for sex, age, BMI, clinic blood pressure(BP) and antihypertensive treatment(if present), underwent:24 hours BP monitoring, echocardiography with tissue Doppler analysis(TDI) for the evaluation of left ventricular(LV)structure and of systolic and diastolic function, carotid ultrasound for intima-media thickness(IMT), carotid distensibility measurement, and pulse wave velocity measurement(PWV). Results: By definition no difference was observed for age, sex, BMI and clinic BP values and a similar Framingham risk score was observed between SLE and controls(1.3±2.7 vs 1.5±2.3%, p=ns). No significant differences were observed for all echocardiographic parameters except LV longitudinal systolic function(Sm), an early index of LV systolic dysfunction(see Table). Carotid IMT and distensibility, as well as PWV and the prevalence of an abnormal aortic stiffness were both similar in the two groups. At the logistic analysis, PWV was independently associated with LV mass in controls and with the steroid weekly dose in SLE patients. Conclusions: In patients with SLE and low activity index of the disease we did not observe significant vascular alterations as compare to controls with similar cardiovascular risk. The early LV systolic impairment observed in this group of patients needs confirmation in larger cohorts.

The independent role of serum uric acid (SUA) as a marker of cardio-renal risk is debated. The aim of this study was to assess the relationship between SUA, metabolic syndrome (MS), and other cardiovascular (CV) risk factors in an Italian population of hypertensive patients with a high prevalence of diabetes.A total of 2429 patients (mean age 62 ± 11 years) among those enrolled in the I-DEMAND study were stratified on the basis of SUA gender specific quartiles. MS was defined according to the NCEP-ATP III criteria, chronic kidney disease (CKD) as an estimated GFR (CKD-Epi)60 ml/min/1.73 m(2) or as the presence of microalbuminuria (albumin-to-creatinine ratio ≥2.5 mg/mmol in men and ≥3.5 mg/mmol in women). The prevalence of MS, CKD, and positive history for CV events was 72%, 43%, and 20%, respectively. SUA levels correlated with the presence of MS, its components, signs of renal damage and worse CV risk profile. Multivariate logistic regression analysis revealed that SUA was associated with a positive history of CV events and high Framingham risk score even after adjusting for MS and its components (OR 1.10, 95% CI 1.03-1.18; P = 0.0060; OR 1.28, 95% CI 1.15-1.42; P0.0001). These associations were stronger in patients without diabetes and with normal renal function.Mild hyperuricemia is a strong, independent marker of MS and high cardio-renal risk profile in hypertensive patients under specialist care. Intervention trials are needed to investigate whether the reduction of SUA levels favorably impacts outcome in patients at high CV risk.

Objective: Wall-to-lumen ratio of retinal arterioles might serve as an in-vivo parameter of vascular damage. Previous studies have shown a correlation between retinal arteriolar structure and blood pressure values, measured both in the clinic and during 24 hours ambulatory monitoring. We analyzed the impact of brachial clinic blood pressure (BP), of central BP and of 24 hours BP values on wall-to-lumen ratio of retinal arterioles. Methods: In 267 subjects (129 males, age range 20–72 years; mean 54±7 years) wall-to-lumen ratio of retinal arterioles was assessed in vivo using scanning laser doppler flowmetry (Heidelberg retina flowmeter, Heidelberg Engineering). In addition clinic and 24 hours BP values were measured. Central hemodynamics and augmentation index (Ai) were assessed by pulse wave analysis. Results: In never treated patients with essential hypertension (n=56) a higher wall-to-lumen ratio (0.37±0.19 vs. 0.30±0.13, P=0.05) was observed in comparison with normotensive individuals (n=115); no significant differences were observed between treated (n=96) and untreated hypertensive patients. Wall to lumen ratio and wall cross sectional area of retinal arterioles were significantly related to clinic systolic BP(r=0.23, P=0.005) and PP(r=0.18, P=0.005), to 24 hours systolic BP(r=0.28, P=0.0001) and PP(r=0.19, P=0.003) and to central systolic BP(r=0.20, P=0.01) and central PP(r=0.21, P=0.001). Multiple regression analysis including all BP indices revealed that only mean systolic 24 hours BP is independently associated with an increased wall-to-lumen ratio of retinal arterioles. Conclusion: in this quite large group of hypertensive patients and normotensive individuals 24 hours systolic BP seems to be the strongest determinant of increased WLR of retinal arterioles.

Only 20-30% out of the treated hypertensive patients in Europe are achieving blood pressure (BP) control. Among other recognized factors, these poor results could be attributable to the fact that for many doctors it is very difficult to detect which is the predominant hemodynamic cause of the hypertension (hypervolemia, hyperinotropy or vasoconstriction). The aim of the study was to use non-invasive thoracic electrical bioimpedance (TEB) to evaluate hemodynamic modulators and subsequent hemodynamic status in uncontrolled hypertensive patients, receiving at least two antihypertensive drugs. A number of 134 uncontrolled hypertensive patients with essential hypertension were evaluated in nine European Hypertension Excellence centers by means of TEB (the HOTMAN(®) System). Baseline office systolic and diastolic BP averaged 156/92 mmHg. Hemodynamic measurements show that almost all patients (98.5%) presented at least one altered hemodynamic modulator: intravascular hypervolemia (96.4%) and/or hypoinotropy (42.5%) and/or vasoconstriction (49.3%). Eleven combinations of hemodynamic modulators were present in the study population, the most common being concomitant hypervolemia, hypoinotropy and vasoconstriction in 51(38%) patients. Six different hemodynamic states (pairs of mean arterial pressure and stroke index) were found. Data suggest that there is a strong relation between hypertension and abnormal hemodynamic modulators. This method might be helpful for treatment individualization of hypertensive patients.

Aim: To perform a genetic screening for the multiple endocrine neoplasia type 1 (MEN1) gene mutations in patients affected by an apparently sporadic form of the disease, referred to an internal medicine unit of a large general hospital. Subjects and methods: In a group of 12 consecutive patients presenting clinical features of MEN type 1 syndrome, we performed a genetic screening for germline MEN1 gene mutations, including complete sequencing of the coding region (exons 2 to 10) and multiplex ligation-dependent probe amplification analysis for large deletion detection. Results: Among these patients affected by apparently sporadic MEN type 1 syndrome, a targeted clinical history could detect indirect support for a diagnosis of familial condition only in 2 cases. The genetic screening identified pathogenic germline MEN1 gene mutations in 3 patients (25%). A previously unknown 18 base-pair deletion within exon 3, c.564_581 delCAATGGGGAGCAGACAGC, resulting in loss of 6 amino acids (pAsp189_Ala194del), was found in heterozygosis in a woman affected by primary hyperparathyroidism and multifocal pancreatic neoplasia. Conclusions: Our results underscore the importance of performing genetic testing also in apparently sporadic MEN1 patients and extend the list of molecular variants leading to inactivation of the MEN1 gene.

Objective: A relevant biological role of circulating endothelial progenitor cells (EPC) was recently demonstrated. EPC are generated in the bone marrow, and interact with damaged endothelium, restoring the integrity of the monolayer. Therefore, aim of the present study was to evaluate EPC in the blood of patients with untreated Graves’ hyperthyroidism (GD), in whom an increased oxidative stress was observed. Design and methods: Twenty-three patients with untreated active GD and 18 matched normal controls (NC) were included in the study. Circulating EPC were isolated from peripheral blood. Mononuclear cells were cultured with endothelial basal medium supplemented with EGM SingleQuots, and were identified by positive double staining after 7 days in culture. Circulating levels of C reactive protein, total antioxidant power, interleukin (IL)-6, IL-18, monocyte chemoattractant protein-1, tumor necrosis facotr-α, soluble vascular cell adhesion molecule (VCAM) and intracellular adhesion molecule were evaluated by enzyme-linked immunosorbent assay kit. EPC number was also evaluated in a subgroup of GD patients after restoration of euthyroidism. Results: Systolic blood pressure resulted increased in GD patients compared with control subjects whereas diastolic blood pressure was not significantly different. Patients with GD showed an increase in circulating levels of IL-18 and VCAM-1 and a reduction of total antioxidant power (p

Ultrasound fine needle aspiration cytology (US-FNAC) represents the most effective test available to distinguish between benign and malignant thyroid nodules, with an accuracy approaching 95%. The major limit of this procedure it is the rate of inadequate specimens which is reported to be from 10% to 31%. Also because cost considerations have always been important and have recently become even more relevant for clinical guidelines in many countries, it is desirable to limit the number of inadequate samples. Recently, we have shown that the use of stylet needles greatly reduces inadequate cytological specimens in thyroid nodules with an intranodular vascular pattern. With the aim to improve our previous results, we have extended our procedure to all thyroid solid nodules. Between February 2004 and March 2006, 312 consecutive patients with thyroid nodule without intranodular vascular pattern at color-Doppler evaluation were enrolled in this prospective study. US-FNAC was performed by two different 25 gauge needles (Neolus [Ns] and Yale Spinal [YS]), and the two procedures were performed in alternate sequence on consecutive patients. Adequate specimens were observed in 145 (92.9%) and 153 (98%) nodules respectively investigated by Ns and in YS (p0.005). The total cost to obtain a cytological diagnosis by Ns was of euro 12210.2 (156+12 repeated US-FNAC), whereas it was of euro 12449.7 by YS (156+3 repeated US-FNAC). Our data suggest that spinal needles are associated with a low proportion of inadequate FNAC, without increase of total direct cost, considering also the number of FNAC repetitions needed; therefore, their routine use could be taken into account.

Calcitonin is a hormone secreted by thyroid C-cells. Its primary effect seems to be a direct inhibition of bone degradation, but the physiological function of calcitonin in humans is still uncertain. The role of this hormone in the development of osteoporosis is unknown, but few authors have shown bone mass reduction in thyroidectomy patients.To investigate the influence of calcitonin deficiency on bone turnover, 9 males (age 31 to 66 years) submitted to total thyroidectomy in 1996 for non-toxic goitre have been studied. These patients received thyroxine treatment at individual dose but never with suppressed TSH levels. Moreover 8 sex-, age- and Body Mass Index-matched normal subjects have also been studied as control group.Calcitonin was undetectable in thyroidectomized patients, while the mean value was 7.1+/-3.2 pg/ml in the control group. At bone ultrasonography 50% of patients showed osteopenia, while only 1 subject showed osteopenia in the control group. The mean calcium serum level of patients was significant lower than in the control group (p0.001). Calcium urinary level was increased in patients than controls. PTH serum levels were statistically decreased (p0.001) in patients more than in controls. Osteocalcin showed a significantly (p0.05) lower bone formation in patients than in controls, while the markers of resorption, deoxypyridinoline and N-terminal telopeptide of type I collagen, suggested an increased bone turnover in calcitonin-deficiency patients.The results of this study show that the chronic lack of calcitonin in total thyroidectomized patients may play a role in increased bone degradation and osteopenia with a higher risk of bone fracture.

In this study we evaluated the delayed effects of a calcium entry blocker on blood pressure and on vascular structural and functional alterations in mesenteric resistance arteries of spontaneously hypertensive rats (SHR). The calcium entry blocker nitrendipine was administered (30 mg/kg per day) according to three different schedules: in one group of SHR from 4 to 8 weeks of age (n = 12), in a second group from 8 to 12 weeks of age (n = 12), and in a third group from 4 to 12 weeks of age (n = 12). Twelve untreated SHR and 12 untreated Wistar-Kyoto rats served as controls. Half the animals of each group were killed at 13 weeks, and the remaining were killed at 38 weeks. After death, relative left ventricular mass was calculated. Vascular morphology and function (responses to norepinephrine and acetylcholine) in mesenteric small arteries were then assessed using a micromyographic technique. Nitrendipine treatment delayed the development of hypertension and determined the regression of structural alterations of mesenteric resistance arteries in SHR. These favorable effects were maintained for several weeks after treatment withdrawal, provided that treatment was started at 4 weeks of age. Considering the functional alterations of mesenteric arteries in SHR (responses to norepinephrine and acetylcholine), nitrendipine treatment determined an improvement of both these dysfunctions as long as reductions of the media-to-lumen ratio and blood pressure, respectively, were maintained.

The possible involvement of peripheral dopaminergic mechanisms in the action of atrial natriuretic peptides was investigated in 10 subjects by administering 200 micrograms h-ANP 99-126 intravenously for 30 min during treatment with 50 mg carbidopa, a peripheral inhibitor of dopamine synthesis, every 8 h, or during placebo. Atrial natriuretic peptide (ANP) infusion during placebo was associated with a significant increase of diuresis, natriuresis, kaliuresis, urinary noradrenaline, and dopamine excretion. Plasma aldosterone significantly decreased. Blood pressure was slightly reduced. The administration of carbidopa significantly reduced urinary dopamine excretion but did not modify natriuresis, diuresis, indexes of adrenergic and renin-aldosterone system activity, blood pressure, or heart rate, both in basal conditions and in response to ANP infusion. We conclude that the effects of exogenous ANP administration are independent from dopaminergic mechanisms that involve the synthesis of dopamine outside the central nervous system, particularly in the kidney.

Physical exercise can increase urinary albumin excretion rate (UAER) in diabetic patients without microalbuminuria at rest (stage II diabetic nephropathy) or with baseline microalbuminuria (stage III diabetic nephropathy). The aim of this study was to compare the acute effects of captopril, an ACE inhibitor, and nifedipine, a calcium channel blocker, on exercise-induced microalbuminuria in hypertensive insulin-dependent (Type I) and non-insulin-dependent (Type II) diabetic patients with early stage nephropathy. Non-obese diabetic patients, 13 Type I (7 with stage II and 6 with stage III nephropathy) and 14 Type II (6 with stage II and 8 with stage III nephropathy), with hypertension, WHO stages I-II, underwent five submaximal cycloergometric tests: the first two in basal conditions, the other three after 24 hour administration of captopril (25 mg twice daily), placebo (1 tab twice daily) or nifedipine AR (20 mg twice daily) according to a randomised, double-blind design. Acute administration of both captopril and nifedipine was able to reduce exercise-induced microalbuminuria in hypertensive Type I and Type II diabetic patients regardless of the stage of their nephropathy. Captopril reduced systolic blood pressure less than nifedipine, in both Type I and Type II diabetics, but was more effective than nifedipine in blunting exercise-induced microalbuminuria, especially in Type I diabetics.

SUMMARY The effect of the angiotensin II antagonist saralasin on plasma aldosterone, plasma angiotensin II and blood pressure was studied in six normal supine subjects both before and during sodium depletion. Before sodium depletion, infusion of saralasin produced no consistent changes; during sodium depletion, infusion of the angiotensin antagonist caused a fall in plasma aldosterone and an increase in plasma angiotensin II in each subject. It is concluded that angiotensin II plays a major part in stimulating aldosterone secretion during sodium depletion in man.

The effects on cardiac function of captopril (CPT) and digoxin (D) were compared in a study of 16 patients with chronic heart failure due to ischemic heart disease (15) and to congestive cardiomyopathy (1) (New York Heart Association class II n.13 and class III n.3). All patients were normotensive and in sinus rhythm. CPT 25 mg every 8 hours (t.i.d.) or D 0.25 mg once daily was given in a single-blind crossover design: A placebo (PLC) t.i.d. was given for 5 to 10 days, then CPT or D, according to a random sequence, replaced three or one of the PLC tablets; after one month, CPT and D were switched to PLC for 5 to 10 days; subsequently, the PLC tablets were replaced by CPT in the patients who previously received D and vice versa, and both treatments were again continued for one month. PLC, CPT, and D tablets were all identical. Diuretics once daily were given throughout the study. Plasma renin activity (PRA), plasma aldosterone (ALDO), plasma noradrenaline (NA), and adrenaline (A) were determined at the end of the two PLC periods and the two active treatments. A hand grip and a bicycle exercise were performed at the end of the two PLC periods and the two active treatments. No difference was noted between the PLC periods. PRA increased with CPT and did not change with D. ALDO was decreased by both CPT and D. NA and A were similarly decreased by both drugs, both supine and standing.(ABSTRACT TRUNCATED AT 250 WORDS)

OBJECTIVE--To investigate whether captopril has any effect on microalbuminuria induced by exercise in normotensive diabetic patients with early stage nephropathy. DESIGN--Randomised, double blind, crossover trial. SETTING--Outpatient department. PATIENTS--22 diabetics with stage II nephropathy (urinary albumin excretion rate less than 20 micrograms/min; 15 with type I diabetes and seven with type II), 32 patients with stage III nephropathy (urinary albumin excretion rate 20-200 micrograms/min; 14 with type I diabetes and 18 with type II), and 10 normal subjects. INTERVENTIONS--Four exercise tests on a cycle ergometer: the first two under basal conditions and the third and fourth after subjects had received captopril (two 25 mg doses in 24 hours) or placebo (two tablets in 24 hours). END POINT--Exercised until 90% of maximum heart rate achieved. MEASUREMENTS AND MAIN RESULTS--Mean urinary excretion one hour after the first two exercise tests was 21 micrograms/min in normal subjects, 101 micrograms/min in diabetic patients with stage II nephropathy, and 333 micrograms/min in those with stage III nephropathy. Similar results were obtained after placebo. After captopril the urinary excretion rate one hour after exercise was significantly decreased in diabetics with stage II (36 micrograms/min) and stage III (107 micrograms/min) disease compared with placebo but not in normal subjects. Systolic and diastolic pressures were similar in the three groups after placebo and captopril had been given. CONCLUSIONS--Captopril significantly reduces microalbuminuria induced by exercise in normotensive diabetics without affecting systemic blood pressure. Captopril may reduce renal intracapillary pressure.