Fabry's Disease: The Utility of a Multidisciplinary Screening Approach.

(1) Background: As a lysosomal storage disorder, Fabry's disease (FD) shows variable clinical manifestations. We applied our multidisciplinary approach to identify any organ damage in a sample of adult patients with different pathogenic variants. (2) Methods: 49 participants (mean age 44.3 ± 14.2 years; 37 females), underwent a multidimensional clinical and instrumental assessment. (3) Results: At diagnosis, mean enzymatic activity was 5.2 ± 4.6 nM/mL/h in females and 1.4 ± 0.5 nM/mL/h in males (normal values > 3.0), whereas globotriaosylsphingosine was 2.3 ± 2.1 nM/L in females and 28.7 ± 3.5 nM/L in males (normal values < 2.0). Overall, cardiovascular, neurological, and audiological systems were the most involved, regardless of the variant detected. Patients with classic variants (10) showed typical multiorgan involvement and, in some cases, prevalent organ damage (cardiovascular, neurological, renal, and ocular). Those with late-onset variants (39) exhibited lower occurrence of multiorgan impairment, although some of them affected the cardiovascular and neurological systems more. In patients with lower enzymatic activity, the most frequent involvement was neurological, followed by peripheral vascular disease. (4) Conclusions: FD patients exhibited wide phenotypic variability, even at single-organ level, likely due to the individual genetic mutation, although other factors may contribute. Compared to the conventional management, a multidisciplinary approach, as that prompted at our Center, allows one to achieve early clinical detection and management.

Capillaroscopy: a useful tool in the early diagnosis of connective tissue disease and non-scleroderma spectrum disorders.

BACKGROUND: Detection of early capillaroscopic alterations in the preclinical phase may prove useful in patients with non-scleroderma connective tissue disease (CTD). We aimed to verify whether certain capillaroscopic alterations, alone or in combination, might be predictive of CTD. METHODS: We retrospectively collected data on patients with Raynaud's phenomenon who underwent capillaroscopy conducted by highly expert examiners with a degree in vascular medicine at our institutions. Included subjects were divided in two groups: those developing rheumatic disease during follow-up, and those without subsequent diagnosis of CTD. Notably, we excluded subjects who presented with an evident scleroderma pattern or rheumatic disease during their initial examination. RESULTS: We included a total of 76 patients, 60 of whom developed CTD during follow-up, which spanned in this group 23±7 months, and 16 who did not develop CTD during follow-up, which spanned 23±9 months. The following features were significantly associated with Raynaud's phenomenon: 1) angiotectonic disorder (P<0.001); 2) nonhomogeneous loop morphology (P<0.001); 3) avascular areas (P<0.001); 4) pseudo-avascular areas (P<0.001), and, albeit to a lesser degree; and 5) ectasias (P<0.050). Notably, the initial capillaroscopic pattern did not undergo any changes in subsequent tests. CONCLUSIONS: Although certain pathological characteristics of the capillaroscopic pattern are non-specific and not diagnostic if considered individually, they can be significantly suggestive for latent CTD when found in combination. At the very least, they warrant an in-depth diagnostic analysis and a lengthy follow-up.

Impact of direct oral anticoagulants on evolution of post-thrombotic syndrome.

BACKGROUND: The effect of direct oral anticoagulants (DOACs) on evolution of a post-thrombotic syndrome (PTS) is unknown. METHODS AND RESULTS: This retrospective study included patients (n = 98) with a PTS occurring after a proximal deep-vein thrombosis (DVT). The PTS progression was assessed by the Villalta scale change over time from when patients were started on DOACs for the prevention of DVT recurrence according to current guidelines. The PTS evolution was compared between patients with good (n = 63) vs. poor (n = 35) DOACs adherence, defined by using a medication possession ratio cut point of 0.80. The mean follow-up was 41.7 ± 17.7 and 27.5 ± 10.5 months in patients with good or poor adherence, respectively. The primary endpoint of PTS improvement (defined when the Villalta score became <5 and/or decreased by ≥30% from baseline) was higher in patients with good vs. poor adherence (66.7% vs. 20%, p < 0.001). None of the patients in the good adherence group experienced at any time of follow-up the co-primary endpoint of PTS worsening (defined as the Villalta score increase ≥30%), which instead occurred in 12 (34.3%) of those with poor adherence (p < 0.001). All study-defined primary endpoints occurred within 2 years. The mean values of the Villalta partial scores related to the subjective symptoms (patient-rated) and to the potentially reversible physician-rated signs were significantly improved in the good adherence group, while they were unchanged among patients with poor adherence. CONCLUSIONS: In this study a good vs. poor DOACs adherence was associated with a more favorable progression of PTS over a long-term follow-up. Larger studies are needed to explore the clinical efficacy of DOACs on PTS manifestations.

Prevalence and morphological changes of carotid kinking and coiling in growth: an echo-color Doppler study of 2856 subjects between aged 0 to 96 years.

Extracranial internal carotid artery (EICA) kinking and coiling are the most frequently reported carotid anomalies in the literature. Embryogenic and acquired causes for such anomalies have been postulated but the prevalence of kinking and coiling has not been well characterized across age categories. The aim of this study is to evaluate the prevalence of EICA coiling and kinking among different age groups to better understand its potential causes and changes during the course of life. A total of 2856 subjects aged 0 to 96 years were studied by echo-color Doppler (ECD). Morphology and anatomical anomalies of the EICA were assessed. Patients with anatomical anomalies were stratified by age groups and the prevalence of EICA abnormalities was calculated. The maximal velocity recorded at the level of the kinking was compared with that measured in the common carotid artery and the peak systolic velocity kinking ratio (PSVKR) was calculated. A total of 284 subjects (9.94% of the sample) were found to have kinking or coiling of the EICA. The prevalence was significantly higher at the extremes of age (≤ 20 and > 60 years old, p < 0.001) supporting the hypothesis of a reduction with growth and a new increase in the elderly. PSVKR was higher in subjects with more severity kinking. This study showed a higher prevalence of EICA coiling and kinking in the very young and in the elderly. This bimodal prevalence distribution supports the hypothesis of a congenital anomaly that resolves with somatic growth, while advanced age with its many anatomical changes leads to its reappearance or worsening. Studies with longitudinal follow-up and paired observation are required to support this hypothesis.

Carotid thin fluttering bands: A new element of arterial wall remodelling? An ultrasound study.

Carotid artery ultrasound is a non-invasive and reproducible technique used for early atherosclerotic assessment. Intimal flap has been described in the presence of dissection or mobile plaque rupture, however presence of carotid thin fluttering bands (TFBs) have not been described yet. To investigate frequency, characteristics and impact of TFBs in carotid lumen of patients who underwent carotid ultrasound scan (CUS). 3341 patients were admitted from January 2009 to January 2014. Patients with history of cerebral ischemia (CI) were excluded. In the cases in which TFBs were observed, a 3-months clinical and CUS follow-up (FU) was performed. TFBs were found in 71 patients (2.1%). The mean age was 63.41 ± 11.20 years (range 42-89). All patients showed a mean increase in intima-media thickness. We identified two subgroups: in 22 patients the TFB was related to a carotid plaque while in 49 no carotid plaque was found. TFB mostly originated in the carotid bulb (88.7%) and was similarly located in carotid arteries (49.3% left-side and 50.7% right-side). CUS and clinical FU were available for all patients (mean duration 25.34 months, median 19). CI occurred in none of the patients. TFB disappeared in 13 patients (18.3%) with no sign or symptoms of CI. In 3 of 49 patients without carotid plaque (6.1%), progressive thickening beneath TFB was observed. TFB is a rare finding. Longer FU is needed to evaluate its prognosis. To date, the pathophysiology is unknown, however it could be related to vascular remodeling.

SYNTAX Score II predicts carotid disease in a multivessel coronary disease population.

BACKGROUND: The SYNTAX Score (SxScore) is an angiographic tool that evaluates CAD complexity, which we previously reported lacking correlation with the presence of carotid disease. Recently, SxScore II has been developed including both angiographic and clinical variables, which could increase the prognostic accuracy for detection of carotid disease. METHODS AND RESULTS: From January 2013 to June 2014, 244 patients with multivessel CAD (mean age 65.37 years, 84% males) underwent carotid ultrasound scan. At least one carotid lesion (CL) was found in 77% of patients with significant carotid disease (SCD) in 23.4% of cases. Logistic regression analysis revealed no relation between SxScore and CL/SCD (p=0.781 and p=0.368) while SxScore II well correlated with CL (SxScore II-PCI: odds ratio [OR] 1.036; 95% confidence interval [CI]:1.006-1.067; p=0.019; SxScore II-CABG: OR 1.045; 95% CI: 1.015-1.076, p=0.003) and SCD (SxScore II-PCI: OR 1.042; 95% CI: 1.012-1.073, p=0.006; SxScore-CABG: OR 1.054; 95% CI: 1.029-1.080, p<0.0001). The areas under the receiver-operating characteristic curves were: for SxScore 0.512 (95% CI: 0.448-0.577; p=0.77), for SxScore II-PCI and SxScore II-CABG 0.600 (95% CI: 0.536-0.662; p=0.01) and 0.645 (95% CI: 0.581-0.705; p=0.0008), respectively, and 0.527 (95% CI 0.462-0.591; p=0.56), 0.619 (95% CI: 0.555-0.681; p=0.01) and 0.681 (95% CI: 0.619-0.739; p=0.0001), respectively, for the identification of SCD. CONCLUSIONS: The SxScore II, with inclusion of clinical variables over angiographic complexity, seems more suited to predict the presence of carotid disease than the SxScore.

Prevalence of asymptomatic lower limb venous thrombosis in infertile women with thrombophilic disorders.

OBJECTIVE: We sought to assess the prevalence of asymptomatic venous thrombosis in infertile women with thrombophilic disorders (TDs). METHODS AND RESULTS: A total of 73 infertile women with TDs underwent duplex ultrasound scan to evaluate superficial and deep venous circulation of lower limbs. A control group of 35 infertile women without TDs was included. A single TD was found in 13 (17.8%) subjects, and 40 (54.8%) women presented a combined defect (more than three alterations). No residual mural thrombosis (RT) was noted in any deep veins. We found RT in 48 (65.8%) patients of TD group, while no RT was found in the control group (p < 0.0001). None of the clinical and prothrombotic factors were predictors of RT (all p > 0.20), and frequency of TD did not correlate with multi-vessel RT (p = 0.252). CONCLUSIONS: No signs of deep vein thrombosis but high prevalence of superficial RT is present in infertile women with TDs. Further studies are needed to assess the prognostic value of our findings.

Early cardiovascular remodelling in Fabry disease.

AIMS: Fabry disease (FD) is a rare X-linked genetic disorder caused by the deficiency or absent activity of lysosomal α-galactosidase A. Cardiovascular remodelling is a hallmark of FD. The present study aimed to comprehensively evaluate the cardiac, vascular and microvascular status in a population of patients with genetic mutations for FD without left ventricular hypertrophy (LVH). METHODS AND RESULTS: This study includes subjects carrying genetic mutations for FD (Fabry disease mutation-carrier, FDMC) without LVH (n = 19). A group of control subjects (n = 19) matched for age, sex, body mass index and cardiovascular risk factors were also included. All subjects underwent echocardiography, carotid ultrasound scan, endothelial flow-mediated dilatation (FMD) and nailfold capillaroscopy (NFC) assessment. When compared to the subjects in the control group, FDMC patients showed significantly lower mean values of systolic myocardial velocity (7.33 ± 1.28 vs. 10.08 ± 1.63 cm/s, p < 0.0001), longitudinal systolic strain (-18.07 ± 1.72 vs. -21.15 ± 2.22%, p < 0.0001), significantly higher E/E' mean values (7.15 ± 1.54 vs. 5.98 ± 1.27, p = 0.016) and intima-media thickness mean values (0.80 ± 0.20 vs. 0.61 ± 0.19 mm, p = 0.005), significantly lower FMD (8.3 ± 4.6 vs. 12.2 ± 5.0%, p = 0.02), more atypical capillaries and irregular NFC architecture in FDMC than control subjects (52.6 vs. 0%, p < 0.0001; 78.9 vs. 36.8%, p = 0.02 respectively). CONCLUSIONS: FD progressively involves cardiac, macrovascular and microvascular systems in an early stage. These features are present even in asymptomatic mutation carriers without LVH.

The SYNTAX score does not predict presence of carotid disease in a multivessel coronary disease population.

BACKGROUND: Numerous reports have shown the relationship between carotid artery atherosclerosis and coronary artery disease (CAD). However, the association between complex CAD evaluated by SYNTAX score (SxScore) and prevalence of carotid lesion (CL) has not been fully investigated. We sought to assess the prevalence of carotid atherosclerosis in patients with multivessel CAD assessed by SxScore and the relationship between SxScore severity and features of carotid atherosclerosis. METHODS AND RESULTS: Subjects were 204 consecutive patients with multivessel CAD assessed by coronary angiography and no previous history of carotid atherosclerosis that underwent carotid ultrasound scan from June 2012 to 2013. Presence of CL, significant carotid disease (SCD) and carotid plaque morphology was evaluated. At least one CL was found in 159 patients (77.9%) with no significant difference among SxScore groups (P = 0.20 and P = 0.54, respectively). High prevalence of complex carotid plaque (CCP) was found without significant different distribution in SxScore groups (P = 0.69). Age was independently associated with the presence of CL [odds ratio (OR) 1.055; 95% confidence interval (CI): 1.015-1.097; P = 0.007] and SCD (OR 1.057; 95% CI: 1.008-1.097; P = 0.019). Age and diabetes were independently associated with CCP (OR 1.58; 95% CI: 1.023-1.095; P = 0.001; OR 1.848; 95% CI: 1.026-3.327; P = 0.041). SxScore was not independently associated with CL, SCD and CCP (all P > 0.2). CONCLUSIONS: We found high prevalence of CL in patients with multivessel complex CAD. However, SxScore does not seem to correlate with carotid atherosclerosis.

Cognitive impairment and "invisible symptoms" are not associated with CCSVI in MS.

BACKGROUND: We investigated the association between chronic cerebrospinal venous insufficiency (CCSVI) and cognitive impairment (CI) in multiple sclerosis (MS). Moreover, we evaluated the association between CCSVI and other frequent self-reported MS symptoms. METHODS: We looked at the presence of CI in incident MS patients with CCVSI in a population-based cohort of Catania, Italy. All subjects were group-matched by age, sex, disease duration and EDSS score with MS patients without CCSVI, serving as controls. CI was assessed with the Brief Repeatable Battery (BRB) and the Stroop Test (ST) and it was defined by the presence of at least three impaired tests. Fatigue and depressive symptoms were assessed with Fatigue Severity Scale (FSS) and Hamilton Depressive Rating Scale (HDRS), respectively. Bladder and sexual symptoms were assessed with the respective items of the Italian version of Guy's Neurological Disability Scale (GNDS). Quality of life was evaluated with Multiple Sclerosis Quality of Life-54 Instrument (MSQOL-54). RESULTS: Out of 61 MS patients enrolled in the study, 27 were CCSVI positive and 34 were CCSVI negative. Of them, 43 were women (70.5%); the mean age was 43.9 ± 11.8 years; the mean disease duration was 159.7 ± 113.7 months; mean EDSS was 3.0 ± 2.6. Of them, 36 (59.0%) were classified relapsing-remitting (RR), 12 (19.7%) secondary progressive (SP), seven (11.5%) primary progressive (PP) and six (9.3%) Clinically Isolated Syndrome (CIS). Overall, CI was detected in 29/61 (47.5%) MS patients; particularly 13/27 (48.1%) in the CCSVI positive group and 16/34 (47.0%) in the CCSVI negative group. Presence of CCSVI was not significantly associated with the presence of CI (OR 1.04; 95% CI 0.37-2.87; p-value = 0.9). Not significant differences were found between the two groups regarding the other MS symptoms investigated. CONCLUSIONS: Our findings suggest a lack of association between CCSVI and CI in MS patients. Fatigue, depressive, bladder/sexual symptoms and self-reported quality of life are not associated with CCSVI.

Multiple sclerosis and CCSVI: a population-based case control study.

BACKGROUND: Chronic cerebrospinal venous insufficiency (CCSVI) has been associated to multiple sclerosis (MS). OBJECTIVE: To evaluate the possible association between CCSVI and MS, using a population-based control design. METHODS: A random cohort of 148 incident MS patients were enrolled in the study. We have also studied 20 patients with clinically isolated syndrome (CIS), 40 patients with other neurological diseases (OND), and 172 healthy controls. Transcranial (TCC) and Echo Color Doppler (ECD) were carried out in 380 subjects. A subject was considered CCSVI positive if ≥2 venous hemodynamic criteria were fulfilled. RESULTS: CCSVI was present in 28 (18.9%) of the MS patients, in 2 (10%) of CIS patients, in 11 (6.4%) of the controls, and in 2 (5%) of the OND patients. A significant association between MS and CCSVI was found with an odds ratio of 3.41 (95% confidence interval 1.63-7.13; p = 0.001). CCSVI was significantly more frequent among MS subjects with a disease duration longer than 144 months (26.1% versus 12.6% of patients with duration shorter than 144 months; p = 0.03) and among patients with secondary progressive (SP) and primary progressive (PP) forms (30.2% and 29.4, respectively) than in patients with relapsing remitting (RR) MS (14.3%). A stronger association was found considering SP and PP forms (age adjusted OR = 4.7; 95% CI 1.83-12.0, p = 0.001); the association was weaker with the RR patients (age adjusted OR = 2.58; 95%CI 1.12-5.92; p = 0.02) or not significant in CIS group (age adjusted OR = 2.04; 95%CI 0.40-10.3; p = 0.4). CONCLUSIONS: A higher frequency of CCSVI has been found in MS patients; it was more evident in patients with advanced MS, suggesting that CCSVI could be related to MS disability.

Arterial stiffness is increased in patients with inflammatory bowel disease.

BACKGROUND AND AIMS: Recent studies have reported early atherosclerosis in patients with inflammatory bowel disease (IBD). In these patients, the chronic low-grade inflammation may predispose to vascular remodelling and arterial stiffening. We aimed at studying arterial stiffness in IBD patients. METHODS: Thirty-two IBD patients without cardiovascular risk factors and 32 matched controls were enrolled (age 19-49 years). SphygmoCor device (AtCor Medical, Sydney, Australia) was used to measure carotid-femoral and carotid-radial (muscular artery) pulse wave velocity (PWV), augmentation index and central blood pressure. RESULTS: Carotid-femoral PWV was higher in IBD patients than in controls (6.6 ±â€Š1.4 vs. 6.0 ±â€Š0.8 m/s, respectively, P < 0.05), as well as carotid-radial PWV (8.5 ±â€Š1.2 vs. 7.2 ±â€Š1.0 m/s, P < 0.001). Central pulse pressure was higher in IBD than in controls (32 ±â€Š6 vs. 28 ±â€Š7 mmHg, P < 0.05). Aging was an important determinant of carotid-femoral PWV in both groups and carotid-radial PWV only in IBD patients. In fully adjusted model performed in both groups of patients considered as a whole, age was positively associated with carotid-femoral PWV [R(2) = 0.10; +0.05 m/s per 1 year of aging, 95% confidence interval (CI) 0.01-0.08 m/s, P < 0.05], as well as IBD (R(2) = 0.10; +0.72 m/s if IBD present, 95% CI 0.19-1.26 m/s, P < 0.05). In IBD patients, carotid-radial PWV was positively associated with the disease duration (R(2) = 0.20; +0.11 m/s per 1 year of aging, 95% CI 0.03-0.19 m/s, P < 0.05). CONCLUSION: Arterial stiffness is increased in patients with IBD independently of conventional cardiovascular risk factors.

Arterial erectile dysfunction and peripheral arterial disease: reliability of a new phenotype of endothelial progenitor cells and endothelial microparticles.

The aim of this study was to evaluate whether the blood concentrations of a new immunophenotype of circulating late endothelial progenitor cells (EPC) and endothelial microparticles (EMP) varies in patients with arterial erectile dysfunction (aED) and abnormalities in other arterial districts. To accomplish this, cavernous artery peak systolic velocity (PSV), acceleration time (AT), and intima-media thickness (IMT) were determined after intracavernous administration of alprostadil by echo-color Doppler in 80 consecutive patients (age range, 50-75 years). Fifteen patients had aED alone (group A) and served as controls; 22 had aED plus atheroma plaques and/or increased IMT of the common carotid artery (group B); 20 had aED plus lower limb artery abnormalities (group C); and 23 had aED plus carotid and lower limb artery abnormalities (group D). EPC and EMP blood concentrations were evaluated by flow cytometry. Blood mononuclear cells with the immunophenotype CD45(neg)/CD34(pos)/CD144(pos) were defined as EPCs, whereas CD45(neg)/CD144(pos)/annexin V(pos) cells were defined as EMPs. Group B and C patients had a similar PSV, AT, and IMT at the level of the cavernous arteries. Their PSV values were significantly lower and mean values of AT and IMT significantly higher compared with group A patients. Patients of group D had a significantly lower PSV and significantly higher AT and IMT compared with all other groups. As far as serum concentrations of EPCs and EMPs, group D patients had significantly higher EPC and EMP mean values compared with all other groups. Group B and C patients had similar EPC and EMP values. This study showed that a more generalized peripheral atherosclerotic process is associated with a more severe penile artery insufficiency and endothelial dysfunction. Moreover, this study confirms the diagnostic reliability of the immunophenotype of EPCs and EMPs chosen in the clinical practice.

Arterial erectile dysfunction: reliability of penile Doppler evaluation integrated with serum concentrations of late endothelial progenitor cells and endothelial microparticles.

We recently showed the diagnostic value of a new immunophenotype of blood endothelial progenitor cells (EPC) (CD45(-)/CD34(+)/CD144(+)) and endothelial microparticles (EMP) (CD45(-)/CD144(+)/annexin V(+)) in patients with arterial erectile dysfunction (AED), particularly in patients with associated late-onset hypogonadism and/or metabolic syndrome. In addition, we evaluated the effects of androgen replacement therapy, aerobic physical activity, and tadalafil administration on these markers. The aim of this study was to evaluate the serum concentrations of EPCs and EMPs in a large cohort of patients with AED according to severity of cavernous arterial insufficiency evaluated by penile Doppler. A total of 120 patients (aged 58.0 ± 6.0 years) with AED were enrolled in this study. Patients were classified into 3 groups based on value of peak systolic velocity (PSV). Group A: 37 patients with PSV <25 cm/s (severe arterial insufficiency); group B: 40 patients with PSV between 25 and 29 cm/s (moderate arterial insufficiency); group C: 43 patients with PSV between 30 and 34 cm/s (mild arterial insufficiency). Twenty patients (aged 60.0 ± 3.0 years) with psychogenic erectile dysfunction (PED) represented the control group. EPC and EMP blood concentrations were evaluated by flow cytometry. Patients with AED had significantly higher blood pressure, triglyceride levels, homeostasis model assessment index of insulin resistance, cavernous artery acceleration time, and intima-media thickness than those with PED, whereas International Index of Erectile Function score, high-density lipoprotein cholesterol level, and cavernous artery PSV were lower than those in PED. Both EPC and EMP levels were significantly higher in patients with AED compared with patients with PED. Among 3 groups of patients with AED, there were no significant differences in metabolic parameters examined, but group A showed significantly higher values of cavernous artery acceleration time and intima-media thickness than group B and group C. Finally, group A showed serum concentrations of EPCs and EMPs significantly higher compared with other groups with AED. Patients with AED showed worse metabolic parameters, cavernous artery parameters, and EPC and EMP levels compared with patients with PED. Among patients with AED, those with PSV <25 cm/s showed worse findings of endothelial dysfunction. This suggests that AED is an expression of endothelial damage and that this original immunophenotype of EPCs and EMPs may be considered a predictor of endothelial dysfunction in patients with AED. Finally, this study confirmed the reliability of penile Doppler evaluation integrated with these serum markers of endothelial dysfunction.

Association of high alpha2-Heremans-Schmid glycoprotein/fetuin concentration in serum and intima-media thickness in patients with atherosclerotic vascular disease and low bone mass.

OBJECTIVE: Alpha2-Heremans-Schmid glycoprotein (AHSG; fetuin), a member of the cystatin superfamily of cysteine protease inhibitors involved in vascular pathology and bone metabolism, has been reported to be reduced in patients with atherosclerosis and medial calcification related to end stage renal disease or dialysis. No data on fetuin in patients with peripheral artery disease associated with low bone mass and normal renal function are available in the literature. In the present study we evaluated serum fetuin concentrations, bone mass, and markers of bone turnover in patients with atherosclerosis of peripheral vessels and normal kidney function. PATIENTS AND METHODS: Ninety consecutive patients with evidence of atherosclerotic plaques at the common carotid or femoral artery were studied. Severity grade of disease was documented by ultrasound measurement of intima-media thickness (IMT). Fasting serum levels of fetuin were measured by sandwich enzyme immunoassay. MAIN RESULTS: The mean patient serum concentration of fetuin was 57.68+/-13.6 ng/ml, significantly higher than that of control subjects (41.6+/-7.6 ng/ml; p<0.001). The mean serum concentration of bone-specific alkaline phosphatase (BAP) were 8.4+/-2.3 microg/l, significantly lower than controls (13.6+/-1.6 microg/l; p<0.001). Fetuin was correlated with IMT (r=0.8530; p<0.0001) and inversely correlated with BAP (r=-0.5503; p<0.0001). Patients had a vertebral and femoral bone mass significantly lower than controls. CONCLUSION: This study documented for the first time that, in patients with atherosclerosis of peripheral vessels, serum fetuin levels were higher than in healthy subjects, and correlated with the severity of disease; further studies are required to analyse the role of AHSG as an independent predictor of atherosclerotic disease and low bone mass in patients with normal renal function.

Propionyl-L-carnitine therapy: effects on endothelin-1 and homocysteine levels in patients with peripheral arterial disease and end-stage renal disease.

BACKGROUND/AIMS: Recent data have addressed the issue of higher levels of homocysteine (Hcy) and endothelin-1 (ET-1) in end-stage renal disease (ESRD) that may be considered an independent predictor for cardiovascular disease. The prevalence of peripheral arterial disease (PAD) in patients with ESRD has been reported to be relevant, highlighting its clinical importance. We aimed to explore the therapeutic role of propionyl-L-carnitine (PLC) in hemodialysis patients with PAD by measuring ankle/brachial index (ABI), ET-1 and Hcy. DESIGN: Randomized, double-blind, placebo-controlled trial. METHODS: Sixty-four patients on hemodialysis with chronic renal insufficiency and PAD were assigned to receive either intravenous PLC (600 mg) or placebo 3 times weekly for 12 months. The ABI and plasma levels of ET-1 and Hcy were measured at baseline, 6 and 12 months. RESULTS: In the PLC-treated group, progressive increases in ABI were observed, while in the placebo group the reverse trend was seen. Highly significant and progressive reductions in plasma levels of ET-1 and Hcy, compared to baseline, were also seen in the PLC-treated group. CONCLUSIONS: Hemodynamic flow, endothelial profile and Hcy levels were ameliorated by the administration of PLC in hemodialysis patients with ESRD and PAD.

A randomised, controlled clinical trial evaluating changes in therapeutic efficacy and oxidative parameters after treatment with propionyl L-carnitine in patients with peripheral arterial disease requiring haemodialysis.

OBJECTIVE: We explored the efficacy of intravenous therapy with propionyl L-carnitine in patients with both peripheral arterial disease (PAD) and chronic renal insufficiency requiring haemodialysis. METHODS: The trial was a randomised, double-blind, placebo-controlled trial. Sixty-four patients on haemodialysis (32 per treatment arm) with chronic renal insufficiency and PAD were assigned to receive either intravenous propionyl L-carnitine 600 mg or placebo 3 times weekly for 12 months. The main outcome measures were the ankle/brachial index (ABI), plasma malondialdehyde (MDA) and 4-hydroxynonenal (4-HNE) concentrations, and the plasma nitrite/nitrate ratio (NO(2)/NO(3)); these were measured at baseline and at 6 and 12 months. RESULTS: Significant increases in ABI were observed in the propionyl L-carnitine group, whereas in the placebo group the reverse trend was seen. In patients treated with propionyl L-carnitine, significant progressive decreases were seen in plasma MDA, 4-HNE and the NO(2)/NO(3) ratio from baseline. In the placebo-treated group, only weakly significant or no differences were seen. CONCLUSION: Intravenous administration of propionyl L-carnitine to haemodialysis patients with PAD improves both haemodynamic flow and the oxidative profile.

Plasma levels and zymographic activities of matrix metalloproteinases 2 and 9 in type II diabetics with peripheral arterial disease.

Deregulation of matrix metalloproteinases (MMPs) is an important factor contributing to the development of vascular lesions. Plasma levels and zymographic activities of MMP-2 and MMP-9 were investigated in type II diabetics with (n = 51) or without (n = 42) peripheral artery disease (PAD) and in normal volunteers (n = 23). Plasma MMP-2 levels were higher in type II diabetics with (p < 0.01) or without (p > 0.05) PAD in comparison with normal volunteers. Similarly, type II diabetics with (p < 0.0001) or without (p > 0.05) PAD had higher plasma MMP-9 levels than normal volunteers. Plasma zymographic activities of both MMP-2 and MMP-9 were positively correlated with their plasma levels. Plasma MMP-2 zymographic activity was higher in type II diabetics with PAD than type II diabetics without PAD (p > 0.05). Plasma MMP-9 zymographic activity was higher in type II diabetics with (p < 0.0001) or without (p < 0.0001) PAD in comparision with normal volunteers. Together, these results indicate that increased plasma levels and zymographic activities of MMP-2 and MMP-9 may contribute to PAD in type II diabetics. In particular, plasma MMP-9 may be a useful marker for the development of vascular disease in type II diabetics.

Early carotid atherosclerosis in women: results of an ultrasonographic study measuring carotid artery intima-media thickness.

Ultrasonography (US) is a useful diagnostic tool in detecting early vascular diseases in women and is particularly relevant in the elderly population. Increased carotid artery intima-media thickness (IMT) is a predictive marker of onset of atherosclerosis and is associated with vascular events. The objective of the present study was to determine carotid artery IMT in asymptomatic women of different age classes and to correlate the results with metabolic and coagulative parameters, age, and menopause. A total of 1200 women age 29-73 years selected from the electoral list of the city of Catania, Italy consented to participate in the US study to determine IMT. The percentage of IMT values exceeding an IMT cutoff value of < 1.3 mm observed in our study groups was significant. Correlations were observed between IMT and total cholesterol (r = .157), high-density lipoprotein (HDL) cholesterol (r = .87), low-density lipoprotein (LDL) cholesterol (r = .149), and fibrinogen (r = .140) values. Increased ultrasonographic markers showing onset of carotid artery remodeling can be observed in asymptomatic women of all ages. Some cardiovascular risk factors are linked to the initial stages of atherosclerosis. We recommend US screening in healthy populations to identify subjects who could develop vascular disease.

Correlation between some metabolic markers of vascular risk and carotid artery intima-media thickness in postmenopausal women.

UNLABELLED: AIM AND SETTING: This study investigated correlations between insulinemia, insulin sensitivity, body mass index, lipids and lipoproteins with intima-media thickness in a group of 25 (age range 40-55 years) postmenopausal women (minimum duration of menopause 2 years) not on hormone replacement treatment. METHODOLOGY: Uni and multivariate correlations showed a direct relationship between insulin pattern, insulin sensitivity, body mass index, low density lipoproteins and increased intima-media thickness. RESULTS: Our multivariate correlation results revealed that intima-media thickness is influenced by the associations of the different metabolic functions investigated. Therefore, carotid wall intima-media thickness represents a dependent variable in postmenopausal women for some metabolisms whose dysfunction leads to atherosclerosis. CONCLUSION: This multielement synergy is able to detect cardiovascular risk and may underlie cardiovascular mortality in postmenopausal women.